Decoding the heterogeneity of Alzheimer's disease diagnosis and progression using multilayer networks.

Alzheimer's disease (AD) is a multifactorial and heterogeneous disorder, which makes early detection a challenge. Studies have attempted to combine biomarkers to improve AD detection and predict progression. However, most of the existing work reports results in parallel or compares normalized findings but does not analyze data simultaneously. We tested a multi-dimensional network framework, applied to 490 subjects (cognitively normal [CN] = 147; mild cognitive impairment [MCI] = 287; AD = 56) from ADNI, to create a single model capable of capturing the heterogeneity and progression of AD. First, we constructed subject similarity networks for structural magnetic resonance imaging, amyloid-ß positron emission tomography, cerebrospinal fluid, cognition, and genetics data and then applied multilayer community detection to find groups with shared similarities across modalities. Individuals were also followed-up longitudinally, with AD subjects having, on average, 4.5 years of follow-up. Our findings show that multilayer community detection allows for accurate identification of present and future AD (≈90%) and is also able to identify cases that were misdiagnosed clinically. From all MCI participants who developed AD or reverted to CN, the multilayer model correctly identified 90.8% and 88.5% of cases respectively. We observed similar subtypes across the full sample and when examining multimodal data from subjects with no AD pathology (i.e., amyloid negative). Finally, these results were also validated using an independent testing set. In summary, the multilayer framework is successful in detecting AD and provides unique insight into the heterogeneity of the disease by identifying subtypes that share similar multidisciplinary profiles of neurological, cognitive, pathological, and genetics information.

Functional near-infrared spectroscopy in developmental psychiatry: a review of attention deficit hyperactivity disorder.

Research has linked executive function (EF) deficits to many of the behavioral symptoms of attention deficit hyperactivity disorder (ADHD). Evidence of the involvement of EF impairment in ADHD is corroborated by accumulating neuroimaging studies, specifically functional magnetic resonance imaging (fMRI) studies. However, in recent years, functional near-infrared spectroscopy (fNIRS) has become increasingly popular in ADHD research due to its portability, high ecological validity, resistance to motion artifacts, and cost-effectiveness. While numerous studies throughout the past decade have used fNIRS to examine alterations in neural correlates of EF in ADHD, a qualitative review of the reliability of these findings compared with those reported using gold-standard fMRI measurements does not yet exist. The current review aims to fill this gap in the literature by comparing the results generated from a qualitative review of fNIRS studies (children and adolescents ages 6-16 years old) to a meta-analysis of comparable fMRI studies and examining the extent to which the results of these studies align in the context of EF impairment in ADHD. The qualitative analysis of fNIRS studies of ADHD shows a consistent hypoactivity in the right prefrontal cortex in multiple EF tasks. The meta-analysis of fMRI data corroborates altered activity in this region and surrounding areas during EF tasks in ADHD compared with typically developing controls. These findings indicate that fNIRS is a promising functional brain imaging technology for examining alterations in cortical activity in ADHD. We also address the disadvantages of fNIRS, including limited spatial resolution compared with fMRI.

Neurite Imaging Reveals Widespread Alterations in Gray and White Matter Neurite Morphology in Healthy Aging and Amnestic Mild Cognitive Impairment.

Aging is the major risk factor for neurodegenerative diseases and affects neurite distributions throughout the brain, yet underlying neurobiological mechanisms remain unclear. Multi-shell diffusion-weighted imaging and neurite orientation dispersion and density imaging (NODDI) now provide in vivo biophysical measurements that explain these biological processes in the cortex and white matter. In this study, neurite distributions were evaluated in the cortex and white matter in healthy older adults and patients with amnestic mild cognitive impairment (aMCI) that provides fundamental contributions regarding healthy aging and neurodegeneration. Older age was associated with reduced neurite density and neurite orientation dispersion (ODI) in widespread cortical regions. In contrast, increased ODI was only observed in the right thalamus and hippocampus with age. For the first time, we also reported a widespread age-associated decrease in neurite density along major white matter tracts correlated with decreased cortical neurite density in the tract endpoints in healthy older adults. We further examined alterations in cortical and white matter neurite microstructures in aMCI patients and found significant neurite morphology deficits in memory networks correlated with memory performance. Our findings indicate that neurite parameters provide valuable information regarding cortical and white matter microstructure and complement myeloarchitectural information in healthy aging and aMCI.

