Vitamin B6 is necessary to maintain normal metabolism and immune response, especially the anti-inflammatory immune response. However, the exact mechanism by which vitamin B6 plays the anti-inflammatory role is still unclear. Here, we report a novel mechanism of preventing excessive inflammation by vitamin B6 via reduction in the accumulation of sphingosine-1-phosphate (S1P) in a S1P lyase (SPL)-dependent manner in macrophages. Vitamin B6 supplementation decreased the expression of pro-inflammatory cytokines by suppressing nuclear factor-κB and mitogen-activated protein kinases signalling pathways. Furthermore, vitamin B6-reduced accumulation of S1P by promoting SPL activity. The anti-inflammatory effects of vitamin B6 were inhibited by S1P supplementation or SPL deficiency. Importantly, vitamin B6 supplementation protected mice from lethal endotoxic shock and attenuated experimental autoimmune encephalomyelitis progression. Collectively, these findings revealed a novel anti-inflammatory mechanism of vitamin B6 and provided guidance on its clinical use.
  Natural orifice transluminal endoscopic surgery has been used for gynecologic operations in recent years. The aim of the study is to describe our initial experience using vaginal-assisted natural orifice transluminal endoscopic surgery (vNOTES) for apical pelvic organ prolapse repair.
 
  After patients underwent vaginal hysterectomy, vNOTES sacrocolpopexy (n = 4) or vNOTES high uterosacral ligament suspension (n = 7) were performed to treat symptomatic apical pelvic organ prolapse. Sociodemographic and clinical characteristics, Pelvic Organ Prolapse Quantification results, and recorded surgical data (eg, duration of surgery, intraoperative complications, additional prolapse and incontinence surgeries) were obtained from patient files and the hospital's database. Information from postoperative follow-up visits, including complications and anatomical results, were also recorded.
 
  The mean age of the patients was 60.7 ± 9.1 years. The mean total operative time was 121.3 ± 22.7 minutes. The mean operative time for vaginal hysterectomy, vNOTES sacrocolpopexy, and vNOTES uterosacral ligament suspension was 46 ± 11.9, 65 ± 38, 25 ± 8.2 minutes, respectively. There were no intraoperative and postoperative complications observed. The mean postoperative 24-hour visual analog scale score was 3.5 ± 1.9 for vNOTES sacrocolpopexy patients and 3.2 ± 0.9 for vNOTES uterosacral ligament suspension patients. Only one patient in the vNOTES sacrocolpopexy group had a recurrence; she experienced stage 2 anterior compartment prolapse 8 months after surgery.
 
  As a treatment for apical pelvic organ prolapse, vNOTES is a feasible approach in both sacrocolpopexy and uterosacral ligament suspension.
 As a treatment for apical pelvic organ prolapse, vNOTES is a feasible approach in both sacrocolpopexy and uterosacral ligament suspension.
  To discuss and contrast different theoretical perspectives of resilience and explore the value these bring to understanding health professional well-being.
 
  Resilience has been used to describe one characteristic of health professionals who work in challenging areas, such as intensive care units, emergency departments and oncology settings. Studies have reported on how health professionals can become more resilient in these settings-with a focus on individuals-describing the conditions needed to become more resilient.
 
  This is a Discussion paper.
 
  This paper draws on the extant literature to explore theoretical perspectives of social constructionism and social constructivism. These perspectives are then linked to recent literature to support the discussion of how resilience can be understood and considered in the context of health professionals.
 
  Resilience is typically conceptualized at an individual level. This manuscript highlights the broader structural factors which impact health practitioner well-being. The benefits of a resilient workforce are known to have an impact on the quality of patient care.
 
  This paper argues that resilience should be considered from a social approach that is sensitive to the context, including the relationships an individual has within their social environment.
 This paper argues that resilience should be considered from a social approach that is sensitive to the context, including the relationships an individual has within their social environment.Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse drug reaction. Our previous whole-exome sequencing study found SIRT1 intronic region single-nucleotide polymorphism (SNP) rs7896005 to be associated with MRONJ in cancer patients treated with intravenous (iv) bisphosphonates (BPs). This study aimed to identify causal variants for this association. In silico analyses identified three SNPs (rs3758391, rs932658, and rs2394443) in the SIRT1 promoter region that are in high linkage disequilibrium (r2  > 0.8) with rs7896005. To validate the association between these SNPs and MRONJ, we genotyped these three SNPs on the germline DNA from 104 cancer patients of European ancestry treated with iv BPs (46 cases and 58 controls). Multivariable logistic regression analysis showed the minor alleles of these three SNPs were associated with lower odds for MRONJ. The odds ratios (95% confidence interval) and p values were 0.351 (0.164-0.751; p = 0.007) for rs3758391, 0.351 (0.164-0.751; p = 0.007) for rs932658, and 0.331 (0.157-0.697; p = 0.0036) for rs2394443, respectively. In the reporter gene assays, constructs containing rs932658 with variant allele A had higher luciferase activity than the reference allele, whereas constructs containing SNP rs3758391 and/or rs2394443 did not significantly affect activity. These results indicate that the promoter SNP rs932658 regulates the expression of SIRT1 and presumably lowers the risk of MRONJ by increasing SIRT1 expression. © 2020 American Society for Bone and Mineral Research (ASBMR).Rheumatoid arthritis (RA) is a chronic inflammatory condition characterized by articular synovitis that eventually leads to the destruction of cartilage and bone in the joints with resulting pain and disability. The current therapies for RA are divided into 4 categories non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, nonbiological disease-modifying anti-rheumatic drugs (DMARDs), and biological DMARDs. Each drug grouping is beset with significant setbacks that not only include limited drug bioavailability and high clearance, but also varying degrees of drug toxicity to normal tissues.  https://www.selleckchem.com/  Recently, nanotechnology has provided a promising tool for the development of novel therapeutic and diagnostic systems in the area of malignant and inflammatory diseases. Among these, magnetic nanoparticles (MNPs) have provided an attractive carrier option for delivery of therapeutic agents. Armed with an extra magnetic probe, MNPs are capable of more accurately targeting the local lesion with avoidance of unpleasant systemic side effects.