SUMMARY Cataracts, or lens opacities, are the leading cause of blindness worldwide. Cataracts increase with age and environmental insults, e.g. oxidative stress. Lens homeostasis depends on functional gap junctions. Knockout or missense mutations of lens gap junction proteins, Cx46 or Cx50, result in cataractogenesis in mice. We have previously demonstrated that protein kinase Cγ (PKCγ) regulates gap junctions in the lens epithelium and cortex. In the current study, we further determined whether PKCγ control of gap junctions protects the lens from cataractogenesis induced by oxidative stress in vitro, using PKCγ knockout and control mice as our models. The results demonstrate that PKCγ knockout lenses are normal at 2 days post-natal when compared to control. However, cell damage, but not obvious cataract, was observed in the lenses of 6-week-old PKCγ knockout mice,suggesting that the deletion of PKCγ causes lenses to be more susceptible to damage. Furthermore, in vitro incubation or lens oxidative stress treatment by H2O2 significantly induced lens opacification (cataract) in the PKCγ knockout mice when compared to controls. Biochemical and structural results also demonstrated that H2O2 activation of endogenous PKCγ resulted in phosphorylation of Cx50 and subsequent inhibition of gap junctions in the lenses of control mice, but not in the knockout. Deletion of PKCγaltered the arrangement of gap junctions on the cortical fiber cell surface,and completely abolished the inhibitory effect of H2O2on lens gap junctions. Data suggest that activation of PKCγ is an important mechanism regulating the closure of the communicating pathway mediated by gap junction channels in lens fiber cells. The absence of this regulatory mechanism in the PKCγ knockout mice may cause those lenses to have increased susceptibility to oxidative damage.
Informed consent for pediatric anesthesia challenges practitioners to navigate complex ethical, medical, and legal ambiguities. A patient's status as a minor does not negate the importance of his or her participation in the decision-making process but, rather, necessitates a nuanced evaluation of age and development to involve the patient to an appropriate extent. Given the complexities involved with pediatric informed consent in anesthesia practice and research, it is important to understand the experience of key stakeholders involved. For this review, we searched Medline, the Cochrane database, PROSPERO, and Clinicaltrials.gov for studies involving pediatric anesthesia informed consent. Inclusion and exclusion criteria were designed to select for studies that included issues related to informed consent as primary outcomes. The following data were extracted from included studies: title, authors, date of publication, study type, intervention, data collection method, participant type (ie, parent, pediatric patient, anesthesia provider), number of participants, pediatric patient age range, and primary outcome measures. Twenty-two articles were included for final review: studies of informed consent in pediatric anesthesia span many aspects of informed consent. Parental understanding has been studied most often (7/22 studies), followed by parental preferences (5/22 studies) and provider-related outcomes (5/22 studies) such as time spent interacting with patients, subjective reporting on amount of training related to informed consent, and provider satisfaction with the informed consent process. Outcomes pertaining to pediatric patients themselves constitute the smallest number of studies, including child anxiety (1/22), child understanding (1/22), and child refusal (1/22). Among the parties involved, parents have been most frequently identified as the subjects of these studies (2719/3805 subjects across all included studies, or 71% of all subjects). Pediatric patients are the least frequently involved subjects of studies that investigate informed consent in pediatric anesthesia (493/3805, or 13% of all subjects). Anesthesia providers and investigators have been study subjects (593/3805, or 16% of all subjects) for a range of topics including time spent interacting with patient, nature of informed consent conversation in relation to trainee status, satisfaction with informed consent process, and priorities for informed consent content. The aim of the present narrative review is to summarize the work that has been done on informed consent for pediatric anesthesia.
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