Glibenclamide Effects on Renal Function and Histology after Acute Hemorrhage in Rats under Sevoflurane Anesthesia

Introduction. Hypovolemia from hemorrhage evokes protective compensatory reactions, such as the renin-angiotensin system, which interferes in the clearance function and can lead to ischemia. This study was designed to evaluate the effects of glibenclamide, a K⁺_ATP channel blocker, on renal function and histology in rats in a state of hemorrhagic shock under sevoflurane anesthesia. Material and Methods. Twenty Wistar rats were randomized into two groups of 10 animals each (G1 and G2), only one of which (G2) received intravenous glibenclamide (1 μg.g^?1), 60 min before bleeding was begun. Both groups were anesthetized with sevoflurane and kept on spontaneous respiration with oxygen-air, while being bled of 30% of volemia in three stages with 10 min intervals. There was an evaluation of renal function—sodium para-aminohippurate and iothalamate clearances, filtration fraction, renal blood flow, renal vascular resistance—and renal histology. Renal function attributes were evaluated at three moments: M1 and M2, coinciding with the first and third stages of bleeding; and M3, 30 min after M2, when the animals were subjected to bilateral nephrectomy before being sacrificed. Results. Significant differences were found in para-aminohippurate clearance, G1 < G2, and higher renal vascular resistance values were observed in G1. Histological examination showed the greater vulnerability of kidneys exposed to sevoflurane alone (G1) with higher scores of vascular and tubular dilatation. There were vascular congestion and tubular vacuolization only in G1. Necrosis and signs of tubular regeneration did not differ in both groups. Conclusion. Treatment with glibenclamide attenuated acutely the renal histological changes after hemorrhage in rats under sevoflurane anesthesia.     

The role of mutual in-feeding in maintaining problematic self-narratives: Exploring one path to therapeutic failure

Abstract

According to the author's narrative model of change, clients may maintain a problematic self-stability across therapy, leading to therapeutic failure, by a mutual in-feeding process, which involves a cyclical movement between two opposing parts of the self. During innovative moments (IMs) in the therapy dialogue, clients’ dominant self-narrative is interrupted by exceptions to that self-narrative, but subsequently the dominant self-narrative returns. The authors identified return-to-the-problem markers (RPMs), which are empirical indicators of the mutual in-feeding process, in passages containing IMs in 10 cases of narrative therapy (five good-outcome cases and five poor-outcome cases) with females who were victims of intimate violence. The poor-outcome group had a significantly higher percentage of IMs with RPMs than the good-outcome group. The results suggest that therapeutic failures may reflect a systematic return to a dominant self-narrative after the emergence of novelties (IMs).     

The effects of photobiomodulation using LED on the repair process of skin graft donor sites

Lasers in Medical Science - The benefits of photobiomodulation (PBM) applied to wounds are well-described in the literature; however, its effects in skin graft donor sites have been poorly studied....     

Phase 2 of collaborative action around the implementation of virtual hearing aid care: Evaluation of a clinical practice guideline

Rationale

Following the onset of the COVID-19 pandemic, a clinical practice guideline (CPG) around virtual hearing aid practices was developed to fill a knowledge gap within the field of audiology. Details outlining the development and mobilization of this draft guideline were outlined as Phase 1 (described in a paired paper).

Aims and Objectives

This study describes Phase 2 of this project as part of the Knowledge-to-Action Framework, including an evaluation of the methodological quality of the guideline and the resulting tailored version of the document (v2.0).

Method

The Appraisal of Guidelines for Research and Evaluation II instrument was used to assess methodological quality and to guide revisions. Twenty-two clinicians, from a variety of clinical backgrounds, participated in the evaluation.

Results and Conclusion

Findings reported across six domains suggest high mean scores, ranging from 78% to 81%, in order of scope and purpose (highest rated), stakeholder involvement, rigour of development, applicability, clarity of presentation, and editorial independence. Specific recommendations made by in international co-creation team during the evaluation informed the final version of the CPG. Future development and evaluation efforts should aim to include greater representation from nontraditional practice contexts to strengthen global applicability.     

