Molloyweaver8353

0 months, respectively. Adverse events such as anorexia, fatigue, pneumonitis, and hypothyroidism were observed. There were two treatment-related deaths due to pneumonitis and thrombocytopenia. Subsequent-line ICI monotherapy in patients with good performance status (PS), receiving steroids for immune-related adverse events (irAEs), and exhibiting partial response (PR) was associated with improved PFS, as well as OS in patients with good PS and PR. CONCLUSIONS Subsequent-line ICI monotherapy in elderly patients, with previously treated NSCLC, was effective, safe and showed outcomes equivalent to those in non-elderly patients. Immunotherapy provides a survival benefit for elderly patients, who exhibit its efficacy and a favorable general condition.Dissimilatory nitrite reductase, a key enzyme in the denitrification pathway, catalyzes the reduction of nitrite to NO. Bioinformatic analysis showed that the genome of a novel nitrite-degrading haloarchaeon Halorussus sp. YCN54 possessed a gene encoding the Cu-containing dissimilatory nitrite reductase (NirKHrs). NirKHrs was heterologously expressed and purified. Protein sequencing indicated that two isoforms of NirKHrs monomer were produced intracellularly. UV-vis spectrum of the purified NirKHrs showed that it belonged to the blue NirK group. NirKHrs showed optimum activity at 4.5 M NaCl, 55 ℃ and pH 7.0, representing a halophilic, slightly thermophilic and neutral enzyme. It exhibited high stability at 30-50 ℃. NirKHrs activity was strongly inhibited by the copper chelating agent due to removal of copper. NirKHrs activity was activated by Mn2+ and Sr2+. It displayed good tolerance to some high polarity organic solvents and nonionic surfactants, such as glycerol, DMSO, DMF and tween-20. Na2S2O4 was an effective electron donor to NirKHrs. The Km and Vmax values of purified NirKHrs for nitrite were 3.2 mM and 477.2 U/mg, respectively, indicating its high activity. These results indicated that NirKHrs may have potential applications for nitrite degradation in high-salt industries, such as salted food and saline wastewater treatment.BACKGROUND Smoking causes a threefold increase in the risk of surgical complications in flaps. Hyperbaric oxygen therapy (HBOT) increases the viability of chronic wounds. However, there are few studies concerning the effects of HBOT on surgical flaps in patients who smoke. This study aimed to analyze the effect of HBOT on the viability of cutaneous flaps in tobacco-exposed rats. METHODS Twenty Wistar rats were exposed to tobacco smoke for two months. Following this period, all animals underwent a dorsal cutaneous flap (3 × 10 cm) surgery and were divided into two groups control (n = 10) and HBOT (n = 10). HBOT was performed in seven daily sessions (2 ATA, 90 min). After seven days, the animals were euthanized. The outcomes were total area, viable area, viable area/total area rate, analysis of dermal appendages and angiogenesis (hematoxylin-eosin), and gene expression analysis of iNOS and VEGF-a biomarkers. RESULTS The HBOT group showed an increase in viable area compared with the control group (84% versus 47%, p = 0.009, respectively). The HBOT group also showed an increase in appendage units (1.69 ± 0.54 versus 1.87 ± 0.58, p = 0.04) and angiogenesis density (1.29 ± 0.45 versus 1.82 ± 0.64, p  less then  0.001) compared to the control group. There was a difference between the control and HBOT groups in iNOS levels (0.926 ± 1.4 versus 0.04 ± 0.1 p = 0.002, respectively). However, this study did not show a difference between the groups concerning the gene expression of VEGF-a. CONCLUSION The use of hyperbaric oxygen therapy increased the viability of cutaneous flaps in tobacco-exposed rats and decreased iNOS mRNA levels; however, it did not change VEGF-a levels. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.Topoisomerase IIα (topo2α) is an essential nuclear enzyme involved in DNA replication, transcription, recombination, chromosome condensation, and highly expressed in many tumors. Thus, topo2α-targeting has become a very efficient and well-established anticancer strategy. Herein, we investigate the cytotoxic and DNA-damaging activity of thiomaltol-containing ruthenium-, osmium-, rhodium- and iridium-based organometallic complexes in human mammary carcinoma cell lines by means of several biological assays, including knockdown of topo2α expression levels by RNA interference. Results suggest that inhibition of topo2α is a key process in the cytotoxic mechanism for some of the compounds, whereas direct induction of DNA double-strand breaks or other DNA damage is mostly rather minor. In addition, molecular modeling studies performed for two of the compounds (with Ru(II) as the metal center) evinces that these complexes are able to access the DNA-binding pocket of the enzyme, where the hydrophilic environment favors the interaction with highly polar complexes. These findings substantiate the potential of these compounds for application as antitumor metallopharmaceuticals.Virtual Reality (VR) is being integrated into many different areas of our lives, from industrial engineering to video-games, and also including teaching and education. We have several examples where VR has been used to engage students and facilitate their 3D spatial understanding, but can VR help also teachers? What are the benefits teachers can obtain on using VR applications? In this paper we present an application (VR4Health) designed to allow students to directly inspect 3D models of several human organs by using Virtual Reality systems. The application is designed to be used in an HMD device autonomously as a self-learning tool and also reports information to teachers in order that he/she becomes aware of what the students do and can redirect his/her work to the concrete