• McAllister McKenzie opublikował 5 miesięcy, 1 tydzień temu

    Duplication of chromosome 15q11.2-q13.1 (dup15q syndrome) results in hypotonia, intellectual disability (ID), and autism symptomatology. Clinical electroencephalography has shown abnormal sleep physiology, but no studies have characterized sleep behaviors. The present study used the Children’s Sleep Habits Questionnaire (CSHQ) in 42 people with dup15q syndrome to examine the clinical utility of this questionnaire and quantify behavioral sleep patterns in dup15q syndrome. Individuals with fully completed forms (56%) had higher cognitive abilities than those with partially completed forms. Overall, caregivers indicated a high rate of sleep disturbance, though ratings differed by epilepsy status. Results suggest that clinicians should use caution when using standardized questionnaires and consider epilepsy status when screening for sleep problems in dup15q syndrome.Relapsed Mantle cell lymphoma (MCL) is often treated with Bruton’s Tyrosine Kinase inhibitors (BTKi); however, post-BTKi relapse can be challenging. Adding venetoclax (VEN) to ibrutinib(IBR) has shown synergy in pre-clinical MCL models. Prior MCL studies of the combination report promising efficacy but have conducted limited dose finding. We sought to identify the optimal dosing combination, based on efficacy and toxicity, utilizing a continual re-assessment method of 6 combinations of IBR (280mg, 420 mg, and 560mg PO daily) and VEN (max dose of 200mg and 400mg PO daily). Eligible participants were not previously exposed to BTKi’s and not high risk for Tumor Lysis Syndrome (TLS). VEN, initiated first at 100mg, then at 20mg PO daily after a TLS event, was started prior to adding IBR and ramped-up based on the dose level. Combination treatment continued for six 28 day cycles. 35 participants were enrolled and treated. One TLS event occurred with starting dose of 100mg VEN; no TLS was seen with 20mg. The optimal dosing combination was considered to be VEN 200mg and IBR 420mg with an ORR of 93.8% (95% CI 73.6-99.7%) and DLT incidence of 6.2% (95% CI 0.3-26.4%). Overall response for all arms was 82.3% (28/34; 95% CI 65.5-93.2%) with a CR rate of 42.4% (14/33; 95% CI 25.5-60.8%). A participant was not allocated to IBR 560mg and VEN 400mg. ORR benefit was not seen with higher dosing combinations and toxicity was higer; a comparison made within the limitations of small cohorts. Resistance was seen in nearly all arms. This trial was registered at http://www.clinicaltrials.gov #NCT02419560.Umbilical cord blood transplantation (UCBT) has increased access to potentially curative therapy for patients with life-threatening disorders of the bone marrow and immune system. The introduction of reduced intensity conditioning (RIC) regimens and double cord unit infusions (DUCBT) has broadened the applicability of UCBT to more frail or larger recipients. The kinetics of chimerism following RIC DUCBT and their clinical utility are poorly understood. The RIC CBT trial reported here sought to prospectively evaluate the role of lineage specific chimerism following DUCBT in adult patients with haematological malignancies in the UK. Fifty-eight patients with a median age of 52 years were recruited, with an overall and progression free survival of 59% (95%CI 45% to 71%) and 52% (95%CI 39% to 64%) respectively at 2 years. Nonrelapse mortality was 4% (95% CI 1% to 13%) at day 100 and the relapse rate was 31% (95%CI 21% to 45%) at 1 year. Peripheral blood lineage specific chimerism was feasible from day 7 post-transplant onwards. Five patterns of chimerism were observed including i) complete single unit dominance (39 patients), ii) sustained donor-donor mixed chimerism (3 patients), iii) sustained donor-recipient mixed chimerism (5 patients), iv) dominance reversion (1 patient) and v) primary graft failure (4 patients). The RIC CBT trial enabled adult patients with high-risk hematological malignancies to safely access UCBT in the UK and provided novel insights into the kinetics of donor and recipient chimerism following RIC DUCBT which are clinically relevant. (Clinical Trials.gov identifier NCT00959231; EudraCT identifier 2004-003845-41).To assess the variation of sea star (Asteroidea) populations in the Northern Gulf of California and look for evidence of sea star ulcerative lesions, counts of sea star species were recorded in 2019 using a standard belt-transect technique of 30 m2. During surveys, scuba divers also measured sea stars’ diameter and examined them for ulcerative lesions. Ulcerative lesions were noted on Phataria unifascialis only. To verify changes in abundance and size of the two most abundant species, P. unifascialis and Pharia pyramidata, historical data from 2009, 2010, and 2016 were used as comparison and using the same methodology. To evaluate differences in abundance or diameter in sea star species over time, analysis of variance tests (ANOVA) were used. We found a significant reduction in diameter for the species P. unifascialis and P. pyramidata over time ( less then 0.0001), but only P. unifascialis also showed a significant decrease in abundance (P=0.018). The decrease in diameter recorded for these two species, along with the signs of ulcerative lesions found on one of them in 2019, suggest that a potential mortality event occurred and, as a result, new younger (i.e., smaller) recruits could be recovering the population. These results highlight the importance of population monitoring to understand complex reef community dynamics.Atmospheric pressure cold plasma has shown multiple biological effects of anti-bacteria and anti-cancer. In this study, the effect of atmospheric pressure cold plasma on respiratory inflammation and oxidant stress is explored. Tunicamycin was used to stimulate human bronchial epithelial cells (HBECs) and A549 cells for inflammatory response and oxidative stress, followed by atmospheric pressure cold plasma treatment. For