Thermite frass biomass and surface modified biowaste coir fiber reinforced biocomposites-Conversion of waste to useful products.

Polymer composites are known for its light weight and specific mechanical characteristics. This study examines sodium hydroxide (NaOH)-treated coir fiber, an agro-leftover, stuffed in a polyester matrix with termite frass powder, a bio-leftover for possible use in light-weight structural applications. Composite samples were made using compression molding and NaOH-treated coir fiber reinforced hybrid polymer composite (TCRHPC) with 40 wt% treated coir fiber and 1, 2, 3, and 4 wt% termite frass powder. TCRHPC samples mechanical, water captivation, tribological, and thermal properties were affected by termite frass powder wt%. The TCRHPC sample with 3 wt% termite frass powder has excellent mechanical properties, which improved by tensile (41.6%), flexural (28.57%), impact (43.7%), and hardness (18.84%) properties. With perfect water captivation and low weight increases in normal water (0.017 g), seawater (0.015 g), and NaOH solution (0.010 g), the identical composite sample with thermal stability up to 238°C also reduced wear mass by 5.27%. Conversely, filler agglomeration and heterogeneous dispersion in composite sample impair thermo-mechanical characteristics of TCRHPC containing 4 wt% termite frass powder. The bonding among polyester, treated coir fiber, and termite frass powder in composites were appraised with the aid of fractographic images of TCRHPC samples. The results show that TCRHPC material suits well for support structures requiring lesser weight.

Association between 15 known or potential breast cancer susceptibility genes and breast cancer risks in Chinese women.

OBJECTIVE: There are many hereditary breast cancer patients in China, and multigene panel testing has been a new paradigm of genetic testing for these patients and their relatives. However, the magnitude of breast cancer risks related to multiple breast cancer susceptibility genes are largely unknown in Chinese women. METHODS: We screened pathogenic variants in 15 established or potential breast cancer susceptibility genes from 8,067 consecutive Chinese female breast cancer patients and 13,129 Chinese cancer-free female controls. These breast cancer patients were unselected for age at diagnosis or family history. RESULTS: We found that pathogenic variants in TP53 [odds ratio (OR): 16.9, 95% confidence interval (CI): 5.2-55.2]; BRCA2 (OR: 10.4, 95% CI: 7.6-14.2); BRCA1 (OR: 9.7, 95% CI: 6.3-14.8); and PALB2 (OR: 5.2, 95% CI: 3.0-8.8) were associated with a high risk of breast cancer. ATM, BARD1, CHEK2, and RAD51D were associated with a moderate risk of breast cancer with ORs ranging from 2-fold to 4-fold. In contrast, pathogenic variants of NBN, RAD50, BRIP1, and RAD51C were not associated with increased risk of breast cancer in Chinese women. The pathogenic variants of PTEN, CDH1, and STK11 were very rare, so they had a limited contribution to Chinese breast cancer. Patients with pathogenic variants of TP53, BRCA1, BRCA2, and PALB2 more often had early-onset breast cancer, bilateral breast cancer, and a family history of breast cancer and/or any cancer. CONCLUSIONS: This study provided breast cancer risk assessment data for multiple genes in Chinese women, which is useful for genetic testing and clinical management of Chinese hereditary breast cancer.

Mortality Prediction of COVID-19 Patients at Intensive Care Unit Admission.

