Notes

Bone strength and density Changes Pursuing Radiotherapy to Vertebral Metastases.
OCTA can be used in treated PD patients (ON) without a significant increase in motion artifacts. Nevertheless, special attention should be paid to image quality during the acquisition of OCTA data, for which an experienced OCTA operator is useful.Kynurenine 3-monooxygenase (KMO) regulates the levels of neuroactive metabolites in the kynurenine pathway (KP), dysregulation of which is associated with Huntington's disease (HD) pathogenesis. KMO inhibition leads to increased levels of neuroprotective relative to neurotoxic metabolites, and has been found to ameliorate disease-relevant phenotypes in several HD models. Here, we crossed KMO knockout mice to R6/2 HD mice to examine the effect of KMO depletion in the brain and periphery. KP genes were dysregulated in peripheral tissues from R6/2 mice and KMO ablation normalised levels of a subset of these. KP metabolites were also assessed, and KMO depletion led to increased levels of neuroprotective kynurenic acid in brain and periphery, and dramatically reduced neurotoxic 3-hydroxykunurenine levels in striatum and cortex. Notably, the increased levels of pro-inflammatory cytokines TNFa, IL1β, IL4 and IL6 found in R6/2 plasma were normalised upon KMO deletion. Despite these improvements in KP dysregulation and peripheral inflammation, KMO ablation had no effect upon several behavioural phenotypes. TMP269 in vitro Therefore, although genetic inhibition of KMO in R6/2 mice modulates several metabolic and inflammatory parameters, these do not translate to improvements in primary disease indicators-observations which will likely be relevant for other interventions targeted at peripheral inflammation in HD.Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS), which worsen patients' health and increase healthcare spending. The aim of this study was to assess the clinical and economic impact of switching from omalizumab (OMA) to mepolizumab (MEP) in patients eligible for both biologics, but not optimally controlled by omalizumab. We retrospectively enrolled uncontrolled severe asthmatic patients who switched from OMA to MEP during the last two years. Information included blood eosinophil count, asthma control test (ACT), spirometry, serum IgE, fractional exhaled nitric oxide (FeNO), OCS intake, drugs, exacerbations/hospitalizations, visits and diagnostic exams. Within the perspective of Italian National Health System, a pre- and post-MEP 12-month standardized total cost per patient was calculated. 33 patients were enrolled five males, mean age 57 years, disease onset 24 years. At OMA discontinuation, 88% were OCS-dependent with annual mean rate of 4.0 clinically significant exacerbations, 0.30 exacerbations needing emergency room visits or hospitalization; absenteeism due to disease was 10.4 days per patient. Switch to MEP improved all clinical outcomes, reducing total exacerbation rate (RR = 0.06, 95% CI 0.03-0.14), OCS-dependent patients (OR = 0.02, 95% CI 0.005-0.08), and number of lost working days (Δ = - 7.9, 95% CI - 11.2 to - 4.6). Pulmonary function improved, serum IgE, FeNO and eosinophils decreased. Mean annual costs were €12,239 for OMA and €12,639 for MEP (Δ = €400, 95% CI - 1588-2389); the increment due to drug therapy (+ €1,581) was almost offset by savings regarding all other cost items (- €1,181). Patients with severe eosinophilic asthma, not controlled by OMA, experienced comprehensive benefits by switching to MEP with only slight increases in economic costs.It is important to pay attention to the indirect effects of the social distancing implemented to prevent the spread of coronavirus disease 2019 (COVID-19) pandemic on children and adolescent health. The aim of the present study was to explore impacts of a reduction in physical activity caused by COVID-19 outbreak in pediatric patients diagnosed with obesity. This study conducted between pre-school closing and school closing period and 90 patients aged between 6- and 18-year-old were included. Comparing the variables between pre-school closing period and school closing period in patients suffering from obesity revealed significant differences in variables related to metabolism such as body weight z-score, body mass index z-score, liver enzymes and lipid profile. We further evaluated the metabolic factors related to obesity. When comparing patients with or without nonalcoholic fatty liver disease (NAFLD), only hemoglobin A1c (HbA1c) was the only difference between the two time points (p  less then  0.05). We found that reduced physical activity due to school closing during COVID-19 pandemic exacerbated obesity among children and adolescents and negatively affects the HbA1C increase in NAFLD patients compared to non-NAFLD patients.Cysteine-rich secretory proteins (CRISPs) are a subgroup of the CRISP, antigen 5 and PR-1 (CAP) superfamily that is characterized by the presence of a conserved CAP domain. Two conserved histidines in the CAP domain are proposed to function as a Zn2+-binding site with unknown function. Human CRISP1 is, however, one of the few family members that lack one of these characteristic histidine residues. The Zn2+-dependent oligomerization properties of human CRISP1 were investigated using a maltose-binding protein (MBP)-tagging approach in combination with low expression levels in XL-1 Blue bacteria. Moderate yields of soluble recombinant MBP-tagged human CRISP1 (MBP-CRISP1) and the MBP-tagged CAP domain of CRISP1 (MBP-CRISP1ΔC) were obtained. Zn2+ specifically induced oligomerization of both MBP-CRISP1 and MBP-CRISP1ΔC in vitro. The conserved His142 in the CAP domain was essential for this Zn2+ dependent oligomerization process, confirming a role of the CAP metal-binding site in the interaction with Zn2+. Furthermore, MBP-CRISP1 and MBP-CRISP1ΔC oligomers dissociated into