Bone characteristics and physical fitness in children and adolescents with visual impairment.

BACKGROUND: Lower habitual physical activity in adolescents with visual impairment (VI) have detrimental effect on their general health such as bone quality and physical fitness. The aim of this study was to demonstrate the bone quality in children with VI and to analyze the correlations of their bone characteristics with anthropometric and physical fitness tests. METHODS: The participants (N.=38) were adolescents (14.85±2.79 yrs) with low vision (N.=18) or blindness (N.=20). Dual-energy X-ray absorptiometry (DEXA) was used to measure bone mineral density (BMD), bone mineral content (BMC) of the total body and L1-L4 of the lumbar spinal region. After anthropometry physical fitness was examined by laboratory test (V̇O2peak) and field tests (strength and running). RESULTS: Height, weight, Body Mass Index (BMI), V̇O2peak were similar in the two groups. Blind boys showed significant higher handgrip strength. Estimated V̇O2peak (from 20-m shuttle running test) was significantly lower in blind children (43.84±4.42 mL/kg/min) than in children with low vision (35.08±5.23 mL/kg/min; P<0.001). BMD and BMC did not differ in subgroups, Z-score of total body BMD was significantly lower in blind children. Means of Z-score in L1-L4 lumbal spinal region were negative values and similar in blind and low vision adolescents' subgroups. A linear regression model in the collective group revealed significant associations of BMD (r2=0.538; P=0.0001) and BMC (r2=0.698; P=0.048) with BMI and handgrip strength test. CONCLUSIONS: Adolescents with VI have generally decreased bone health and physical fitness level. BMI and handgrip strength are predictors of total body BMD and BMC; suggesting that these measures may be adequate to estimate bone health.

Assessing the value of complex refractive index and particle density for calibration of low-cost particle matter sensor for size-resolved particle count and PM2.5 measurements.

Low-cost optical scattering particulate matter (PM) sensors report total or size-specific particle counts and mass concentrations. The PM concentration and size are estimated by the original equipment manufacturer (OEM) proprietary algorithms, which have inherent limitations since particle scattering depends on particles' properties such as size, shape, and complex index of refraction (CRI) as well as environmental parameters such as temperature and relative humidity (RH). As low-cost PM sensors are not able to resolve individual particles, there is a need to characterize and calibrate sensors' performance under a controlled environment. Here, we present improved calibration algorithms for Plantower PMS A003 sensor for mass indices and size-resolved number concentration. An aerosol chamber experimental protocol was used to evaluate sensor-to-sensor data reproducibility. The calibration was performed using four polydisperse test aerosols. The particle size distribution OEM calibration for PMS A003 sensor did not agree with the reference single particle sizer measurements. For the number concentration calibration, the linear model without adjusting for the aerosol properties and environmental conditions yields an absolute error (NMAE) of ~ 4.0% compared to the reference instrument. The calibration models adjusted for particle CRI and density account for non-linearity in the OEM's mass concentrations estimates with NMAE within 5.0%. The calibration algorithms developed in this study can be used in indoor air quality monitoring, occupational/industrial exposure assessments, or near-source monitoring scenarios where field calibration might be challenging.

OPA1 gene therapy prevents retinal ganglion cell loss in a Dominant Optic Atrophy mouse model.

Dominant optic atrophy (DOA) is a rare progressive and irreversible blinding disease which is one of the most frequent forms of hereditary optic neuropathy. DOA is mainly caused by dominant mutation in the OPA1 gene encoding a large mitochondrial GTPase with crucial roles in membrane dynamics and cell survival. Hereditary optic neuropathies are commonly characterized by the degeneration of retinal ganglion cells, leading to the optic nerve atrophy and the progressive loss of visual acuity. Up to now, despite increasing advances in the understanding of the pathological mechanisms, DOA remains intractable. Here, we tested the efficiency of gene therapy on a genetically-modified mouse model reproducing DOA vision loss. We performed intravitreal injections of an Adeno-Associated Virus carrying the human OPA1 cDNA under the control of the cytomegalovirus promotor. Our results provide the first evidence that gene therapy is efficient on a mouse model of DOA as the wild-type OPA1 expression is able to alleviate the OPA1-induced retinal ganglion cell degeneration, the hallmark of the disease. These results displayed encouraging effects of gene therapy for Dominant Optic Atrophy, fostering future investigations aiming at clinical trials in patients.

Oxygen venular saturation correlates with a functional loss in primary open-angle glaucoma and normal-tension glaucoma patients.