Background Coronavirus-2019 (COVID-19) patients admitted to the intensive care unit (ICU) have mortality rates between 30%-50%. Identifying patient factors associated with mortality can help identify critical patients early and treat them accordingly. Patients and methods In this retrospective study, the records of patients admitted to the COVID-19 ICU in a single tertiary care hospital from April 2020 to September 2020 were analysed. The clinical and laboratory parameters between patients who were discharged from the hospital (survival cohort) and those who died in the hospital (mortality cohort) were compared. A multivariate logistic regression model was constructed to identify parameters associated with mortality.  Results A total of 147 patients were included in the study. The age of the patients was 55 (45, 64), median (IQR), years. At admission, 23 (16%) patients were on mechanical ventilation and 73 (50%) were on non-invasive ventilation. Sixty patients (40%, 95% CI: 32.8 to 49.2%) had died. Patients who died had a higher Charlson comorbidity index (CCI): 3 (2, 4) vs. 2 (1, 3), p = 0.0019, and a higher admission sequential organ failure assessment (SOFA) score: 5 (4, 7) vs. 4 (3, 4), p < 0.001. Serum urea, serum creatinine, neutrophils on differential leukocyte count, neutrophil to lymphocyte ratio (N/L ratio), D-dimer, serum lactate dehydrogenase (LDH), and C-reactive protein were higher in the mortality cohort. The ratio of partial pressure of arterial oxygen to fraction of inspired oxygen, platelet count, lymphocytes on differential leukocyte count, and absolute lymphocyte count was lower in the mortality cohort. The parameters and cut-off values used for the multivariate logistic regression model included CCI > 2, SOFA score > 4, D-dimer > 1346 ng/mL, LDH > 514 U/L and N/L ratio > 27. The final model had an area under the curve of 0.876 (95% CI: 0.812 to 0.925), p < 0.001 with an accuracy of 78%. All five parameters were found to be independently associated with mortality.  Conclusions CCI, SOFA score, D-dimer, LDH, and N/L ratio are independently associated with mortality. A model incorporating the combination of these clinical and laboratory parameters at admission can predict COVID-19 ICU mortality with good accuracy.

A comparison of a ketogenic diet with a LowGI/nutrigenetic diet over 6 months for weight loss and 18-month follow-up.

BACKGROUND: Obesity and its related metabolic disturbances represent a huge health burden on society. Many different weight loss interventions have been trialled with mixed efficacy, as demonstrated by the large number of individuals who regain weight upon completion of such interventions. There is evidence that the provision of genetic information may enhance long-term weight loss, either by increasing dietary adherence or through underlying biological mechanisms. METHODS: The investigators followed 114 overweight and obese subjects from a weight loss clinic in a 2-stage process. 1) A 24-week dietary intervention. The subjects self-selected whether to follow a standardized ketogenic diet (n = 53), or a personalised low-glycemic index (GI) nutrigenetic diet utilising information from 28 single nucleotide polymorphisms (n = 61). 2) After the 24-week diet period, the subjects were monitored for an additional 18 months using standard guidelines for the Keto group vs standard guidelines modified by nutrigenetic advice for the low-Glycaemic Index nutrigenetic diet (lowGI/NG) group. RESULTS: After 24 weeks, the keto group lost more weight: - 26.2 ± 3.1 kg vs - 23.5 ± 6.4 kg (p = 0.0061). However, at 18-month follow up, the subjects in the low-GI nutrigenetic diet had lost significantly more weight (- 27.5 ± 8.9 kg) than those in the ketogenic diet who had regained some weight (- 19.4 ± 5.0 kg) (p < 0.0001). Additionally, after the 24-week diet and 18-month follow up the low-GI nutrigenetic diet group had significantly greater (p < 0.0001) improvements in total cholesterol (ketogenic - 35.4 ± 32.2 mg/dl; low-GI nutrigenetic - 52.5 ± 24.3 mg/dl), HDL cholesterol (ketogenic + 4.7 ± 4.5 mg/dl; low-GI nutrigenetic + 11.9 ± 4.1 mg/dl), and fasting glucose (ketogenic - 13.7 ± 8.4 mg/dl; low-GI nutrigenetic - 24.7 ± 7.4 mg/dl). CONCLUSIONS: These findings demonstrate that the ketogenic group experienced enhanced weight loss during the 24-week dietary intervention. However, at 18-month follow up, the personalised nutrition group (lowGI/NG) lost significantly more weight and experienced significantly greater improvements in measures of cholesterol and blood glucose. This suggests that personalising nutrition has the potential to enhance long-term weight loss and changes in cardiometabolic parameters. TRIAL REGISTRATION: NCT04330209, Registered 01/04/2020, retrospectively registered.

Development and validation of next generation sequencing based 35-gene hereditary cancer panel.

