Kjeldsendeleuran4584
Visual and molecular changes occurring upon aging are rather well characterized. Still, aging signs show great significant inter-individual variations, and little is known concerning the link between perceived age and cutaneous microcirculation.
To investigate this point, we recruited Caucasian women in their mid-50's to mid-70's and subsampled women looking older or younger than their age. We studied their facial skin color, as well as their microvascular reactivity to local heating assessed in the forearm skin. We also used skin biopsies from some of these women for gene expression or immunohistochemical analysis.
Clinical and instrumental analysis of skin color revealed that subjects who look 5years younger differ only by a higher glowing complexion. Our most striking result is that subjects looking 5years younger than their age present a higher microcirculation reactivity in forearm skin. Transcriptome comparison of skin samples from women looking older or younger than their age revealed 123 annotated transcripts differentially expressed, among which MYL9 relates to microcirculation. MYL9 is downregulated in the group of women looking younger than their real age. Microscopy shows that the labeling of MYL9 and CD31 are altered and heterogeneous with age, as is the morphology of microvessels.
Therefore, assessing generalized vascular reactivity in non-photo-exposed skin to focus on the intrinsic aging allows subtle discrimination of perceived age within elderly healthy subjects.
Therefore, assessing generalized vascular reactivity in non-photo-exposed skin to focus on the intrinsic aging allows subtle discrimination of perceived age within elderly healthy subjects.
Enhanced recovery after surgery protocols and increased attention to value-based care have led to the reconsideration of routine postoperative admission in female pelvic medicine and reconstructive surgery (FPMRS) cases. We aimed to assess trends in same-day discharge (SDD) and associated readmissions and emergency room visits in a single-surgeon 10-year experience.
The electronic medical record was queried for 30-day outcomes (readmission and emergency department visits with associated indications) for all cases performed between June 2010 and August 2020 by a single FPMRS surgeon. Non-FPMRS specialty cases were excluded. Patient characteristics and 30-day outcomes were compared based on SDD status for the overall cohort as well as the subset of cases traditionally involving an overnight stay (i.e., robotic transabdominal, apical prolapse repair).
1793 surgeries were identified and analyzed, including 357 apical prolapse repairs, 370 slings, 392 neuromodulation and 114 complex mesh excisions. ALK inhibitor The majority (79.1%) had SDD. For admitted patients, mean length of stay was 1.5 (1.3) days. Among cases traditionally involving overnight stay, rates of SDD were significantly higher in 2020 than 2010 (84% vs. 32%, p < 0.001), and increased over time. Overall rates of 30-day readmission and ED visits were low (1.9% and 2.6%, respectively) and did not differ based on SDD status (p = 0.76). Readmissions occurred at mean 11.6 (7.0) days, most commonly for urinary tract infection (13/34).
SDD is not associated with increased 30-day readmission or ED visits across a wide breadth of FPMRS cases. SDD is safe and feasible in the majority of FPMRS cases.
SDD is not associated with increased 30-day readmission or ED visits across a wide breadth of FPMRS cases. SDD is safe and feasible in the majority of FPMRS cases.
To compare the efficacy of the treatment with transcutaneous perineal electrostimulation versus intracavitary electrostimulation to reduce the frequency of urinary incontinence after radical prostatectomy and the impact on the quality of life (QoL).
This single-blind equivalence-randomized controlled trial equally (11) randomly allocated men with urinary incontinence post radical prostatectomy into surface electrodes perineal group (intervention group, IG) and intra-anal probe group (control group, CG). Outcomes included changes in the 24h-Pad Test (main variable), and ICIQ-SF (International Consultation on Incontinence Questionnaire Short-Form), SF-12 (Short Form Health Survey), and I-QOL (incontinence quality of life questionnaire) questionnaires. Clinical data were collected at baseline, 6 and 10 weeks. For the comparisons between variables, χ
test and Student's t test were used. Equivalence was analyzed by estimating the mean change (90% confidence interval) of urinary incontinence based on the Pad erved in both groups was statistically significant and clinically relevant.
