Nephrons and non-relapse mortality: simplified comorbidity index and acute kidney injury are associated with NRM in adults undergoing allogeneic hematopoietic cell transplant.

The Simplified Comorbidity Index (SCI) is a recently published 5-component, pre-transplant tool to predict non-relapse mortality (NRM) in allogeneic hematopoietic cell transplantation (alloHCT) patients. The SCI captures chronic kidney disease (CKD) using estimated glomerular filtration rate (eGFR) based on the CKD-EPI equation (KDIGO 2021 CKD-EPI), which may be more sensitive to predict risk of NRM than the creatinine cut-off in the 16-component, Hematopoietic Cell Transplant-Comorbidity Index (HCT-CI). We retrospectively assessed the ability of the SCI to risk-stratify patients and the impact of acute kidney injury (AKI) to NRM in adults who underwent alloHCT at the University of Minnesota. We included 373 patients who underwent their first alloHCT between 2015 and 2019. Through multivariate analysis, we found that patients with an SCI of greater than 4 had a higher risk of NRM. Additionally, we noted that AKIs stages 2-3 prior to day +100 was independently associated with a 3-fold greater NRM than patients who did not experience clinically significant AKI.

Hydrophobically Modified Isosorbide Dimethacrylates as a Bisphenol-A (BPA)-Free Dental Filling Material.

A series of bio-based hydrophobically modified isosorbide dimethacrylates, with para-, meta-, and ortho- benzoate aromatic spacers (ISBGBMA), are synthesized, characterized, and evaluated as potential dental restorative resins. The new monomers, isosorbide 2,5-bis(4-glyceryloxybenzoate) dimethacrylate (ISB4GBMA), isosorbide 2,5-bis(3-glyceryloxybenzoate) dimethacrylate (ISB3GBMA), and isosorbide 2,5-bis(2-glyceryloxybenzoate) dimethacrylate (ISB2GBMA), are mixed with triethylene glycol dimethacrylate (TEGDMA) and photopolymerized. The resulting polymers are evaluated for the degree of monomeric conversion, polymerization shrinkage, water sorption, glass transition temperature, and flexural strength. Isosorbide glycerolate dimethacrylate (ISDGMA) is synthesized, and Bisphenol A glycerolate dimethacrylate (BisGMA) is prepared, and both are evaluated as a reference. Poly(ISBGBMA/TEGDMA) series shows lower water sorption (39-44 µg/mm3) over Poly(ISDGMA/TEGDMA) (73 µg/mm3) but higher than Poly(BisGMA/TEGDMA) (26 µg/mm3). Flexural strength is higher for Poly(ISBGBMA/TEGDMA) series (37-45 MPa) over Poly(ISDGMA/TEGDMA) (10 MPa) and less than Poly(BisGMA/TEGDMA) (53 MPa) after immersion in phosphate-buffered saline (DPBS) for 24 h. Poly(ISB2GBMA/TEGDMA) has the highest glass transition temperature at 85 °C, and its monomeric mixture has the lowest viscosity at 0.62 Pa·s, among the (ISBGBMA/TEGDMA) polymers and monomer mixtures. Collectively, this data suggests that the ortho ISBGBMA monomer is a potential bio-based, BPA-free replacement for BisGMA, and could be the focus for future study.

Vascular endothelial growth factor: Potential predictor of treatment response in major depression.