Evaluation of Phobia, Knowledge, Attitude and Practice about SARS-CoV-2 Infection, a Study on Healthcare Workers and Their 1st Degree Relatives.

Background: Phobia as a psychological disorder seems to be aggravated during health crises like the current COVID-19 outbreak. On the other hand, people's knowledge about a situation can help decrease the resulting fear. Study design: This is a cross-sectional analytical study to evaluate the COVID-19 related phobia and to measure knowledge, attitude, and practice of our target Iranian population about COVID-19. Methods: In this study, DSM-5 specific phobia questionnaire, adapted to SARS-CoV2-19 infection, was used to evaluate the COVID-19 related phobia. Moreover, the knowledge, attitude, and practice (KAP) questionnaire, specific for SARS-CoV-2 infection, was applied. Results: Phobia score was significantly higher in 1st-degree relatives of healthcare staff (20.38±5.82) than healthcare staff (18.36±5.68) (p=0.021). Females showed a significantly more severe phobia (20.27±5.41) than males (17.72±5.35, p=0.001). COVID-19 phobia was significantly more severe in those with past psy-chiatric conditions than in those without psychiatric history (p<0.05). The 1st-degree relatives of healthcare staff had a significantly lower level of knowledge about SARS-CoV-2 infection (8.19±1.65) than healthcare staff (9.08±1.28, p=0.001). Additionally, age had a positive significant correlation with knowledge and practice towards SARS-CoV-2 infection. Conclusion: Both Iranian healthcare staff and 1st-degree relatives of healthcare workers are suffering from moderate COVID-19 phobia. Females are more concerned than males about COVID-19. Phobia is more severe in people with underlying psychiatric conditions than other people. The knowledge level of Iranian healthcare workers and 1st-degree relatives of healthcare staff about COVID-19 is acceptable but it needs improvement in certain areas.

Quantitative measurement of macromolecular tissue properties in white and gray matter in healthy aging and amnestic MCI.

Healthy and pathological aging influence brain microstructure via complex processes. Discerning these processes requires measurements that are sensitive to specific biological properties of brain tissue. We integrated a novel quantitative R1 measure with multi-shell diffusion weighted imaging to map age-associated changes in macromolecular tissue volume (MTV) along major white matter tracts in healthy older adults and patients with amnestic Mild Cognitive Impairment (aMCI). Reduced MTV in association tracts was associated with older age in healthy aging, was correlated with memory performance, and distinguished aMCI from controls. We also mapped changes in gray matter tissue properties using quantitative R1 measurements. We documented a widespread decrease in R1 with advancing age across the cortex and decreased R1 in aMCI compared with controls in regions implicated in episodic memory. Our data are the first to characterize MTV loss along major white matter tracts in aMCI and suggest that qMRI is a sensitive measure for detecting subtle degeneration of white and gray matter tissue that cannot be detected by conventional MRI and diffusion measures.

Cognitive impairment and associations with structural brain networks, endocrine status, and risk genotypes in patients with newly diagnosed prostate cancer referred to androgen-deprivation therapy.

