Underexposed features of CHARGE syndrome: immunological, adrenal, and scapular function

CHARGE syndrome is a rare and complex genetic condition. Children with this syndrome may have a combination of various congenital defects, developmental and behavioral problems. Abnormalities such as heart defects, blindness or deafness, receive a lot of attention. This is certainly important, but in this thesis we have focused on less obvious features: the immune system, the adrenal and shoulder function. Our studies show that children with CHARGE syndrome may have a reduced immune reaction to infections because they have insufficient immune cells. They also have an insufficient response to vaccinations. The thymus is an important organ for the production of immune cells, but we could not confirm in what extent the thymus might play a role in our findings. We have demonstrated that abnormalities in the adrenal function rarely occur. We also showed that reduced shoulder function, due to abnormalities in the nerves innervating the muscles, could be the only visible sign of CHARGE syndrome. The results of our research should be included in current guideline(s) to create more awareness among doctors so that patients can receive optimal care, also for underexposed features. For example, we advise to do specific blood tests and to consider revaccinations in patients who have recurrent infections. Standard testing for the adrenal function is not required which may give patients and their parents some relief. The thesis ends with a message on how important it is that patients, doctors, researchers and policy makers work together to tackle underexposed issues in rare diseases

Systemic medical management of diabetic retinopathy

10.4103/0974-9233.120010Middle East African Journal of Ophthalmology204301-30

Combined genotype and haplotype tests for region-based association studies

10.1186/1471-2164-14-569BMC Genomics141-BGME

High-salt intake affects retinal vascular tortuosity in healthy males: an exploratory randomized cross-over trial.

The retinal microcirculation is increasingly receiving credit as a relatively easily accessible microcirculatory bed that correlates closely with clinical cardiovascular outcomes. The effect of high salt (NaCl) intake on the retinal microcirculation is currently unknown. Therefore, we performed an exploratory randomized cross-over dietary intervention study in 18 healthy males. All subjects adhered to a two-week high-salt diet and low-salt diet, in randomized order, after which fundus photographs were taken and assessed using a semi-automated computer-assisted program (SIVA, version 4.0). Outcome parameters involved retinal venular and arteriolar tortuosity, vessel diameter, branching angle and fractal dimension. At baseline, participants had a mean (SD) age of 29.8 (4.4) years and blood pressure of 117 (9)/73 (5) mmHg. Overall, high-salt diet significantly increased venular tortuosity (12.2%, p = 0.001). Other retinal parameters were not significantly different between diets. Changes in arteriolar tortuosity correlated with changes in ambulatory systolic blood pressure (r = - 0.513; p = 0.04). In conclusion, high-salt diet increases retinal venular tortuosity, and salt-induced increases in ambulatory systolic blood pressure associate with decreases in retinal arteriolar tortuosity. Besides potential eye-specific consequences, both phenomena have previously been associated with hypertension and other cardiovascular risk factors, underlining the deleterious microcirculatory effects of high salt intake

The life history and ecology of the Pink-tailed Worm-lizard Aprasia parapulchella Kluge a review

This review synthesises research on the Pink-tailed Worm-lizard Aprasia parapukhella - a threatened species with life-history traits and habitat and dietary preferences that make it particularly vulnerable to decline. Further information on the ecology of A. parapukhella is required in order to develop effective approaches to conservation and management, particularly given the conservation status of the species. Aprasia parapukhella is a dietary specialist living in the burrows of small ants, the eggs and larvae of which it preys upon. It is late maturing (adult size probably attained in the third or fourth year of life), has a small clutch, is thought to be longlived and has specific habitat preferences. It has a strong association with landscapes that are characterised by outcroppings of lightly-embedded surface rocks.The lizard is associated with a particular suite of ant species and ground cover tending towards open native vegetation (grasses and shrubs) at most sites, but with regional differences. Although the highest densities have been recorded in areas without tree cover, the species has also been found in open-forest and woodland.The relative density of populations and the snout-vent length and weight of specimens reveal regional differences, suggesting that further analysis of the genetic status of the population across its range is warranted. There is still much to learn about the ecology of the species, in particular with respect to movement, breeding, dispersal and the relationship between lizards and ants. Further survey for new populations remains a key priority

Additive effect of cerebral atrophy on cognition in dementia-free elderly with cerebrovascular disease