OBJECTIVES: The aim of the study was to evaluate baseline plasma VEGF levels as a potential predictor of response to antidepressant pharmacotherapy. The study also sought to determine whether baseline plasma VEGF would be useful in predicting treatment outcome when two pharmacodynamically diverse agents with established antidepressant efficacy, escitalopram and quetiapine, were administered monotherapeutically to MDD patients. METHODS: Two groups of qualifying MDD subjects were enrolled. One group was treated with escitalopram and the other with quetiapine. Plasma concentrations of VEGF were measured using Randox Technologies at baseline, and at weeks 8 and 12 of treatment. RESULTS: We stratified the MDD patients into those who remitted and those who failed to respond. Mean baseline VEGF for the remitters and non-responders was 9.61 and 5.40 pg/ml, respectively (P < 0.0005). Using optimal data analysis a cut score of 7.49 pg/ml for baseline plasma VEGF distinguished remitters from non-responders with a 63% overall accuracy. The remission rate was comparable for both drugs (73 and 81% for quetiapine and escitalopram, respectively). VEGF levels did not significantly change following antidepressant treatment with either escitalopram or quetiapine when measured at 8 and 12 weeks; this result held true for both remitters and non-responders. CONCLUSIONS: Our results suggest that VEGF may predict response to antidepressant treatment and may ultimately prove to be a potential biomarker that can be measured with a routine blood draw at the point of service.

Vascular Endothelial Growth Factor: a potential diagnostic biomarker for major depression.

Despite intense research efforts undertaken by investigators throughout the world over the past half century to identify a specific biomarker for major depressive disorder (MDD), none have so far met the rigorous test of specificity, reliability and reproducibility. Vascular Endothelial Growth Factor (VEGF) has been implicated in the neurotrophic model of depression and several studies have assessed VEGF levels in depressed patients. The results have been discrepant largely due to design and assay differences among studies. The aim of this study was to assess plasma VEGF levels in a cohort of MDD subjects prior to treatment with psychotropic medication and compare them to those of healthy control (HC) subjects. Prospective study participants underwent extensive medical and psychiatric assessments before they were enrolled. Plasma concentrations of VEGF were measured by the technique marketed by Randox Technologies. The mean baseline VEGF for the healthy and depressed groups was 5.91 pg/ml (SD: 3.04) and 10.51 pg/ml (SD: 9.04), respectively, and this difference was statistically significant (p = 0.001). We detected a very low univariate relationship between VEGF and demographic and clinical variables. Using the Optimal Data Analysis a cut score of 6.64 pg/ml for baseline plasma VEGF distinguished depressed from healthy subjects with a 63% overall accuracy. We conclude these results support a role of plasma VEGF as a useful biomarker of depression that can be measured with a routine blood draw at the point of service. The specificity of this potential biomarker must be confirmed in studies that include other psychiatric disease entities.

VEGF and depression: a comprehensive assessment of clinical data.

Vascular Endothelial Growth Factor (VEGF), initially identified as an angiogenic mitogen, is believed to play a role in hippocampal neurogenesis and response to stress. It exerts neuroprotective effects and influences synaptic transmission. The possible role of VEGF in depression has been hypothesized in the context of the neurotrophic model of depression, which postulates that stress can lead to decreased level of neurotrophins. Since VEGF has emerged as a potential component in the pathophysiology of stress and stress-related disorders, animal and clinical studies have attempted to delineate its precise role. In this review article we provide a synopsis of basic studies that are of direct relevance to the clinical findings in depression and antidepressant drug action. We have classified the studies on the basis of higher, lower or no different levels of VEGF as compared to control subjects. It became evident that there is conflicting data regarding VEGF levels in depressed patients. The fact that no definitive trend is apparent in the published data is likely attributable to differences in study designs. However, promising leads have emerged in our effort to understand and clarify this wide variation in results. Further study could establish the potential use of VEGF as a biomarker to aid in making a correct diagnosis and a successful treatment plan. Delineating the relationship of VEGF and depression ultimately has the potential to shed light on the still elusive neural mechanisms underlying the pathophysiology of depression and the mechanisms by which antidepressants exert their effects.

The practical nurse: a case for COMFORT communication training.

