For over 100 years cardiac electrophysiology has been measured in the clinic. The electrical signals that can be measured span from noninvasive ECG and body surface potentials measurements through to detailed invasive measurements of local tissue electrophysiology. These electrophysiological measurements form a crucial component of patient diagnosis and monitoring; however, it remains challenging to quantitatively link changes in clinical electrophysiology measurements to biophysical cellular function. Multi-scale biophysical computational models represent one solution to this problem. These models provide a formal framework for linking cellular function through to emergent whole organ function and routine clinical diagnostic signals. In this review, we describe recent work on the use of computational models to interpret clinical electrophysiology signals. We review the simulation of human cardiac myocyte electrophysiology in the atria and the ventricles and how these models are being used to link organ scale function to patient disease mechanisms and therapy response in patients receiving implanted defibrillators, \cardiac resynchronisation therapy or suffering from atrial fibrillation and ventricular tachycardia. There is a growing use of multi-scale biophysical models to interpret clinical data. This allows cardiologists to link clinical observations with cellular mechanisms to better understand cardiopathophysiology and identify novel treatment strategies. This article is categorized under Cardiovascular Diseases > Computational Models Cardiovascular Diseases > Biomedical Engineering Cardiovascular Diseases > Molecular and Cellular Physiology.

Kidney transplant is the best treatment for end-stage renal disease (ESRD); however, access is limited by severe organ shortage. Public Health Service increased risk donors (PHS-IRD) represent a significant portion of available organs which are discarded at disproportional rates.

Pediatric nephrologists were surveyed regarding PHS-IRD kidneys to understand attitudes and perceived barriers to the use of these grafts in children. We sought to elucidate what methods may help increase the likelihood of PHS-IRD acceptance.

Twenty-two responses were received from United States pediatric nephrologists representing 11 UNOS regions (response rate 5.9%). Of respondents, 50% had been practicing for 20+ years, 77% in academic hospitals, and 63% in cities with over 1000000 people. All respondents worked in an institution with a kidney transplant program. 41% reported that they would not accept PHS-IRD kidneys under any circumstance, 45% would accept depending on the candidate’s medical status, and 14% routinely accepted PHS-IRD kidneys. Infectious transmission was the biggest disincentive reported (59%), with only 55% of respondents feeling comfortable counseling families on the associated risks. 82% of respondents did not perceive all PHS-IRD as the same, and 90% supported stratifying PHS-IRD into tiers based on risk, which would increase the likelihood of organ acceptance (82%) and assist in counseling families (91%).

With improved utilization, PHS-IRD kidneys offer a step toward decreasing the organ shortage. These findings suggest hesitance in use of PHS-IRD kidneys for pediatric recipients. Further stratification of risk could aid in provider organ acceptance and counseling patients.

With improved utilization, PHS-IRD kidneys offer a step toward decreasing the organ shortage. These findings suggest hesitance in use of PHS-IRD kidneys for pediatric recipients. Further stratification of risk could aid in provider organ acceptance and counseling patients.Genomic full-length sequence of HLA-B*400143 was identified by group-specific sequencing in a Chinese individual.

The prevalence of cardiometabolic disease following spinal cord injury is known to be high. However, it is unknown whether engaging in high-intensity exercise, which is advocated by recent guidelines, is beneficial or feasible for these individuals.

To assess the effects of high-intensity, whole-body exercise on the prevalence of cardiometabolic disease in individuals with spinal cord injury.

Combination of a randomized controlled trial and an open label intervention study of functional electrical stimulation legs plus arms rowing.

Outpatient academic rehabilitation hospital.

Forty individuals with spinal cord injury, with American Spinal Injury Association (ASIA) impairments scales A-D and neurological levels of injury C1-T12.

Six months of high-intensity, hybrid-functional electrical stimulation rowing.

Change in VO

, serum lipids, and insulin resistance, prevalence of cardiometabolic disease.

Individuals averaged 42.1 ± 22.0 minutes of hybrid-functional electrical stimulation rowing a weeith hybrid functional electrical stimulation rowing does not decrease the prevalence of cardiometabolic disease after spinal cord injury.