Plasma Apolipoprotein L1 Levels Do Not Correlate with CKD

Polymorphisms in APOL1 are associated with CKD, including HIV-related CKD, in individuals of African ancestry. The apolipoprotein L1 (APOL1) protein circulates and is localized in kidney cells, but the contribution of APOL1 location to CKD pathogenesis is unclear. We examined associations of plasma APOL1 levels with plasma cytokine levels, dyslipidemia, and APOL1 genotype in a nested case-control study (n=270) of HIV-infected African Americans enrolled in a multicenter prospective observational study. Patients were designated as having CKD when estimated GFR (eGFR) decreased to <60 ml/min per 1.73 m² (eGFR<60 cohort) or protein-to-creatinine ratios became >3.5 g/g (nephrotic proteinuria cohort). Circulating APOL1 levels did not associate with APOL1 genotype, CKD status, or levels of proinflammatory cytokines, but did correlate with fasting cholesterol, LDL cholesterol, and triglyceride levels. At ascertainment, CKD-associated polymorphisms (risk variants) in APOL1 associated with the eGFR<60 cohort, but not the nephrotic-range proteinuria cohort. Of note, in both the eGFR<60 and nephrotic proteinuria cohorts, CKD cases with two APOL1 risk variants had significant declines in eGFR over a median of 4 years compared with individuals with one or no risk variants. APOL1 risk genotype was not associated with changes in proteinuria. Higher circulating proinflammatory cytokine levels were independently associated with CKD but not APOL1 genotype. In conclusion, the function of variant APOL1 proteins derived from circulation or synthesized in the kidney, but not the level of circulating APOL1, probably mediates APOL1-associated kidney disease in HIV-infected African Americans.Nondiabetic CKD in individuals of African ancestry have been linked to polymorphisms in the gene for apolipoprotein L1 (APOL1),^1–5 a protein component of HDL particles with a known function in the immune clearance of Trypanosoma brucei infections.⁶ CKD is associated with two coding variants of the APOL1 gene known as G1 and G2, both of higher allele frequency in African and African descendent populations compared with white populations where they are almost absent. Evidence suggests that the prevalence of the G1 and G2 variants may have increased in African populations because of a selective advantage from their ability to kill a broader range of Trypanosoma species.^1,2,7 Individuals carrying at least one G1 or G2 allele have additional protection from trypanosomiasis; however, individuals with two G1 or G2 alleles are at increased risk for nondiabetic CKD.^2,4,5The pathogenic mechanisms responsible for CKD associated with APOL1 risk variants are unknown. We recently showed that, in addition to being secreted and circulated in the blood,⁸ APOL1 is localized in podocytes, proximal tubular epithelial cells, and small-artery endothelium in normal kidney.⁹ Thus, the contribution of circulating versus kidney-localized variant APOL1s to CKD pathogenesis is unknown. In kidney transplantation, two studies suggest that graft loss is associated with the APOL1 genotype of the allograft, not the recipient.^10,11 However, the association of APOL1 plasma levels with CKD phenotypes or APOL1 genotype has not been studied.To address these issues, we examined circulating APOL1 levels with APOL1 genotype and renal function in HIV-infected African Americans in the AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) cohort because the occurrence of HIV-associated nephropathy (HIVAN) and renal outcomes in HIV-infected patients are strongly associated with APOL1 risk alleles.^12–14 In addition, we examined the relationship between circulating APOL1 levels and proinflammatory cytokines known to induce APOL1 expression and previously associated with CKD and HIV/AIDS progression.^15,16 Additional analyses examined associations of APOL1 levels with dyslipidemia and the role of APOL1 genotype on CKD progression using longitudinal data.     

Training of goal directed arm movements with motion interactive video games in children with cerebral palsy – A kinematic evaluation

Objective: The main aim of this study was to evaluate the quality of goal-directed arm movements in 15 children with cerebral palsy (CP) following four weeks of home-based training with motion interactive video games. A further aim was to investigate the applicability and characteristics of kinematic parameters in a virtual context in comparison to a physical context.

Method: Kinematics and kinetics were captured while the children performed arm movements directed towards both virtual and physical targets.

Results: The children’s movement precision improved, their centre of pressure paths decreased, as did the variability in maximal shoulder angles when reaching for virtual objects. Transfer to a situation with physical targets was mainly indicated by increased movement smoothness.

Conclusion: Training with motion interactive games seems to improve arm motor control in children with CP. The results highlight the importance of considering both the context and the task itself when investigating kinematic parameters.