Holbrookflynn8158

tween catheter insertion and catheter failure was longer in the innovation group compared with the standard group (50·4 [IQR 29·6-69·4] h vs 30·0 [16·6-52·6] h; p=0·0017). find more Minor skin reactions occurred in nine (2%) patients in the chlorhexidine plus alcohol group and seven (1%) patients in the povidone iodine plus alcohol group.

For skin antisepsis, chlorhexidine plus alcohol provides greater protection of peripheral venous catheter-related infectious complications than does povidone iodine plus alcohol. Use of innovative devices extends the catheter complication-free dwell time.

Becton Dickinson.

For the Chinese, Portuguese, Spanish, Turkish and Russian translations of the abstract see Supplementary Materials section.

For the Chinese, Portuguese, Spanish, Turkish and Russian translations of the abstract see Supplementary Materials section.Ferroptosis is a type of nonapoptotic cell death driven by lipid peroxidation. Here, we show a key role of MGST1 in inhibiting ferroptosis in cell cultures and mouse xenograft models. Ferroptosis activators induce MGST1 upregulation in human pancreatic ductal adenocarcinoma (PDAC) cell lines in an NFE2L2-dependent manner. The genetic depletion of MGST1 or NFE2L2 has a similar effect in promoting ferroptosis, whereas the re-expression of MGST1 restores the resistance of NFE2L2-knockdown cells to ferroptosis. MGST1 inhibits ferroptotic cancer cell death partly by binding to ALOX5, resulting in reduced lipid peroxidation. The expression of MGST1 is positively correlated with NFE2L2 expression in pancreatic tumors, which is implicated in the poor prognosis of patients with PDAC. These findings not only provide a valuable insight into the defense mechanism against ferroptotic cell death, but also indicate that targeting the MGST1 redox-sensitive pathway may be a promising strategy for the treatment of PDAC.

The optimal radiotherapy dose for indolent non-Hodgkin lymphoma is uncertain. We aimed to compare 24 Gy in 12 fractions (representing the standard of care) with 4 Gy in two fractions (low-dose radiation).

FoRT (Follicular Radiotherapy Trial) is a randomised, multicentre, phase 3, non-inferiority trial at 43 study centres in the UK. We enrolled patients (aged >18 years) with indolent non-Hodgkin lymphoma who had histological confirmation of follicular lymphoma or marginal zone lymphoma requiring radical or palliative radiotherapy. No limit on performance status was stipulated, and previous chemotherapy or radiotherapy to another site was permitted. Radiotherapy target sites were randomly allocated (11) either 24 Gy in 12 fractions or 4 Gy in two fractions using minimisation and stratified by histology, treatment intent, and study centre. Randomisation was centralised through the Cancer Research UK and University College London Cancer Trials Centre. Patients, treating clinicians, and investigators were n4 Gy and 79·8% (74·8-83·9) after 4 Gy; corresponding rates at 5 years were 89·9% (85·5-93·1) after 24 Gy and 70·4% (64·7-75·4) after 4 Gy (hazard ratio 3·46, 95% CI 2·25-5·33; p<0·0001). The difference at 2 years remains outside the non-inferiority margin of 10% at -13·0% (95% CI -21·7 to -6·9). The most common events at week 12 were alopecia (19 [7%] of 287 sites with 24 Gy vs six [2%] of 301 sites with 4 Gy), dry mouth (11 [4%] vs five [2%]), fatigue (seven [2%] vs five [2%]), mucositis (seven [2%] vs three [1%]), and pain (seven [2%] vs two [1%]). No treatment-related deaths were reported.

Our findings at 5 years show that the optimal radiotherapy dose for indolent lymphoma is 24 Gy in 12 fractions when durable local control is the aim of treatment.

Cancer Research UK.

Cancer Research UK.Feedback control has enabled the success of automated technologies by mitigating the effects of variability, unknown disturbances, and noise. While it is known that biological feedback loops reduce the impact of noise and help shape kinetic responses, many questions remain about how to design molecular integral controllers. Here, we propose a modular strategy to build molecular quasi-integral feedback controllers, which involves following two design principles. The first principle is to utilize an ultrasensitive response, which determines the gain of the controller and influences the steady-state error. The second is to use a tunable threshold of the ultrasensitive response, which determines the equilibrium point of the system. We describe a reaction network, named brink controller, that satisfies these conditions by combining molecular sequestration and an activation/deactivation cycle. With computational models, we examine potential biological implementations of brink controllers, and we illustrate different example applications.Adipose precursor cells (APCs) exhibit regional variation in response to obesity, for unclear reasons. Here, we reveal that HIFα-induced PDGFRβ signaling within murine white adipose tissue (WAT) PDGFRβ+ cells drives inhibitory serine 112 (S112) phosphorylation of PPARγ, the master regulator of adipogenesis. Levels of PPARγ S112 phosphorylation in WAT PDGFRβ+ cells are depot dependent, with levels of PPARγ phosphorylation in PDGFRβ+ cells inversely correlating with their capacity for adipogenesis upon high-fat-diet feeding. HIFα suppression in PDGFRβ+ progenitors promotes subcutaneous and intra-abdominal adipogenesis, healthy WAT remodeling, and improved metabolic health in obesity. These metabolic benefits are mimicked by treatment of obese mice with the PDGFR antagonist Imatinib, which promotes adipocyte hyperplasia and glucose tolerance in a progenitor cell PPARγ-dependent manner. Our studies unveil a mechanism underlying depot-specific responses of APCs to high-fat feeding and highlight the potential for APCs to be targeted pharmacologically to improve metabolic health in obesity.The adipose tissue stroma is a rich source of molecularly distinct stem and progenitor cell populations with diverse functions in metabolic regulation, adipogenesis, and inflammation. The ontology of these populations and the mechanisms that govern their behaviors in response to stimuli, such as overfeeding, however, are unclear. Here, we show that the developmental fates and functional properties of adipose platelet-derived growth factor receptor beta (PDGFRβ)+ progenitor subpopulations are tightly regulated by mitochondrial metabolism. Reducing the mitochondrial β-oxidative capacity of PDGFRβ+ cells via inducible expression of MitoNEET drives a pro-inflammatory phenotype in adipose progenitors and alters lineage commitment. Furthermore, disrupting mitochondrial function in PDGFRβ+ cells rapidly induces alterations in immune cell composition in lean mice and impacts expansion of adipose tissue in diet-induced obesity. The adverse effects on adipose tissue remodeling can be reversed by restoring mitochondrial activity in progenitors, suggesting therapeutic potential for targeting energy metabolism in these cells.