BACKGROUND: Evidence suggests that patients with prostate cancer (PCPs) receiving androgen-deprivation therapy (ADT) are at risk for cognitive impairment. Research with other populations with cancer indicates that cognitive impairment may also occur before systemic treatment. The authors assessed cognitive impairment in untreated PCPs referred to ADT and explored associations with structural brain networks, endocrine status, and selected genotypes. METHODS: Forty untreated PCPs and 27 healthy controls (HCs) who completed a questionnaire package underwent neuropsychological testing, magnetic resonance imaging, and blood sampling. Cognitive impairment was defined as a z score ≤-2 on 1 neuropsychological test or ≤-1.5 on 2 neuropsychological tests. Structural brain networks were investigated using diffusion-weighted imaging and graph theory. Associations of cognitive performance with patient-reported outcome measures (PROMs), brain networks, testosterone levels, and genotypes (apolipoprotein ε [APOE], catechol-O-methyltransferase [COMT], and brain-derived neurotrophic factor [BDNF]) were explored. RESULTS: PCPs performed poorer than HCs on 7 of 15 neuropsychological tests and exhibited a higher frequency of cognitive impairment (57.5% vs 22.2%; P ≤ .01 to .03). All neuropsychological outcomes were associated with ≥1 PROM (P ≤ .01 to .04). Compared with the HC group, the PCP group exhibited altered global network organization as well as disrupted regional network characteristics in frontal and temporal regions (P < .01). PCPs had lower testosterone levels (P < .01) than HCs, which correlated with better visuospatial performance (r = -0.33; P = .04). No effects were found of APOE, COMT, or BDNF. CONCLUSIONS: The current results suggest that untreated PCPs may demonstrate cognitive impairment and that psychological and behavioral symptoms (PROMs), as well as impairment in structural brain networks, might be the underlying mechanisms.

Oocyte vitrification induces loss of DNA methylation and histone acetylation in the resulting embryos derived using ICSI in dromedary camel.

Oocyte cryopreservation has become an important component of assisted reproductive technology with increasing implication in female fertility preservation and animal reproduction. However, the possible adverse effects of oocyte cryopreservation on epigenetic status of the resulting embryos is still an open question. This study evaluated the effects of MII-oocyte vitrification on gene transcripts linked to epigenetic reprogramming in association with the developmental competence and epigenetic status of the resulting embryos at 2-cell and blastocyst stages in dromedary camel. The cleavage rate of vitrified oocytes following intracytoplasmic sperm injection was significantly increased compared with the control (98.2 ± 2 vs. 72.7 ± 4.1%, respectively), possibly due to the higher susceptibility of vitrified oocytes to spontaneous activation. Nonetheless, the competence of cleaved embryos derived from vitrified oocytes for development to the blastocyst and hatched blastocyst was significantly reduced compared with the control (7.7 ± 1.2 and 11.1 ± 11.1 compared with 28.1 ± 2.6 and 52.4 ± 9.9%, respectively). The relative transcript abundances of epigenetic reprogramming genes DNMT1, DNMT3B, HDAC1, and SUV39H1 were all significantly reduced in vitrified oocytes relative to the control. Evaluation of the epigenetic marks showed significant reductions in the levels of DNA methylation (6.1 ± 0.3 vs. 9.9 ± 0.5, respectively) and H3K9 acetylation (7.8 ± 0.2 vs. 10.7 ± 0.3, respectively) in 2-cell embryos in the vitrification group relative to the control. Development to the blastocyst stage partially adjusted the effects that oocyte vitrification had on the epigenetic status of embryos (DNA methylation: 4.9 ± 0.4 vs. 6.2 ± 0.6; H3K9 acetylation: 5.8 ± 0.3 vs. 8 ± 0.9, respectively). To conclude, oocyte vitrification may interfere with the critical stages of epigenetic reprogramming during preimplantation embryo development.

Platelet rich plasma efficiently substitutes the beneficial effects of serum during in vitro oocyte maturation and helps maintain the mitochondrial activity of maturing oocytes.

Platelets contain most of the potent mitogenic factors present in serum and follicular fluid and intraovarian injection of autologous platelet rich plasma (PRP) was shown to improve ovarian function and development of preantral follicles. This study evaluated the effect of PRP on caprine oocyte maturation in vitro and subsequent fertilization and embryonic development. Cumulus oocyte complexes were cultured in a maturation medium supplemented with (1) fetal bovine serum (FBS, control), (2) PRP, extracted from healthy female goats, (3) polyvinyl alcohol (PVA), and (4) PVA plus PRP (PVA-PRP). The degree of cumulus expansion was scored, and denuded oocytes were used for assessment of nuclear maturation, mitochondrial activity, lipid content, redox status, yield and quality of in vitro embryo development, and cryosurvival of the resulting blastocysts. PRP supported the same beneficial effects of FBS on cumulus expansion, nuclear maturation, in vitro developmental competence of oocytes, and survival of vitrified-warmed blastocysts. Moreover, PRP protected oocytes from undesirable effects FBS exerted on the mitochondrial activity and intracytoplasmic lipid content of maturing oocyte. Although PVA could support the same beneficial effects of neither FBS nor PRP on oocyte maturation, its combined addition with PRP improved the yield and quality of oocyte maturation at rates closely similar to PRP. PRP efficiently substitutes beneficial effects of serum during in vitro oocyte maturation and helps maintain the mitochondrial activity of maturing oocytes.

