Whitneyholmberg3838
The wsCVs for PVWM CBF with single and multi-PLD acquisitions were 5.7 (95% CI (3.4,7.7)) % and 6.1 (95% CI (3.8,8.3))%, which were similar to those obtained from WB, GM and WM CBF even though the PVWM region is the most weakly perfused region of brain parenchyma. Correlations between relative PVWM CBF derived from ASL and from [15O]-water PET were also comparable to the other ROIs. Finally, the ATT of the PVWM region was found to be 1.27 ± 0.27s, which was not an outlier for the arterial circulation of the brain. These findings suggest that PVWM CBF can be reliably measured with the current state-of-the-art ASL methods.A family of complexes of the type [Ru(tpbn)(IP-R)(4-pic)]Cl2 (tbpn=2,2'-(4-(tert-butyl)pyridine-2,6-diyl)bis(1,8-napthyridine); 4-pic=4-picoline; IP-R=imidazo[4,5-f][1,10]phenanthroline attached to an aromatic group R for 2-8 and H for 1) were prepared as near-infrared (NIR) absorbing coordination complexes to test whether triplet intraligand excited states (3IL) of higher energy than the lowest-lying triplet metal-to-ligand charge transfer excited states (3MLCT) could effectively generate cytotoxic singlet oxygen (1O2) and elicit in vitro photodynamic therapy (PDT) effects. Aromatic groups ranged from benzene to anthracene, with corresponding triplet state energies that were all significantly higher (approximately 3.7-1.8 eV) than the 3MLCT state estimated at 1.5 eV. Complexes 1-8 absorbed NIR light, with their longest-wavelength peak maxima occurring near 725 nm that extended out to 800 nm. The 1O2 quantum yields for the aromatic-containing compounds were extremely small (ΦΔ=0.07), with correspondingly mode states in order the create potent NIR-activatable Ru(II) complexes for PDT.This study examined the developmental pathways from fathers' psychopathology in early childhood to child peer victimization (bullying and cyber victimization) in late adolescence via family relationships and early adolescent psychosocial functioning (anxiety, emotion regulation, social problems). A conceptual model with pathways through inter-parental aggression and fathers' parenting (harshness and sensitivity) was tested. Participants were 227 families (51% female children recruited as infants) who participated in a longitudinal study examining the role of parental alcohol problems and associated risks on developmental and family processes from infancy to late adolescence. Multi-method (observational, parent report, adolescent report) assessments of family processes and child outcomes were conducted across all time points. Fathers' alcohol problems and depressive symptoms in early childhood was prospectively associated with inter-parental aggression in middle childhood and social problems in early adolescence. For boys only, early adolescent social problems were predictive of bullying victimization. Fathers' antisocial behavior in early childhood was associated with less sensitive parenting in middle childhood. Fathers' sensitivity in middle childhood was protective, being associated with lower cyber victimization in late adolescence. Fathers' sensitivity was also associated with higher emotion regulation in early adolescence; however, counter to expectations, higher emotion regulation was associated with more bullying and cyber victimization. Findings shed light on differences in the etiological pathways to bullying and cyber victimization, as well as how distinct forms of paternal psychopathology in early childhood associate with family relationships, child adjustment, and vulnerability to peer victimization in late adolescence.
Home dialysis confers similar survival and greater quality of life than in-center hemodialysis for adults with ESKD but remains underutilized. We examined challenges and facilitators to implementation of home dialysis and identified stakeholder-centered strategies for improving it.
We conducted a qualitative, cross-sectional, multisite evaluation that included five geographically dispersed Veterans Health Administration (VHA) home dialysis programs. Participants included patients with ESKD receiving home dialysis, their informal caregivers, and home dialysis staff. Semistructured telephone interviews were conducted and audio-recorded from 2017 through 2018, to assess perceived barriers and facilitators to patient home dialysis use in VHA. Transcribed interviews were analyzed thematically by each participant group.
Participants included 22 patients receiving home dialysis (18 on peritoneal dialysis [PD] and four hemodialysis [HD]); 20 informal caregivers, and 19 home dialysis program staff. Ten themes emcreasing home visits, providing health data feedback, and reducing patient burden.
Stakeholder-centered challenges were rigorously identified. Facilitators and recommendations can inform efforts to support home dialysis implementation.
Stakeholder-centered challenges were rigorously identified. Facilitators and recommendations can inform efforts to support home dialysis implementation.SGLTs are sodium glucose transporters found on the luminal membrane of the proximal tubule, where they reabsorb some 180 g (1 mol) of glucose from the glomerular filtrate each day. The natural glucoside phlorizin completely blocks glucose reabsorption. Oral SGLT2 inhibitors are rapidly absorbed into the blood stream, where theyremain in the circulation for hours. On glomerular filtration, they bind specifically to SGLT2 in the luminal membrane of the early proximal tubule to reduce glucose reabsorption by 50%-60%. Because of glucose excretion, these drugs lower plasma glucose and glycosylated hemoglobin levels in patients with type 2 diabetes mellitus. The drugs also protect against heart and renal failure. The aim of this review is to summarize what is known about the physiology of renal SGLTs and the pharmacology of SGLT drugs.
