Assessment of Temporary Warfarin Reversal in Patients With Left Ventricular Assist Devices: the KVAD Study.

BACKGROUND: Patients with left ventricular assist devices (LVADs) require interruption of warfarin for invasive procedures, but parenteral bridging is associated with many complications. Four-factor prothrombin complex concentrate (4F-PCC) can temporarily restore hemostasis in patients undergoing anticoagulation with warfarin. OBJECTIVES: This pilot study evaluated the strategy of using variable-dose 4F-PCC to immediately and temporarily reverse warfarin before invasive procedures without holding warfarin in patients with LVADs. The duration of effect of 4F-PCC on factor levels and time to reestablish therapeutic anticoagulation post procedure were assessed. METHODS: Adult patients with LVADs and planned invasive procedures were enrolled from a single center. Warfarin was continued uninterrupted. The 4F-PCC dose administered immediately pre-procedure was based on study protocol. International normalized ratio (INR)- and vitamin K-dependent factor levels were collected before and during the 48 hours after 4F-PCC administration. The use of parenteral bridging, International Society for Thrombosis and Haemostasis major and clinically relevant nonmajor bleeding (CRNMB) and thromboembolic events at 7 and 30 days were collected. RESULTS: In 21 episodes of 4F-PCC reversal, median baseline INR was 2.7 (IQR 2.2-3.2). The median dosage of 4F-PCC administered was 1794 units (IQR 1536-2130). At 24 and 48 hours post 4F-PCC administration, median INRs were 1.8 (IQR 1.7-2.0) and 2.0 (IQR 1.9-2.4). Two patients required postoperative bridging. One patient experienced major bleeding within 72 hours, and 2 experienced CRNMB within 30 days. There were no thromboembolic events. Baseline and post 4F-PCC vitamin K-dependent factor levels corresponded with changes in INR values. The median time to achieve therapeutic INR post-procedure was 2.5 days (IQR, 1-4). CONCLUSION: Administration of 4F-PCC for temporary reversal of warfarin for invasive procedures in patients with LVADs allowed for continued warfarin dosing with minimal use of post-intervention bridging, limited bleeding and no thromboembolic events.

Preparation of C60 Nanowhiskers-SnO2 Nanocomposites and Photocatalytic Degradation of Organic Dyes.

C60 nanowhiskers were prepared using a liquid-liquid interfacial precipitation (LLIP) method. Tin oxide (SnO2) nanoparticles were synthesized by a reaction of tin (IV) chloride pentahydrate with ammonium nitrate in an electric furnace. The C60 nanowhiskers-SnO2 nanocomposites were calcined in an electric furnace at 700 °C under an inert argon gas atmosphere for 2 h. The crystallinity, morphology and optical properties of the samples were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, Raman spectroscopy and UV-vis spectrophotometry. The photocatalytic activity of the C60 nanowhiskers-SnO2 nanocomposites in the degradation of the organic dyes, such as methylene blue, methyl orange, rhodamine B, and brilliant green, under ultraviolet light at 254 nm by UV-vis spectrophotometry was evaluated and compared with that of C60 nanowhiskers and SnO2 nanoparticles. The experimental results showed that C60 nanowhiskers-SnO2 nanocomposites exhibited remarkably higher photocatalytic degradation of organic dyes compared to C60 nanowhiskers and SnO2 nanoparticles.

Preparation of ZnS-graphene nanocomposites under electric furnace and photocatalytic degradation of organic dyes.

Zinc sulfide (ZnS) nanoparticles were synthesized from zinc nitrate hexahydrate and thiourea under microwave irradiation. The ZnS-graphene nanocomposites were calcined in an electric furnace at 700 degrees C under an inert argon gas atmosphere for 2 hr. The heated ZnS-graphene nanocomposites were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy and UV-vis spectrophotometry. After heat treatment, ZnS-graphene nanocomposites had a more porous and larger surface area, than the unheated ZnS-graphene nanocomposites. The photocatalytic activity of the heated ZnS-graphene nanocomposites in the degradation of organic dyes, such as methylene blue, methyl orange, and rhodamine B, under ultraviolet light at 254 nm by UV- vis spectrophotometer was evaluated and compared with that of the unheated ZnS nanoparticles, heated ZnS nanoparticles, unheated ZnS-graphene nanocomposites. Among the our experimental results as a photocatalyst, the heated ZnS-graphene nanocomposites exhibited remarkably higher photocatalytic degradation of organic dyes as compared to other nanomaterials such as unheated ZnS nanoparticles and heated ZnS-graphene nanocomposites.

Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus.