BACKGROUND: Understanding the genetic basis of cancer risk is a major international endeavor. The emergence of next-generation sequencing (NGS) in late 2000's has further accelerated the discovery of many cancer susceptibility genes. The use of targeted NGS-based multigene testing panels to provide comprehensive analysis of cancer susceptible genes has proven to be a viable option, with the accurate and robust detection of a wide range of clinically relevant variants in the targeted genes being crucial. METHODS: We have developed and validated a targeted NGS-based test for hereditary cancer risk assessment using Illumina's NGS platform by analyzing the protein-coding regions of 35 hereditary cancer genes with a bioinformatics pipeline that utilizes standard practices in the field. This 35-gene hereditary cancer panel is designed to identify germline cancer-causing mutations for 8 different cancers: breast, ovarian, prostate, uterine, colorectal, pancreatic, stomach cancers and melanoma. The panel was validated using well-characterized DNA specimens [NIGMS Human Genetic Cell Repository], where DNA had been extracted using blood of individuals whose genetic variants had been previously characterized by the 1000 Genome Project and the Coriell Catalog. RESULTS: The 35-gene hereditary cancer panel shows high sensitivity (99.9%) and specificity (100%) across 4820 variants including single nucleotide variants (SNVs) and small insertions and deletions (indel; up to 25 bp). The reproducibility and repeatability are 99.8 and 100%, respectively. CONCLUSIONS: The use of targeted NGS-based multigene testing panels to provide comprehensive analysis of cancer susceptible genes has been considered a viable option. In the present study, we developed and validated a 35-gene panel for testing 8 common cancers using next-generation sequencing (NGS). The performance of our hereditary cancer panel is assessed across a board range of variants in the 35 genes to support clinical use.

Differential DNA Methylation Patterns in Patients with Epilepsy due to Malformations of Cortical Development: A Pilot Study.

OBJECTIVE: To study the DNA methylation profiles in brain tissue of patients with refractory epilepsy due to malformations of cortical development (MCDs). MATERIALS AND METHODS: Clinical, neuroimaging, and pathology characteristics were defined for 13 patients who underwent resective surgery for epilepsy. Methylation analysis was performed using Illumina® 450k Methylation Microarray. Data analysis was completed, and pathway identification was done using the R/Bioconductor package. RESULTS: Genes associated with Ephrin-Reelin pathway, potassium channels, and glutathione metabolism were differentially methylated in the MCD group when compared with patients who had no evidence of MCD. CONCLUSIONS: Our preliminary data reveal that epigenetic pathways may have a role in the pathobiogenesis of MCDs.

CYP2D6 allele frequencies, copy number variants, and tandems in the population of Hong Kong.

BACKGROUND: CYP2D6 plays a crucial role in drug metabolism of several drugs. It is known to be highly polymorphic with enzymatic activity ranging from poor to ultrarapid metabolic rates. While the frequencies of CYP2D6 alleles are generally known in different Asian populations, data on frequencies of the copy number variations (CNV) and tandems in CYP2D6 in which they occur are less well studied in these populations. METHODS: A cohort of 800 consecutive, unrelated individuals were referred to Prenetics Limited (Prenetics) iGenes test by physicians in Hong Kong as part of their care with informed consent. These clinical samples were deidentified prior to further analysis. Genotyping and copy number determination of CYP2D6 were performed using target specific TaqMan® SNP genotyping and copy number assays. The phenotypes of CYP2D6 were predicted based on its genotypes and is dependent on the biallelic expression of alleles. RESULTS: Among the Asian group (n = 735, 92%), the observed frequency of CYP2D6*36-*10 tandems was 34.1%. We also identified duplication of CYP2D6 alleles in 86 (11.7%) individuals of the study cohort. The frequency of all CYP2D6 duplicated alleles was 154 (10.5%) while only 28 (1.9%) of the duplications were of functional alleles (ie CYP2D6*1 and CYP2D6*2). CONCLUSION: The present study provides a comprehensive analysis on the occurrences of CNV and tandems of the CYP2D6 gene in the Hong Kong population. The results contribute to the overall knowledge of pharmacogenomics and may accelerate the implementation of precision medicine in Asia.

Can Functional Polymorphisms in VEGF and MMP Predict Intraventricular Hemorrhage in Extremely Preterm Newborns?