monomers upon Zn2+ removal by EDTA. Condensation of proteins is characteristic for maturing sperm in the epididymis and this process was previously found to be Zn2+-dependent. The Zn2+-induced oligomerization of human recombinant CRISP1 may shed novel insights into the formation of functional protein complexes involved in mammalian fertilization.Protein engineering has great potential for devising multifunctional recombinant proteins to serve as next-generation protein therapeutics, but it often requires drastic modifications of the parental protein scaffolds e.g., additional domains at the N/C-terminus or replacement of a domain by another. A discovery platform system, called RaPID (Random non-standard Peptides Integrated Discovery) system, has enabled rapid discovery of small de novo macrocyclic peptides that bind a target protein with high binding specificity and affinity. Capitalizing on the optimized binding properties of the RaPID-derived peptides, here we show that RaPID-derived pharmacophore sequences can be readily implanted into surface-exposed loops on recombinant proteins and maintain both the parental peptide binding function(s) and the host protein function. We refer to this protein engineering method as lasso-grafting and demonstrate that it can endow specific binding capacity toward various receptors into a diverse set of scaffolds that includes IgG, serum albumin, and even capsid proteins of adeno-associated virus, enabling us to rapidly formulate and produce bi-, tri-, and even tetra-specific binder molecules.To further improve the effect of gene modules identification, combining the Newman algorithm in community detection and K-means algorithm framework, a new method of gene module identification, GCNA-Kpca algorithm, was proposed. The core idea of the algorithm was to build a gene co-expression network (GCN) based on gene expression data firstly; Then the Newman algorithm was used to initially identify gene modules based on the topology of GCN, and the number of clusters and clustering centers were determined; Finally the number of clusters and clustering centers were input into the K-means algorithm framework, and the secondary clustering was performed based on the gene expression profile to obtain the final gene modules. The algorithm took into account the role of modularity in the clustering process, and could find the optimal membership module for each gene through multiple iterations. Experimental results showed that the algorithm proposed in this paper had the best performance in error rate, biological significance and CNN classification indicators (Precision, Recall and F-score). The gene module obtained by GCNA-Kpca was used for the task of key gene identification, and these key genes had the highest prognostic significance. Moreover, GCNA-Kpca algorithm was used to identify 10 key genes in hepatocellular carcinoma (HCC) CDC20, CCNB1, EIF4A3, H2AFX, NOP56, RFC4, NOP58, AURKA, PCNA, and FEN1. According to the validation, it was reasonable to speculate that these 10 key genes could be biomarkers for HCC. And NOP56 and NOP58 are key genes for HCC that we discovered for the first time.Deficit irrigation (DI) has been emerging as an important technique for enhancing crop water productivity (WP). However, advantage of DI under varying nitrogen (N) application rates remains unclear. Field experiments were conducted during 2012-2014 to investigate the impacts of six irrigation levels[FI (full irrigation), DI10, DI20, DI30, DI40 and DI50, with irrigation amount of 100, 90, 80, 70, 60 and 50% of ETc, respectively) and four N application rates (N0, N10, N20 and N30, with 0, 10, 20 and 30 kg N ha-1, respectively) on WP, yield, quality, and net economic return of peanut in hot arid region of India. We used Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) method to obtain the optimal combination of irrigation and N rates. Both irrigation level and nitrogen dose had significant effects on yield and quality parameters examined in the study. Relative to FI, DI40 and DI50 significantly reduced yield (40.2-62.1%), economic benefit (70.8-118.5%), WP (8.2-33.0%), and kernel oil content (7.5-11.9%), but DI20 increased WP by 17.1% with only marginal reduction in economic benefit (2.6%), and yield (3.2%). Compared to N0, the N30 had 1.7, 1.1, and 1.6-folds increased yield, oil content in the kernel, and WP, respectively. Among all treatments, DI0N30 had the greatest yield and net return; DI20N30 had greatest WP and oil content in the kernel. TOPSIS analysis showed that DI20N30 was optimal in balancing of WP, yield, net return, and quality of peanut in northwestern arid India. The results have direct implications for improving irrigation water and N management for irrigated crops in arid regions.Viewing pictures of social interaction can facilitate approach behaviors. We conducted two studies to investigate if social interaction cues, empathy, and/or social touch modulate facial electromyographic (EMG) reactivity (as evidenced by the zygomaticus major and corrugator supercilii muscles) and mood states. We presented bonding pictures (depicting social interaction) and control pictures (without social interaction) while continuously recording zygomatic and corrugator EMG activities. In both studies, picture blocks were paired by valence and arousal. All participants were college students. In study 1, participants (n = 80, 47 women) read relevant priming texts immediately before viewing each block of 14 pictures. In study 2, participants did not read (n = 82, 63 women) priming texts before each block of 28 pictures. In study 1 and study 2, participants also completed mood states questionnaires to assess sociability and altruistic behavior. Empathy and social touch frequency were also assessed by self-reported questionnaires.
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