RIG-I is a cytosolic pathogen recognition receptor that engages viral RNA in infected cells to trigger innate immune defenses through its adaptor protein MAVS. MAVS resides on mitochondria and peroxisomes, but how its signaling is coordinated among these organelles has not been defined. Here we show that a major site of MAVS signaling is the mitochondrial-associated membrane (MAM), a distinct membrane compartment that links the endoplasmic reticulum to mitochondria. During RNA virus infection, RIG-I is recruited to the MAM to bind MAVS. Dynamic MAM tethering to mitochondria and peroxisomes then coordinates MAVS localization to form a signaling synapse between membranes. Importantly, the hepatitis C virus NS3/4A protease, which cleaves MAVS to support persistent infection, targets this synapse for MAVS proteolysis from the MAM, but not from mitochondria, to ablate RIG-I signaling of immune defenses. Thus, the MAM mediates an intracellular immune synapse that directs antiviral innate immunity.

Control of innate immune signaling and membrane targeting by the Hepatitis C virus NS3/4A protease are governed by the NS3 helix α0.

Hepatitis C virus (HCV) infection is sensed in the host cell by the cytosolic pathogen recognition receptor RIG-I. RIG-I signaling is propagated through its signaling adaptor protein MAVS to drive activation of innate immunity. However, HCV blocks RIG-I signaling through viral NS3/4A protease cleavage of MAVS on the mitochondrion-associated endoplasmic reticulum (ER) membrane (MAM). The multifunctional HCV NS3/4A serine protease is associated with intracellular membranes, including the MAM, through membrane-targeting domains within NS4A and also at the amphipathic helix α(0) of NS3. The serine protease domain of NS3 is required for both cleavage of MAVS, a tail-anchored membrane protein, and processing the HCV polyprotein. Here, we show that hydrophobic amino acids in the NS3 helix α(0) are required for selective cleavage of membrane-anchored portions of the HCV polyprotein and for cleavage of MAVS for control of RIG-I pathway signaling of innate immunity. Further, we found that the hydrophobic composition of NS3 helix α(0) is essential to establish HCV replication and infection. Alanine substitution of individual hydrophobic amino acids in the NS3 helix α(0) impaired HCV RNA replication in cells with a functional RIG-I pathway, but viral RNA replication was rescued in cells lacking RIG-I signaling. Therefore, the hydrophobic amphipathic helix α(0) of NS3 is required for NS3/4A control of RIG-I signaling and HCV replication by directing the membrane targeting of both viral and cellular substrates.

Posttraumatic stress disorder and posttraumatic stress symptoms among adults with hemophilia A and B.

Background: Persons with hemophilia may encounter various traumatic experiences related to their bleeding disorder throughout their lifetime. Little is known about the clinical impact of disease-related trauma on this population. Objectives: To explore the prevalence of posttraumatic stress disorder (PTSD) and posttraumatic stress symptoms in adults with hemophilia A and B and characterize the traumatic experiences they report. Methods: An online survey tool collecting data on participant characteristics and a validated questionnaire containing the PTSD checklist for Diagnostic and Statistical Manual of Mental Disorders 5 were distributed via Research Electronic Data Capture to adults with hemophilia A and B during their annual visit to their hemophilia treatment center. Participants were asked about traumatic experiences specific to their hemophilia prior to self-administering the PTSD checklist for Diagnostic and Statistical Manual of Mental Disorders 5 questionnaire. Results: Survey responses from 178 individuals across 3 hemophilia treatment centers were included in the analysis, representing a 70% response rate. One hundred one (56.7%) participants identified a hemophilia-related traumatic event, and 21 (11.8%) participants met criteria for a provisional diagnosis of PTSD. Multivariable analysis showed higher odds of a positive PTSD screen in participants with noninfectious (odds ratio [OR], 13.89; 95% CI, 2.23-86.62) and infectious comorbidities (OR, 11.18; 95% CI, 1.34-93.45) and in participants with >1 mental health comorbidity (OR, 10.07; 95% CI, 2.39-42.52). On the contrary, age >46 years (OR, 0.6; 95% CI, 0.01-0.62) and higher education (OR, 0.25; 95% CI, 0.07-0.88) reduced odds of PTSD. Conclusion: Persons with hemophilia are at risk of developing PTSD and posttraumatic stress symptoms. These data support the need for trauma screening, psychosocial services in the bleeding disorders community, and provision of trauma-informed care by providers.

Absolute neutrophil count by Duffy status among healthy Black and African American adults.

