Exploring the support needs of Australian parents of young children with Usher syndrome: a qualitative thematic analysis.

BACKGROUND: Advancements in genetic testing have led to Usher syndrome now being diagnosed at a much earlier age than in the past, enabling the provision of early intervention and support to children and families. Despite these developments, anecdotal reports suggest there are substantial gaps in the services and supports provided to parents of children with Usher syndrome. The current study investigated the support needs of parents of children with Usher syndrome Type 1 when their child was aged 0 to 5 years. METHOD: Purposive sampling was used, and six semi-structured interviews were conducted with Australian parents of children with Usher syndrome, Type 1. Data was analysed using modified reflexive thematic analysis. RESULTS: Four key themes were identified as being central to the support needs of parents of children with Usher syndrome aged 0 to 5 years. (1) Social Needs referred to parents' need for various sources of social support, (2) Informational Needs described the lack of information parents received regarding Usher syndrome from treating professionals, (3) Practical Needs included supports needed to assist parents in managing the day-to-day tasks of caring for a child with a disability, and (4) Emotional Needs represented the emotional support (both formal and informal) that parents needed to be a positive support to their child. CONCLUSIONS: Findings provide rich information for relevant support groups, policy makers, individual healthcare professionals, and professional governing bodies regarding the education of stakeholders and the development and implementation of best-practice treatment guidelines.

Persistent systemic monocyte and neutrophil activation in neonatal encephalopathy.

AIM: Circulating immune cell activation is associated with worse outcome in adult and animal models of brain injury. Our aim was to profile the systemic inflammatory response over the first week of life in infants at risk of neonatal encephalopathy and correlate early neutrophil and monocyte endotoxin and activation responses with outcome. METHODS: Prospective observational study in a tertiary referral university hospital including 22 infants requiring resuscitation at birth who had serial (five time points) neutrophil and monocyte CD11b (marker of cell adhesion) (intracellular Reactive oxygen intermediates) ROI (cell activation), and Toll-like receptor (endotoxin recognition) before and after endotoxin stimulation ex vivo compared to neonatal controls. RESULTS: All neonates requiring resuscitation at delivery (n = 122 samples) had higher neutrophil and monocyte CD11b and TLR-4 expressions compared with adults and neonatal controls. Neonates with abnormal neuroimaging and/or severe neonatal encephalopathy had increased CD11b, ROI and TLR-4. Increased PMN TLR-4 expression was associated with increased mortality in infants with neonatal encephalopathy (NE). CONCLUSION: Innate immune dysregulation in the first week of life is associated with severity of outcome in neonatal brain injury in this cohort and may be amenable to immunomodulation.

Neonatal brain injury and systemic inflammation: modulation by activated protein C ex vivo.

Infection and inflammation can be antecedents of neonatal encephalopathy (NE) and increase the risk of neurological sequelae. Activated protein C (APC) has anti-coagulant and anti-inflammatory effects and provides neuroprotection in brain and spinal cord injury. We examined neutrophil and monocyte responses to lipopolysaccharide (LPS) in infants with NE compared with healthy adult and neonatal controls, and also studied the effect of APC. Whole blood was incubated with LPS and APC and Toll-like receptor (TLR)-4 (LPS recognition), CD11b expression (activation) and intracellular reactive oxygen intermediate (ROI; function) release from neutrophils and monocytes was examined by flow cytometry serially from days 1 to 7. We found a significant increase in neutrophil ROI in infants with NE on day 3 following LPS compared to neonatal controls and this augmented response was reduced significantly by APC. Neutrophil and monocyte CD11b expression was increased significantly on day 1 in infants with NE compared to neonatal controls. LPS-induced neutrophil TLR-4 expression was increased significantly in infants with NE on days 3 and 7 and was reduced by APC. LPS-induced monocyte TLR-4 was increased significantly in infants with NE on day 7. Neutrophil and monocyte activation and production of ROIs may mediate tissue damage in infants with NE. APC modified LPS responses in infants with NE. APC may reduce the inflammatory responses in NE and may ameliorate multi-organ dysfunction. Further study of the immunomodulatory effects of protein C may be warranted using mutant forms with decreased bleeding potential.

Topical prostaglandin analogues do not affect selective laser trabeculoplasty outcomes.

PURPOSE: To investigate the effect of topical prostaglandin analogue use on the efficacy of selective laser trabeculoplasty (SLT) intraocular pressure (IOP) lowering in patients with open-angle glaucoma. PATIENTS AND METHODS: This retrospective study included 123 consecutive patients who underwent 180 degrees SLT for the first time. Eyes were grouped into those that received prostaglandin analogues before and after SLT (n=74) and those that did not (n=49). The main outcome measure was IOP lowering after SLT. Success was defined as > or =20% reduction in IOP without further glaucoma intervention. RESULTS: There was no significant difference in IOP lowering at 6 months post-laser between the prostaglandin and non-prostaglandin groups (3.9+/-4.8 vs 4.6+/-3.6 mm Hg, P=0.43). Long-term SLT success rates were also not significantly different between the treatment groups (Kaplan-Meier survival analysis, P=0.68). IOP lowering at 6 months was similar in eyes that received no glaucoma medications, monotherapy with or without a prostaglandin analogue, or combination therapy with or without prostaglandin analogues (P=0.81). Logistic regression analysis showed that various patient characteristics including age, sex, type of glaucoma, previous glaucoma surgery, and other glaucoma risk factors did not predict a successful SLT outcome. However, higher pre-operative IOP was found to predict SLT success (odds ratio=1.12, 95% CI=1.02-1.24, P=0.02). CONCLUSION: The IOP lowering efficacy of SLT is not influenced by the use of topical prostaglandin analogues.

