Sanchezprater1631

peripheral CD57

CD8 T cells and tumor-infiltrating lymphocytes suggest that accumulation of peripheral CD57

CD8 T cells is reflective of an ongoing antitumor T-cell response. Our findings provide evidence and rationale for using circulating CD8 T cells expressing CD57 as a readily accessible blood-based biomarker for selecting patients with mUC for atezolizumab therapy.

Collectively, we show high frequencies of CD57 among neoantigen-specific and bulk CD8 T cells in patients responding to atezolizumab. The TCR repertoire overlap between peripheral CD57+ CD8 T cells and tumor-infiltrating lymphocytes suggest that accumulation of peripheral CD57+ CD8 T cells is reflective of an ongoing antitumor T-cell response. Our findings provide evidence and rationale for using circulating CD8 T cells expressing CD57 as a readily accessible blood-based biomarker for selecting patients with mUC for atezolizumab therapy.

An important mechanism, by which cancer cells achieve immune escape, is the release of extracellular adenosine into their microenvironment. Adenosine activates adenosine A

and A

receptors on immune cells constituting one of the strongest immunosuppressive mediators. In addition, extracellular adenosine promotes angiogenesis, tumor cell proliferation, and metastasis. Cancer cells upregulate ectonucleotidases, most importantly CD39 and CD73, which catalyze the hydrolysis of extracellular ATP to AMP (CD39) and further to adenosine (CD73). Inhibition of CD39 is thus expected to be an effective strategy for the (immuno)therapy of cancer. However, suitable small molecule inhibitors for CD39 are not available. Our aim was to identify drug-like CD39 inhibitors and evaluate them in vitro.

We pursued a repurposing approach by screening a self-compiled collection of approved, mostly ATP-competitive protein kinase inhibitors, on human CD39. The best hit compound was further characterized and evaluated in various el CD39 inhibitor with high metabolic stability and optimized physicochemical properties; according to our knowledge, it is the first brain-permeant CD39 inhibitor. Our discovery will provide the basis (i) to develop more potent and balanced dual CD39/ALK inhibitors, and (ii) to optimize the ceritinib scaffold towards interaction with CD39 to obtain potent and selective drug-like CD39 inhibitors for future in vivo studies.

CD39 inhibition might contribute to the effects of the powerful anticancer drug ceritinib. Ceritinib is a novel CD39 inhibitor with high metabolic stability and optimized physicochemical properties; according to our knowledge, it is the first brain-permeant CD39 inhibitor. Our discovery will provide the basis (i) to develop more potent and balanced dual CD39/ALK inhibitors, and (ii) to optimize the ceritinib scaffold towards interaction with CD39 to obtain potent and selective drug-like CD39 inhibitors for future in vivo studies.

Skin carotenoid measurement by reflection spectroscopy (RS) offers a non-invasive biomarker of carotenoid intake, but feasibility, reliability, and validity are not established in infants.

To determine feasibility and reliability of 4 month-old infant skin carotenoid score (SCS) measurement and its correlation with total carotenoid intake and plasma concentrations.

SCSs were measured in a prospective, observational study by a modified, portable RS device at the index finger and heel of the foot in 4-months olds (n=21). Infant plasma, human milk, and formula carotenoid concentrations were measured by HPLC-PDA, and carotenoid intake was estimated from 7-day food diaries corrected for actual milk carotenoid content. Mean SCS, time to acquire measurements, replicate intraclass correlations, and bivariate correlations between SCS, carotenoid intake, and plasma carotenoids were examined. Exploratory analyses of returning 6- (n=12), and 8- (n=9) month old infants were conducted.

Mean±SD finger and heel SCS s are feasibly and reliably measured by RS, and may provide a biomarker of carotenoid intake in 4-month olds. ClinicalTrials.gov [NCT03996395].

Infant skin carotenoids are feasibly and reliably measured by RS, and may provide a biomarker of carotenoid intake in 4-month olds. ClinicalTrials.gov [NCT03996395].Silicon (Si)-based materials have been considered as one of the most promising anodes for the development of high-energy-density lithium-ion batteries (LIBs). However, poor interfacial stability and structural degradation are critical challenges for the successful application of Si-based anodes in LIBs. Herein, the use of a novel fluorinated carbonate (trifluoropropylene carbonate, TFPC) with high reduction potential and rapid film-forming ability as an electrolyte cosolvent is reported, which overcomes the deterioration of the electrode structure that hinders the battery quality. X-ray photoelectron spectroscopy combined with Fourier transform infrared spectroscopy technology investigated the composition and distribution of the solid electrolyte interface (SEI) layer formed on the Si/C anode. Notably, a stable SEI with an organic and inorganic bilayer structure was formed in this electrolyte design, and excellent mechanical properties and ionic conductivity were achieved. Moreover, the Li intercalation mechanism is elucidated by in situ Raman characterization. selleck kinase inhibitor Benefited from this unique SEI, the Si/C-based batteries exhibit compelling cycling and rate performance. This work provides an in-depth understanding of the Li intercalation mechanism of the Si/C electrode, as well as a novel electrolyte, for high-performance LIBs.