HBECs and A549 cells, atmospheric pressure cold plasma was able to alleviate tunicamycin-induced cell proliferation inhibition, inflammation and oxidant stress, and enhance nuclear factor-erythroid-2-related factor 2 (NRF2) pathway activation. Moreover, NRF2/ARE (anti-oxidant response elements) pathway was involved in the regulation of atmospheric pressure cold plasma on tunicamycin-induced oxidative stress. These results suggest the positive effect of atmospheric pressure cold plasma on inflammation and oxidant stress of respiratory system, indicating the therapeutic potential of atmospheric pressure cold plasma for respiratory diseases.Bioorthogonal transformation of imaging and therapeutic substrates using transition metal catalysts (TMCs) provides a toolkit with diverse applications in biomedicine. Controlled localization of bioorthogonal catalysis is key for enhancing their therapeutic efficacy by minimizing off-target effects. Red blood cells (RBCs) are highly biocompatible and are susceptible to hemolysis by bacterial toxins, providing them with intrinsic targeting to bacterial infections. A hitchhiking strategy using RBCs is reported, that activates bioorthogonal catalysis at infection sites. A library of nanoparticles embedded with TMCs (nanozymes) featuring diverse functional groups with different binding ability to RBCs is generated. These engineered nanozymes bind to RBCs and subsequently release upon hemolysis by bacterial toxins, resulting in selective accumulation at the site of bacterial infections. The antimicrobial action is specific catalytic activation of pro-antibiotics eradicated pathogenic biofilms without harming non-virulent bacterial species.In the field of molecular electronics, the interplay between molecular orientation and the resulting electronic transport is of central interest. At the single molecule level, this topic is extensively studied with the aid of break junction setups. In such experiments, two metal electrodes are brought into contact, and the conductance is typically measured when the electrodes are pulled apart in the presence of molecules, until a molecule bridges the two electrodes. However, the molecular junctions formed in this pull process reflect only part of the rich possible junction configurations. Here, we show that the push process, in which molecular junctions are formed by bringing the electrodes towards each other, allows the fabrication of molecular junction structures that are not necessarily formed in the pull process. We also find that in the extreme case, molecular junctions can be formed only in the push process that is typically ignored. Our findings demonstrate that tracking the two inverse processes of molecular junction formation, reveals a more comprehensive picture of the variety of molecular configurations in molecular junctions.Since the interface between ionic liquids (ILs) and solids always plays a critical role in important applications such as coating, lubrication, energy storage and catalysis, it is essential to unravel the molecular structure and dynamics of ILs confined to solid surfaces. Here we report direct observation of a unique double-layering quantized growth of three IL (i.e. [Emim][FAP], [Bmim][FAP] and [Hmim][FAP]) nanofilms on mica. AFM results show that the IL nanofilms initially grow only by covering more surface areas at the constant film thickness of 2 monolayers (ML) until a quantized increase in the film thickness by another 2 ML occurs. Based on the AFM results, we propose a double-layering model describing the molecular structure of IL cations and anions on the mica surface. The interesting double-layering structure can be explained as the result of several competing interactions at the IL-mica interface. Meanwhile, the time-dependent AFM results indicate that the topography of IL nanofilms could change with time and mobility of the nanofilm is lower for ILs with longer alkyl chains, which can be attributed to the stronger solvophobic interaction. The findings here have important implications on the molecular structure and dynamics of ILs confined to solid surfaces.Iron deficiency anaemia (IDA) has been receiving worldwide attention. Developing safe and effective iron supplements is of great significance for IDA treatment. Tegillarca granosa (T. granosa), a traditional aquaculture bivalve species in China, is considered to be an excellent source of micronutrients, but the distribution and bioavailability of these minerals have yet to be investigated. The present research was conducted to determine the contents and in vitro enzymatic digestibility of minerals in T. granosa, using beef and wheat flour as reference foods. Meanwhile, two iron-binding proteins, hemoglobin and ferritin, were extracted from T. granosa, and their structures, iron accessibility and bioavailability were investigated. Moreover, the effects of ascorbic acid (AA) and citric acid (CA), two commonly applied dietary factors, on these parameters were evaluated. Our results indicated that the mineral levels varied significantly among different food matrices, with T. granosa showing the highest contents of the tested elements. Comparison of iron absorption of meat versus wheat flour and hemoglobin versus ferritin confirmed that heme iron exhibited higher bioavailability than non-heme iron. The addition of the two organic acids notably enhanced the cellular iron uptake of T. granosa-derived proteins. This could be because AA/CA weakened hydrogen bonds within proteins and caused disordered secondary structures, thereby improving their enzymatic digestibility and releasing more soluble iron to be available for absorption. The results of this study provided a basis for the development of T. granosa-derived protein-based iron supplements, promoting the diverse utilization of marine aquatic resources.

Szperamy.pl
Logo
Enable registration in settings - general
Compare items
  • Total (0)
Compare
0