Mayfranklin2935

84 to -19.48 min; MD range for insomnia severity -6.40 to -3.93) and waitlist (MD range for sleep efficiency 7.68%-12.32%; MD range for TST 12.67-30.49 min; MD range for SOL -19.07 to -10.46 min; MD range for WASO -47.10 to -19.15 min; MD range for insomnia severity -7.59 to -5.07). The effects of different CBT-I formats persisted at short-term follow-up (4 wk-6 mo). Individual, group, and digital assisted CBT-I delivery formats would be the more appropriate choices for insomnia in adults, based on post-intervention and short-term effects. Further trials are needed to investigate the long-term effects of different CBT-I formats.The role of the microbiome in health and disease is attracting the attention of researchers seeking to engineer microorganisms for diagnostic and therapeutic applications. Recent progress in synthetic biology may enable the dissection of host-microbiota interactions. Sophisticated genetic circuits that can sense, compute, memorize, and respond to signals have been developed for the stable commensal bacterium Bacteroides thetaiotaomicron, dominant in the human gut. In this review, we highlight recent advances in expanding the genetic toolkit for B. thetaiotaomicron and foresee several applications of this species for microbiome engineering. We provide our perspective on the challenges and future opportunities for the engineering of human gut-associated bacteria as living therapeutic agents.

Matrix metalloproteinases (MMPs) of atherosclerotic tissue contribute to plaque rupture triggering acute coronary syndromes (ACS). Several MMPs, including MMP-2, are also contained in platelets and released upon activation. An increase in circulating levels of MMP-2 has been reported in patients undergoing percutaneous coronary interventions (PCI), but its time-course and origin remain unclear. Aims of our study were to assess the time-course of MMP-2 release in blood of stable and unstable coronary artery disease patients undergoing PCI and to unravel the possible contribution of platelets to its release.

Peripheral blood samples were drawn immediately before, 4 and 24h after PCI from patients with ACS (NSTEMI or STEMI, n=21) or with stable angina (SA, n=21). Platelet-poor plasma and washed platelet lysates were prepared and stored for subsequent assay of MMP-2 and β-thromboglobulin (β-TG), a platelet-specific protein released upon activation.

Plasma MMP-2 and β-TG increased significantly 4h after PCI Given that previous mechanicistic studies have shown that MMP-2 may sustain platelet activation and unstabilize downstream-located plaques and in the long term favour restenosis and atherosclerosis progression, these data may encourage the search for therapeutic agents blocking MMP-2 release or activity in ACS.As transcranial electrical stimulation (tES) protocols advance, assumptions underlying the technique need to be retested to ensure they still hold. Whilst the safety of stimulation has been demonstrated mainly for a small number of sessions, and small sample size, adverse events (AEs) following multiple sessions remain largely untested. Similarly, whilst blinding procedures are typically assumed to be effective, the effect of multiple stimulation sessions on the efficacy of blinding procedures also remains under question. This is especially relevant in multisite projects where small unintentional variations in protocol could lead to inter-site difference. We report AE and blinding data from 1,019 participants who received up to 11 semi-consecutive sessions of active or sham transcranial alternating current stimulation (tACS), direct current stimulation (tDCS), and random noise stimulation (tRNS), at 4 sites in the UK and US. We found that AEs were often best predicted by factors other than tES, such as testing site or session number. Results from the blinding analysis suggested that blinding was less effective for tDCS and tACS than tRNS. The occurrence of AEs did not appear to be linked to tES despite the use of smaller electrodes or repeated delivery. However, blinding efficacy was impacted in tES conditions with higher cutaneous sensation, highlighting a need for alternative stimulation blinding protocols. This may be increasingly necessary in studies wishing to deliver stimulation with higher intensities.

Biomarkers that predict the risk of immune-mediated adverse events (irAEs) among patients with non-small cell lung cancer (NSCLC) may reduce morbidity and mortality associated with these treatments.

We carried out high resolution human leucocyte antigen (HLA)-I typing on 179 patients with NSCLC treated with anti-program death (PD)-1/program death ligand (PDL)-1. Toxicity data were collected and graded as per common terminology criteria for adverse event (CTCAE) v5.0. We used 14.8-week for landmark analysis to address lead-time bias to investigate the correlation between HLA-I/II zygosity, supertypes and alleles with irAE. Furthermore, we assessed the association for irAE with clinical benefit rate (CBR), progression-free survival (PFS)and overall survival (OS).

Homozygosity at one or more HLA-I loci, but not HLA-II, was associated with a reduced risk of irAE (relative risk (RR)=0.61, 95% CI 0.33-0.95, P=0.035) especially pneumonitis or any grade 3 toxicity. Patients with HLA-A03 supertype had a higher risk of developing irAE (RR=1.42, 95% CI 1.02-2.01, P=0.039). The occurrence of any irAE was significantly associated with improved CBR (RR=1.48, P<0.0001), PFS (HR=0.45, P=0.0003) and OS (HR=0.34, P<0.0001).

