De Novo Mutations in the Motor Domain of KIF1A Cause Cognitive Impairment,Spastic Paraparesis,Axonal Neuropathy,and Cerebellar Atrophy

KIF1A is a neuron‐specific motor protein that plays important roles in cargo transport along neurites. Recessive mutations in KIF1A were previously described in families with spastic paraparesis or sensory and autonomic neuropathy type‐2. Here, we report 11 heterozygous de novo missense mutations (p.S58L, p.T99M, p.G102D, p.V144F, p.R167C, p.A202P, p.S215R, p.R216P, p.L249Q, p.E253K, and p.R316W) in KIF1A in 14 individuals, including two monozygotic twins. Two mutations (p.T99M and p.E253K) were recurrent, each being found in unrelated cases. All these de novo mutations are located in the motor domain (MD) of KIF1A. Structural modeling revealed that they alter conserved residues that are critical for the structure and function of the MD. Transfection studies suggested that at least five of these mutations affect the transport of the MD along axons. Individuals with de novo mutations in KIF1A display a phenotype characterized by cognitive impairment and variable presence of cerebellar atrophy, spastic paraparesis, optic nerve atrophy, peripheral neuropathy, and epilepsy. Our findings thus indicate that de novo missense mutations in the MD of KIF1A cause a phenotype that overlaps with, while being more severe, than that associated with recessive mutations in the same gene.     

Using a social robot to teach gestural recognition and production in children with autism spectrum disorders

While it has been argued that children with autism spectrum disorders are responsive to robot-like toys, very little research has examined the impact of robot-based intervention on gesture use. These children have delayed gestural development. We used a social robot in two phases to teach them to recognize and produce eight pantomime gestures that expressed feelings and needs. Compared to the children in the wait-list control group (N?=?6), those in the intervention group (N?=?7) were more likely to recognize gestures and to gesture accurately in trained and untrained scenarios. They also generalized the acquired recognition (but not production) skills to human-to-human interaction. The benefits and limitations of robot-based intervention for gestural learning were highlighted.

• Implications for Rehabilitation

• Compared to typically-developing children, children with autism spectrum disorders have delayed development of gesture comprehension and production.

• Robot-based intervention program was developed to teach children with autism spectrum disorders recognition (Phase I) and production (Phase II) of eight pantomime gestures that expressed feelings and needs.

• Children in the intervention group (but not in the wait-list control group) were able to recognize more gestures in both trained and untrained scenarios and generalize the acquired gestural recognition skills to human-to-human interaction.

• Similar findings were reported for gestural production except that there was no strong evidence showing children in the intervention group could produce gestures accurately in human-to-human interaction.

     

Sonographic diagnosis of neuritis ossificans of the median nerve

We report the sonographic appearance of a rare case of neuritis ossificans of the median nerve at the wrist, which appeared as a hyperechoic lesion around the nerve. Diagnosis was confirmed with magnetic resonance imaging (MRI).     

Permanent Bilateral Vision Loss in Eclamptic Posterior Reversible Encephalopathy Syndrome

Posterior reversible encephalopathy syndrome (PRES) classically consists of reversible vasogenic oedema in the posterior circulation territories, which is reversible both clinically and radiologically in the majority of patients after the control of hypertension. The authors describe a 27-year-old eclamptic patient with PRES in accelerated hypertension who revealed permanent vision loss associated with bilateral Purtscher retinopathy. One of the two competing theories that explain vasogenic brain oedema in PRES is excessive autoregulation leading to the dilation of cerebral arterial vessels, particularly in the occipito-parietal vasculatures. Dysfunction of endothelial cells that results in constriction of vessels has also been hypothesised as a cause of PRES. The concurrence of bilateral vaso-occlusive retinopathy and PRES supports the hypothesis that vasoconstriction is a more plausible mechanism of vasogenic oedema in PRES.     

Oxygen permeability of soft contact lenses in different pH, osmolality and buffering solution

AIM: To determine the effect of pH, osmolality, and buffering system on the oxygen permeability (Dk) of soft contact lenses.METHODS: Two hydrogel lenses (nelfilcon A and etafilcon A) and 2 silicone hydrogel lenses (lotrafilcon A and balafilcon A) were used in the study. These lenses were incubated in phosphate-buffered saline (PBS) and borate-buffered saline (BBS) solutions adjusted by 0.8 pH increments to a pH in the range of 5.8-9.0 or in hypotonic (280 mOsmol/kg), isotonic (310 mOsmol/kg) and hypertonic (380 mOsmol/kg) PBS solutions. Polarographic method was used for measuring the Dk and lenses were stacked as 4 layers to correct the boundary effect.RESULTS: Dk values of all contact lenses measured in BBS solutions were more stable than those in PBS solutions. Especially the etafilcon A lens showed a relative big change compared with other types of contact lenses at the same conditions. When the osmolality of PBS solution increased from hypotonic to hypertonic, Dk of all contact lenses decreased. Variations in Dk existed depending on lens materials, etafilcon A lens was the most affected and nelfilcon A was the least affected by osmolality.CONCLUSION:From the result obtained, it is revealed that Dk of contact lenses is changed by the pH, osmolality, and buffering condition of tear. Thus, Dk of contact lens can be varied by the lens wearers' physiological and/or pathological conditions.     

