Fluctuations in clinical symptoms with changes in serum 25(OH) vitamin D levels in autistic children: Three cases report.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder caused by complicated interactions between genetic and environmental factors. Clinical trials, including case reports, case-control studies, and a double-blinded randomized clinical study, have suggested that high-dose vitamin D3 regimens may ameliorate the core symptoms of ASD. Vitamin D3 supplementation was effective in about three-quarters of children with ASD. To further investigate the relationship between vitamin D and ASD symptoms in vitamin D-responsive autistic children, changes in symptoms were assessed in three children with ASD who were given vitamin D3 supplementation followed by a long interruption. The core symptoms of ASD were remarkably improved during the vitamin D3 supplementation period when serum 25-hydroxyvitamin D [25(OH)]D levels reached over 40.0 ng/mL. However, symptoms reappeared after the supplementation was stopped, when serum 25(OH)D levels fell below 30.0 ng/mL but were again improved with re-administration of vitamin D3 after the interruption, when serum 25(OH)D levels exceeded 40.0 ng/mL. Overall, these results showed that the core symptoms of ASD fluctuated in severity with changes in serum 25(OH)D levels in children, indicating that maintaining a responsive 25(OH)D level is important for treating ASD. Maintaining a serum 25(OH)D level between 40.0 and 100.0 ng/ml may be optimal for producing therapeutic effects in vitamin D-responsive individuals with ASD.

Tri-Spiral Donor for High Efficiency and Versatile Blue Thermally Activated Delayed Fluorescence Materials.

Blue thermally activated delayed fluorescence (TADF) emitters that can simultaneously achieve high efficiency in doped and nondoped organic light-emitting diodes (OLEDs) are rarely reported. Reported here is a strategy using a tri-spiral donor for such versatile blue TADF emitters. Impressively, by simply extending the nonconjugated fragment and molecular length, aggregation-caused emission quenching (ACQ) can be greatly alleviated to achieve as high as a 90 % horizontal orientation dipole ratio and external quantum efficiencies (EQEs) of up to 33.3 % in doped and 20.0 % in nondoped sky-blue TADF-OLEDs. More fascinatingly, a high-efficiency purely organic white OLED with an outstanding EQE of up to 22.8 % was also achieved by employing TspiroS-TRZ as a blue emitter and an assistant host. This compound is the first blue TADF emitter that can simultaneously achieve high electroluminescence (EL) efficiency in doped, nondoped sky-blue, and white TADF-OLEDs.

Clinical improvement following vitamin D3 supplementation in Autism Spectrum Disorder.

OBJECTIVE: High prevalence of vitamin D deficiency was previously reported in children with Autism Spectrum Disorder (ASD), but little is known about the efficacy of vitamin D3 treatment in ASD, although data from pilot studies seem promising. We hypothesized that serum vitamin D levels are reduced in ASD and correlate with the severity of disease. Also, we hypothesized that vitamin D3 treatment may be beneficial for a considerable portion of children with ASD. METHODS: In total, 215 children with ASD and 285 healthy control children were recruited in our study. Thirty seven of 215 ASD children received vitamin D3 treatment. The Autism Behaviour Checklist (ABC) and the Childhood Autism Rating Scale (CARS) were used to assess autism symptoms. High-performance liquid chromatography was used to assess the serum 25-hydroxyvitamin D [25(OH) D] level. Evaluations of ABC, CARS, and serum 25(OH) D levels were performed before and after 3 months of treatment. RESULTS: Serum levels of 25(OH) D were significantly lower in ASD children than typically developing children. Levels of serum 25(OH) D were negatively correlated with ABC total scores and language subscale scores. After vitamin D3 supplementation, symptom scores were significantly reduced on the CARS and ABC. In addition, the data also suggest that treatment effects were more pronounced in younger children with ASD. CONCLUSION: Vitamin D deficiency might contribute to the aetiology of ASD. Supplementation of vitamin D3, which is a safe and cost-effective form of treatment, may significantly improve the outcome of some children with ASD, especially younger children (identifier ChiCTR-CCC-13004498). CLINICAL TRIAL REGISTRATION: The trial 'Association of Polymorphisms of Vitamin D Metabolism-Related Genes With Autism and the Treatment of Autism with Vitamin D' has been registered at www.chictr.org/cn/proj/show.aspx? proj=6135 (identifier ChiCTR-CCC-13004498).