Comparative trachea transcriptome analysis between avian infectious bronchitis virus and avian pathogenic E. coli individual infection and co-infection in SPF chickens.

Avian infectious bronchitis virus (IBV) and avian pathogenic Escherichia coli (APEC) are two important respiratory pathogens in the chicken. The co-infection can lead to chronic complications and considerable economic losses in the poultry industry worldwide. In the present study, we compared differential transcriptional profiles in the trachea tissue of three infected groups (IBV, APEC, and co-infection) with the control group to investigate transcriptome profile changes at the early stage of the infection. After the challenge of SPF chickens with IBV IS-1494 like (GI-23) and APEC, serotype O78: K80, or co-infection, the trachea tissue was used for RNA extraction, and changes in the transcriptome were investigated by Illumina RNA-seq technique. Up-regulated and down-regulated differentially expressed genes (DEGs) in the transcriptome of each group's trachea were identified. Gene ontology category, KEGG pathway, and gene interaction networks (STRING analysis) were analyzed to identify relationships among differentially expressed genes. In general, the numbers of up-regulated genes were higher than of down-regulated genes. In the co-infection group, a more severe immune response and macrophage infiltration occurred; an important cluster of pathway signaling in this group's up-regulated genes was an apoptotic cluster, cytokine-mediated signaling cluster, and the PAMPs recognizing cluster. This is the first study to provide a general overview of transcriptome changes in the trachea at the early stage of infection with these pathogens. Keywords: avian infectious bronchitis virus; avian pathogenic E. coli; transcriptome; RNA-Seq.

Mind over motor mapping: Driver response to changing vehicle dynamics.

Improvements in vehicle safety require understanding of the neural systems that support the complex, dynamic task of real-world driving. We used functional near infrared spectroscopy (fNIRS) and pupilometry to quantify cortical and physiological responses during a realistic, simulated driving task in which vehicle dynamics were manipulated. Our results elucidate compensatory changes in driver behavior in response to changes in vehicle handling. We also describe associated neural and physiological responses under different levels of mental workload. The increased cortical activation we observed during the late phase of the experiment may indicate motor learning in prefrontal-parietal networks. Finally, relationships among cortical activation, steering control, and individual personality traits suggest that individual brain states and traits may be useful in predicting a driver's response to changes in vehicle dynamics. Results such as these will be useful for informing the design of automated safety systems that facilitate safe and supportive driver-car communication.

Altered Brain Network Segregation in Fragile X Syndrome Revealed by Structural Connectomics.

Fragile X syndrome (FXS), the most common inherited cause of intellectual disability and autism spectrum disorder, is associated with significant behavioral, social, and neurocognitive deficits. Understanding structural brain network topology in FXS provides an important link between neurobiological and behavioral/cognitive symptoms of this disorder. We investigated the connectome via whole-brain structural networks created from group-level morphological correlations. Participants included 100 individuals: 50 with FXS and 50 with typical development, age 11-23 years. Results indicated alterations in topological properties of structural brain networks in individuals with FXS. Significantly reduced small-world index indicates a shift in the balance between network segregation and integration and significantly reduced clustering coefficient suggests that reduced local segregation shifted this balance. Caudate and amygdala were less interactive in the FXS network further highlighting the importance of subcortical region alterations in the neurobiological signature of FXS. Modularity analysis indicates that FXS and typically developing groups' networks decompose into different sets of interconnected sub networks, potentially indicative of aberrant local interconnectivity in individuals with FXS. These findings advance our understanding of the effects of fragile X mental retardation protein on large-scale brain networks and could be used to develop a connectome-level biological signature for FXS.