The prevalence of adverse birth outcomes is highest in resource-limited settings such as sub-Saharan Africa. Maternal consumption of diets with adequate nutrients during pregnancy may protect against these adverse outcomes.

To determine the association between maternal dietary animal source foods (ASF) consumption and the risk of adverse birth outcomes among HIV-negative pregnant women in Tanzania.

Using dietary intake data from 7564 HIV-negative pregnant, we used Poisson regression with the empirical variance (GEE) to estimate the relative risk (RR) of adverse birth outcomes (preterm birth, very preterm birth, small for gestation age (SGA), low birth weight (LBW), stillbirth and neonatal death) for higher versus lower ASF frequency of intake.

Median (interquartile range) daily dietary intake of animal protein was 17 (1-48) grams. Higher ASF protein intake frequency was associated with lower risk of neonatal death (Q4 vs Q1 RR 0.59; 95% CI 0.38, 0.90; P for trend = 0.01). Higher fish intake was associerse birth outcomes in urban Tanzania. Promoting prenatal dietary intake of ASF may improve birth outcomes in this region and similar resource-limited settings.Clinical Trial Registry Number NCT00197548.

To describe current UK clinical practice around the use of intrathecal diamorphine as analgesia for major elective laparoscopic colorectal surgery.

Online self-administered survey.

Acute public hospitals in the UK (National Health Service - NHS) .

Consultant anaesthetists involved in colorectal surgery lists.

Rate of intrathecal opioids used by anaesthetists for elective laparoscopic colorectal procedures; minimum, most common and maximum doses of intrathecal diamorphine used, timing of administration of intrathecal injection, and relationship between the number of patients anaesthetised for laparoscopic colorectal resections per month by each anaesthetist, and the doses of intrathecal diamorphine they administer.

In total, 479 responses were received. Of these, 399 (83%) use intrathecal opioid routinely 351/399 (88%) use diamorphine, 35 (8.8%) use morphine, 8 (2%) use fentanyl, and 7 (1.3%) use other drugs. The median intrathecal diamorphine dose most commonly administered by anaesthetists was 500 µg (IQR 400-750 [(range 200-1500])). The median of the maximum dose administered by anaesthetists was 600 µg (IQR 500-1000 [(range 200-2000])). Greater intrathecal diamorphine dosing was positively associated with higher number of cases per month (rho=0.113, pp=0.033).

Intrathecal diamorphine is widely used by UK anaesthetists for patients undergoing major elective laparoscopic colorectal surgery. However, there is little consensus regarding optimal dosing. Therefore, high-quality randomised dose-response trials are needed to investigate the relationship between doses of intrathecal diamorphine and patient outcomes.

Intrathecal diamorphine is widely used by UK anaesthetists for patients undergoing major elective laparoscopic colorectal surgery. However, there is little consensus regarding optimal dosing. Therefore, high-quality randomised dose-response trials are needed to investigate the relationship between doses of intrathecal diamorphine and patient outcomes.

To determine which factors contribute to the decision of mothers to participate with their child in follow-up (FU) examinations after participation in a randomised controlled trial (RCT) prior to conception.

A cross-sectional survey, including Likert-scale items. Comparisons will be made between respondents who participated in all FU rounds of data collection and those who did not participate in any FU round with their child.

Women who participated in an RCT investigating the effect of a preconception lifestyle intervention (LIFEstyle study Netherlands Trial Register NTR1530) were invited to participate with their child in three FU data collections when the child had a mean age of 4.2 years, 4.6 years and 6.5 years, respectively. FU rounds included a health questionnaire, physical examination and cardiac assessment, successively.

Sixty-seven respondents were included, of whom 7 (10%) did not participate in any FU round and 24 (36%) participated in all FU rounds. Women who participated with their child after maternal participation in an RCT, we suggest to involve women in the design of the FU study, to emphasise possible perceived benefits of participation and to encourage women to actively involve their child in the decision of participation.

This study explored how various markers of objective and subjective socioeconomic status (SES) are associated with cognitive impairment among older Indian adults.

A cross-sectional study was conducted using large nationally representative survey data.

This study used data from the Longitudinal Ageing Study in India (2017-2018). The sample included 31 464 older adults aged 60 years and above.

Outcome variable was cognitive impairment, measured through broad domains of memory, orientation, arithmetic function, and visuo-spatial and constructive skills. We estimated descriptive statistics and presented cross-tabulations of the outcome. Χ

test was used to evaluate the significance level of differences in cognitive impairment by subjective (ladder) and objective SES measures (monthly per-capita consumption expenditure (MPCE) quintile, education and caste status). Multivariable linear and logistic regression analyses were conducted to fulfil the objectives.

A proportion of 41.7% and 43.4% of older adultarget for future study on socioeconomic indicators of cognitive impairment.

Subjective measures of SES were linked to cognitive outcomes, even more strongly than objective measures of SES; considering the relative ease of obtaining such measures, subjective SES measures are a promising target for future study on socioeconomic indicators of cognitive impairment.