Many people of African ancestry have lower absolute neutrophil counts (ANCs) without increased risk for infection. This is associated with the Duffy-null phenotype (nonexpression of the Duffy antigen on red blood cells), which is commonly found in those of African descent. Currently, there are no studies that compare the ANC of individuals with Duffy-null phenotype to those with Duffy non-null phenotypes within a self-identified Black population. The aim of this study was to assess the impact of Duffy status on ANCs based on complete blood counts with differential and Duffy testing in a healthy population of self-identified Black individuals at a single primary care center. This study found that 66.7% (80 of 120) of Black individuals have the Duffy-null phenotype and that there is a significant difference in ANCs between Duffy-null and Duffy non-null individuals (median, 2820 cells per µL vs 5005 cells per µL; P < .001). Additionally, 19 of 80 (23.8%) Duffy-null individuals had an ANC of <2000 cells per µL compared with no (0) Duffy non-null individuals. The Duffy-null phenotype is clinically insignificant; however, inappropriate reference ranges can propagate systemic racism. Therefore, we advocate for the development of Duffy-null-specific ANC reference ranges as well as replacing the term benign ethnic neutropenia with Duffy-nullassociated neutrophil count.

Impact of sickle cell trait on morbidity and mortality from SARS-CoV-2 infection.

The COVID-19 pandemic has highlighted racial health disparities within the United States. Although social determinants of health are the most likely drivers of this disparity, it is possible that genetic traits enriched in the black population like sickle cell trait (SCT) could worsen the morbidity and mortality of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients admitted for SARS-CoV-2 infection who identified as black or African American were included in the study (n = 166). Blood remnants were tested for SCT, and clinical data were abstracted from the chart. There was no difference in mortality between those with SCT and those without. There was no difference in respiratory complications between groups, but those without SCT had a much higher burden of chronic lung disease (P = .004). Those with SCT had higher creatinine on admission (P = .004), but no difference in in-hospital renal complications (P = .532). Notably, 12% of the cohort had SCT, which is higher than the expected 7.31% (P = .025). Our study did not show any evidence of increased end organ damage, morbidity, or mortality from SARS-CoV-2 infection among patients with SCT but did show differences in admission creatinine and preexisting lung disease.

Effects of lateral-offset sole shoes on knee adduction moment in women with medial compartment knee osteoarthritis.

This study aimed to determine the impact of wearing a lateral-offset sole shoe (LOSS) on knee adduction moment (KAM) in patients with medial knee osteoarthritis (OA). From December 2012 to November 2016, patients with medial knee OA were recruited. Ninety-three knees (50 left, 43 right) of 93 female patients were analyzed. The first peak KAMs were measured with patients (i) walking barefoot; (ii) walking in conventional shoes; and (iii) walking in LOSSs. The patients had grade 1 (n = 19), grade 2 (n = 49), grade 3 (n = 20), and grade 4 (n = 5) knee OA. First peak KAMs differed significantly in all three conditions (p = 0.031). In the post hoc analysis, first peak KAMs were significantly lower during LOSS walking than during conventional shoe walking (p = 0.001), but there were no differences in peak KAMs between barefoot and LOSS walking (p = 0.784). In the subgroup analysis, patients with grades 2 and 3 OA showed significantly lower first peak KAMs during LOSS walking than during conventional shoe walking (p = 0.029 and p = 0.011, respectively). Both the peak eversion ankle angle and moment of barefoot walking showed a significant increase compared with LOSS and conventional shoe walking, while there was no significant difference between LOSS and conventional shoe walking (p = 0.612 and p = 0.197, respectively). Our results suggest that LOSS wearing caused significant KAM reductions compared with conventional shoe wearing. Since LOSS wearing does not cause changes in the peak eversion ankle angle and moment during the load response, it may be an effective method to reduce the KAM in women with knee OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1694-1700, 2018.

Thermally robust perpendicular Co/Pd-based synthetic antiferromagnetic coupling enabled by a W capping or buffer layer.

Perpendicularly magnetized tunnel junctions (p-MTJs) that contain synthetic antiferromagnetic (SAF) frames show promise as reliable building blocks to meet the demands of perpendicular magnetic anisotropy (PMA)-based spintronic devices. In particular, Co/Pd multilayer-based SAFs have been widely employed due to their outstanding PMA features. However, the widespread utilization of Co/Pd multilayer SAFs coupled with an adjacent CoFeB reference layer (RL) is still a challenge due to the structural discontinuity or intermixing that occurs during high temperature annealing. Thus, we address the thermally robust characteristics of Co/Pd multilayer SAFs by controlling a W layer as a potential buffer or capping layer. The W-capped Co/Pd multilayer SAF, which acts as a pinning layer, exhibited a wide-range plateau with sharp spin-flip and near-zero remanence at the zero field. Structural analysis of the W-capped multilayer SAF exhibited single-crystal-like c-axis oriented crystalline features after annealing at 400 °C, thereby demonstrating the applicability of these frames. In addition, when the W layer serving as a buffer layer in the Co/Pd multilayer SAF was coupled with a conventional CoFeB RL, higher annealing stability up to 425 °C and prominent antiferromagnetic coupling behavior were obtained.