Licensed practical nurses provide the majority of bedside care in long-term care facilities and home care settings, and their communication with patients and families is pivotal to interventions aimed at reducing burdensome transitions to acute care settings. Although good communication skills are required for practical nurses, they receive limited instruction in their training. The goal of this study was to assess the effects of communication training for the practical nurse. A pre-post survey design was used to assess the COMFORT communication training curriculum provided to licensed practical nursing students. A comparison of mean scores on communication skills attitudes and perceived nursing competency revealed statistically significant improvement in attitudes and self-efficacy. This study shows promise for the feasibility and utilization of the COMFORT curriculum for nurse communication training. Further research should address the nurse's ability to perform COMFORT communication skills in the clinical setting.

Some aspects of the airborne transmission of infection.

The relationship between the human body and the dissemination of potentially pathogenic particles and droplets is described. Airborne transmission of infection in operating theatres and a burns unit and the part played by the human microclimate and its interaction with ventilating air flows is discussed. The mechanisms by which different garment assemblies used for surgery can enhance particle dispersion are illustrated and the way that floor cleaning can increase the concentration of airborne organisms is described. The development of the successful use of ultra-clean air systems in orthopaedic implant surgery is reviewed. Relationships between contact and airborne transmission of disease are explored and ways by which containment strategies and metrics used in pharmaceutical and electronics manufacturing can be applied to the design and monitoring of healthcare areas is discussed. It is suggested that currently available techniques involving architectural, ventilation and operational aspects of healthcare provision, when properly applied, can markedly improve treatment outcomes that may otherwise be compromised by hospital-acquired infections involving both bacteria and viruses.

Adenovirus-mediated overexpression of O-GlcNAcase improves contractile function in the diabetic heart.

To examine whether excessive protein O-GlcNAcylation plays a role in the dysfunction of the diabetic heart, we delivered adenovirus expressing O-GlcNAcase (Adv-GCA) into the myocardium of STZ-induced diabetic mice. Our results indicated that excessive cellular O-GlcNAcylation exists in the diabetic heart, and that in vivo GCA overexpression reduces overall cellular O-GlcNAcylation. Myocytes isolated from diabetic hearts receiving Adv-GCA exhibited improved calcium transients with a significantly shortened T(decay) (P<0.01) and increased sarcoplasmic reticulum Ca2+ load (P<0.01). These myocytes also demonstrated improved contractility including a significant increase in +dL/dt and -dL/dt and greater fractional shortening as measured by edge detection (P<0.01). In isolated perfused hearts, developed pressure and -dP/dt were significantly improved in diabetic hearts receiving Adv-GCA (P<0.05). These hearts also exhibited a 40% increase in SERCA2a expression. Phospholamban protein expression was reduced 50%, but the phosphorylated form was increased 2-fold in the diabetic hearts receiving Adv-GCA. We conclude that excess O-GlcNAcylation in the diabetic heart contributes to cardiac dysfunction, and reducing this excess cellular O-GlcNAcylation has beneficial effects on calcium handling and diabetic cardiac function.

Microvascular and biochemical compensation during ventricular hypertrophy in male rainbow trout.

We investigated whether there are compensatory changes in the coronary microvasculature, cardiac lipid metabolism, and myocyte ultrastructure associated with ventricular enlargement in male rainbow trout. Epicardial tissue was sampled at different stages of sexual maturation, and we estimated arterial capillary density, intercapillary diffusion distance, and applied a diffusion model to predict PO(2) at different workloads. We also measured biochemical indices of lipid metabolism and estimated fractional volumes of mitochondria and myofibrils in myocytes. Immature fish with nonenlarged ventricles had the highest capillary length densities (1620+/-158 mm mm(-3)). Maturing trout with moderate ventricular hypertrophy had lower capillary length densities (1103+/-58 mm mm(-3)) and similar diffusion distances (13.9+/-0.7 microm) compared with immature fish (11.7+/-0.9 microm). The largest ventricles had intermediate capillary length densities (1457+/-288 mm mm(-3)) and diffusion distances (12.8+/-0.8 microm). Modelling predicted that enlarged ventricles would not become anoxic even at maximal workloads. Biochemical markers of fatty acid metabolism and aerobic capacity were unchanged with hypertrophy. Volume densities of mitochondria and myofibrils were also not influenced by cardiac growth. In summary, ventricle hypertrophy results in expansion of the coronary capillary bed and the maintenance of the epicardial capacities for fat and oxidative metabolism.