BACKGROUND: The pathophysiology of intraventricular hemorrhage (IVH) is multifactorial. This study attempts to identify genetic and clinical factors contributing to IVH in newborns with a focus on those born ≤28 weeks of gestation. METHODS: This was a prospective study of 382 consecutive newborns admitted to the neonatal intensive care unit. DNA purification was conducted using standard methods. TaqMan SNP assays were conducted for functional polymorphisms in VEGF (RS699947, RS2010963, RS3025039, and RS1570360) and MMP2 (RS243685 and RS2285053) genes. An RFLP assay was done for a polymorphism in MMP9 (RS3918242). RESULTS: The GG genotype in VEGF RS1570360 (p = 0.013) and the CC genotype in VEGF RS699947 (p = 0.036) were associated with a lower incidence of IVH amongst newborns ≤28 weeks of gestation. Chorioamnionitis, Caucasian race, and patent ductus arteriosus were associated with a higher incidence of IVH. A binary logistic regression analysis of clinical and SNP data that was significant from bivariate analysis demonstrated that VEGF RS1570360 was significantly associated with IVH (p = 0.017). CONCLUSION: This study demonstrated that the GA/AA genotype in VEGF RS1570360 and the AA/AC genotype in VEGF RS699947 were associated with higher incidence rates of IVH in newborns ≤28 weeks of gestation. A future study is warranted to comprehensively examine VEGF polymorphisms in association with IVH.

Relationship between genotype and arcuate fasciculus morphology in six young children with global developmental delay: Preliminary DTI stuy.

PURPOSE: To investigate whether different genetic mutations observed in children with global developmental delay (GD) are associated with unique patterns of the arcuate fasciculus dysmorphology. MATERIALS AND METHODS: Six children with GD (age: 36.8 ± 14.1 months, 5 boys) having mutations in MID1, CDK4, SFRP1, EN2, RXRG-GLRB, or MECP2, and five children with typical development (TD, age: 38.5 ± 20.5 months, 4 boys) underwent a 3 Tesla MRI including diffusion weighted imaging (DWI). Five language pathway segments in the left hemisphere, "C1 : Broca's to Wernicke's area," "C2 : Broca's to premotor area," "C3 : premotor to Wernicke's area," "C4 : Wernicke's to inferior parietal area," and "C5 : premotor to inferior parietal area" were objectively identified using the DWI "maximum a posteriori probability" classifier. RESULTS: Affinity propagation clustering analysis found that three arcuate pathway segments, C1,2,4 , of MID1, CDK4, EN2, and MECP2 had a similar pattern of volume ratio while those of SFRP1 and RXRG-GLRB had a heterogeneous pattern of volume ratio (net similarity = -0.01). Using receiver operating characteristic curve analysis, the fiber ratios of C1,2,4 showed a high probability to discriminate between GD and TD, yielding an accuracy of 0.91, 0.91, 1.00, respectively. The fiber volumes of C1 and C4 showed a strong correlation with expressive language (R2 = 0.6019; P-value = 0.033) and receptive language (R2 = 0.6379; P-value = 0.028), respectively. CONCLUSION: The findings of the present study provide preliminary evidence to suggest that different segments of the arcuate fasciculus are formed under the regulation of different genes which, when mutated, may result in developmental delay. J. Magn. Reson. Imaging 2016;44:1504-1512.

Recurrent cerebral abscess secondary to a persistent left superior vena cava.

Cerebral abscess is a serious neurological condition that is often of unclear etiology. Management is usually medical therapy with or without direct drainage, and when patients have recurrent episodes a structural abnormality should be considered. Persistent left superior vena cava is an uncommon condition in the absence of other forms of congenital heart disease. This venous connection most often enters the right-sided atrium through the coronary sinus but occasionally can connect directly to the left atrium near the wall between the orifice of the left pulmonary veins and left atrial appendage. This later congenital connection results in systemic venous return entering the left atrium directly. Thus allowing unfiltered, lower saturation blood entering the systemic system. This then places the patient at risk for systemic hypoxemia, paradoxical embolic events, and cerebral abscess. In our case report with recurrent cerebral abscess and a persistent left superior vena cava, we demonstrate when to consider this diagnosis, how to make the diagnosis, and a nonsurgical approach to repair the veno-atrial shunt.