Large-area, lithography-free, low-cost SERS sensor with good flexibility and high performance.

Cost-effective, sensitive and bio-compatible surface-enhanced Raman spectroscopy (SERS) substrate has been in high demand since the Raman spectrum was designated as a significant tool for analyzing the composition of liquids, gases and solids in 1998 [1]. In this research, we presented the design, fabrication and characterization of an improved gold-based SERS substrate. With fine tuning of the SiO2 thickness we achieved a 3.391 times improvement and achieved an enhancement factor of 1.55 * 10(7) which is 15 times better than the current gold-standard Klarite substrate. Such improvement is ascribed to the localized surface plasmon resonance (SPR) and propagating SPR, which is proved by full-wave finite-difference time-domain simulations.

Serum concentration of 25-hydroxyvitamin D in autism spectrum disorder: a systematic review and meta-analysis.

Vitamin D may play an important role in the etiology of Autism Spectrum Disorders (ASD). Vitamin D is regarded as a neuroactive steroid affecting brain development and function. It plays an essential role in myelination, which is important for connectivity in the brain. Studies have shown that decreased vitamin D levels in patients, decreased maternal vitamin D levels during pregnancy, and decreased exposure to solar UVB might increase the risk for ASD. In addition, autism symptoms and global functioning may improve after vitamin D supplementation. Here, we sought to aggregate information from previous publications on vitamin D levels and ASD, in order to achieve a higher statistical power and thereby to determine the validity of vitamin D deficiency as a risk factor for ASD. For this meta-analysis, 11 studies met the inclusion and exclusion criteria, accounting for a total of 870 ASD patients and 782 healthy controls. Levels of serum 25(OH) D in participants with ASD were significantly lower than controls, suggesting that lower vitamin D level might be a risk factor for ASD.

[Serum levels of 25-hydroxyvitamin D in children with autism spectrum disorders].

OBJECTIVE: To examine serum 25-hydroxyvitamin D levels in children with autism spectrum disorders (ASD) and to explore the relationship between vitamin D level and ASD. METHODS: Serum levels of 25-hydroxyvitamin D levels were determined by the HPLC-MS/MS method in 117 children with newly diagnosed ASD and 109 healthy controls. Vitamin D status were classified into normal (>30 ng/mL), insufficiency (10-30ng/mL) and deficiency (<10 ng/mL) according to 25-hydroxyvitamin D levels. RESULTS: Serum level of 25-hydroxyvitamin D (19±9 ng/mL)in children with ASD was significantly lower than that in healthy controls (36±13 ng/mL; P<0.01). The rate of vitamin D insufficiency plus deficiency in the ASD group was significantly higher than in the control group (89.7% vs 52.3%; P<0.01). CONCLUSIONS: Vitamin D insufficiency or deficiency is common in children with ASD and might be as one of the environmental or genetic factors for ASD.

Liquid refractive index sensing independent of opacity using an optofluidic diffraction sensor.

We have implemented a multifunctional optofluidic sensor that can monitor changes in the refractive index and pressure of biofluid simultaneously and can detect free-solution molecular interaction in situ. In this Letter, we demonstrate two major improvements of this sensor proven by both simulation and experiments. One improvement is the broader measurement range of refractive index by making the diffraction grating with high-index polymer. The other improvement is the separation of refractive index sensing from opacity sensing by using the relative power ratio of diffraction orders. This simple, compact and low-cost multifunctional optofluidic sensor has the potential to be used for in situ biofluid monitoring.

Black silicon solar thin-film microcells integrating top nanocone structures for broadband and omnidirectional light-trapping.