Effects of a blend of essential oils and overcrowding stress on the growth performance, meat quality and heat shock protein gene expression of broilers.

Overcrowding stress is common in the poultry industry. Chickens exposed to long-term stressful situations are characterised by welfare impairment and immunosuppression. 1. The present study evaluated the effects of a blend of essential oils (EOB; cinnamaldehyde and thymol) and stocking density on the performance, gut microflora, meat quality and physiological stress markers of broilers. 2. One-day-old Ross 308 male broiler chickens (n = 360) were allocated to 4 experimental groups from d 22 to 42. Each treatment had 6 replicates of 15 chicks. Two groups were subjected to a high stocking density (HSD) of 20 birds/m2 and the other two groups were kept at a low stocking density (LSD) of 10 birds/m2. 3. The results of this study indicate that overcrowding stress decreased growth performance parameters, blood immunoglobulin (Ig)G and heterophil:lymphocyte (H:L) ratio but increased IgA and IgM levels. HSD reduced water-loss rate and pH decline at 45 min post mortem in the breast muscle. 4. Essential oils supplementation elevated H:L ratio but decreased breast meat redness and pH24. 5. Significant interactions between EOB and stocking density were observed for corticosterone (CS) level and mRNA levels of heat shock protein 70 (HSP70) in brain and heart. Although HSD increased CS and HSP70 when compared to LSD, the effects of the former were inconsistent with EOB supplemented diets. 6. In conclusion, dietary EOB supplementation could improve some of the biomarkers associated with overcrowding stress in broiler chickens.

Cathepsin B inhibitor improves developmental competency and cryo-tolerance of in vitro ovine embryos.

BACKGROUND: Cathepsin B is a lysosomal cysteine protease involved in apoptosis and oocytes which have lower developmental competence show higher expression of Cathepsin B. Furthermore, expression of Cathepsin B show a decreasing trend from oocyte toward blastocyst stage. RESULTS: Present study assessed the effect of cathepsin B inhibitor, E-64, on developmental competency and cryo-survival of pre-implantation ovine IVF derived embryos. Cathepsin B inhibitor was added during day 3 to 8 of development. One µM E-64 was defined as the optimal concentration required for improving blastocyst rate. This concentration also reduced DNA fragmentation and BAX as apoptotic markers while increasing total cell number per blastocyst and improving anti-apoptotic marker, the BCL2. We further showed that addition of 1.0 µM of E-64 during day 3 to 8 of development improved re-expansion and hatching rates of blastocysts post vitrification. E-64 also reduced rate of DNA fragmentation and BAX expression and increased total cell number per blastocyst and BCL2 expression post vitrification. However, addition of E-64 post vitrification reduced the hatching rate. CONCLUSION: Therefore, it can be concluded that inhibition of cathepsin B in IVC, not only improves quality and quantity of blastocysts but also improves the cryo-survival of in vitro derived blastocysts.

Differential expression of innate immune response genes in clinical phases of chronic hepatitis B infection.

We investigated innate immune gene expression in clinical phases of chronic hepatitis B infection, including immune tolerant (IT), immune active (IA), inactive carrier (IC) and hepatitis B e antigen (HBeAg)-negative phases, as well as healthy controls. Expression levels of interferon types I, II and III, their receptor subunits, IRFs, TLRs and other IFN-induced genes in peripheral blood mononuclear cells were compared. Forty HBsAg-positive treatment-naïve subjects without co-infection with HIV, HCV or HDV were enrolled. To complement the viral load, the expression levels of 37 innate immune genes were measured by qPCR. The highest response of the innate immune system was observed in the IT and HBeAg-negative phases, and the IC phase had the lowest response; 31 of the 37 studied genes reached their maximum mRNA expression levels in the IT and HBeAg-negative phases, and the minimum expression levels of 23 genes were found in the IC phase. The highest mRNA expression levels of IFNs, IFN receptor subunits, IRFs and TLRs genes in all clinical phases were IFN-λ2 and 3, IFN-γR2, IRF7 and TLR7, and the lowest levels of mRNA expression were observed for IFN-α, IFN-λR1, IRF8 and TLR2. We conclude that innate immune response genes are expressed differentially among chronic HBV phases, and this difference may help to develop new precise and noninvasive methods to determine the progression of disease in chronic HBV patients.

