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Endogenous molecules, such as heat shock proteins (HSP), can function as danger signals when released into the extracellular environment in response to cell stress, where they elicit an immune response such as cytokine secretion. There has also been some suggestion that contamination of exogenous HSPs with lipopolysaccharide (LPS) may be responsible for these effects. This study investigates the effects of exogenous HSPA1A and HSPB1 on the activation of immune cells and the resulting secretion of cytokines, which are involved in inflammatory responses. To address whether exogenous HSPs can directly activate cytokine secretion, naïve U937 cells, differentiated U937 cells and peripheral blood mononuclear cells (PBMCs) were treated with either exogenously applied HSPA1A or HSPB1 and then secreted IL‐1β, TNF‐α and IL‐10 were measured by ELISA. Both HSPs were able to induce a dose‐dependent increase in IL‐10 secretion from naïve U937 cells and dose‐dependent IL‐1β, TNF‐α and IL‐10 secretion were also observed in differentiated U937 cells and PBMCs. We also observed that CD14 affects the secretion levels of IL‐1β, TNF‐α and IL‐10 from cells in response to exogenous HSP treatment. In addition, HSPA1A and HSPB1 were shown to interact with CD14, CD36 and CD11b extracellular receptor proteins. Several approaches used in this study indicate that HSP‐induced cytokine secretion is largely independent of any contaminating LPS in the samples. [ABSTRACT FROM AUTHOR]

A state‐space model (SSM) of infiltration estimates daily groundwater recharge using time‐series of groundwater‐level altitude and meteorological inputs (liquid precipitation, snowmelt, and evapotranspiration). The model includes diffuse and preferential flow through the unsaturated zone, where preferential flow is a function of liquid precipitation and snowmelt rates and a threshold rate, above which there is direct recharge to the water table. Model parameters are estimated over seasonal periods and the SSM is coupled with the Kalman Filter (KF) to assimilate recent observations (hydraulic head) and meteorological inputs into recharge estimates. The approach can take advantage of real‐time hydrologic and meteorological data to deliver real‐time recharge estimates. The model is demonstrated on daily observations from two bedrock wells in carbonate aquifers of northwestern New York (USA) between 2013 and 2018. Meteorological inputs for liquid precipitation and snowmelt are compiled from SNODAS (2021). Results for recharge during winter and spring seasons show preferential flow events to the water table from liquid precipitation, snowmelt, or a combination of the two. Recharge estimates summed annually are consistent with previous estimates of recharge reported from groundwater flow and surface‐process models. Results from the SSM and KF point to errors in meteorological inputs, such as the snowmelt rate, that are not compatible with hydraulic head observations. Whereas liquid and solid precipitation are measured at discrete stations and extrapolated to 1‐km2 grid cells, snowmelt is a meteorological modeled outcome that may not represent conditions in the vicinity of monitoring well locations. Article Impact Statement: A state‐space model interprets time‐series of water table altitude, precipitation, and snowmelt to estimate groundwater recharge. [ABSTRACT FROM AUTHOR]

Objective: Thyroid status in the months following radioiodine (RI) treatment for Graves' disease can be unstable. Our objective was to quantify frequency of abnormal thyroid function post‐RI and compare effectiveness of common management strategies. Design: Retrospective, multicentre and observational study. Patients: Adult patients with Graves' disease treated with RI with 12 months' follow‐up. Measurements: Euthyroidism was defined as both serum thyrotropin (thyroid‐stimulating hormone [TSH]) and free thyroxine (FT4) within their reference ranges or, when only one was available, it was within its reference range; hypothyroidism as TSH ≥ 10 mU/L, or subnormal FT4 regardless of TSH; hyperthyroidism as TSH below and FT4 above their reference ranges; dysthyroidism as the sum of hypo‐ and hyperthyroidism; subclinical hypothyroidism as normal FT4 and TSH between the upper limit of normal and <10 mU/L; and subclinical hyperthyroidism as low TSH and normal FT4. Results: Of 812 patients studied post‐RI, hypothyroidism occurred in 80.7% and hyperthyroidism in 48.6% of patients. Three principal post‐RI management strategies were employed: (a) antithyroid drugs alone, (b) levothyroxine alone, and (c) combination of the two. Differences among these were small. Adherence to national guidelines regarding monitoring thyroid function in the first 6 months was low (21.4%–28.7%). No negative outcomes (new‐onset/exacerbation of Graves' orbitopathy, weight gain, and cardiovascular events) were associated with dysthyroidism. There were significant differences in demographics, clinical practice, and thyroid status postradioiodine between centres. Conclusions: Dysthyroidism in the 12 months post‐RI was common. Differences between post‐RI strategies were small, suggesting these interventions alone are unlikely to address the high frequency of dysthyroidism. [ABSTRACT FROM AUTHOR]