Recently developed classes of monocrystalline silicon solar microcells (µ-cell) can be assembled into modules with characteristics (i.e., mechanically flexible forms, compact concentrator designs, and high-voltage outputs) that would be impossible to achieve using conventional, wafer-based approaches. In this paper, we describe a highly dense, uniform and non-periodic nanocone forest structure of black silicon (bSi) created on optically-thin (30 µm) µ-cells for broadband and omnidirectional light-trapping with a lithography-free and high-throughput plasma texturizing process. With optimized plasma etching conditions and a silicon nitride passivation layer, black silicon µ-cells, when embedded in a polymer waveguiding layer, display dramatic increases of as much as 65.7% in short circuit current, as compared to a bare silicon device. The conversion efficiency increases from 8.1% to 11.5% with a small drop in open circuit voltage and fill factor.

Elastomeric 2D grating and hemispherical optofluidic chamber for multifunctional fluidic sensing.

We present an optofluidic sensor based on an elastomeric two-dimensional (2D) grating integrated inside a hemispherical fluid chamber. A laser beam is diffracted before (reflection) and after (transmission) going through the grating and liquid in the dome chamber. The sensing mechanism is investigated and simulated with a finite-difference time-domain-based electromagnetic method. For the experiment, by analyzing the size, power, and shape of the 2D diffraction patterns, we can retrieve multiple parameters of the liquid, including the refractive index, pressure, and opacity with high sensitivity. We demonstrate that the glucose concentration can be monitored when mixed in a different concentrated phosphate-buffered saline solution. The free-solution binding of bovine serum albumin (BSA) and anti-BSA IgG is detected with this optical sensor. This low-cost, multifunctional, and reliable optofluidic sensor has the potential to be used as a monitor of biofluid, such as blood in hemodialysis.

Lithography-free sub-100 nm nanocone array antireflection layer for low-cost silicon solar cell.

A high-density and -uniformity sub-100 nm surface-oxidized silicon nanocone forest structure is created and integrated onto the existing texturization microstructures on a photovoltaic device surface by a one-step high-throughput plasma-enhanced texturization method. We suppressed the broadband optical reflection on chemically textured grade-B silicon solar cells for up to 70.25% through this nanomanufacturing method. The performance of the solar cell is improved with the short-circuit current increased by 7.1%, fill factor increased by 7.0%, and conversion efficiency increased by 14.66%. Our method demonstrates the potential to improve the photovoltaic device performance with low-cost and high-throughput nanomanufacturing technology.

Metallic nanocone array photonic substrate for high-uniformity surface deposition and optical detection of small molecules.

Molecular probe arrays printed on solid surfaces such as DNA, peptide, and protein microarrays are widely used in chemical and biomedical applications especially genomic and proteomic studies (Pollack et al 1999 Nat. Genet. 23 41-6, Houseman et al 2002 Nat. Biotechnol. 20 270-4, Sauer et al 2005 Nat. Rev. Genet. 6 465-76) as well as surface imaging and spectroscopy (Mori et al 2008 Anal. Biochem. 375 223-31, Liu et al 2006 Nat. Nanotechnol. 1 47-52, Liu 2010 IEEE J. Sel. Top. Quantum Electron. 16 662-71). Unfortunately the printed molecular spots on solid surfaces often suffer low distribution uniformity due to the lingering 'coffee stain' (Deegan et al 1997 Nature 389 827-9) problem of molecular accumulations and blotches, especially around the edge of deposition spots caused by solvent evaporation and convection processes. Here we present, without any surface chemistry modification, a unique solid surface of high-aspect-ratio silver-coated silicon nanocone arrays that allows highly uniform molecular deposition and thus subsequent uniform optical imaging and spectroscopic molecular detection. Both fluorescent Rhodamine dye molecules and unlabeled oligopeptides are printed on the metallic nanocone photonic substrate surface as circular spot arrays. In comparison with the printed results on ordinary glass slides and silver-coated glass slides, not only high printing density but uniform molecular distribution in every deposited spot is achieved. The high-uniformity and repeatability of molecular depositions on the 'coffee stain'-free nanocone surface is confirmed by laser scanning fluorescence imaging and surface enhanced Raman imaging experiments. The physical mechanism for the uniform molecular deposition is attributed to the superhydrophobicity and localized pinned liquid-solid-air interface on the silver-coated silicon nanocone surface. The unique surface properties of the presented nanocone surface enabled high-density, high-uniformity probe spotting beneficial for genomic and proteomic microarrays and surface molecular imaging.