Objective: To explore the additive effect of neurodegenerative diseases, measured by atrophy, on neurocognitive function in Asian dementia-free elderly with cerebrovascular disease (CeVD). Methods: The present study employed a cross-sectional design and was conducted between 2010 and 2015 among community-dwelling elderly participants recruited into the study. Eligible participants were evaluated with an extensive neuropsychological battery and neuroimaging. The weighted CeVD burden scale comprising markers of both small- and large-vessel diseases was applied, with a score of ≥2, indicating significant CeVD burden. Cortical atrophy (CA) and medial temporal atrophy (MTA) were graded using the global cortical atrophy scale and Schelten's scale, respectively. Global and domain-specific (attention, executive function, language, visuomotor speed, visuoconstruction, visual memory, and verbal memory) neurocognitive performance was measured using a locally validated neuropsychological battery (Vascular Dementia Battery, VDB). Results: A total of 819 dementia-free participants were included in the analysis. Among none-mild CeVD subjects, there was no significant difference in the global cognitive performance across atrophy groups (no atrophy, CA, and CA+MTA). However, in moderate-severe CeVD subjects, CA+MTA showed significantly worse global cognitive performance compared with those with CA alone (mean difference=-0.35, 95% CI -0.60 to -0.11, p=0.002) and those without atrophy (mean difference=-0.46, 95% CI -0.74 to -0.19, p<0.001, p<0.001). In domain-specific cognitive performance, subjects with CA+MTA performed worse than other groups in visual memory (p=0.005), executive function (p=0.001) and visuomotor speed (p<0.001) in moderate-severe CeVD but not in none-mild CeVD. Conclusions and relevance: Atrophy and moderate-severe CeVD burden showed an additive effect on global and domain-specific cognitive performance. This study highlights the importance of investigating the mechanisms of clinico-pathological interactions between neurodegenerative processes and vascular damage, particularly in the pre-dementia stage

A CsI(Tl) Scintillating Crystal Detector for the Studies of Low Energy Neutrino Interactions

Scintillating crystal detector may offer some potential advantages in the low-energy, low-background experiments. A 500 kg CsI(Tl) detector to be placed near the core of Nuclear Power Station II in Taiwan is being constructed for the studies of electron-neutrino scatterings and other keV-MeV range neutrino interactions. The motivations of this detector approach, the physics to be addressed, the basic experimental design, and the characteristic performance of prototype modules are described. The expected background channels and their experimental handles are discussed.Comment: 34 pages, 11 figures, submitted to Nucl. Instrum. Method

The Impact of Strategic White Matter Hyperintensity Lesion Location on Language

Objective: The impact of white matter hyperintensities (WMH) on language possibly depends on lesion location through disturbance of strategic white matter tracts. We examined the impact of WMH location on language in elderly Asians. Design: Cross-sectional. Setting: Population-based. Participants: Eight-hundred nineteen residents of Singapore, ages (≥65 years). Measurements: Clinical, cognitive and 3T magnetic resonance imaging assessments were performed on all participants. Language was assessed using the Modified Boston Naming Test (MBNT) and Verbal Fluency (VF). Hypothesis-free region-of-interest-based (ROI) analyses based on major white matter tracts were used to determine the association between WMH location and language. Conditional dependencies between the regional WMH volumes and language were examined using Bayesian-network analysis. Results: ROI-based analyses showed that WMH located within the anterior thalamic radiation (mean difference: −0.12, 95% confidence interval [CI]: −0.22; −0.02, p = 0.019) and uncinate fasciculus (mean difference: −0.09, 95% CI: −0.18; −0.01, p = 0.022) in the left hemisphere were significantly associated with worse VF but did not survive multiple testing. Conversely, WMH volume in the left cingulum of cingulate gyrus was significantly associated with MBNT performance (mean difference: −0.09, 95% CI: −0.17; −0.02, p = 0.016). Bayesian-network analyses confirmed the left cingulum of cingulate gyrus as a direct determinant of MBNT performance. Conclusion: Our findings identify the left cingulum of cingulate gyrus as a strategic white matter tract for MBNT, suggesting that language – is sensitive to subcortical ischemic damage. Future studies on the role of sporadic ischemic lesions and vascular cognitive impairment should not only focus on total WMH volume but should also take WMH lesion location into account when addressing language