Patients with ESKD on maintenance dialysis receive dialysis in common spaces with other patients and have a higher risk of severe SARS-CoV-2 infections. They may have persistently or intermittently positive SARS-CoV-2 RT-PCR tests after infection. We describe the clinical course of SARS-CoV-2 infection and the serologic response in a convenience sample of patients with ESKD to understand the duration of infectivity.
From August to November 2020, we enrolled patients on maintenance dialysis with SARS-CoV-2 infections from outpatient dialysis facilities in Atlanta, Georgia. We followed participants for approximately 42 days. We assessed COVID-19 symptoms and collected specimens. Oropharyngeal (OP), anterior nasal (AN), and saliva (SA) specimens were tested for the presence of SARS-CoV-2 RNA, using RT-PCR, and sent for viral culture. Serology, including neutralizing antibodies, was measured in blood specimens.
Fifteen participants, with a median age of 58 (range, 37‒77) years, were enrolled. Median duratio-competent virus detected.
Patients with ESKD on maintenance dialysis remained persistently and intermittently SARS-CoV-2-RT-PCR positive. However, of the 15 participants, only one had infectious virus, on day 14 after symptom onset. Most participants mounted an antibody response, including neutralizing antibodies. Participants continued having RT-PCR-positive results in the presence of SARS-CoV-2-specific antibodies, but without replication-competent virus detected.
Children who are critically ill with AKI suffer from high morbidity and mortality rates, and lack treatment options. Emerging evidence implicates the role of complement activation in AKI pathogenesis, which could potentially be treated with complement inhibitors. The purpose of this study is to evaluate the association between complement activation fragments and severity of AKI in children who are critically ill.
A biorepository of samples from children who are critically ill from a prior multisite study was leveraged to identify children with stage 3 AKI and matched to patients without AKI on the basis of PELOD-2 (illness severity) scores. Specimens were analyzed for plasma and urine complement activation fragments of factor B, C3a, C4a, and sC5b-9. The primary outcomes were MAKE30 and severe AKI rates.
In total, 14 patients with stage 3 AKI (five requiring RRT) were matched to 14 patients without AKI. Urine factor Ba and plasma C4a levels increased stepwise as severity of AKI increased, from no AKI to. Thioflavine S Dyes inhibitor Very high levels of urine Ba or plasma C4a may identify patients at risk for severe AKI, hemodialysis, and MAKE30 outcomes. The fragments may be useful as a functional biomarker of complement activation and may identify those patients to study complement inhibition to treat or prevent AKI in children who are critically ill. These findings suggest the need for further specific investigations of the role of complement activation in children who are critically ill and at risk of AKI.
Despite advances in immune suppression, kidney allograft rejection and other injuries remain a significant clinical concern, particularly with regards to long-term allograft survival. Evaluation of immune activity can provide information about rejection status and help guide interventions to extend allograft life. Here, we describe the validation of a blood gene expression classifier developed to differentiate immune quiescence from both T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR).
A five-gene classifier (DCAF12, MARCH8, FLT3, IL1R2, and PDCD1) was developed on 56 peripheral blood samples and validated on two sample sets independent of the training cohort. The primary validation set comprised 98 quiescence samples and 18 rejection samples seven TCMR, ten ABMR, and one mixed rejection. The second validation set included eight quiescence and 11 rejection samples seven TCMR, two ABMR, and two mixed rejection. AlloSure donor-derived cell-free DNA (dd-cfDNA) was also evaluated.
AlfDNA. Together, these biomarkers offer a more comprehensive assessment of allograft health and immune quiescence.
Validation of AlloMap Kidney demonstrated the ability to differentiate between rejection and immune quiescence using a range of scores. The diagnostic performance suggests that assessment of the mechanisms of immunologic activity is complementary to allograft injury information derived from AlloSure dd-cfDNA. Together, these biomarkers offer a more comprehensive assessment of allograft health and immune quiescence.Among a large racially and ethnically diverse US population, the prevalence of diagnosed ADPKD between 2002 and 2018 was 42.6 per 100,000 persons.ADPKD prevalence (per 100,000) was higher in (non-Hispanic) White (63.2) and Black (73.0) patients compared with Hispanic (39.9) and Asian (48.9) patients.Given the variable penetrance of ADPKD, our findings suggest race may be a factor in the clinical presentation and diagnosis of ADPKD.
Pathogenic variants in single genes encoding podocyte-associated proteins have been implicated in about 30% of steroid-resistant nephrotic syndrome (SRNS) patients in children. However,
gene biallelic variants have been identified in only seven patients so far, and most are missense variants of unknown significance. Furthermore, no functional analysis had been conducted for all but one of these variants. Here, we report three patients with
gene biallelic truncating variants manifesting infantile nephrotic syndrome, and one patient with SRNS with biallelic
missense variants.
We conducted comprehensive gene screening of Japanese patients with severe proteinuria. With the use of targeted next-generation sequencing, 62 podocyte-related genes were screened in 407 unrelated patients with proteinuria. For the newly discovered
variants, we conducted
heterotrimer formation assays.
Biallelic truncating variants in the
gene (NM_005560) were detected in three patients from two families. All patients presented with proteinuria within 6 months of age.