Microglial MHC class II is dispensable for experimental autoimmune encephalomyelitis and cuprizone‐induced demyelination

Microglia are resident immune cells in the CNS, strategically positioned to clear dead cells and debris, and orchestrate CNS inflammation and immune defense. In steady state, these macrophages lack MHC class II (MHCII) expression, but microglia activation can be associated with MHCII induction. Whether microglial MHCII serves antigen presentation for critical local T‐cell restimulation in CNS auto‐immune disorders or modulates microglial signaling output remains under debate. To probe for such scenarios, we generated mice harboring an MHCII deficiency in microglia, but not peripheral myeloid cells. Using the CX₃CR1^CreER‐based approach we report that microglial antigen presentation is obsolete for the establishment of EAE, with disease onset, progression, and severity unaltered in mutant mice. Antigen presentation‐independent roles of microglial MHCII were explored using a demyelination model induced by the copper chelator cuprizone. Absence of microglial I‐A^b did not affect the extent of these chemically induced white matter alterations, nor did it affect microglial proliferation or gene expression associated with locally restricted de‐ and remyelination.     

Optimization design of thumbspica splint using finite element method

De Quervain’s tenosynovitis is often observed on repetitive flexion of the thumb. In the clinical setting, the conservative treatment is usually an applied thumbspica splint to immobilize the thumb. However, the traditional thumbspica splint is bulky and heavy. Thus, this study used the finite element (FE) method to remove redundant material in order to reduce the splint’s weight and increase ventilation. An FE model of a thumbspica splint was constructed using ANSYS9.0 software. A maximum lateral thumb pinch force of 98 N was used as the input loading condition for the FE model. This study implemented topology optimization and design optimization to seek the optimal thickness and shape of the splint. This new design was manufactured and compared with the traditional thumbspica splint. Ten thumbspica splints were tested in a materials testing system, and statistically analyzed using an independent t test. The optimal thickness of the thumbspica splint was 3.2 mm. The new design is not significantly different from the traditional splint in the immobilization effect. However, the volume of this new design has been reduced by about 35%. This study produced a new thumbspica splint shape with less volume, but had a similar immobilization effect compared to the traditional shape. In a clinical setting, this result can be used by the occupational therapist as a reference for manufacturing lighter thumbspica splints for patients with de Quervain’s tenosynovitis.     

Effects of aging, Parkinson's disease, and dopaminergic medication on response selection and control

We examined effects of short-term and long-term dopaminergic medication in Parkinson's disease on conflict monitoring or response selection processes. These processes were examined using event-related potentials (ERPs), while subjects performed a stimulus-response (S-R) compatibility task. An extended sample of young and elderly controls, Parkinson's disease patients with a medication history (PDs) and initially diagnosed, drug-naïve de novo PD patients (de novo PDs) were enrolled. Both PD groups were measured twice (on and off-medication or before and 8 weeks after medication onset).The results show that dopaminergic intervention selectively reduced the pathologically enhanced response selection in compatible S-R relations. This medication effect was already evident after short-term treatment, not differing from long-term treatment and performance in elderly controls. Contrary, age-related attenuations of the N2 in incompatible S-R relations, probably reflecting impaired conflict processing or response control, are unaffected by medication. The results suggest that compatible and incompatible S-R relations demand different neuronal mechanisms within the basal ganglia, as only the former are affected by agonizing the dopaminergic system.     

Production of protein hormones by cultured trophoblast cells isolated from term and early placentae

PROBLEM: To compare the capacity of de novo hormone synthesis by cultured trophoblast cells isolated from early and term placenta as cytotrophoblast, and to determine the ability of these cells to proliferate in culture. METHOD OF STUDY: Cytotrophoblast cells were isolated from term (TP, 38-42 weeks) and early placentae (EP, 8-13 weeks) by enzymatic digestion and subsequent purification on a percoll gradient. The net synthesis of the hormones human placental lactogen (hPL) and human chorionic gonadotropin (hCG) was determined as the release during culture + cell content after culture - cell content before culture. Proliferation was determined using a dedicated colorimetric reagent (CellTiter 96). RESULTS: Using a percoll gradient we were able to isolate three cell bands with densities of 1.051, 1.058, and 1.063 g/mL, which were predominantly cytotrophoblast cells as shown by immunocytochemical analysis. The cytotrophoblast cells with the highest density (1.063 g/mL) were used because they were found to release the highest amount of hormones and have shown the lowest rate of cell death after 6 days in culture. Both hCG and hPL showed different patterns of release during the first 2-3 days of culture between TP and EP. While the release by EP cytotrophoblast cells continued during 6 days of culture (n = 4), the concentrations for TP cytotrophoblast (n = 4) reached a plateau between 4 and 6 days. Net de novo synthesis calculated for 3 x 10(4) TP trophoblast cells cultured for 6 days (mean +/- SD, n = 4) was 8.65 +/- 9.05 mU for hCG and 0.95 +/- 0.45 ng for hPL. For EP, it was 395.5 +/- 265.5 mU for hCG and 148.8 +/- 84.2 ng for hPL. Net synthesis of hCG was > 10-fold (TP) and > 70-fold (EP) higher than the initial cell content. While at term, hPL synthesis was only a fraction of the initial cell content, production by EP cytotrophoblast was 106 times the initial cell content. The extent of cell death after 6 days in culture was significantly (P < 0.02) higher for term (30-40%) than for early trophoblast (10-20%). Using a proliferation detection agent during the first 3 days of culture with first trimester cytotrophoblast cells, we did not find any changes in the proliferative activity. CONCLUSIONS: There are differences in the functional activity between trophoblast cells obtained from first and third trimester. The in vitro findings are difficult to reconcile with the different patterns of plasma concentrations of the two hormones observed in vitro during the course of pregnancy.