Enlisting the eccentric photoscreener in a public hospital eye department.

We analysed retrospectively non-acute new referrals of children to Waikato Hospital over one year. It was found that children were required to wait unacceptably long to be seen. Almost half the children with established amblyopia were not seen until after the age of five years (42% were not referred until after that age). On the other hand, half the children seen had no significant pathology, and the high level of non-attendance also wasted clinic time. An attempt was made to address these problems by holding regular screening clinics using a photoscreener, assessing all children within three weeks of referral so that children with pathology could be examined and treated promptly. Preliminary investigations into mass community photoscreening produced an average recall rate of 11% (54% of whom fell into our definition of pathological). We feel that enlisting the photoscreener has provided a much more efficient paediatric service, which it is hoped will lead to a reduction in visual loss due to amblyopia.

Simplified derivation of angular order and dynamics of rodlike fluorophores in models and membranes. Simultaneous estimation of the order and fluidity parameters for diphenylhexatriene by only coupling steady-state illumination polarization and lifetime of fluorescence.

We compare numerous values of average degrees of order, (S), and of average correlation times, (phi), as given by many authors for 1-6-diphenyl-1-3-5-hexatriene (DPH) in membrane models. From these comparisons, a relationship arises between (phi),(S), and the absolute temperature, T. This means that each of these variables is a function of both the others: omega [(phi), (S), T] equal 0, and this function defines a surface in a three-dimensional space. Note that omega identical for a large variety of sonicated lipid vesicles. This statement is a new formation of the conclusions of Van Blitterswijk W. J., R. P. Van Hoeven, and B. W. Van Dermeer, 1981, Biochim. Biophys. Acta, 644:323-332, in the light of other recent studies (Kinosita K., Jr., R. Kataoka, Y. Kimura, O. Gotoh, and A. Ikegami, 1981, Biochemistry, 20:4270-4277). It seemed useful to seek an approximate analytical expression for the omega function (supposed unique). Various arguments have led us to define the omega function as the ratio of a diffusive (Arrhenius-type) numerator, v(T), divided by a temperature-independent denominator, sigma((s)) (Kinosita, K., Jr., S. Kawato, and A. Ikegami, 1977, Biophys. J., 20:289-305; Lipari, G., and A. Szabo, 1980, Biophys. J., 30:489-506). However, one could not a priori discard a dependence of the activation energy of v(T) on both the temperature and/or on (S). The analytical form of the proposed approximate omega function and the numerical values of the constants involved are checked for much of the data obtained from DPH/biomembranes systems described in the literature. As a consequence of this new relationship, a simplified procedure is proposed to obtain the order parameter, (S), in unknown systems. In this procedure the starting experimental quantities are only in the steady-state fluorescence anisotropy, (r), the weighted average fluorescence lifetime, tau, and T. In turn, evaluation of a weighted average correlation time, (phi), sometimes becomes simultaneously possible, at least for membranes in their liquid-crystal phase, but with less accuracy than for the determination of (S). Because the method is founded on results arising from transient experiments, it seems difficult to conceive that it could replace these techniques in a generalized manner. However, because fast tests are frequently required in routine studies on biomembranes, the method could still have a broad application provided that some transient-control measurements are performed at the limits of the experimental range studied.

Is an average viscosity tenable in lipid bilayers and membranes? A comparison of semi-empirical equivalent viscosities given by unbound probes: a nitroxide and a fluorophore.

Relative variations of fluidity in bilayers and membranes are currently evaluated by numerous physical methods, but comparison between different systems remain difficult because the effects of order (anisotropy) and fluidity are involved in the diffusion coefficients for correlation times, or frictional coefficients) given by experiment. The present report represents an attempt to generalize the use of isotropic liquids as viscosity standards for disordered lipidic systems. It advances a simple check to verify the quasi-isotropic behaviour of probe environments and avoids the introduction of estimated values of the molecular dimensions in Perrin-Einstein relations. The equivalent viscosities obtained with 1,6-diphenyl hexatriene and with 2-pentyl-2'-butyl-4,4'-dimethyl oxazolidinoxyl are strikingly similar in egg lecithin vesicles above 0 degrees C, while in dipalmitoylphosphatidylcholine dispersions above their transition temperature, a discrepancy of about 30% seems to remain, even at high temperatures.

Variations in microviscosity values induced by different rotational behaviour of fluorescent probes in some aliphatic environments.

Recently there have been large developments in the indirect estimation of phospholipid bilayer and membrane microviscosities through the use of fluorescent probes with the help of paraffin oils as standard solvents. Before applying this semi-empirical method to membrane systems, it seemed necessary to test: first, a large variety of probes (this has been done by many authors) and secondly, a large variety of aliphatic oils (there is little literature on these tests). The present paper shows the variations of the rotational relaxation rates of three probes in relation to the viscosities of some aliphatic oils. When changing the oil but keeping constant the macroscopic viscosity, large differences appear in the relaxation rates of a given fluorphore (a ratio of 30/1 is observed in the extreme cases). The microviscosities of membranes deduced from the probe motion will consequently exhibit large uncertainty, as is shown with dipalmitoyl phosphatidylcholine. The cause of these different behaviours must be looked for in the properties of the oil. Particularly, the anisotropy of the solute-solvent interaction in the site where the probe is located depends in part on the internal order of the solvent which is used as a reference.