Polybenzimidazole/Nafion hybrid membrane with improved chemical stability for vanadium redox flow battery application

In order to increase the chemical stability of polybenzimidazole (PBI) membrane against the highly oxidizing environment of a vanadium redox flow battery (VRFB), PBI/Nafion hybrid membrane was developed by spray coating a Nafion ionomer onto one surface of the PBI membrane. The acid–base interaction between the sulfonic acid of the Nafion and the benzimidazole of the PBI created a stable interfacial adhesion between the Nafion layer and the PBI layer. The hybrid membrane showed an area resistance of 0.269 Ω cm² and a very low vanadium permeability of 1.95 × 10⁻⁹ cm² min⁻¹. The Nafion layer protected the PBI from chemical degradation under accelerated oxidizing conditions of 1 M VO₂⁺/5 M H₂SO₄, and this was subsequently examined in spectroscopic analysis. In the VRFB single cell performance test, the cell with the hybrid membrane showed better energy efficiency than the Nafion cell with 92.66% at 40 mA cm⁻² and 78.1% at 100 mA cm⁻² with no delamination observed between the Nafion layer and the PBI layer after the test was completed.

Novel polybenzimidazole (PBI)/Nafion hybrid membranes for the VRFB are made by spray coating a Nafion layer to protect PBI from chemical degradation.     

Variation and heritability of Hb F and F-cells among beta-thalassemia heterozygotes in Hong Kong

Enhanced fetal hemoglobin (Hb F) production can partially compensate for the lack of adult hemoglobin (Hb A) in patients with beta-thalassemia major or intermedia, and ameliorate the clinical severity of these diseases. To further elucidate factors governing Hb F levels, we evaluated demographic, clinical, laboratory, and genetic characteristics in 241 unrelated adult beta-thalassemia carriers in Hong Kong. They had wide variations in Hb F and F-cell numbers skewing toward higher levels. Individuals who coinherited the Xmn IT-allele in the (G)gamma-globin gene promoter had higher Hb F and more F-cells compared with those lacking the Xmn I T-allele. However, both groups exhibited a similarly wide spread of Hb F and F-cells. The correlation of Hb F and F-cells corresponded well to both linear and exponential models, suggesting multiple mechanisms for Hb F augmentation. The heritabilities of Hb F and F-cells were calculated in 66 families (111 parents who were beta-thalassemia carriers and 82 asymptomatic offspring) to be 0.7 to 0.9. The Xmn I polymorphism accounted for 9% of the Hb F and 13% of the F-cell heritabilities. These results suggest that these family members are well suited for genome wide association studies that will identify genetic loci regulating Hb F production, and likely novel pharmacological targets for reactivating Hb F production in adults.     

Anti-cyclic citrullinated peptide antibody isotypes in rheumatoid arthritis: association with disease duration, rheumatoid factor production and the presence of shared epitope

OBJECTIVE: Anti-cyclic citrullinated peptide (anti-CCP) antibodies of IgG isotype are specific diagnostic markers of rheumatoid arthritis (RA). Recent evidence also points to their direct involvement in the pathophysiology. Little information is available, however, regarding the isotype distribution of anti-CCP antibodies and the characteristics of IgA and IgM anti-CCP. METHODS: IgG, IgA and IgM anti-CCP2 and rheumatoid factor (RF) levels were measured in the sera of 119 RA patients and 118 controls, including patients with other rheumatic diseases and healthy subjects. We analyzed the diagnostic performance of IgA and IgM anti-CCP2 antibodies and their relationship with IgG anti-CCP2, RFs, disease duration and the presence of HLA-DRB1 shared epitope (SE) alleles. RESULTS: Patients with RA had significantly higher serum IgA and IgM anti-CCP2 antibody levels than healthy subjects and patients with other rheumatic diseases (p<0.0001). IgG, IgA and IgM anti-CCP2 antibodies were present in 74.8%, 52.9% and 44.5% of RA patients, and their diagnostic specificity was 95.8%, 95.8% and 91.6%, respectively. The presence of anti-CCP2 antibodies was significantly associated with SE alleles (p=0.03). The frequency of IgM anti-CCP2 positivity was lower in longstanding disease compared to early RA (p=0.03). CONCLUSION: IgA and IgM anti-CCP2 antibodies are present in RA patients, and they are similarly specific for RA as IgG anti-CCP2. The higher frequency of IgM anti-CCP2 antibodies in early RA suggests that they are mostly generated during the first phase of immune response; nonetheless, their production seems to be sustained in some patients. Further analysis of IgM and IgA anti-CCP2 antibodies may provide insights into the pathogenesis of RA.