Treatment Effect of Bumetanide in Children With Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.

Background: The therapeutic effect of bumetanide on autism spectrum disorder (ASD) seems to be controversial. To obtain better evidence on the efficacy of bumetanide, a systematic review and meta-analysis were performed. Methods: Randomized, placebo-controlled trials (RCTs) of bumetanide treatment in children with ASD were identified through systematic review from database inception to January 17, 2021. Subsequently, a meta-analysis was carried out to examine the effect of bumetanide on the severity of symptoms of ASD as assessed by the Childhood Autism Rating Scale (CARS) and Social Responsive Scale (SRS); core symptoms according to criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 of the American Psychiatric Association [social affect (SA), restricted, repetitive patterns of behavior, interests, or activities (RRB) and sensory symptoms]; and the therapeutic effect as assessed by Clinical Global Impressions-Efficacy (CGI-E). Results: In total, six RCTs involving 496 participants with ASD were identified in our study. The results showed that bumetanide could significantly improve the severity of the ASD symptoms measured by CARS and SRS. There was also evidence that bumetanide had positive effect on the core symptoms of ASD such as the SA and RRB, but there was no statistically significant effect on sensory symptoms. A significant positive effect on CGI-E scores in ASD patients was also observed. Conclusion: Our meta-analysis provided some support that bumetanide could improve the symptoms of children with ASD. However, additional large-scale longitudinal studies that provide clearer information and better control for confounding factors are needed to confirm our findings.

Prevalence and Developmental Profiles of Autism Spectrum Disorders in Children With Global Developmental Delay.

BACKGROUND: Previous studies have mostly explored the comorbidities of Global developmental delay (GDD) in children with Autism Spectrum Disorders (ASD) from the perspective of ASD. The study focus on the perspective of GDD to investigate the prevalence and developmental profiles of ASD in GDD and to explore the correlation between the developmental level and symptoms of autism. METHODS: Clinical data of 521 children with GDD aged from 24 to 60 months were retrospectively analyzed. Analyses were performed first for the whole sample and then subdivided into two subgroups (GDD+ASD-, GDD+ASD+) according to whether had ASD. Symptoms of autism were evaluated by the Autism Behavior Checklist and the Childhood Autism Rating Scale. The Chinese version of the Gesell Developmental Schedules was used to evaluate the level of children's mental development. RESULT: The prevalence of ASD in children with GDD was 62.3%. The total average developmental quotient (DQ) of GDD was mildly deficient and was negatively correlated with symptoms of autism (p < 0.05); language ability was severe and extremely severe deficient (P < 0.05). GDD+ASD- group and GDD+ASD+ group have some common points as well as differences in the developmental features. The language delay of children in both subgroups was the most obviously defected, thereafter followed by the item of personal social activity. In the GDD+ASD+ group, the DQ of gross motor skills>fine motor skills>adaptability (p < 0.05). There were no significant differences among the DQ of gross motor skills, fine motor skills and adaptability in GDD+ASD- group (p > 0.05). The GDD+ASD-group had better adaptability, fine motor skills, language ability, personal social activity than that of the GDD+ASD+ group, but the gross motor skills in GDD+ASD- group were worse (p < 0.05). CONCLUSION: GDD children have a high proportion of comorbid ASD, and GDD children with poorer developmental levels are more likely to have ASD symptoms. Development profiles in both GDD+ASD- children and GDD+ASD+ children have common features but there are also differences. GDD+ASD+ group is worse than GDD+ASD- group in terms of the overall development level.

Spiral Donor Design Strategy for Blue Thermally Activated Delayed Fluorescence Emitters.