Sustained high-intensity exercise with hybrid functional electrical stimulation rowing does not decrease the prevalence of cardiometabolic disease after spinal cord injury.Mesothelioma is a rare, aggressive malignancy with poor outcome, and has limited treatment options. The aim of this study was to perform a comprehensive analysis of programmed death ligand 1 (PD-L1) and B7 homolog 3 (B7-H3) expression in mesothelioma. We investigated the protein expression of PD-L1 and B7-H3 and their potential correlation with histological subtype, which might help to develop new therapies targeting these immune checkpoint molecules. Expression analysis of PD-L1 and B7-H3 was performed by immunohistochemistry using serial tissue sections of specimens obtained from 31 patients with mesothelioma. Tumors were classified into 22 epithelioid, 6 sarcomatoid, and 3 biphasic types. Of the 31 patients, 13 (41.9%) were positive for PD-L1 and 28 (90.3%) were B7-H3 positive. Twelve of the 13 PD-L1 positive patients were positive for B7-H3. PD-L1 and B7-H3 were widely co-expressed in biphasic and sarcomatoid type tumor cells. These findings might provide a rationale for the use of combination therapy for mesothelioma by targeting PD-L1 and B7-H3, as well as the development of anti-B7-H3 or anti-PD-L1 single agents.The capability of viscoelastic measurement parameters to screen anticoagulation activity of edoxaban in relation to its plasma concentrations was evaluated in 15 healthy male volunteers. Blood samples were drawn before the oral administration of edoxaban 60 mg and 2, 4, 6, 8, and 24 hours after administration. At each time, standard coagulation tests were performed, blood viscoelastic properties were measured with a thromboelastometry device ROTEM delta analyzer (Instrumentation Laboratory, Werfen, Barcelona, Spain), and edoxaban plasma concentrations were measured. Our primary interest was the possible correlation between edoxaban plasma concentrations and values for ROTEM ExTEM, and FibTEM. We also studied the correlation of edoxaban plasma concentrations with the results of standard coagulation tests. We saw the effect of a single dose of edoxaban most clearly in clotting time (CT) of ROTEM ExTEM and FibTEM. Changes in these parameters correlated significantly with edoxaban plasma concentrations up to 6 hours from the ingestion of the drug. Activated partial thromboplastin time, prothrombin time, and anti-factor Xa were also affected. Peak changes were observed 2 and 4 hours after administration of edoxaban. The changes were mostly reversed after 8 hours. In conclusion, ROTEM CT correlates significantly with edoxaban plasma concentrations and can be used to estimate the effect of edoxaban. ROTEM should be considered as part of the assessment of coagulation, with the big advantage of being readily available on site.The basic model of SCD physiology states that vaso-occlusion occurs when hemoglobin S-containing red blood cells (RBC) undergo sickling before they escape the capillary into a larger vessel. We have shown that mental stress, pain and cold, and events reported by patients to trigger SCD vaso-occlusive crisis (VOC), cause rapid and significant decrease in blood flow, reducing the likelihood that RBC could transit the microvasculature before sickling occurs. However, the critical link between decrease in microvascular blood flow and the incidence of future sickle VOC has never been established experimentally in humans. Using data from centrally adjudicated, overnight polysomnograms (PSG), previously collected in a prospective multi-center cohort sleep study, we analyzed the beat-to-beat amplitudes of vasoconstriction reported by the fingertip photoplethysmogram in 212 children and adolescents with SCD and developed an algorithm that detects vasoconstriction events and quantifies the magnitude (Mvasoc ), duration, and frequency of vasoconstriction that reflect the individual’s inherent peripheral vasoreactivity. The propensity to vasoconstrict, quantified by median Mvasoc , predicted the incidence rate of post-PSG severe acute vaso-occlusive pain events (P = .006) after accounting for age and hemoglobin. Indices of sleep-disordered breathing contributed to median Mvasoc but did not predict future pain rate. Median Mvasoc was not associated with vaso-occlusive pain events that occurred prior to each PSG. These results show that SCD individuals with high inherent propensity to vasoconstrict have more frequent severe acute pain events. Our empirical findings are consistent with the fundamental SCD hypothesis that decreased microvascular flow promotes microvascular occlusion.Peroxidase-mimicking nanozymes such as Fe3 O4 nanoparticles are promising substitutes for natural enzymes like horseradish peroxidase. However, most such nanozymes work efficiently only in acidic conditions. In this work, the influence of various liposomes on nanozyme activity was studied. By introducing negatively charged liposomes, peroxidase-mimicking nanozymes achieved oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) in neutral and even alkaline conditions, although the activity towards anionic 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) was inhibited. The Fe3 O4 nanoparticles adsorbed on the liposomes without disrupting membrane integrity as confirmed by fluorescence quenching, dye leakage assays, and cryo-electron microscopy. Stabilization of the blue-colored oxidized products of TMB by electrostatic interactions was believed to be the reason for the enhanced activity. This work has introduced lipids to nanozyme research, and it also has practically important applications for using nanozymes at neutral pH, such as the detection of hydrogen peroxide and glucose.First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .