COMPARISON OF GROUND REACTION FORCES BETWEEN IN-PLACE AND FORWARD WATER RUNNING AT TWO LEVELS OF IMMERSION

This study compared GRF of in-place and forward water running at two levels of immersion. Twenty healthy subjects executed both exercises at a self selected speed at hip and chest immersion. Variables analyzed were: vertical peak (Fy), anterior peak (Fx anterior) and posterior peak (Fx posterior). Two-factor repeated measures ANOVA was used with

FORCE ANALYSIS OF THE UNDERWATER STATIONARY RUNNIG

It aimed to analyze the vertical component of the ground reaction force in the underwater stationary running. The sample was composed by 6 subjects divided in two groups (Male Group and Female Group). The underwater stationary running was performed in two immersion levels: in the hip level and in the xiphoid process level. An underwater force plate was used. For data analysis descriptive statistics was used. The mean values of vertical GRF were 2,08BW for the MG and 1,69BW for the FG in the hip level; 1,15BW for the MG and 1,12BW for the FG in the xiphoid process level. The results showed the vertical component of the GRF is affected by the immersion level and by the frequency of the activity. Both factors should be considered by professionals who work with therapeutic or physical conditioning programs using the underwater stationary running

How Heterogeneous Pore Scale Distributions of Wettability Affect Infiltration into Porous Media

Wettability is an important parameter that significantly determines hydrology in porous media, and it especially controls the flow of water across the rhizosphere—the soil-plant interface. However, the influence of spatially heterogeneous distributions on the soil particles surfaces is scarcely known. Therefore, this study investigates the influence of spatially heterogeneous wettability distributions on infiltration into porous media. For this purpose, we utilize a two-phase flow model based on Lattice-Boltzmann to numerically simulate the infiltration in porous media with a simplified geometry and for various selected heterogeneous wettability coatings. Additionally, we simulated the rewetting of the dry rhizosphere of a sandy soil where dry hydrophobic mucilage depositions on the particle surface are represented via a locally increased contact angle. In particular, we can show that hydraulic dynamics and water repellency are determined by the specific location of wettability patterns within the pore space. When present at certain locations, tiny hydrophobic depositions can cause water repellency in an otherwise well-wettable soil. In this case, averaged, effective contact angle parameterizations such as the Cassie equation are unsuitable. At critical conditions, when the rhizosphere limits root water uptake, consideration of the specific microscale locations of exudate depositions may improve models of root water uptake

RELATIVE ERROR ANALYSIS DURING REPRODUCTION OF ISOMETRIC FORCE OF KNEE EXTENSORS IN YOUNG ADULTS

This study compared the force reproduction of isometric knee extension at 60°, between the target forces at 30%, 50% and 70% of the maximum voluntary isometric force (MVIF) in young adults. Twenty young males took part in the study. The trials were performed on an instrumented chair developed for the study. Feedback was given to the participants during three trials prior the beginning of data collection in each analyzed target force. Participants performed 10 trials without any feedback for the target force at 30% and 50% of the MVIF and 3 trials for the target force at 70% of MVIF. The relative error decreased as the target force increased. The differences were significant between 30% and 70% (p=0.01) and between 50% and 70% (p=0.03). The reproduction of higher forces during isometric extension of the knee will produce lower relative errors for this specific task

The impact of capsaicinoids on APP processing in Alzheimer's disease in SH-SY5Y cells

The vanilloid capsaicin is a widely consumed spice, known for its burning and "hot" sensation through activation of TRPV1 ion-channels, but also known to decrease oxidative stress, inflammation and influence tau-pathology. Beside these positive effects, little is known about its effects on amyloid-precursor-protein (APP) processing leading to amyloid-β (Aβ), the major component of senile plaques. Treatment of neuroblastoma cells with capsaicinoids (24 hours, 10 µM) resulted in enhanced Aβ-production and reduced Aβ-degradation, leading to increased Aβ-levels. In detailed analysis of the amyloidogenic-pathway, both BACE1 gene-expression as well as protein-levels were found to be elevated, leading to increased β-secretase-activity. Additionally, γ-secretase gene-expression as well as activity was enhanced, accompanied by a shift of presenilin from non-raft to raft membrane-domains where amyloidogenic processing takes place. Furthermore, impaired Aβ-degradation in presence of capsaicinoids is dependent on the insulin-degrading-enzyme, one of the major Aβ-degrading-enzymes. Regarding Aβ-homeostasis, no differences were found between the major capsaicinoids, capsaicin and dihydrocapsaicin, and a mixture of naturally derived capsaicinoids; effects on Ca2+-homeostasis were ruled out. Our results show that in respect to Alzheimer's disease, besides the known positive effects of capsaicinoids, pro-amyloidogenic properties also exist, enhancing Aβ-levels, likely restricting the potential use of capsaicinoids as therapeutic substances in Alzheimer's disease