Vitamin K2 improves developmental competency and cryo-tolerance of in vitro derived ovine blastocyst.

Vitamin K2 (VK2), acts as an electron carrier in mitochondria and thereby effects reactive oxygen species (ROS) and ATP production. This study evaluates role of VK2 on in vitro developmental competency and cryo-survival of pre-implantation ovine embryos. Initially the optimal and beneficial concentration of VK2 on compaction and blastocyst formation rates was defined (0.1 µM). Subsequently, it was shown that 0.1 µM VK2, at blastocyst stage, reduces H2O2 production, increase the expression of mitochondrial related gene and improved embryos quality. We further assessed presence VK2 supplementation before and/or after vitrification of in vitro derived blastocysts. Our results reveal that presence of VK2 before and after vitrification improves rates of blastocysts re-expansion (88.19± 3.37% vs 73.68± 1.86%, P < 0.05) and hatching (49.55± 4.37% vs 32.7± 3.32%) compared to control group. These observation were consistent with reduction in H2O2 production and improved in expression of mitochondrial related genes. However, VK2 before or after vitrification, not only had no positive effect on these two parameters, but also significantly reduced these parameters. Therefore, in concordance with pervious report in bovine, we show that VK2 supplementation post genomic activation (Day 3-7) improved developmental competency of ovine in vitro derived embryos. We also showed that presence of VK2 after vitrification improves the cryo-survival of ovine embryos.

Molecular investigation of bacterial communities during the manufacturing and ripening of semi-hard Iranian Liqvan cheese.

Liqvan (or Lighvan) is a traditional Iranian cheese from the East Azerbaijan province of Iran, which is made of raw ewe's milk without the addition of a starter. The grazing pastures, environmental conditions and the ancient regional production methods allocate a distinctive microbial ecology to this type of cheese, and these factors are consequently associated with the quality of the product. In this study, the microbiota of the milk, curd and cheese has been investigated using culture independent approaches. Denaturing gradient gel electrophoresis (DGGE) of the bacteria, 16S rRNA based high-throughput sequencing and enumeration of the live bacterial community by means of quantitative PCR (qPCR) have been used for this purpose. The results showed that the main bacterial population in the milk belonged to both microbial contaminants and lactic acid bacteria (LAB). However, both of these populations were totally replaced by LAB during ripening. The present survey contributes by describing the microbiota of this ancient cheese in more detail during fermentation and ripening.

Predicting saltwater intrusion into aquifers in vicinity of deserts using spatio-temporal kriging.

The primary objective of this study was to provide a detailed framework to use the spatio-temporal kriging to model the spatio-temporal variations of salinity data and predict saltwater intrusion into freshwater aquifers in the vicinity of deserts. EC data, measured in extraction wells in the Mahvelat plain located in the Northeastern part of Iran, available from 2007 to 2013, were used to demonstrate the developed framework. The source of data was not a well-designed measurement network. Therefore, to homogenize the data, spatial analysis was used to find EC distribution in the area in each year of study. To conduct the spatial analysis, a guideline and a systematic process were developed to select an appropriate kriging method and optimize its parameters. This process can be applied to different variables. After spatial analysis of EC data for all the years of the analysis period using empirical Bayesian kriging (EBK) method with manually optimized parameters, spatio-temporal and corresponding variogram analysis was conducted using R software. This process was based on a separable product-sum model applied to the data from 2007 to 2012. The data of 2013 and the data available for the years 1999 and 2006 were used for evaluating the performance of the spatio-temporal model. The EC distribution maps, developed for different years until 2021, show a high level of EC in the north, south, and west of the study area and growing saltwater intrusion into the central freshwater aquifer. This result can be attributed to the over-exploitation of the aquifer and hydraulic head and gradient distribution in the area. The framework provided in this study for spatio-temporal analysis of unstructured EC data is useful for groundwater managers in making proper decisions.