Diabetes and the accompanying hyperglycemia impairs cardiomyocyte calcium cycling through increased nuclear O-GlcNAcylation.

Diabetic cardiomyopathy is characterized by impaired cardiac contractility leading to poor myocardial performance. We investigated the role that the hexosamine pathway, and especially altered nuclear O-Glc-NAcylation, plays in the development of diabetic cardiomyopathy. Incubating neonatal rat cardiomyocytes in high glucose (25 mM) resulted in prolonged calcium transients when compared with myocytes incubated in normal glucose (5.5 mM), which is consistent with delayed myocardial relaxation. High glucose-treated myocytes also exhibited reduced sarcoendoplasmic reticulum Ca(2+)-ATPase 2a (SERCA2a) mRNA and protein expression, decreased SERCA2a promoter activity, and increased O-GlcNAcylation of nuclear proteins compared with myocytes treated with normal glucose. Exposure of myocytes to 8 mM glucosamine or an adenovirus expressing O-GlcNAc-transferase (OGT) resulted in prolonged calcium transient decays and significantly reduced SERCA2a protein levels, whereas treatment with an adenovirus encoding O-GlcNAcase (GCA) resulted in improved calcium transients and SERCA2a protein levels in myocytes exposed to high glucose. Effects of elevated glucose or altered O-GlcNAcylation were also observed on essential transcription factors involved in cardiomyocyte function. High glucose-treated myocytes (with or without OGT adenovirus) exhibited increased levels of O-GlcNAcylated specificity protein 1 compared with control myocytes, whereas infecting high glucose-treated myocytes with GCA adenovirus reduced the degree of specificity protein 1 Glc-NAcylation. Treatment of myocytes with 25 mM glucose, 8 mM glucosamine, or OGT adenovirus also significantly reduced levels of myocytes enhancer factor-2A protein compared with control myocytes, whereas infection with GCA adenovirus resulted in improved myocytes enhancer factor-2 expression. Our results suggest that the hexosamine pathway, and O-GlcNAcylation in particular, is important in impaired cardiac myocyte function and the development of diabetic cardiomyopathy.

Missense mutations but not allelic variants alter the function of ATM by dominant interference in patients with breast cancer.

The human genetic disorder ataxia-telangiectasia (A-T) is characterized by hypersensitivity to ionizing radiation and an elevated risk of malignancy. Epidemiological data support an increased risk for breast and other cancers in A-T heterozygotes. However, screening breast cancer cases for truncating mutations in the ATM (A-T mutated) gene has failed largely to reveal an increased incidence in these patients. It has been hypothesized that ATM missense mutations are implicated in breast cancer, and there is some evidence to support this. The presence of a large variety of rare missense variants in addition to common polymorphisms in ATM makes it difficult to establish such a relationship by association studies. To investigate the functional significance of these changes we have introduced missense substitutions, identified in either A-T or breast cancer patients, into ATM cDNA before establishing stable cell lines to determine their effect on ATM function. Pathogenic missense mutations and neutral missense variants were distinguished initially by their capacity to correct the radiosensitive phenotype in A-T cells. Furthermore missense mutations abolished the radiation-induced kinase activity of ATM in normal control cells, caused chromosome instability, and reduced cell viability in irradiated control cells, whereas neutral variants failed to do so. Mutant ATM was expressed at the same level as endogenous protein, and interference with normal ATM function seemed to be by multimerization. This approach represents a means of identifying genuine ATM mutations and addressing the significance of missense changes in the ATM gene in a variety of cancers including breast cancer.