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Piezo1 upregulation in PASMCs from LPAL rats was directly related to Yes-associated protein (YAP)/ TEA domain transcription factor 4 (TEAD4). Piezo1 expression was also upregulated in the whole-lung tissue of LPAL rats. The endothelial upregulation of Piezo1 was related to transcriptional regulation by RELA (p65) and lung inflammation.

The upregulation of Piezo1 in both PASMCs and ECs coordinates with each other via different cell signaling pathways to cause pulmonary vascular remodeling in LPAL-PH rats, providing novel insights into the cell-type specific pathogenic roles of Piezo1 in shear stress-associated experimental PH.

The upregulation of Piezo1 in both PASMCs and ECs coordinates with each other via different cell signaling pathways to cause pulmonary vascular remodeling in LPAL-PH rats, providing novel insights into the cell-type specific pathogenic roles of Piezo1 in shear stress-associated experimental PH.

The incidence of venous thromboembolism (VTE) in children is increasing, attributed in part to increased utilization of central venous catheters (CVCs). Children with protein losing disorders (PLDs) and low serum albumin may have an increased incidence of thrombosis. We sought to determine the prevalence of PLDs and hypoalbuminemia at the time of diagnosis of VTE in pediatric patients and its relationship to central venous catheters.

We performed a single institution retrospective study of 65 consecutive hospitalized pediatric patients with an acute VTE. Data collected included clinical diagnoses, type of thrombosis, presence or absence of a CVC, and serum albumin level, if available.

Of 65 patients with acute VTE, 51% (33/65) had catheter-related thrombosis (CRT), including 71% (19/27) of patients <12years of age and 37% (14/38) of patients aged 12 to 23 (P=0.008). Eleven VTEs occurred in patients with a diagnosis of a PLD; of these, ten (91%) were CRT and one (9%) was a non-CRT (P=0.003). Serum albumin levels obtained within four days of diagnosis of VTE were available for 38 patients. An albumin level below the lower limit of the age-adjusted normal reference range was documented in 27/38 (71%) patients with VTE compared to 1011/3028 (33%) of all pediatric patients admitted to the hospital during a two-year period (P<0.0001). Albumin levels were low in 19/22 (86%) patients with CRT compared with 8/16 (50%) patients with non-CRT (P=0.019).

Low serum albumin levels are highly prevalent among pediatric patients with VTE, especially in those patients with CRT.

Low serum albumin levels are highly prevalent among pediatric patients with VTE, especially in those patients with CRT.

Patients with myeloproliferative neoplasms (MPNs) are at increased risk of both thromboembolic and hemorrhagic complications. Among the risk factors for bleeding is the development of an acquired qualitative von Willebrand factor defect with loss of larger VWF plasma multimers, resulting in acquired von Willebrand syndrome (aVWS). The diagnosis of aVWS is challenging, because no single automated test is sufficient to prove or exclude aVWS. We aimed to compare different diagnostic tools used for the detection of MPN-associated aVWS in daily practice.

Patients with polycythemia vera (PV) or essential thrombocythemia (ET), who had been routinely assessed for quantitative and qualitative abnormalities of plasma VWF, were retrospectively studied.

Sixty-four patients (37 with PV and 27 with ET) were analyzed. Using multimer analysis of plasma VWF, aVWS with a loss of VWF high-molecular-weight multimers was detected in 51.4% and 55.6% of PV and ET patients, respectively.

GPIbM/Ag threshold of <0.8 was defined as useful screening tool for aVWS, with acceptable sensitivity (88.2%) and specificity (76.7%) and good agreement with VWF multimer analysis (κ=0.653). VWFGPIbM/Ag showed better performance than VWFCB/Ag. Regarding hematological parameters, there was no difference in hematocrit between patients with and without aVWS. However, leukocyte and platelet counts were significantly increased in the aVWS cohort.

For the first time, we identified a VWFGPIbM/Ag ratio of <0.8 as simple screening tool for aVWS in patients with PV or ET. This observation, however, should be confirmed in a larger patient cohort.

