Zinc finger protein 804A (ZNF804A) and verbal deficits in individuals with autism

Background

In a genome-wide association study of autism, zinc finger protein 804A (ZNF804A) single nucleotide polymorphisms (SNPs) were found to be nominally associated in verbally deficient individuals with autism. Zinc finger protein 804A copy number variations (CNVs) have also been observed in individuals with autism. In addition, ZNF804A is known to be involved in theory of mind (ToM) tasks, and ToM deficits are deemed responsible for the communication and social challenges faced by individuals with autism. We hypothesized that ZNF804A could be a risk gene for autism.

Methods

We examined the genetic association and CNVs of ZNF804A in 841 families in which 1 or more members had autism. We compared the expression of ZNF804A in the postmortem brains of individuals with autism (n = 8) and controls (n = 13). We also assessed in vitro the effect of ZNF804A silencing on the expression of several genes known to be involved in verbal efficiency and social cognition.

Results

We found that rs7603001 was nominally associated with autism (p = 0.018). The association was stronger (p = 0.008) in the families of individuals with autism who were verbally deficient (n = 761 families). We observed ZNF804A CNVs in 7 verbally deficient boys with autism. In ZNF804A knockdown cells, the expression of synaptosomal-associated protein, 25kDa (SNAP25) was reduced compared with controls (p = 0.009). The expression of ZNF804A (p = 0.009) and SNAP25 (p = 0.009) were reduced in the anterior cingulate gyrus (ACG) of individuals with autism. There was a strong positive correlation between the expression of ZNF804A and SNAP25 in the ACG (p < 0.001).

Limitations

Study limitations include our small sample size of postmortem brains.

Conclusion

Our results suggest that ZNF804A could be a potential candidate gene mediating the intermediate phenotypes associated with verbal traits in individuals with autism.     

Changes in cerebral blood flow during steady-state cycling exercise: a study using oxygen-15-labeled water with PET

Cerebral blood flow (CBF) during dynamic exercise has never been examined quantitatively using positron emission tomography (PET). This study investigated changes in CBF that occur over the course of a moderate, steady-state cycling exercise. Global and regional CBF (gCBF and rCBF, respectively) were measured using oxygen-15-labeled water (H₂¹⁵O) and PET in 10 healthy human subjects at rest (Rest), at the onset of exercise (Ex1) and at a later phase in the exercise (Ex2). At Ex1, gCBF was significantly (P<0.01) higher (27.9%) than at Rest, and rCBF was significantly higher than at Rest in the sensorimotor cortex for the bilateral legs (M1_Leg and S1_Leg), supplementary motor area (SMA), cerebellar vermis, cerebellar hemispheres, and left insular cortex, with relative increases ranging from 37.6% to 70.5%. At Ex2, gCBF did not differ from Rest, and rCBF was significantly higher (25.9% to 39.7%) than at Rest in only the M1_Leg, S1_Leg, and vermis. The areas showing increased rCBF at Ex1 were consistent with the central command network and the anatomic pathway for interoceptive stimuli. Our results suggest that CBF increases at Ex1 in parallel with cardiovascular responses then recovers to the resting level as the steady-state exercise continues.     

Early and frequent development of ocular hypertension in children with nephrotic syndrome

Background

Prednisolone, the first-line treatment for children with nephrotic syndrome, causes severe side effects. One of these side effects is ocular hypertension, which can result in severe and permanent visual disturbance. However, the exact prevalence, severity and timing of development of ocular hypertension have yet to be fully explored in this pediatric patient group.

Methods

In this retrospective cohort study, children with nephrotic syndrome treated with prednisolone for their first episode were analyzed. Intraocular pressure was screened with an iCare® tonometer and confirmed with Goldmann applanation tonometry before the initiation of prednisolone treatment and at 1 and 4 weeks thereafter.

Results

A total of 26 children with nephrotic syndrome were included in this study, of whom eight (30.8 %) required treatment with eye drops for ocular hypertension. The median time interval between the diagnosis of ocular hypertension and start of treatment was 9 (range 5–31) days. At relapse of nephrotic syndrome, all children who had undergone treatment for ocular hypertension in their first episode again required treatment for ocular hypertension.

Conclusions

Routine ophthalmologic examination should be conducted from the early phase after the start of prednisolone treatment. In addition, children with episodes of ocular hypertension may be at greater risk of its reappearance with relapse of the nephrotic syndrome.     

Association between “loco-check” and EuroQol,a comprehensive instrument for assessing health-related quality of life: a study of the Japanese general population

Background The concept of “locomotive syndrome” (LS) was proposed by the Japanese Orthopaedic Association (JOA) in 2007 to refer to the risk of elderly individuals becoming bedridden because of reduced function of locomotive organs, for example muscles, bones, and joints. The purpose of this study was to clarify the association between LS screening results based on “loco-check” and health-related quality of life (HRQoL) assessed by use of EuroQol.Materials and methods Four-hundred and forty-two Japanese subjects (183 males and 259 females) were evaluated for LS and HRQoL by use of “loco-check,” EuroQol-5 dimensions (EQ-5D), and EuroQol-VAS (EQ-VAS). If the subjects answered “yes” to one or more of the seven items of “loco-check,” they were assigned to a locomotive syndrome suspected group (L group). If they answered “no” to all seven items, they were assigned to a locomotive syndrome not suspected group (NL group). We investigated the association between the screening LS results obtained by use of “loco-check” and HRQoL status determined by use of EQ-5D utility value and EQ-VAS score.Results LS was suspected among 39.6 % of the subjects on the basis of “loco-check.” In univariate analysis, significantly higher age, higher female-to-male ratio, and more reduced HRQoL were observed in the L group than in the NL group, according to EQ-5D and EQ-VAS. Logistic regression analysis showed that EQ-5D utility value and EQ-VAS score were associated with LS and the difference was statistically significant. Furthermore, correlations were found between the number of items with a “yes” answer on “loco-check”, EQ-5D, or EQ-VAS. That is, a larger number of items with a “yes” answer on “loco-check” was associated with reduced HRQoL assessed by use of EQ-5D and EQ-VAS.Conclusions We demonstrated that a finding of LS on the basis of “loco-check” is significantly associated with EQ-5D utility value and EQ-VAS score, and that a population identified as having LS by use of “loco-check” also had reduced HRQoL. Furthermore, it is speculated that the severity of reduced HRQoL because of locomotive dysfunction can be determined by use of “loco-check”.     

Strength estimation of a moving 125Iodine source during implantation in brachytherapy: application to linked sources

This study sought to demonstrate the feasibility of estimating the source strength during implantation in brachytherapy. The requirement for measuring the strengths of the linked sources was investigated. The utilized sources were ¹²⁵I with air kerma strengths of 8.38–8.63 U (μGy m² h^–1). Measurements were performed with a plastic scintillator (80 mm × 50 mm × 20 mm in thickness). For a source-to-source distance of 10.5 mm and at source speeds of up to 200 mm s^–1, a counting time of 10 ms and a detector-to-needle distance of 5 mm were found to be the appropriate measurement conditions. The combined standard uncertainty (CSU) with the coverage factor of 1 (k = 1) was ∼15% when using a grid to decrease the interference by the neighboring sources. Without the grid, the CSU (k = 1) was ∼5%, and an 8% overestimation due to the neighboring sources was found to potentially cause additional uncertainty. In order to improve the accuracy in estimating source strength, it is recommended that the measurment conditions should be optimized by considering the tradeoff between the overestimation due to the neighboring sources and the intensity of the measured value, which influences the random error.