Ultrathin W space layer-enabled thermal stability enhancement in a perpendicular MgO/CoFeB/W/CoFeB/MgO recording frame.

Perpendicularly magnetized tunnel junctions (p-MTJs) show promise as reliable candidates for next-generation memory due to their outstanding features. However, several key challenges remain that affect CoFeB/MgO-based p-MTJ performance. One significant issue is the low thermal stability (Δ) due to the rapid perpendicular magnetic anisotropy (PMA) degradation during annealing at temperatures greater than 300 °C. Thus, the ability to provide thermally robust PMA characteristics is a key steps towards extending the use of these materials. Here, we examine the influence of a W spacer on double MgO/CoFeB/W/CoFeB/MgO frames as a generic alternative layer to ensure thermally-robust PMAs at temperatures up to 425 °C. The thickness-dependent magnetic features of the W layer were evaluated at various annealing temperatures to confirm the presence of strong ferromagnetic interlayer coupling at an optimized 0.55 nm W spacer thickness. Using this W layer we achieved a higher Δ of 78 for an approximately circular 20 nm diameter free layer device.

Immediate coronal plane kinetic effects of novel lateral-offset sole shoes and lateral-wedge insole shoes in healthy individuals.

To investigate kinetic differences in the coronal plane between healthy individuals wearing shoes with lateral-offset soles and shoes with lateral-wedge insoles while walking, hip abduction, knee adduction, and ankle abduction moments were estimated using a 3-dimensional motion analysis system under 3 different conditions: wearing conventional shoes (control), wearing lateral-offset sole shoes (condition A), and wearing lateral-wedge insole shoes (condition B). Forty-eight healthy individuals (24 men and 24 women) were tested. Condition A resulted in a significantly reduced peak knee adduction moment compared with the control (condition A=0.316 Nm/kg; control=0.380 Nm/kg; P=.006). The peak knee adduction moment of condition B was also lower than that of the control (condition B=0.299 Nm/kg; P=.002); however, the peak knee adduction moment was not significantly different between conditions A and B (P=.386). Condition B resulted in an increased mean ankle abduction moment in the stance phase compared with the control and condition A (control=0.007 Nm/kg; condition A=0.013 Nm/kg; condition B=0.023 Nm/kg) (control vs condition A, P=.051; control vs condition B, P<.001; condition A vs condition B, P=.002). The hip abduction moments were not significantly different between the control and condition A, control and condition B, or conditions A and B. Wearing lateral-offset sole shoes reduces the peak knee adduction moment and exerts less influence on ankle moment than does wearing lateral-wedge insole shoes. Neither lateral-offset sole shoes nor lateral-wedge insole shoes induce kinetic changes in the coronal plane of the hip.

Randomized controlled trial for clinical effects of varying types of insoles combined with specialized shoes in patients with rheumatoid arthritis of the foot.

OBJECTIVE: To determine the effects of specialized shoes with insoles in patients with rheumatoid arthritis and the differences in terms of type of insole and anatomical location of foot pathology. DESIGN: Single-blinded randomized controlled trial. SETTING: Outpatients of physical medicine and rehabilitation clinic at university hospital. SUBJECTS: Forty-two patients with rheumatoid foot lesions were randomly assigned to two different orthotic intervention groups. The anatomical locations of the foot lesions were recorded (hindfoot or forefoot). INTERVENTION: Participants were provided with an extra deep forefoot-rockered shoe and either a custom-made semi-rigid insole or a ready-made simple soft insole. They wore the provided footwear for at least 3 hours a day over six months. MAIN OUTCOME MEASURES: Primary outcome measures were foot pain visual analogue scale (VAS) scores and Foot Function Index (FFI). Secondary outcome measures were erythrocyte sedimentation rate and C-reactive protein levels in blood, amounts of medications and active joint counts. These were checked at baseline and post intervention. RESULTS: Eight patients dropped out at follow-up after six months of treatment. At six-month follow-ups, VAS scores and total Foot Function Index scores had decreased significantly in both groups versus baseline but intergroup comparison showed no significant differences in view of type of insoles and anatomical locations of foot pathology. CONCLUSIONS: We were unable to identify differences between the types of insoles in terms of their clinical effects or between anatomical locations of foot lesions in the two groups, but both groups improved. Therapeutic shoes plus soft insoles might be effective enough in terms of foot pain and foot function for specific patients with rheumatoid foot problems regardless of the location of foot pathology.