N-Aryl mercaptoacetamides as potential multi-target inhibitors of metallo-β-lactamases (MBLs) and the virulence factor LasB from Pseudomonas aeruginosa

Increasing antimicrobial resistance is evolving to be one of the major threats to public health. To reduce the selection pressure and thus to avoid a fast development of resistance, novel approaches aim to target bacterial virulence instead of growth. Another strategy is to restore the activity of antibiotics already in clinical use. This can be achieved by the inhibition of resistance factors such as metallo-β-lactamases (MBLs). Since MBLs can cleave almost all β-lactam antibiotics, including the “last resort” carbapenems, their inhibition is of utmost importance. Here, we report on the synthesis and in vitro evaluation of N-aryl mercaptoacetamides as inhibitors of both clinically relevant MBLs and the virulence factor LasB from Pseudomonas aeruginosa. All tested N-aryl mercaptoacetamides showed low micromolar to submicromolar activities on the tested enzymes IMP-7, NDM-1 and VIM-1. The two most promising compounds were further examined in NDM-1 expressing Klebsiella pneumoniae isolates, where they restored the full activity of imipenem. Together with their LasB-inhibitory activity in the micromolar range, this class of compounds can now serve as a starting point for a multi-target inhibitor approach against both bacterial resistance and virulence, which is unprecedented in antibacterial drug discovery

A multicentre, patient- and assessor-blinded, non-inferiority, randomised and controlled phase II trial to compare standard and torque teno virus-guided immunosuppression in kidney transplant recipients in the first year after transplantation:TTVguideIT

Background: Immunosuppression after kidney transplantation is mainly guided via plasma tacrolimus trough level, which cannot sufficiently predict allograft rejection and infection. The plasma load of the non-pathogenic and highly prevalent torque teno virus (TTV) is associated with the immunosuppression of its host. Non-interventional studies suggest the use of TTV load to predict allograft rejection and infection. The primary objective of the current trial is to demonstrate the safety, tolerability and preliminary efficacy of TTV-guided immunosuppression. Methods: For this purpose, a randomised, controlled, interventional, two-arm, non-inferiority, patient- and assessor-blinded, investigator-driven phase II trial was designed. A total of 260 stable, low-immunological-risk adult recipients of a kidney graft with tacrolimus-based immunosuppression and TTV infection after month 3 post-transplantation will be recruited in 13 academic centres in six European countries. Subjects will be randomised in a 1:1 ratio (allocation concealment) to receive tacrolimus either guided by TTV load or according to the local centre standard for 9 months. The primary composite endpoint includes the occurrence of infections, biopsy-proven allograft rejection, graft loss, or death. The main secondary endpoints include estimated glomerular filtration rate, graft rejection detected by protocol biopsy at month 12 post-transplantation (including molecular microscopy), development of de novo donor-specific antibodies, health-related quality of life, and drug adherence. In parallel, a comprehensive biobank will be established including plasma, serum, urine and whole blood. The date of the first enrolment was August 2022 and the planned end is April 2025. Discussion: The assessment of individual kidney transplant recipient immune function might enable clinicians to personalise immunosuppression, thereby reducing infection and rejection. Moreover, the trial might act as a proof of principle for TTV-guided immunosuppression and thus pave the way for broader clinical applications, including as guidance for immune modulators or disease-modifying agents.</p

Oral Anticoagulants in the Oldest Old with Recent Stroke and Atrial Fibrillation

OBJECTIVE: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin-K-antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years. METHODS: Individual patient data analysis from 7 prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (<3 months) aged ≥85 versus <85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all-cause death. We used simple, adjusted and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk. RESULTS: In total, 5,984 of 6,267 (95.5%) patients were eligible for analysis. Of those, 1,380 (23%) were aged ≥85 years and 3,688 (62%) received a DOAC. During 6,874 patient-years follow-up, the impact of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome did not differ between patients aged ≥85 (HR≥85y =0.65, 95%-CI [0.52, 0.81]) and <85 years (HR<85y =0.79, 95%-CI [0.66, 0.95]) in simple (pinteraction =0.129), adjusted (pinteraction =0.094) or weighted (pinteraction =0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and <85 years (+1.90 to +3.36 events/100 patient-years for ICH-weights 1.5 to 3.1). INTERPRETATION: The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old