Thermally activated delayed fluorescence (TADF) emitters with a spiral donor show tremendous potential toward high-level efficient blue organic light-emitting diodes (OLEDs). However, the underlying design strategy of the spiral donor used for blue TADF emitters remains unclear. As a consequence, researchers often do "try and error" work in the development of new functional spiral donor fragments, making it slow and inefficient. Herein, we demonstrate that the energy level relationships between the spiral donor and the luminophore lead to a significant effect on the photoluminescent quantum yields (PLQYs) of the target materials. In addition, a method involving quantum chemistry simulations that can accurately predict the aforementioned energy level relationships by simulating the spin density distributions of the triplet excited states of the spiral donor and corresponding TADF emitters and the triplet excited natural transition orbitals of the TADF emitters is established. Moreover, it also revealed that the steric hindrance in this series of molecules can form a nearly unchanged singlet (S1) state geometry, leading to a reduced nonradiative decay and high PLQY, while a moderated donor-acceptor (D-A) torsion in the triplet (T1) state can induce a strong vibronic coupling between the charge-transfer triplet (3CT) state and the local triplet (3LE) state, achieving an effective reverse intersystem crossing (RISC) process. Furthermore, an electric-magnetic coupling is formed between the high-lying 3LE state and the charge-transfer singlet (1CT) state, which may open another RISC channel. Remarkably, in company with the optimized molecular structure and energy alignment, the pivotal TADF emitter DspiroS-TRZ achieved 99.9% PLQY, an external quantum efficiency (EQE) of 38.4%, which is the highest among all blue TADF emitters reported to date.

Surface-enhanced Raman nanodomes.

We demonstrate a surface-enhanced Raman scattering (SERS) substrate consisting of a closely spaced metal nanodome array fabricated on flexible plastic film. We used a low-cost, large-area replica molding process to produce a two-dimensional periodic array of cylinders that is subsequently overcoated with SiO(2) and silver thin films to form dome-shaped structures. Finite element modeling was used to investigate the electromagnetic field distribution of the nanodome array structure and the effect of the nanodome separation distance on the electromagnetic field enhancement. The SERS enhancement from the nanodome array substrates was experimentally verified using rhodamine 6G as the analyte. With a separation distance of 17 nm achieved between adjacent domes using a process that is precisely controlled during thin film deposition, a reproducible SERS enhancement factor of 1.37 × 10(8) was demonstrated. The nanoreplica molding process presented in this work allows for simple, low-cost, high-throughput fabrication of uniform nanoscale SERS substrates over large surface areas without the requirement for high resolution lithography or defect-free deposition of spherical microparticle monolayer templates.

Rigorous surface enhanced Raman spectral characterization of large-area high-uniformity silver-coated tapered silica nanopillar arrays.

Surface enhanced Raman spectroscopy (SERS) has been increasingly utilized as an analytical technique with significant chemical and biological applications (Qian et al 2008 Nat. Biotechnol. 26 83; Fujita et al 2009 J. Biomed. Opt. 14 024038; Chou et al 2008 Nano Lett.8 1729; Culha et al 2003 Anal. Chem. 75 6196; Willets K A 2009 Anal. Bioanal. Chem. 394 85; Han et al 2009 Anal. Bioanal. Chem. 394 1719; Sha et al 2008 J. Am. Chem. Soc. 130 17214). However, production of a robust, homogeneous and large-area SERS substrate with the same ultrahigh sensitivity and reproducibility still remains an important issue. Here, we describe a large-area ultrahigh-uniformity tapered silver nanopillar array made by laser interference lithography on the entire surface of a 6 inch wafer. Also presented is the rigorous optical characterization method of the tapered nanopillar substrate to accurately quantify the Raman enhancement factor, uniformity and repeatability. An average homogeneous enhancement factor of close to 10(8) was obtained for benzenethiol adsorbed on a silver-coated nanopillar substrate.

Clinical improvement following vitamin D3 supplementation in children with chronic tic disorders.