Exome sequencing and diffusion tensor imaging in developmental disabilities.

BACKGROUND: We had previously shown that arcuate fasciculus is poorly developed in patients with intellectual and developmental disabilities (IDD) using diffusion tensor imaging (DTI). In the present study, we used exome sequencing to identify the candidate variants in IDD patients with and without DTI abnormalities. METHODS: Eighteen children with IDD (age: 67 ± 36 mo, 9 females) were included in the present study. The DTI was used to determine the integrity of arcuate fasciculus. The next-generation sequencing was performed on the Solid 4 platform. A novel, analytical strategy was developed to identify a set of candidate genes of interest. We then searched for novel, nonsynonymous variants in the patients within this subset of genes and in known IDD genes. RESULTS: Seven novel, nonsynonymous (all of them were heterozygous, missense) variants belonged to ultraconserved genes that are known to cause abnormal brain morphology in mutant mice. Similarly, three novel, nonsynonymous (all of them were heterozygous, missense) variants belonged to known IDD genes. Two patients with underdeveloped arcuate fasciculus had novel, nonsynonymous variants in genes (MID1 and EN2) regulating axon guidance pathway. CONCLUSION: Exome sequencing identified several new genetic causes of IDD.

SCN2A mutation is associated with infantile spasms and bitemporal glucose hypometabolism.

BACKGROUND: Genetic mutations play a crucial role in the etiology of cryptogenic infantile spasms, but the cause is still unknown in a significant proportion of patients. Whole exome sequencing technology shows great promise in identifying genetic causes of infantile spasms. METHODS: In this study whole exome sequencing was performed with 2-deoxy-2-((18)F)fluoro-d-glucose positron emission tomography scan of an infant boy with infantile spasms. Exome sequencing was also performed in the parents to identify any de novo mutations. RESULTS: The positron emission tomography scan showed a pattern of bilateral symmetric temporal lobe glucose hypometabolism. A total of 8171 nonsynonymous variants were identified in the child. Despite the large number of nonsynonymous variants, there was only a single de novo missense mutation in SCN2A in the child (NCBI hg19 assembly, position: Chr2:166234116, K1422E). Subsequent Sanger sequencing confirmed the de novo status of this variant. This mutation has never been reported in 6500 individuals of the exome variant server database. Similarly, this variant is not reported in the Online Mendelian Inheritance in Man Database or the Human Gene Mutation Database. It has previously been shown that SCN2A mutations are associated with hippocampal hyperexcitability. Therefore, this study indicates that infantile spasms and bitemporal hypometabolism in this patient might have been caused by hippocampal hyperexcitability due to SCN2A mutation. CONCLUSIONS: The simultaneous presence of an SCN2A mutation and bitemporal hypometabolism in this patient with infantile spasms suggests a plausible hippocampal origin. However, additional mechanistic and clinical studies are required to validate this link.

Nonstructural protein 2 (nsP2) of Chikungunya virus (CHIKV) enhances protective immunity mediated by a CHIKV envelope protein expressing DNA Vaccine.

Chikungunya virus (CHIKV) is an important emerging mosquito-borne alphavirus, indigenous to tropical Africa and Asia. It can cause epidemic fever and acute illness characterized by fever and arthralgias. The epidemic cycle of this infection is similar to dengue and urban yellow fever viral infections. The generation of an efficient vaccine against CHIKV is necessary to prevent and/or control the disease manifestations of the infection. In this report, we studied immune response against a CHIKV-envelope DNA vaccine (pEnv) and the role of the CHIKV nonstructural gene 2 (nsP2) as an adjuvant for the induction of protective immune responses in a relevant mouse challenge model. When injected with the CHIKV pEnv alone, 70% of the immunized mice survived CHIKV challenge, whereas when co-injected with pEnv+pnsP2, 90% of the mice survived viral challenge. Mice also exhibited a delayed onset signs of illness, and a marked decrease in morbidity, suggesting a nsP2 mediated adjuvant effect. Co-injection of the pnsP2 adjuvant with pEnv also qualitatively and quantitatively increased antigen specific neutralizing antibody responses compared to vaccination with pEnv alone. In sum, these novel data imply that the addition of nsP2 to the pEnv vaccine enhances anti-CHIKV-Env immune responses and maybe useful to include in future CHIKV clinical vaccination strategies.

