Down syndrome (DS) is a common cause of mental retardation accompanied by cognitive impairment. Comprehensive studies suggested a link between development and ageing, as nearly all individuals with DS develop Alzheimer disease (AD)-like pathology. However, there is still a paucity of data on tau in early DS to support this notion.Using morphometric immunohistochemistry we compared tau phosphorylation in normal brains and in brains of individuals with DS from early development until early postnatal life.We observed in DS a critical loss of physiological phosphorylation of tau. Rhombencephalic structures showed prominent differences between controls and DS using antibodies AT8 (Ser-202/Thr-205) and AT180 (Thr-231). In contrast, in the subiculum only a small portion of controls deviated from DS using antibodies AT100 (Thr-212/Ser-214) and AT270 (Thr-181). With exception of the subiculum, phosphorylation-independent tau did not differ between groups, as confirmed by immunostaining for the HT-7 antibody (epitope between 159 and 163 of the human tau) as well.Our observations suggest functional tau disturbance in DS brains during development, rather than axonal loss. This supports the role of tau as a further important player in the pathophysiology of cognitive impairment in DS and related AD.
BackgroundData on walking impairment during the acute phase of deep vein thrombosis (DVT) is limited. ObjectivesThis study aimed to assess the degree of walking impairment in patients with acute DVT, with a particular focus on the relation to the DVT's anatomical location. MethodsPatients with sonographically confirmed DVT were eligible for inclusion in this cohort study.Pain-free walking distance (PWD) and maximum walking distance (MWD) were determined using standardized treadmill ergometer tests and analyzed in relation to DVT location.The impact of previous DVT on walking capacity was evaluated in an exploratory analysis. ResultsThe study included 64 patients (31% women, median age 55 years).The median (IQR) time from diagnosis to exercise test was 3 (1-5) days.Patients with suprainguinal DVT demonstrated significantly shorter median (IQR) MWD than those with infrainguinal DVT (130 (61-202) meters vs. 565 (128-750) meters, p<0.01), while PWD did not to significantly differ (PWD 20 (0-30) meters vs. 40 (0-222) meters, p=0.14).The proportion of patients who had to terminate treadmill tests prematurely was higher in patients with suprainguinal DVT (91.7% vs. 57.7%;p=0.04).PWD and MWD seemed to be similar in patients with and without a history of DVT.Premature test termination and suprainguinal DVT location were associated with reduced quality of life, as measured by the EQ-5D-5L questionnaire and visual analogue scale. J o u r n a l P r e -p r o o fConclusions Suprainguinal DVT was linked to a more pronounced walking impairment compared to infrainguinal DVT.Limited walking capacity was associated with a reduced quality of life.
Background: For primary Raynaud phenomenon (PRP), an otherwise unexplained vasospastic disposition is assumed. To test the hypothesis of an additional involvement of distinct ultrastructural microvascular alterations, we compared the nailfold capillary pattern of patients with PRP and healthy controls. Methods: A total of 120 patients with PRP (with a median duration of vasospastic symptoms of 60 [IQR: 3–120] months) were compared against 125 controls. In both groups, nailfold capillaroscopy was performed to record the presence of dilatations, capillary edema, tortuous capillaries, ramifications, hemorrhages, and reduced capillary density and to determine a semiquantitative rating score. Further, the capacity of finger skin rewarming was investigated by performing infrared thermography in combination with cold provocation. Results: Unspecific morphologic alterations were found in both, PRP, such as controls, whereby the risk for PRP was four times as high in the presence of capillary dilations (CI: 2.3–7.6) and five times as high if capillary density was reduced (CI: 1.9–13.5). Capillary density correlated with thermoregulatory capacity in both hands in the PRP group, but not in controls. In addition, a negative correlation between the microangiopathy score and the percentage degree of rewarming in both hands was found for patients with PRP only. Conclusion: We found specific differences within the microvascular architecture between patients with PRP and controls. As a conclusion, PRP may not be an entirely benign vasospastic phenomenon, but might be associated with subtle microcirculatory vasculopathy. In addition, we suggest that the implementation of a scoring system might serve as guidance in the diagnostic process at least of patients with long-standing PRP.
COVID-19 vaccine–related adverse events are mostly minor to moderate, and serious events are rare. Single cases of Raynaud's phenomenon (RP) in temporal proximity to COVID-19 vaccination have been reported. Demographic data, medical history, and detailed information regarding vaccination status and RP characteristics were obtained from patients with confirmed RP after COVID-19 vaccination. Fifteen participants reported the initial manifestation of RP, which occurred in 40% after the first, in 33% after the second, and in 27% after the third vaccination. RP development and occurrence of episodes were not linked to any specific vaccine type. New onset of disease was observed in 40% of the vaccinees after BNT162b2, in 33% after mRNA-1273, and in 27% after ChAdOx1 vaccination. Three out of four participants with preexisting RP prior to COVID-19 vaccination reported aggravation in frequency and intensity after immunization. Although COVID-19 vaccination is pivotal in controlling the pandemic, the observed temporal association between vaccine administration and RP occurrence warrants global activities to support pharmacovigilance for the detection of adverse reactions, one of which may include RP.
