Milesnygaard3472

The use of CD34 + cell-based therapies has largely been focused on haematological conditions. However, there is increasing evidence that umbilical cord blood (UCB) CD34 + -derived cells have neuroregenerative properties. Due to low cell numbers of CD34 + cells present in UCB, expansion is required to produce sufficient cells for therapeutic purposes, especially in adults or when frequent applications are required. However, it is not known whether expansion of CD34 + cells has an impact on their function and neuroregenerative capacity. We addressed this knowledge gap in this study, via expansion of UCB-derived CD34 + cells using combinations of LDL, UM171 and SR-1 to yield large numbers of cells and then tested their functionality. CD34 + cells expanded for 14 days in media containing UM171 and SR-1 resulted in over 1000-fold expansion. The expanded cells showed an up-regulation of the neurotrophic factor genes BDNF, GDNF, NTF-3 and NTF-4, as well as the angiogenic factors VEGF and ANG. In vitro functionality testing showed that these expanded cells promoted angiogenesis and, in brain glial cells, promoted cell proliferation and reduced production of reactive oxygen species (ROS) during oxidative stress. Collectively, this study showed that our 14-day expansion protocol provided a robust expansion that could produce enough cells for therapeutic purposes. These expanded cells, when tested in in vitro, maintained functionality as demonstrated through promotion of cell proliferation, attenuation of ROS production caused by oxidative stress and promotion of angiogenesis.The number of human LncRNAs has now exceeded all known protein-coding genes. Most studies of human LncRNAs have been conducted in cell culture systems where various mechanisms of action have been worked out. On the other hand, efforts to elucidate the function of human LncRNAs in an in vivo setting have been limited. In this brief review, we highlight some strengths and weaknesses of studying human LncRNAs in the mouse. Special consideration is given to bacterial artificial chromosome transgenesis and genome editing. The integration of these technical innovations offers an unprecedented opportunity to complement and extend the expansive literature of cell culture models for the study of human LncRNAs. Two different examples of how BAC transgenesis and genome editing can be leveraged to gain insight into human LncRNA regulation and function in mice are presented the random integration of a vascular cell-enriched LncRNA and a targeted approach for a new LncRNA immediately upstream of the ACE2 gene, which encodes the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent underlying the coronavirus disease-19 (COVID-19) pandemic.A modified Fontan procedure is performed to palliate single ventricle malformations. This hemodynamic arrangement sets systemic venous pressure unphysiologically high which predisposes the patient to severe long-term complications. As a means of self-care, exercise may ease transpulmonary flow. check details We investigated the effects of 6-month exercise prescription on pediatric Fontan patients. Eighteen stable Fontan patients (14 ± 2.6 years, 160.4 ± 11.3 cm, and 51.4 ± 14.4 kg) were recruited. Baseline fitness was assessed by physical activity questionnaire, body composition, cardiorespiratory performance, and muscle fitness tests. Exercise prescription was individually tailored for a 6-month training period at home. At entrance to the study, Fontan patients had lower than normal maximal oxygen uptake (VO2max) of 28. ± 5.9 ml/kg/min (61 ± 11% of normal). VO2max significantly correlated with weekly amount of habitual exercise and muscle mass of the lower limbs (p  less then  0.001 for both). After 6 months of training, the patients had improved their anaerobic threshold of 18 ± 3.5 vs 20 ± 4.8 ml/kg/min, p = 0.007, and workload tolerance of 119 ± 39 vs 132.4 ± 44 W, p = 0.001. At EUROFIT tests, the patient muscle fitness was below age-matched reference, but correlations existed between VO2max and lower limb muscle tests. Our patients with Fontan hemodynamics were able to positively respond to an exercise program by enhancing submaximal performance which should be beneficial for getting through daily activities. Future studies should correlate whether hemodynamic findings at Fontan completion influence physical activity and exercise reserves, and whether these predict predisposition to chronic complications.

The effects of hypnotics on automobile driving have been attracting increasing attention. However, few driving simulators (DSs) have been confirmed to have acceptable reliability and validity for assessing the next-day residual effects of zopiclone as a positive control on driving performance.

To investigate whether a new DS could permit detection of the next-day residual effects of zopiclone on driving performance.

In this double-blind, randomized, placebo-controlled crossover trial, 28 healthy males received zopiclone 7.5mg at bedtime on days 1 and 8 and placebo on the other days over a period of 16days. The participants took part in three driving tasks-road-tracking, car-following, and harsh-braking-using a DS on days 2 and 9 at 9-h post-dosing. Scores on the Karolinska Sleepiness Scale and Profile of Mood States-Second Edition were then assessed, as was the serum concentration of zopiclone.

The estimated differences in the standard deviation of lateral position (cm) in the road-tracking task between the zopiclone and placebo groups on days 2 and 9 were 3.75cm (90% confidence interval (CI) 1.71-5.79) and 4.07cm (90% CI 2.02-6.11), respectively. The estimated differences in the distance coefficient of variation in the car-following task and in the brake reaction time in the harsh-braking task between the zopiclone and placebo groups on day 2 were 4.31 (90% CI 1.94-6.69) and 24.6ms (90% CI 12.7-36.4), respectively.

The DS used in this study has sufficient sensitivity to detect the next-day residual effects of zopiclone on driving performance.