PURPOSE: To investigate whether there are differences in retinal oxygen saturation in upper and lower visual field hemispheres in primary open-angle glaucoma (POAG) and in normal-tension glaucoma (NTG). METHODS: This study enrolled POAG and NTG patients exhibiting differences between the upper and lower total deviation (TD) that were either more than 10 or <5 dB. Retinal oxygen saturation measurements in these patients with glaucoma were performed by a non-invasive spectrophotometric retinal oximeter. The Student's t-test was used for statistical analysis. RESULTS: Evaluations of the worse and better hemifields in the patients with POAG who exhibited differences in the upper and lower hemifield TD that was <5 dB (n = 25) showed that there were no statistically significant differences for the retinal venous saturation of oxygen (SaO2 ). However, there was a higher mean SaO2 in the worse (57.0 ± 7.5%) versus the better (54.3 ± 7.0%) hemifield in the patients with NTG (n = 22; p = 0.007). Evaluations of the patients with more than a 10-dB difference in the upper and lower hemifield TD showed statistically significant differences for the retinal venous SaO2 in the venous vessels between the POAG (n = 19) and the NTG (n = 26) patients. CONCLUSION: Although there was no significant difference in retinal SaO2 in the venules between the better and worse hemifield when the difference between the better and worse hemifield in the patients with POAG was <5 dB, there was a higher SaO2 in the venous vessels in the worse hemifield in the patients with NTG.

Impaired cone function and cone degeneration resulting from CNGB3 deficiency: down-regulation of CNGA3 biosynthesis as a potential mechanism.

The cone cyclic nucleotide-gated (CNG) channel is essential for central and color vision and visual acuity. This channel is composed of two structurally related subunits, CNGA3 and CNGB3; CNGA3 is the ion-conducting subunit, whereas CNGB3 is a modulatory subunit. Mutations in both subunits are associated with achromatopsia and progressive cone dystrophy, with mutations in CNGB3 alone accounting for 50% of all known cases of achromatopsia. However, the molecular mechanisms underlying cone diseases that result from CNGB3 deficiency are unknown. This study investigated the role of CNGB3 in cones, using CNGB3(-/-) mice. Cone dysfunction was apparent at the earliest time point examined (post-natal day 30) in CNGB3(-/-) mice. When compared with wild-type (WT) controls: photopic electroretingraphic (ERG) responses were decreased by approximately 75%, whereas scotopic ERG responses were unchanged; visual acuity was decreased by approximately 20%, whereas contrast sensitivity was unchanged; cone density was reduced by approximately 40%; photoreceptor apoptosis was detected; and outer segment disorganization was observed in some cones. Notably, CNGA3 protein and mRNA levels were significantly decreased in CNGB3(-/-) mice; in contrast, mRNA levels of S-opsin, Gnat2 and Pde6c were unchanged, relative to WT mice. Hence, we show that loss of CNGB3 reduces biosynthesis of CNGA3 and impairs cone CNG channel function. We suggest that down-regulation of CNGA3 contributes to the pathogenic mechanism by which CNGB3 mutations lead to human cone disease.

Changes of cognition and regional cerebral activity during acute hypoglycemia in normal subjects: A H2 15O positron emission tomographic study.

Blurred vision and cognitive difficulties are prominent symptoms during acute insulin-induced hypoglycemia. Our hypothesis was that changes in cerebral activity reflect these symptoms. Positron emission tomography (PET) with oxygen-15-labelled water was used to measure relative changes in regional cerebral blood flow (rCBF) as a marker of cerebral activity. Hypoglycemia was induced by intravenous insulin infusion in 19 healthy men performing two different cognitive tasks of varying complexity. The hypoglycemic stimulus [plasma glucose 2.2 mmol/liter (0.4)] produced a significant hormonal counterregulatory response. During the low cognitive load, rCBF decreased in response to hypoglycemia in a large bilateral area in the posterior part of the temporal lobe, and rCBF increased bilaterally in the anterior cingulate gyrus, the right frontal gyrus, the fusiform gyrus, thalamus, and the left inferior part of the frontal gyrus. During the high cognitive load, rCBF decreased bilaterally in a large region in the posterior part of the temporal gyrus and increased in the left and right anterior cingulate gyrus, left and right frontal gyrus, right parahippocampal and lingual gyrus, and left superior temporal gyrus. Visual impairment during hypoglycemia was associated with deactivation in the ventral visual stream. The anterior cingulate gyrus was activated during hypoglycemia in a load-dependent manner. Areas on the frontal convexity were differentially activated in response to the cognitive load during hypoglycemia. Our findings suggest that hypoglycemia induces changes in sensory processing in a cognition-independent manner, whereas activation of areas of higher order functions is influenced by cognitive load as well as hypoglycemia.

Visual deficits in a mouse model of Batten disease are the result of optic nerve degeneration and loss of dorsal lateral geniculate thalamic neurons.

Juvenile neuronal ceroid lipofuscinosis (JNCL) is an autosomal recessive disorder of childhood caused by mutations in CLN3. Although visual deterioration is typically the first clinical sign to manifest in affected children, loss of Cln3 in a mouse model of JNCL does not recapitulate this retinal deterioration. This suggests that either the loss of CLN3 does not directly affect retinal cell survival or that nuclei involved in visual processing are affected prior to retinal degeneration. Having previously demonstrated that Cln3(-/-) mice have decreased optic nerve axonal density, we now demonstrate a decrease in nerve conduction. Examination of retino-recipient regions revealed a decreased number of neurons within the dorsal lateral geniculate nucleus (LGNd). We demonstrate decreased transport of amino acids from the retina to the LGN, suggesting an impediment in communication between the retina and projection nuclei. This study defines a novel path of degeneration within the LGNd, providing a mechanism for causation of JNCL visual deficits.