For the first time, we identified a VWFGPIbM/Ag ratio of <0.8 as simple screening tool for aVWS in patients with PV or ET. This observation, however, should be confirmed in a larger patient cohort.Hundreds of millions of people suffer anxiety disorders globally, demonstrating need for scalable and effective interventions. Adverse childhood experiences contribute to this mental health burden. The stress-buffering hypothesis, which posits social factors moderate prior adversity and subsequent mental health outcomes, provides one theoretical avenue to consider observations that group-based microfinance programs improve social capital. We investigate associations between adverse childhood experiences, generalized anxiety among adults and social capital associated with participation in a group-based microfinance program in rural Kenya. Adult participants (n = 400 women) responded to standardized measures of childhood adversity in June 2018, group-affiliated social capital and generalized anxiety in June 2019. Cumulative adverse childhood experiences predicted higher anxiety, which was statistically moderated by the presence of group-affiliated interpersonal trust. This study is the first to find social capital associated with participation in a group-based microfinance program statistically moderates expected associations between adverse childhood experiences and adult generalized anxiety. Future study should be conducted using a cluster-randomized control design to further assess the potential of this intervention method to ameliorate associations between past adversity and current mental health.Accessible, brief, and self-directed intervention are needed to improve treatment access for individuals with co-occuring PTSD and alcohol misuse. This pilot study tests the feasibility, acceptability, and preliminary efficacy of a brief text message intervention based on cognitive behavioral therapy plus message framing (CBT + Framing) compared to active control providing kind support and attention (KAM), to reduce PTSD symptoms and alcohol use. Two waves of community-based data collection (Wave 1 n = 50; Wave 2 n = 59) were completed. Participants self-reported symptoms at baseline, post-intervention, and 8-week follow-up. Engagement and retention were high, suggesting messages were feasible and acceptable. learn more Across waves and conditions, from baseline to follow-up primary outcomes of PTSD symptoms (medium to large effects), weekly drinks (medium effects), and heavy episodic drinking (small to medium effects) decreased. Consistent with hypotheses, CBT + Framing outperformed KAM for PTSD at post in Wave 2 and for number of heavy drinking episodes at both post and follow-up in Wave 1. Contrary to hypotheses, KAM outperformed CBT + Framing for PTSD at post in Wave 1, and minimal differences were observed between conditions for weekly drinks in both waves. Future studies should continue to develop and test brief, accessible interventions.The CX3C chemokine receptor 1 (CX3CR1), a member of the class A of G Protein-Coupled Receptors (GPCR) superfamily, and its ligand fractalkine constitute an important biochemical axis that influence many cellular pathways involving homeostatic and inflammatory processes. They participate in the activation, chemotaxis and recruitment of multiple immunological cells such as microglia, macrophages and monocytes, and play a critical role in neuroinflammatory conditions such as Alzheimer's disease and multiple sclerosis, in the recovery from central nervous system injuries, in several chronic, peripheral inflammatory entities and in some infective processes including HIV-AIDS. In this work we present the study of the CX3CR1 receptor employing extensive atomistic Molecular Dynamics (MD) simulations with the aim to characterize the conformational ensemble of the receptor in the presence of its antagonist and agonist ligands. We analyzed the receptor conformational changes and described interactions within its key regions and the bounded ligands to identify their notable differences. Finally, we classify the features that would allow the identification of patterns that characterize a functional state to contribute to the understanding of the complexity of the GPCR superfamily.Porous solids with channel sizes that are not much above the size of small hydrocarbons can yield extremely large adsorption selectivity. Our Grand Canonical Monte-Carlo simulations indicate exceptionally high selectivity for the separation of methane, ethane and propane from natural gas. At 250 K the C3H8/CH4 separation on MIL-127 at low pressure has a selectivity of more than 1000 and the C3H8/CH4 separation on CNT (9,9) is even above 2000. This is due to the strong molecule lattice interaction in narrow channels which leads to large enthalpies of adsorption. The Arrhenius law for the Henry coefficients is analysed in order to show that the effect is due to this enthalpy rather than to steric reasons.

Progressive supranuclear palsy (PSP) and idiopathic normal pressure hydrocephalus (iNPH) share several clinical and radiological features, making the differential diagnosis challenging. In this study, we aimed to differentiate between these two diseases using a machine learning approach based on cortical thickness and volumetric data.

Twenty-three iNPH patients, 50 PSP patients and 55 control subjects were enrolled. All participants underwent a brain 3T-MRI, and cortical thickness and volumes were extracted using Freesurfer 6 on T1-weighted images and compared among groups. Finally, the performance of a machine learning approach with random forest using the extracted cortical features was investigated to differentiate between iNPH and PSP patients.

iNPH patients showed cortical thinning and volume loss in the frontal lobe, temporal lobe and cingulate cortex, and thickening in the superior parietal gyrus in comparison with controls and PSP patients. PSP patients only showed mild thickness and volume reduerential diagnosis and in the selection of patients for shunt procedures.

There are detailed findings on hip and knee joint parameters determined via functional calibration methods for use in instrumented 3D-gait analysis but these methods have not yet been addressed to the foot.

Are functional calibration methods feasible for determining foot joint parameters and may they help for clinical interpretation of foot deformities?

Rigid segments were formed by markers on forefoot and hindfoot via a least square method. The position of the midfoot joint articulating both foot segments was then determined via a functional calibration motion. This two-stage procedure was applied on a cohort of 17 typically developed adults and one subject with severe planovalgus foot deformity for determining the location of the midfoot joint and kinematics of hindfoot and forefoot.

The position of the midfoot joint center could be estimated in the typically developed cohort and also in the demonstration case with planovalgus foot deformity. Depending on the choice of marker set for hindfoot and forefoot, the position of the joint center varied in the anatomic midfoot region with most robust results when addressing the marker on the navicular to the hindfoot.

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