Infantile spasms are associated with abnormal copy number variations.

The authors tested the hypothesis that de novo copy number variations (CNVs) implicated in known genomic disorders ("pathogenic CNVs") are significant predisposing factors of infantile spasms. The authors performed a genome-wide analysis of single-nucleotide polymorphism genotyping microarray data to identify the role of de novo/known pathogenic large CNVs in 13 trios of children affected by infantile spasms. A rare, large (4.8 Mb) de novo duplication was detected in the 15q11-13 region of 1 patient. In addition, 3 known pathogenic CNVs (present in the patient as well as 1 of the parents) were detected in total. In 1 patient, a known pathogenic deletion was detected in the region of 2q32.3. Similarly, in 1 other patient, 2 known pathogenic deletions in the regions of 16p11.2 and Xp22.13 (containing CDKL5) were detected. These findings suggest that some specific pathogenic CNVs predispose to infantile spasms and may be associated with different phenotypes.

Increased L-[1-11 C] leucine uptake in the leptomeningeal angioma of sturge-weber syndrome: a PET study.

BACKGROUND AND PURPOSE: We used L-[1-(11) C]leucine (LEU) positron emission tomography (PET) to measure amino acid uptake in children with Sturge-Weber syndrome (SWS), and to relate amino acid uptake measures with glucose metabolism. METHODS: LEU and 2-deoxy-2[(18) F]fluoro-D-glucose (FDG) PET were performed in 7 children (age: 5 months-13 years) with unilateral SWS. Asymmetries of LEU uptake in the posterior brain region, underlying the angioma and in frontal cortex, were measured and correlated with glucose hypometabolism. Kinetic analysis of LEU uptake was performed in 4 patients. RESULTS: Increased LEU standard uptake value (SUV, mean: 15.1%) was found in the angioma region in 6 patients, and smaller increases in LEU SUV (11.5%) were seen in frontal cortex in 4 of the 6 patients, despite normal glucose metabolism in frontal regions. High LEU SUV was due to both increased tracer transport (3/4 patients) and high protein synthesis rates (2/4). FDG SUV asymmetries in the angioma region were inversely related to LEU SUV asymmetries (r=-.83, P= .042). CONCLUSIONS: Increased amino acid uptake in the angioma region and also in less affected frontal regions may provide a marker of pathological mechanisms contributing to chronic brain damage in children with SWS.

Relationship between aberrant brain connectivity and clinical features in Angelman Syndrome: a new method using tract based spatial statistics of DTI color-coded orientation maps.

AIM: In order to relate brain structural abnormalities to clinical features of Angelman Syndrome (AS), we determined the locations of abnormal regional white matter architecture in AS children using a sensitive and objective whole brain approach to analyze diffusion tensor imaging (DTI) color-coded orientation maps. METHODS: Using tract based spatial statistics (TBSS) of DTI color-coded orientation maps, the fraction of fibers oriented in the anteroposterior (AP), mediolateral (ML) and superioinferior (SI) directions were determined in whole brain white matter of 7 children with AS (mean age: 70±25.78 months, 5 males) and 7 children with typical development (TD, mean age: 79.8±17.25 months, 4 males). TBSS of FA map was also performed for comparison. RESULTS: Children with AS had a significantly lower AP component than the TD group in 9 clusters (3 bilateral and 3 unilateral). Bilateral clusters were located in inferior fronto-occipital fasciculus, anterior thalamic radiation and arcuate fasciculus regions. Unilateral clusters involved left brainstem, left cingulum and right uncinate regions. Similarly, children with AS had significantly lower ML component than the TD group in 4 clusters (2 in corpus callosum and 2 unilateral clusters). Unilateral clusters were located in the left cingulum and left anterior thalamic radiation regions. SI component was lower in children with AS in two clusters compared to TD (corticospinal tract and corpus callosum). FA map clusters mostly corresponded with component clusters. INTERPRETATION: Children with AS have a global impairment of white matter integrity including AP, ML and SI components in whole brain suggesting a potential underlying error with axon guidance mechanisms during brain development possibly due to loss of UBE3A gene expression. Some of this aberrant connectivity can be related to the clinical features of AS.