PURPOSE: Vitamin D deficiency has been found in children with chronic tic disorders (CTDs). Our previous data showed that serum 25-hydroxyvitamin D [25(OH)D] level in children with CTDs was lower than that of the healthy controls and lower serum 25(OH)D level was associated with increased severity of the tic disorder. Thus, we intend to further verify this phenomenon and examine the effect of vitamin D3 on CTDs. PATIENTS AND METHODS: In total, 120 children with CTDs and 140 normal controls were enrolled in this study, with 36/120 of those in the CTD group receiving vitamin D3 treatment for 3 months. The Yale Global Tic Severity Scale (YGTSS) and Clinical Global Impression of Severity of Illness (CGI-SI) were, respectively, used to evaluate the tic severity. High-performance liquid chromatography and tandem mass spectrometry were used to measure serum 25(OH)D level. RESULTS: Those children with CTDs exhibited significantly lower 25(OH)D levels than did healthy controls, and these reduced 25(OH)D levels were linked to increasing severity of tic symptoms. After treatment with supplemental vitamin D3, serum 25(OH)D level and scores of YGTSS total, motor tics, phonic tics, total tic, impairment, and CGI-SI improved significantly in children with CTDs without any adverse reactions. CONCLUSION: Supplementation vitamin D3, given its low cost and excellent safety, may be an effective means of improving symptoms in certain children with CTDs.

DNA methylation changes related to nutritional deprivation: a genome-wide analysis of population and in vitro data.

BACKGROUND: DNA methylation has recently been identified as a mediator between in utero famine exposure and a range of metabolic and psychiatric traits. However, genome-wide analyses are scarce and cross-sectional analyses are hampered by many potential confounding factors. Moreover, causal relations are hard to identify due to the lack of controlled experimental designs. In the current study, we therefore combined a comprehensive assessment of genome-wide DNA methylation differences in people exposed to the great Chinese famine in utero with an in vitro study in which we deprived fibroblasts of nutrition. METHODS: We compared whole blood DNA methylation differences between 25 individuals in utero exposed to famine and 54 healthy control individuals using the HumanMethylation450 platform. In vitro, we analyzed DNA methylation changes in 10 fibroblast cultures that were nutritionally deprived for 72 h by withholding fetal bovine serum. RESULTS: We identified three differentially methylated regions (DMRs) in four genes (ENO2, ZNF226, CCDC51, and TMA7) that were related to famine exposure in both analyses. Pathway analysis with data from both Chinese famine samples and fibroblasts highlighted the nervous system and neurogenesis pathways as the most affected by nutritional deprivation. CONCLUSIONS: The combination of cross-sectional and experimental data provides indications that biological adaptation to famine leads to DNA methylation changes in genes involved in the central nervous system.

Comparative genetic architectures of schizophrenia in East Asian and European populations.

Schizophrenia is a debilitating psychiatric disorder with approximately 1% lifetime risk globally. Large-scale schizophrenia genetic studies have reported primarily on European ancestry samples, potentially missing important biological insights. Here, we report the largest study to date of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide-significant associations in 19 genetic loci. Common genetic variants that confer risk for schizophrenia have highly similar effects between East Asian and European ancestries (genetic correlation = 0.98 ± 0.03), indicating that the genetic basis of schizophrenia and its biology are broadly shared across populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries identified 208 significant associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping reduced the sets of candidate causal variants in 44 loci. Polygenic risk scores had reduced performance when transferred across ancestries, highlighting the importance of including sufficient samples of major ancestral groups to ensure their generalizability across populations.

Bench to bedside review: Possible role of vitamin D in autism spectrum disorder.

Autism spectrum disorder (ASD) is a group of dysfunctions in social interaction, communication, and behaviors. Studies have demonstrated that vitamin D deficiency during pregnancy and in individuals increased the risk of ASD. A genetic polymorphism study has pinpointed that genotype AA/A-allele of GC rs4588 in children is associated with ASD, which encodes the vitamin D binding protein. Translating the mentioned points into clinical practice, several clinical trials have demonstrated that vitamin D supplementation can improve the core symptoms in children with ASD. One paper also showed that possible prophylactic effect for the reoccurrence of ASD by vitamin D supplement during pregnancy and early childhood. Herein, this review aims to address the recent advances in this field and to clarify the possible role of vitamin D in ASD.