Assessment of radiant temperature in a closed incubator

In closed incubators, radiative heat loss (R) which is assessed from the mean radiant temperature [Formula: see text] accounts for 40–60% of the neonate’s total heat loss. In the absence of a benchmark method to calculate [Formula: see text]—often considered to be the same as the air incubator temperature—errors could have a considerable impact on the thermal management of neonates. We compared [Formula: see text] using two conventional methods (measurement with a black-globe thermometer and a radiative “view factor” approach) and two methods based on nude thermal manikins (a simple, schematic design from Wheldon and a multisegment, anthropometric device developed in our laboratory). By taking the [Formula: see text] estimations for each method, we calculated metabolic heat production values by partitional calorimetry and then compared them with the values calculated from [Formula: see text] and [Formula: see text] measured in 13 preterm neonates. Comparisons between the calculated and measured metabolic heat production values showed that the two conventional methods and Wheldon’s manikin underestimated R, whereas when using the anthropomorphic thermal manikin, the simulated versus clinical difference was not statistically significant. In conclusion, there is a need for a safety standard for measuring [Formula: see text] in a closed incubator. This standard should also make available estimating equations for all avenues of the neonate’s heat exchange considering the metabolic heat production and the modifying influence of the thermal insulation provided by the diaper and by the mattress. Although thermal manikins appear to be particularly appropriate for measuring [Formula: see text], the current lack of standardized procedures limits their widespread use

Editorial: JAK inhibition in autoimmune and inflammatory diseases

publishedVersionNon peer reviewe

Editorial: JAK inhibition in autoimmune and inflammatory diseases

publishedVersionNon peer reviewe

The rationale for Janus kinase inhibitors for the treatment of spondyloarthritis

The pathogenesis of SpA is multifactorial and involves a range of immune cell types and cytokines, many of which utilize Janus kinase (JAK) pathways for signaling. In this review, we summarize the animal and pre-clinical data that have demonstrated the effects of JAK blockade on the underlying molecular mechanisms of SpA and provide a rationale for JAK inhibition for the treatment of SpA. We also review the available clinical trial data evaluating JAK inhibitors tofacitinib, baricitinib, peficitinib, filgotinib and upadacitinib in PsA, AS and related inflammatory diseases, which have demonstrated the efficacy of these agents across a range of SpA-associated disease manifestations. The available clinical trial data, supported by pre-clinical animal model studies demonstrate that JAK inhibition is a promising therapeutic strategy for the treatment of SpA and may offer the potential for improvements in multiple articular and extra-articular disease manifestations of PsA and AS

A docking model of key components of the DISC complex: death domain superfamily interactions redefined

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116305/1/feb2s0014579301021627.pd

Overall Survival by Response to First-line Induction Treatment with Atezolizumab plus Platinum-based Chemotherapy or Placebo plus Platinum-based Chemotherapy for Metastatic Urothelial Carcinoma

Standard-of-care first-line treatment for metastatic urothelial carcinoma (mUC) is platinum-based chemotherapy (CTx). Maintenance immunotherapy is a treatment option for patients without progressive disease (PD) after induction CTx. IMvigor130 was a randomised, phase 3 study evaluating atezolizumab plus platinum-based CTx (arm A), atezolizumab monotherapy (arm B), or placebo plus platinum-based CTx (arm C) as first-line treatment for mUC. The primary progression-free survival (PFS) analysis showed a statistically significant PFS benefit favouring arm A versus arm C, which did not translate into overall survival (OS) benefit at the final OS analysis. We report exploratory analyses based on response to combination induction treatment (arm A vs arm C) using final OS data. Post-induction OS was analysed for patients without PD during induction (4-6 CTx cycles) who received at least one dose of single-agent atezolizumab/placebo maintenance treatment. Post-progression OS was analysed for patients with PD during induction CTx. Addition of atezolizumab to CTx did not impact OS outcomes, regardless of response to induction CTx, with hazard ratios of 0.84 (95% confidence interval [CI] 0.63-1.10) for patients without PD and 0.75 (95% CI 0.54-1.05) for those with PD during induction CTx. Treatment effects appeared to be greatest for patients treated with cisplatin and for those with PD-L1-high tumours. Patient summary: The IMvigor130 trial showed that addition of atezolizumab to chemotherapy (CTx) did not improve survival over CTx alone in patients with bladder cancer. Overall, patients whose cancer did not progress during initial treatment tended to live longer than patients whose cancer did progress, but addition of atezolizumab to CTx did not help either group live longer in comparison to CTx alone. However, the results suggest that patients who received a certain CTx drug (cisplatin) or who had high levels of a marker called PD-L1 in their tumour may get the most improvement from addition of atezolizumab to CTx. The IMvigor130 trial is registered on ClinicalTrials.gov as NCT02807636. (c) 2023 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Estrogen regulation of TRPM8 expression in breast cancer cells

<p>Abstract</p> <p>Background</p> <p>The calcium-permeable cation channel TRPM8 (melastatin-related transient receptor potential member 8) is over-expressed in several cancers. The present study aimed at investigating the expression, function and potential regulation of TRPM8 channels by ER alpha (estrogen receptor alpha) in breast cancer.</p> <p>Methods</p> <p>RT-PCR, Western blot, immuno-histochemical, and siRNA techniques were used to investigate TRPM8 expression, its regulation by estrogen receptors, and its expression in breast tissue. To investigate the channel activity in MCF-7 cells, we used the whole cell patch clamp and the calcium imaging techniques.</p> <p>Results</p> <p>TRPM8 channels are expressed at both mRNA and protein levels in the breast cancer cell line MCF-7. Bath application of the potent TRPM8 agonist Icilin (20 μM) induced a strong outwardly rectifying current at depolarizing potentials, which is associated with an elevation of cytosolic calcium concentration, consistent with established TRPM8 channel properties. RT-PCR experiments revealed a decrease in TRPM8 mRNA expression following steroid deprivation for 48 and 72 hours. In steroid deprived medium, addition of 17-beta-estradiol (E₂, 10 nM) increased both TRPM8 mRNA expression and the number of cells which respond to Icilin, but failed to affect the Ca²⁺entry amplitude. Moreover, silencing ERα mRNA expression with small interfering RNA reduced the expression of TRPM8. Immuno-histochemical examination of the expression of TRPM8 channels in human breast tissues revealed an over-expression of TRPM8 in breast adenocarcinomas, which is correlated with estrogen receptor positive (ER⁺) status of the tumours.</p> <p>Conclusion</p> <p>Taken together, these results show that TRPM8 channels are expressed and functional in breast cancer and that their expression is regulated by ER alpha.</p