Establishment of reverse transcription polymerase chain reaction assay for simultaneous detection of human parainfluenza virus types 1 to 4 in children with influenza like illnesses.

OBJECTIVES: The aim of this study was to develop an in-house multiplex reverse transcription polymerase chain reaction (mRT-PCR), which can recognize HPIV1-4 in clinical samples. BACKGROUND: Human parainfluenza virus (HPIV) is one of the major causes of viral respiratory infections and can affect people at any age, especially infants and young children. METHODS: Four sets of specific primers targeting conserved areas of hemagglutinin-neuraminidase (HN) genes of HPIV1-4, were designed and tested with type-related plasmid controls. Specificity and sensitivity of mPCR were tested. One-step mRT-PCR was set up using a viral panel containing 10 respiratory viruses, including HPIVs. One hundred nasopharyngeal samples of respiratory infection patients were tested using the set One-step mRT-PCR. RESULTS: The specificity of set mPCR for HPIV1-4 using plasmid positive controls was proved and reaction sensitivity was measured. The specificity of set mRT-PCR was confirmed and 4 and 5 out of 100 clinical samples were HPIV1 and HPIV2 positive, respectively. CONCLUSION: The developed one-step mRT-PCR in this study is an effective and specific assay for clinical diagnosis of HPIV1 to 4 (Tab. 1, Fig. 6, Ref. 28).

Task-based neurofeedback training: A novel approach toward training executive functions.

Cognitive training is an emergent approach to improve cognitive functions in various neurodevelopmental and neurodegenerative diseases. However, current training programs can be relatively lengthy, making adherence potentially difficult for patients with cognitive difficulties. Previous studies suggest that providing individuals with real-time feedback about the level of brain activity (neurofeedback) can potentially help them learn to control the activation of specific brain regions. In the present study, we developed a novel task-based neurofeedback training paradigm that benefits from the effects of neurofeedback in parallel with computerized training. We focused on executive function training given its core involvement in various developmental and neurodegenerative diseases. Near-infrared spectroscopy (NIRS) was employed for providing neurofeedback by measuring changes in oxygenated hemoglobin in the prefrontal cortex. Of the twenty healthy adult participants, ten received real neurofeedback (NFB) on prefrontal activity during cognitive training, and ten were presented with sham feedback (SHAM). Compared with SHAM, the NFB group showed significantly improved executive function performance including measures of working memory after four sessions of training (100min total). The NFB group also showed significantly reduced training-related brain activity in the executive function network including right middle frontal and inferior frontal regions compared with SHAM. Our data suggest that providing neurofeedback along with cognitive training can enhance executive function after a relatively short period of training. Similar designs could potentially be used for patient populations with known neuropathology, potentially helping them to boost/recover the activity in the affected brain regions.

Altered Integration of Structural Covariance Networks in Young Children With Type 1 Diabetes.

Type 1 diabetes mellitus (T1D), one of the most frequent chronic diseases in children, is associated with glucose dysregulation that contributes to an increased risk for neurocognitive deficits. While there is a bulk of evidence regarding neurocognitive deficits in adults with T1D, little is known about how early-onset T1D affects neural networks in young children. Recent data demonstrated widespread alterations in regional gray matter and white matter associated with T1D in young children. These widespread neuroanatomical changes might impact the organization of large-scale brain networks. In the present study, we applied graph-theoretical analysis to test whether the organization of structural covariance networks in the brain for a cohort of young children with T1D (N = 141) is altered compared to healthy controls (HC; N = 69). While the networks in both groups followed a small world organization-an architecture that is simultaneously highly segregated and integrated-the T1D network showed significantly longer path length compared with HC, suggesting reduced global integration of brain networks in young children with T1D. In addition, network robustness analysis revealed that the T1D network model showed more vulnerability to neural insult compared with HC. These results suggest that early-onset T1D negatively impacts the global organization of structural covariance networks and influences the trajectory of brain development in childhood. This is the first study to examine structural covariance networks in young children with T1D. Improving glycemic control for young children with T1D might help prevent alterations in brain networks in this population. Hum Brain Mapp 37:4034-4046, 2016. © 2016 Wiley Periodicals, Inc.