The Neuronal EGF-Related Gene Nell2 Interacts with Macf1 and Supports Survival of Retinal Ganglion Cells after Optic Nerve Injury

Nell2 is a neuron-specific protein containing six epidermal growth factor-like domains. We have identified Nell2 as a retinal ganglion cell (RGC)-expressed gene by comparing mRNA profiles of control and RGC-deficient rat retinas. The aim of this study was to analyze Nell2 expression in wild-type and optic nerve axotomized retinas and evaluate its potential role in RGCs. Nell2-positive in situ and immunohistochemical signals were localized to irregularly shaped cells in the ganglion cell layer (GCL) and colocalized with retrogradely-labeled RGCs. No Nell2-positive cells were detected in 2 weeks optic nerve transected (ONT) retinas characterized with approximately 90% RGC loss. RT-PCR analysis showed a dramatic decrease in the Nell2 mRNA level after ONT compared to the controls. Immunoblot analysis of the Nell2 expression in the retina revealed the presence of two proteins with approximate MW of 140 and 90 kDa representing glycosylated and non-glycosylated Nell2, respectively. Both products were almost undetectable in retinal protein extracts two weeks after ONT. Proteome analysis of Nell2-interacting proteins carried out with MALDI-TOF MS (MS) identified microtubule-actin crosslinking factor 1 (Macf1), known to be critical in CNS development. Strong Macf1 expression was observed in the inner plexiform layer and GCL where it was colocalizied with Thy-1 staining. Since Nell2 has been reported to increase neuronal survival of the hippocampus and cerebral cortex, we evaluated the effect of Nell2 overexpression on RGC survival. RGCs in the nasal retina were consistently more efficiently transfected than in other areas (49% vs. 13%; n = 5, p<0.05). In non-transfected or pEGFP-transfected ONT retinas, the loss of RGCs was approximately 90% compared to the untreated control. In the nasal region, Nell2 transfection led to the preservation of approximately 58% more cells damaged by axotomy compared to non-transfected (n = 5, p<0.01) or pEGFP-transfected controls (n = 5, p<0.01)

Therapeutic approach to FSGS in children

Therapy of primary focal segmental glomerulosclerosis (FSGS) in children incorporates conservative management and immunosuppression regimens to control proteinuria and preserve kidney function. In long-term cohort studies in adults and children with primary FSGS, renal survival has been directly associated with degree of proteinuria control. This educational article reviews the current therapeutic approach toward children with primary FSGS

A combination of ascorbic acid and α-tocopherol to test the effectiveness and safety in the fragile X syndrome: study protocol for a phase II, randomized, placebo-controlled trial

BACKGROUND: Fragile X syndrome (FXS) is an inherited neurodevelopmental condition characterised by behavioural, learning disabilities, phisical and neurological symptoms. In addition, an important degree of comorbidity with autism is also present. Considered a rare disorder affecting both genders, it first becomes apparent during childhood with displays of language delay and behavioural symptoms. Main aim: To show whether the combination of 10 mg/kg/day of ascorbic acid (vitamin C) and 10 mg/kg/day of α-tocopherol (vitamin E) reduces FXS symptoms among male patients ages 6 to 18 years compared to placebo treatment, as measured on the standardized rating scales at baseline, and after 12 and 24 weeks of treatment. Secondary aims: To assess the safety of the treatment. To describe behavioural and cognitive changes revealed by the Developmental Behaviour Checklist Short Form (DBC-P24) and the Wechsler Intelligence Scale for Children–Revised. To describe metabolic changes revealed by blood analysis. To measure treatment impact at home and in an academic environment. METHODS/DESIGN: A phase II randomized, double-blind pilot clinical trial. Scope: male children and adolescents diagnosed with FXS, in accordance with a standardized molecular biology test, who met all the inclusion criteria and none of the exclusion criteria. Instrumentation: clinical data, blood analysis, Wechsler Intelligence Scale for Children–Revised, Conners parent and teacher rating scale scores and the DBC-P24 results will be obtained at the baseline (t0). Follow up examinations will take place at 12 weeks (t1) and 24 weeks (t2) of treatment. DISCUSSION: A limited number of clinical trials have been carried out on children with FXS, but more are necessary as current treatment possibilities are insufficient and often provoke side effects. In the present study, we sought to overcome possible methodological problems by conducting a phase II pilot study in order to calculate the relevant statistical parameters and determine the safety of the proposed treatment. The results will provide evidence to improve hyperactivity control and reduce behavioural and learning problems using ascorbic acid (vitamin C) and α-tocopherol (vitamin E). The study protocol was approved by the Regional Government Committee for Clinical Trials in Andalusia and the Spanish agency for drugs and health products. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01329770 (29 March 2011