Sensitive diffusion tensor imaging quantification method to identify language pathway abnormalities in children with developmental delay.

OBJECTIVE: To investigate whether abnormal regional white matter architecture in the perisylvian region could be used as an easy and sensitive quantitative method to demonstrate language pathway abnormalities in children with developmental delay (DD). STUDY DESIGN: We performed diffusion tensor imaging in 15 DD subjects (age, 61.1 ± 20.9 months) and 15 age-matched typically developing (TD) children (age, 68.4 ± 19.2 months). With diffusion tensor imaging color-coded orientation maps, we quantified the fraction of fibers in the perisylvian region that are oriented in anteroposterior (AP) and mediolateral (ML) directions, and their ratio (AP/ML) was calculated. RESULTS: The AP/ML ratio was more sensitive than tractography in characterizing perisylvian regional abnormalities in DD children. The AP/ML ratio of the left perisylvian region was significantly lower in DD children compared with TD children (P = .03). The ML component of bilateral perisylvian regions was significantly higher in DD children compared with TD children (P = .01 [left] and P = .004 [right]). No significant difference was found in the AP component in the two groups. A significant negative correlation of the left ML component with Vineland communication skills was observed (r = -0.657, P = .011). CONCLUSIONS: The AP/ML ratio appears to be a sensitive indicator of regional white matter architectural abnormalities in the perisylvian region of DD children.

Long-term outcome in children with intractable epilepsy showing bilateral diffuse cortical glucose hypometabolism pattern on positron emission tomography.

The objective of this study is to determine the long-term outcome of children with intractable epilepsy who have diffuse cortical hypometabolism on 2-deoxy-2-((18)F)fluoro-D-glucose positron emission tomography (FDG-PET) scans. Seventeen children with intractable epilepsy showing bilateral, diffuse cortical hypometabolism on FDG-PET were followed up through telephone interview from 1 year 4 months to 11 years 4 months (mean: 5 years 7 months ± 2 years 1 month) after their PET scans. One child succumbed to Sanfilippo disease at age 20 years. Only 2 children were seizure free. Fifty percent had walking difficulties, 56.25% were not toilet trained, all had speech difficulties, 43.75% had behavioral problems, 37.5% had poor eye contact, 75% had socialization difficulties, and 87.5% attended special schools. Three children were found to have genetic causes, including a 4-MB deletion of the mitochondrial genome, MECP2 duplication, and Lafora disease. In conclusion, the long-term outcome in this patient population is poor, and they tend to suffer from genetic/neurodegenerative diseases.

Role of proinflammatory cytokines and chemokines in chronic arthropathy in CHIKV infection.

Chikungunya virus (CHIKV) has caused large outbreaks worldwide in recent years. Acute-phase CHIKV infection has been reported to cause mild to severe febrile illness, and in some patients, this may be followed by long-lasting polyarthritis. The mainstay of treatment includes nonsteroidal anti-inflammatory drugs and other disease-modifying agents, the use of which is based on the assumption of an immunological interference mechanism in the pathogenesis. The present study has been designed to generate preliminary evidence to test this hypothesis. The levels of 30 cytokines were estimated in serum samples of acute CHIKV-infected patients, fully-recovered patients, patients with chronic CHIKV arthritis, and controls, using a quantitative multiplex bead ELISA. The levels of the proinflammatory cytokines IL-1 and IL-6 were elevated in acute patients, but IFN-γ/ß and TNF-α levels remained stable. IL-10, which might have an anti-inflammatory effect, was also elevated, indicating a predominantly anti-inflammatory response in the acute phase of infection. Elevation of MCP-1, IL-6, IL-8, MIP-1α, and MIP-1ß was most prominent in the chronic phase. These cytokines and chemokines have been shown to play important roles in other arthritides, including epidemic polyarthritis (EPA) caused by Ross River virus (RRV) and rheumatoid arthritis (RA).The immunopathogenesis of chronic CHIKV arthritis might have similarities to these arthritides. The novel intervention strategies being developed for EPA and RA, such as IL-6 and IL-8 signaling blockade, may also be considered for chronic CHIKV arthritis.