necessities of the student. We evaluate both the students' and the teachers' perception by doing an experiment and asking them to fill-in a questionnaire at the end of the experiment.INTRODUCTION The purpose of the present study was to investigate the role of short stem implants for primary total hip arthroplasty in middle-aged patients. selleck chemicals For this purpose, a meta-analysis of the current literature was conducted. The focus was on clinical outcomes,radiological parameters, and further complications of both components. MATERIAL AND METHODS The study was performed according to the PRISMA guidelines. All randomized and non-randomized clinical trials comparing short stem versus standard stem prostheses for THA were considered for inclusion. Only studies reporting data concerning uncemented stems for primary total hip arthroplasty were included. Only studies reporting data concerning patients with a mean age of 45 to 69 were included. RESULTS A total of 2197 procedures in 2116 patients were analysed. The mean follow-up was 30.2 months. The short stem group showed a statistically significant higher WOMAC score and a reduced total estimated blood loss compared with the standard stem group. The short stem group showed a reduced rate of femoral fractures, dislocations, and revision, but without statistical significance. CONCLUSIONS According to the main findings of this meta-analysis and current evidence, we encourage the use of the uncemented short stems during primary total hip arthroplasty in middle-aged patients.PURPOSE To investigate the effect of C3/4 disc degeneration on cervical spondylosis with dizziness (CSD) and to assess the curative effect of anterior cervical decompression and fusion (ACDF) in patients with CSD. METHOD Four hundred nineteen patients who underwent ACDF for treatment of myelopathy or radiculopathy were divided into dizziness and non-dizziness group. The visual analog scale (VAS) score and Japanese Orthopaedic Association (JOA) score were used to determine the intensity of dizziness and neurological symptoms, respectively. Cervical disc degeneration was evaluated using Miyazaki's classification system. Some parameters were measured using cervical radiographs. The surgical effects on CSD were compared between surgery with and without C3/4 level. Multivariate logistic regression analysis was used to determine the risk factors for CSD. RESULTS The pre-operative incidence of CSD was 33.9%. Women were more likely to develop dizziness than men (p  less then  0.05), CSD was significantly associated with C3/4 disc degeneration (69.7%, p  less then  0.001), and smokers were more subject to dizziness (p  less then  0.05). Regression analysis showed that female (OR = 1.611, p = 0.031), smoking (OR = 1.719, p = 0.032), Miyazaki grade of C3/4 ≥ IV (OR = 2.648, p  less then  0.001), and instability on C3/4 (OR = 1.672, p = 0.024) were risk factors for CSD. Treatment of CSD by ACDF involving C3/4 was more effective than not involving C3/4 (efficacy rate, 73.2% vs 51.7%, p  less then  0.05). CONCLUSION The CSD is a common clinical manifestation in elderly patients, especially patients with cervical spondylosis at the C3/4 level. Female, smoking, instability on C3/4, and C3/4 Miyazaki grade ≥ IV could be considered significant risk factors for CSD. CSD is more likely to be alleviated by ACDF involving C3/4.Biological sex influences inflammatory response, as there is a greater incidence of acute inflammation in men and chronic inflammation in women. Here, we report that acute inflammation is attenuated by X-inactive specific transcript (Xist), a female cell-specific nuclear long noncoding RNA crucial for X-chromosome inactivation. Lipopolysaccharide-mediated acute inflammation increased Xist levels in the cytoplasm of female mouse J774A.1 macrophages and human AML193 monocytes. In both cell types, cytoplasmic Xist colocalizes with the p65 subunit of NF-κB. This interaction was associated with reduced NF-κB nuclear migration, suggesting a novel mechanism to suppress acute inflammation. Further supporting this hypothesis, expression of 5' XIST in male cells significantly reduced IL-6 and NF-κB activity. Adoptive transfer of male splenocytes expressing Xist reduced acute paw swelling in male mice indicating that Xist can have a protective anti-inflammatory effect. These findings show that XIST has functions beyond X chromosome inactivation and suggest that XIST can contribute to sex-specific differences underlying inflammatory response by attenuating acute inflammation in women.It is well-established that Lysine-specific demethylase 1 (LSD1, also known as KDM1A) roles as a lysine demethylase canonically acting on H3K4me1/2 and H3K9me1/2 for regulating gene expression. Though the discovery of non-histone substrates methylated by LSD1 has largely expanded the functions of LSD1 as a typical demethylase, recent groundbreaking studies unveiled its non-catalytic functions as a second life for this demethylase. We and others found that LSD1 is implicated in the interaction with a line of proteins to exhibit additional non-canonical functions in a demethylase-independent manner. Here, we present an integrated overview of these recent literatures charging LSD1 with unforeseen functions to re-evaluate and summarize its non-catalytic biological roles beyond the current understanding of its demethylase activity. Given LSD1 is reported to be ubiquitously overexpressed in a variety of tumors, it has been generally considered as an innovative target for cancer therapy. We anticipate that these non-canonical functions of LSD1 will arouse the consideration that extending the LSD1-based drug discovery to targeting LSD1 protein interactions non-catalytically, not only its demethylase activity, may be a novel strategy for cancer prevention.