Variability in public health ethics education in EUPHA and ASPHER members

Public health professionals face decisions that have far-reaching ethical implications. Despite this, the field of public health ethics is relatively new, and teaching and training in ethics for public health professionals is “highly variable in quantity and content” [Doudenkova et al 2017]. Building on a prior body of research, surveys of ASPHER and EUPHA members were undertaken to explore current levels of ethics education. Methods Online surveys were distributed to ASPHER and EUPHA members with the aims of a) exploring the current status of ethics education in public health courses in ASPHER institutions and b) understanding the ethics education of individual public health practitioners in EUPHA. Results The ASPHER survey was completed by teaching staff at 35 different institutions between April and August 2019. The EUPHA survey was completed by 232 professionals between October 2019 and January 2020. ASPHER Survey: 39% (n = 12) of institutions awarding master's degrees in public health had one or more degrees in which no ethics was taught. Only 48% (n = 13) of institutions had someone in their academic team formally qualified to teach ethics by holding a master's degree, PhD or further academic role in ethics. EUPHA Survey: Despite 79% (n = 165) of respondents encountering ethical dilemmas on at least a monthly basis, 21% (n = 48) reported that they had never had any ethics education or training, and 50% (n = 101) respondents thought that they had too little training in ethics for their professional role. Conclusions There remains a significant proportion of those studying or working in public health who do not receive any public health ethics training or education. Key messages Ethics education in public health remains variable among ASPHER organisations and EUPHA members, a significant minority lacking any ethics training. To ensure ethically reflective and sensitive public health practitioners, access to ethics education is key

Impact of nursing home deaths on life expectancy calculations in small areas

Study objective: The drive to tackle health inequalities at the local level has increased interest in mortality data for small populations. There is some concern that nursing homes may affect measures of mortality for small populations, but there has been little in depth analysis of this. Design and setting: Deaths between 1997 and 2001 and population figures from the GP register (Exeter) database and census 2001 were used to produce life expectancy (LE) figures for all electoral wards in West Sussex. The proportion of those dying within each ward that had been residents of nursing homes was calculated and the relation between these variables and deprivation investigated. Results: There was a significant linear relation between nursing home deaths and LE (p<0.0001), which explained 36% of variation in LE between wards. Deprivation accounted for around 35% of the variation in LE (p<0.0001) but was not correlated with nursing home deaths (p⩾0.0982). Multiple linear regression shows that over 60% of the variation in LE at ward level can be explained by both nursing home deaths and deprivation (p<0.0001) and that the two variables explain similar proportions of this variation. The relation between LE and nursing home deaths within wards grouped by deprivation suggests that the impact of nursing homes is strongest in deprived wards. Conclusions: This finding has important implications for LE calculations in small populations. Further investigation is now needed to examine the impact of nursing homes in other areas, on other mortality measures, and in larger populations

Higher-order aberrations after implantation of iris-fixated rigid or foldable phakic intraocular lenses

PURPOSE: To evaluate higher-order aberrations (HOAs) after implantation of Artiflex phakic intraocular lenses (pIOLs). SETTING: Department of Ophthalmology, Academic Hospital Maastricht, Maastricht, The Netherlands. METHODS: This retrospective comparative case series comprised 27 eyes (14 patients) that had Artiflex pIOL implantation and 22 eyes (13 patients) that had Artisan pIOL implantation. Refractive data, pupil size, IOL decentration, and HOA values were recorded and compared. Laboratory analysis was performed. Follow-up was 1 year. RESULTS: In the Artiflex group, the mean spherical equivalent (SE) changed from -9.95 diopters (D) +/- 1.43 (SD) (range -6.75 to -12.13 D) to -0.30 +/- 0.53 D (range -1.94 to 0.56 D). Postoperatively, trefoil-y increased (increase factor 1.73) and spherical aberration decreased (increase factor 0.55). The mean pIOL decentration was 0.24 +/- 0.12 mm; 96.3% were decentered 0.5 mm or less. There was a significant correlation between pIOL decentration and postoperative spherical aberration and coma-y. In the Artisan group, the mean SE changed from -9.90 +/- 2.74 D (range -4.00 to -14.50 D) to -0.20 +/- 0.42 D (range -0.75 to 0.50 D). Postoperatively, trefoil-y and spherical aberration increased (increase factors 3.32 and 6.84, respectively). Laboratory analysis confirmed the negative and positive spherical aberration profile of the Artiflex pIOL and Artisan pIOL, respectively. CONCLUSIONS: Artiflex pIOL implantation decreased spherical aberration, while Artisan pIOL implantation increased spherical aberration. Trefoil-y increased in both groups. These changes might be explained by incision size differences in relation to trefoil and differences in optic design in relation to spherical aberration