Homozygosity at one or more HLA-I loci may serve as biomarker to predict patients who are unlikely to experience severe irAEs among patients with NSCLC and treated with anti-PD1/PDL1, but less likely to derive clinical benefit. Patients with HLA-I homozygous might benefit from additional therapy.

Homozygosity at one or more HLA-I loci may serve as biomarker to predict patients who are unlikely to experience severe irAEs among patients with NSCLC and treated with anti-PD1/PDL1, but less likely to derive clinical benefit. Patients with HLA-I homozygous might benefit from additional therapy.

Mutations in STK11/LKB1 gene present a negative impact on tumour immune microenvironment, especially with concomitant activating KRAS mutation. These recent data may explain a decreased response to immunotherapy treatment in STK11 mutant non-small cell lung cancer (NSCLC).

The primary objective is to evaluate, in a real-life setting, overall survival (OS) in patients with NSCLC according to the presence of STK11 mutation. The secondary objective is to assess time to treatment failure (TTF) for the first-line chemotherapy or immunotherapy.

This observational multicentric study was conducted in Nouvelle-Aquitaine (France), for 24 months. Clinical, histopathological and imagery data were collected in each centre while the next-generation sequencing analysis was performed in Bordeaux Hospital University. Patient's data were longitudinally followed from NSCLC diagnosis date to the occurrence of censoring events (therapeutic failure or death, as applicable) or until the study end date.

median OS from the first drug administration was significantly longer for STK11^wt patients than STK11^mut patients (16.2 months [11 - nr] versus 4.7 months [2.5-9.4]; Log-rank test P<0.001). The Presence of STK11 mutation was significantly associated with shortened OS (RR=2.26 [1.35-3.79], P=0.002). First-line TTF was significantly shorter in STK11^mut population and the presence of the mutation was significantly associated with an increase in treatment failures (RR=1.87 [1.21-2.89], P=0.005). The type of treatment (chemotherapy, immunotherapy) does not influence the amplitude of reduced TTF in patients with STK11^mut.

The presence of STK11 mutation is associated with poor prognosis in NSCLC.

The presence of STK11 mutation is associated with poor prognosis in NSCLC.

Survival of patients with colon and rectal cancer has improved in all Nordic countries during the past decades. The aim of this study was to further assess survival trends in patients with colon and rectal cancer in the Nordic countries by age at diagnosis and to present additional survival measures.

Data on colon and rectal cancer cases diagnosed in the Nordic countries between 1990 and 2016 were obtained from the NORDCAN database. Relative survival was estimated using flexible parametric models. Both age-standardized and age-specific measures for women and men were estimated from the models, as well as reference-adjusted crude probabilities of death and life-years lost.

The five-year age-standardized relative survival of colon and rectal cancer patients continued to improve for women and men in all Nordic countries, from around 50% in 1990 to about 70% at the end of the study period. In general, survival was similar across age and sex. The largest improvement was seen for Danish men and women with rectal cancer, from 41% to 69% and from 43% to 71%, respectively. The age-standardized and reference-adjusted five-year crude probability of death in colon cancer ranged from 30% to 36% across countries, and for rectal cancer from 20% to 33%. The average number of age-standardized and reference-adjusted life-years lost ranged between six and nine years.

There were substantial improvements in colon and rectal cancer survival in all Nordic countries 1990-2016. Of special note is that the previously observed survival disadvantage in Denmark is no longer present.

There were substantial improvements in colon and rectal cancer survival in all Nordic countries 1990-2016. Of special note is that the previously observed survival disadvantage in Denmark is no longer present.Distraction osteogenesis (DO) is a widely used surgical technique to repair bone defects, partly owing to its high efficiency in inducing osteogenesis; however, the process of osteogenesis is complex, and the precise mechanism is still unclear. Among the factors identified for an effective DO procedure, well-controlled inflammation is essential. We aimed to explore how microRNA(miR)-146a, a negative regulator of inflammation, influences osteogenesis in DO. First, we established canine right mandibular DO and bone fracture models to evaluate the expression level of miR-146a in response to these procedures. Second, bone marrow mesenchymal stem cells (BMSCs) were isolated from healthy puppies and cultured with lipopolysaccharide (LPS) to observe how inflammation affects osteogenesis. Finally, the osteogenesis activity of BMSCs transfected with lentiviral vector either overexpressing (miR-146a-up) or inhibited for miR-146a expression was evaluated. miR-146a-up-transfected BMSCs were injected locally into the distraction gaps of the DO model canines. On days 42 and 56 post-surgery, the bone volume/tissue volume and bone mineral density values were evaluated via using micro-computed tomography, and newly formed tissues were harvested and evaluated via histological staining. The expression of miR-146a in both the DO canine model and LPS-stimulated BMSCs increased. Overexpression of miR-146a enhanced cell proliferation, migration, and osteogenic differentiation. Mepazine Additionally, the newly formed callus was improved in canine mandibles injected with miR-146a-up-transfected BMSCs. In summary, miR-146a regulates mandibular DO by improving osteogenesis, and can serve as a potential target to shorten the therapy period of DO.