Higher CSF/serum free-T4 ratio is associated with improvement of quality of life during treatment with L-thyroxine

Up to 20% of individuals with primary hypothyroidism treated with L-thyroxine still suffer from severe symptoms. These are supposedly brain derived and involve both cognitive and emotional domains. Previously, no consistent relationship has been found between thyroid hormones (TH) or TSH levels in blood and quality of life (QoL). Recently, we reported an association between cerebrospinal fluid (CSF)/serum free-thyroxine (f-T4) ratio and QoL, in juvenile hypothyroid patients. Here, we investigated if CSF/serum f-T4 ratio and QoL estimates correlate also during L-thyroxine treatment. Moreover, the CSF biomarker neurogranin (Ng) was used as a biomarker for synaptic function and integrity in clinical research. Ng is partially controlled by TH and therefore we investigated the relationship between QoL parameters and Ng levels. Patients diagnosed with primary hypothyroidism were investigated using vital parameters, serum and CSF analyses of TH, TSH, Ng and QoL questionnaires. Similar procedures were performed after 6 months of treatment. The most marked associations with QoL were found for CSF/serum f-T4 ratio, which was strongly related to several QoL parameters such as the mental subscore of SF-36 (r = 0.83, p <.0005). Ng, which did not differ from that in our healthy controls, was lower in some patients during treatment and higher in others. However, the change in Ng during treatment was significantly correlated with QoL parameters including the mental subscore of SF-36 (r = −0.86, p <.0001). In addition, the CSF/serum f-T4 ratio correlated with the change in Ng (r = −0.75, p =.001). Our results suggest that the ratio between CSF and serum f-T4 is an important biomarker for QoL during treatment of patients with primary hypothyroidism, so far in research, but in the future maybe also in clinical settings. Moreover, this ratio also correlates with the changes in Ng levels during L-thyroxine treatment, further supporting the impact of the TH balance between serum and CSF on QoL

Building a human cortex: the evolutionary differentiation of Cajal-Retzius cells and the cortical hem

As apart of a research project, financially supported by the CDL, to study the thermal effects of waste heat discharged into natural water recipients, this report describes a numerical model for this purpose anda number of verifications against real data. The model is based on the conservation laws for mass momentum and energy. It is time-dependent, three-dimensional and has the possibility of using a varying horizontal resolution depending on the nature of the problem. A coordinate transformation in the vertical direction gives the model the same number of calculating points in the vertical all over the modelled area, which increases the confidence in the vertical description considerably. This is of great value, as most of the discharges and the pollution problems are in shallow areas, where other medels in general will have a poor resolution. Applications of the model to different types of recipients are presented and the effects of important mixing mechanisms are illustrated. The model results have been verified against field measurements, and important plume characteristics like area of heated surface water, vertical extent of the plume,and centerline temperature decay have all been successfully simulated. The verification study demonstrates in addition that recirculation of cooling water is well described by the model. The verification studies suggest enlarged use of this type of model studies both in the planning of new locations for power plants and in the monitoring of the environmental effects of the discharged heat. This model can be used both to predict thermal effects in the immediate neighbourhood of the power plant and to predict distribution and long term variations in wider surroundings. Of special interest is the use of the model when locations of the inlet and outlet are to be considered