Surface and intra-anal electrostimulation treatments reduced significantly losses of urine, but differences in grams of urine loss throughout the therapy between groups were not significant, suggesting that the efficacy of the two treatments is not statistically different. Nonetheless, the improvement observed in both groups was statistically significant and clinically relevant.The nine-amino-acid activation domain (9aaTAD) is defined by a short amino acid pattern including two hydrophobic regions (positions p3-4 and p6-7). The KIX domain of mediator transcription CBP interacts with the 9aaTAD domains of transcription factors MLL, E2A, NF-kB, and p53. In this study, we analyzed the 9aaTADs-KIX interactions by nuclear magnetic resonance. The positions of three KIX helixes α1-α2-α3 are influenced by sterically-associated hydrophobic I611, L628, and I660 residues that are exposed to solvent. The positions of two rigid KIX helixes α1 and α2 generate conditions for structural folding in the flexible KIX-L12-G2 regions localized between them. The three KIX I611, L628, and I660 residues interact with two 9aaTAD hydrophobic residues in positions p3 and p4 and together build a hydrophobic core of five residues (5R). Numerous residues in 9aaTAD position p3 and p4 could provide this interaction. Following binding of the 9aaTAD to KIX, the hydrophobic I611, L628, and I660 residues are no longer exposed to solvent and their position changes inside the hydrophobic core together with position of KIX α1-α2-α3 helixes. The new positions of the KIX helixes α1 and α2 allow the KIX-L12-G2 enhanced formation. The second hydrophobic region of the 9aaTAD (positions p6 and p7) provides strong binding with the KIX-L12-G2 region. Similarly, multiple residues in 9aaTAD position p6 and p7 could provide this interaction. In conclusion, both 9aaTAD regions p3, p4 and p6, p7 provide co-operative and highly universal binding to mediator KIX. The hydrophobic core 5R formation allows new positions of the rigid KIX α-helixes and enables the enhanced formation of the KIX-L12-G2 region. This contributes to free energy and is the key for the KIX-9aaTAD binding. Therefore, the 9aaTAD-KIX interactions do not operate under the rigid key-and-lock mechanism what explains the 9aaTAD natural variability.
Radiation pneumonitis (RP) is the main source of toxicity in thoracic radiotherapy. This study proposed a deep learning-based dual-omics model, which aims to improve the RP prediction performance by integrating more data points and exploring the data in greater depth.
The bimodality data were the original dose (OD) distribution and the ventilation image (VI) derived from four-dimensional computed tomography (4DCT). The functional dose (FD) distribution was obtained by weighting OD with VI. A pre-trained three-dimensional convolution (C3D) network was used to extract the features from FD, VI, and OD. The extracted features were then filtered and selected using entropy-based methods. The prediction models were constructed with four most commonly used binary classifiers. Cross-validation, bootstrap, and nested sampling methods were adopted in the process of training and hyper-tuning.
Data from 217 thoracic cancer patients treated with radiotherapy were used to train and validate the prediction model. The 4DCT-based VI showed the inhomogeneous pulmonary function of the lungs. More than half of the extracted features were singular (of none-zero value for few patients), which were eliminated to improve the stability of the model. The area under curve (AUC) of the dual-omics model was 0.874 (95% confidence interval 0.871-0.877), and the AUC of the single-omics model was 0.780 (0.775-0.785, VI) and 0.810 (0.804-0.811, OD), respectively.
The dual-omics outperformed single-omics for RP prediction, which can be contributed to (1) using more data points; (2) exploring the data in greater depth; and (3) incorporating of the bimodality data.
The dual-omics outperformed single-omics for RP prediction, which can be contributed to (1) using more data points; (2) exploring the data in greater depth; and (3) incorporating of the bimodality data.To examine the association of health and hospital workers' fears of coronavirus disease 2019 (COVID-19) with anxiety, anxiety sensitivity, depression, and sociodemographic variables during the COVID-19 pandemic. A total of 527 participants (237 men/289 women) were included, 222 of the participants were doctors, 99 nurses, 22 assistant health personnel, and 182 hospital personnel without health education. Participants filled in the sociodemographic data form, Beck Depression Inventory, Beck Anxiety Inventory, Anxiety Sensitivity Index-3, and Fear of COVID-19 Inventory. In linear regression analysis, independent predictors of the fear of COVID-19 were determined as Beck Anxiety Inventory (p less then 0.001), Beck Depression Inventory (p = 0.001), and Anxiety Sensitivity Index-3 Physical subscale (p = 0.001). The fear of COVID-19 is associated with the physical subscale of anxiety, depression, and anxiety sensitivity.The ribosomal gene DNA (rDNA) often forms secondary constrictions in the chromosome; however, the molecular mechanism involved remains poorly understood. Here, we report that occurrence of rDNA constriction was increased in the chromosomes in human cancer cell lines compared with normal cells and that decondensed rDNA was significantly enhanced after partial inhibition of rDNA transcription. rDNA transcription was found during the S phase when replication occurred, and thus, DNA replication inhibitors caused constriction formation through hindering rDNA transcription. Inhibition of ataxia ATR (telangiectasia-mutated and RAD3-related) induced rDNA constriction formation. Replication stress or transcription inhibition increased R-loop formation. Topoisomerase I and RNase H1 suppressed secondary constriction formation. These data demonstrate that transcription stress causes the accumulation of stable R-loops (RNA-DNA hybrid) and subsequent constriction formation in the chromosomes.Myeloid-derived suppressor cells (MDSC) represent a highly immunosuppressive population that expands in tumor bearing hosts and inhibits both T and NK cell antitumor effector functions. Among MDSC subpopulations, the polymorphonuclear (PMN) one is gaining increasing interest since it is a predominant MDSC subset in most cancer entities and inherits unique properties to facilitate metastatic spread. In addition, further improvement in distinguishing PMN-MDSC from neutrophils has contributed to the design of novel therapeutic approaches. In this review, we summarize the current view on the origin of PMN-MDSC and their relation to classical neutrophils. Furthermore, we outline the metastasis promoting features of these cells and promising strategies of their targeting to improve the efficacy of cancer immunotherapy.