The DS used in this study has sufficient sensitivity to detect the next-day residual effects of zopiclone on driving performance.

The maxillectomy defect is complex and the best means to achieve optimal reconstruction, and dental rehabilitation is a source of debate. The refinements in zygomatic implant techniques have altered the means and speed by which rehabilitation can be achieved and has also influenced the choice regarding ideal flap reconstruction. The aim of this study is to report on how the method of reconstruction and oral rehabilitation of the maxilla has changed since 1994 in our Institution, and to reflect on case mix and survival.

Consecutive head and neck oncology cases involving maxillary resections over a 27-year period between January 1994 and November 2020 were identified from hospital records and previous studies. Case note review focussed on clinical characteristics, reconstruction, prosthetic rehabilitation, and survival.

There were 186 patients and the tumour sites were alveolus for 56% (104), hard palate for 19% (35), maxillary sinus for 18% (34) and nasal for 7% (13). 52% (97) were Brown class 2 defects. Forty-five patients were managed by obturation and 78% (142/183) had free tissue transfer. The main flaps used were radial (52), anterolateral thigh (27), DCIA (22), scapula (13) and fibula (11). There were significant changes over time regarding reconstruction type, use of primary implants, type of dental restoration, and length of hospital stay. Overall survival after 24months was 64% (SE 4%) and after 60months was 42% (SE 4%).

These data reflect a shift in the reconstruction of the maxillary defect afforded by the utilisation of zygomatic implants.

These data reflect a shift in the reconstruction of the maxillary defect afforded by the utilisation of zygomatic implants.

In our modern society, artificial light is available around the clock and most people expose themselves to electrical light and light-emissive screens during the dark period of the natural light/dark cycle. Such suboptimal lighting conditions have been associated with adverse metabolic effects, and redesigning indoor lighting conditions to mimic the natural light/dark cycle more closely holds promise to improve metabolic health. Our objective was to compare metabolic responses to lighting conditions that resemble the natural light/dark cycle in contrast to suboptimal lighting in individuals at risk of developing metabolic diseases.

Therefore, we here performed a non-blinded, randomised, controlled, crossover trial in which overweight insulin-resistant volunteers (n = 14) were exposed to two 40h laboratory sessions with different 24h lighting protocols while staying in a metabolic chamber under real-life conditions. In the Bright day-Dim evening condition, volunteers were exposed to electric bright light (ch Initiative an initiative with support from the Dutch Heart Foundation (CVON2014-02 ENERGISE).

We acknowledge the financial support from the Netherlands Cardiovascular Research Initiative an initiative with support from the Dutch Heart Foundation (CVON2014-02 ENERGISE).

Insufficient antimicrobial exposure is associated with worse outcomes in sepsis. We evaluated whether therapeutic drug monitoring (TDM)-guided antibiotic therapy improves outcomes.

Randomized, multicenter, controlled trial from January 2017 to December 2019. Adult patients (n = 254) with sepsis or septic shock were randomly assigned 11 to receive continuous infusion of piperacillin/tazobactam with dosing guided by daily TDM of piperacillin or continuous infusion with a fixed dose (13.5g/24h if eGFR ≥ 20mL/min). Target plasma concentration was four times the minimal inhibitory concentration (range ± 20%) of the underlying pathogen, respectively, of Pseudomonas aeruginosa in empiric situation. Primary outcome was the mean of daily total Sequential Organ Failure Assessment (SOFA) score up to day 10.

Among 249 evaluable patients (66.3 ± 13.7years; female, 30.9%), there was no significant difference in mean SOFA score between patients with TDM (7.9 points; 95% CI 7.1-8.7) and without TDM (8.2 points; 95% CI tion.In this work, the biomolecule glutathione was used to prepare cyan fluorescent carbon dots (GSH@CDs) by a hydrothermal method. The GSH@CDs were adopted as the scaffolds to synthesize fluorescent gold nanoclusters (GSH@CDs-Au NCs) with two independent emission peaks at 430 nm and 700 nm. A fluorescent method for the Cu2+ and Ag+ ion assay was established based on the fluorescence quenching or enhancement at 700 nm of GSH@CDs-Au NCs. The fluorescent test strips were successfully prepared for visual detection of Cu2+ ions and Ag+ ions based on GSH@CDs-Au NCs. In addition, GSH@CDs-Au NCs were found to possess well peroxidase-like activity.Analysis of the dipicolinic acid (DPA) released from Clostridium botulinum spores during thermal processing is crucial to obtaining a mechanistic understanding of the factors involved in spore heat resistance and related food safety applications. Here, we developed a novel mixed-mode liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for detection of the DPA released from C. botulinum type A, nonproteolytic types B and F strains, and nonpathogenic surrogate Clostridium sporogenes PA3679 spores. DPA was retained on a mixed-mode C18/anion exchange column and was detected using electrospray ionization (ESI) positive mode within a 4-min analysis time. The intraday and interday precision (%CV) was 1.94-3.46% and 4.04-8.28%, respectively. Matrix effects were minimal across proteolytic type A Giorgio-A, nonproteolytic types QC-B and 202-F, and C. sporogenes PA3679 spore suspensions (90.1-114% of spiked DPA concentrations). DPA recovery in carrot juice and beef broth ranged from 105 to 118%, indicating limited matrix effects of these food products.