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Objective: To determine to what extent the clinical response to methylphenidate (MPH) is affected by psychiatric comorbidities in children diagnosed with attention-deficit hyperactivity disorder (ADHD).Methods: Children (n = 267) aged 6 to 12 years diagnosed with ADHD participated in a double-blind, placebo-controlled, 2-week medication trial of MPH. Children were assessed using parent and teacher ratings and laboratory measures. Clinical response to MPH was determined by integrating all obtained measures.Results: Meeting criteria for conduct disorder (CD) was 27.7% of children, 40.8% for oppositional defiant (ODD), 47.2% for anxiety, and 7.9% for depressive disorders. The presence of CD or ODD was associated with good response to MPH. In contrast, children diagnosed with only comorbid anxiety were more likely to receive poor response rating independent of age, sex, or socioeconomic status. Low family income was found to be predictive of good response to MPH.Conclusions: The response to MPH in children with ADHD may be dependent on the type of comorbid disorder present.Clinical Trial Registration Number: NCT00483106. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether children with attention-deficit hyperactivity disorder (ADHD) and learning disabilities respond differently to methylphenidate (MPH) compared with children with ADHD only. METHODS: We conducted a prospective, double-blind, placebo-controlled, randomized, 2-week crossover trial of MPH, during which response to MPH was assessed. Learning ability was appraised using the Wide Range Achievement Test, Revised (WRAT-R), for English-speaking students and the Test de rendement pour francophones for French-speaking students. The study was conducted at the Douglas Hospital, a McGill University-affiliated teaching hospital in Montréal. Ninety-five children, aged 6-12 years, who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), criteria for ADHD participated in the study, which ran from 2001 to 2004. The outcome measure used was the Consensus Clinical Response, an indicator of the degree of clinical improvement shown when taking MPH. RESULTS: The proportion of children with learning disabilities who responded to MPH (55%) was significantly smaller (chi(2)1 = 4.5, p = 0.034) than the proportion of children without learning disabilities who responded adequately to MPH (75%). This difference was mainly because of children with mathematics disability being particularly unresponsive to MPH (chi(2)1 = 4.5, p = 0.034). Children with reading disability did not show this pattern of poor response (chi(2)1 = 1.0, p = 0.33). CONCLUSION: Children with ADHD and comorbid learning disability tended to respond more poorly to MPH. In particular, children with disability in mathematics responded less to MPH than those without disability in mathematics. Additional therapy may be indicated for this group of patients. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Genetic and nonshared environmental factors (experienced by 1 family member to the exclusion of the others) have been strongly implicated in the causes of attention-deficit hyperactivity disorder (ADHD). Pregnancy, labour/delivery and neonatal complications (PLDNC) have often been associated with ADHD; however, no investigations aimed at delineating the shared or nonshared nature of these factors have been reported. We aimed to identify those elements of the PLDNC that are more likely to be of a nonshared nature. METHODS: We used an intrafamily study design, comparing the history of PLDNC between children diagnosed with ADHD, according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), and their unaffected siblings. Children with ADHD were recruited from the outpatient, day-treatment program of the Child Psychiatry Department, Douglas Hospital, Montreal. The unaffected sibling closest in age to the child with ADHD was used as a control. The history of PLDNC was assessed using the Kinney Medical and Gynecological Questionnaire and the McNeil-Sjostrom Scale for both children with ADHD and their siblings. Seventy children with ADHD along with 50 of their unaffected siblings agreed to participate in the study. Child Behavior Checklist (CBCL), Continuous Performance Test (CPT) and Restricted Academic Situation Scale (RASS) scores were also used as measures of ADHD symptoms in children with ADHD. RESULTS: The children with ADHD had significantly higher rates of neonatal complications compared with their unaffected siblings (F4,196 = 3.67, p < 0.006). Furthermore, neonatal complications in the children with ADHD were associated with worse CBCL total and externalizing scores and with poorer performance on the CPT. CONCLUSIONS: These results suggest that neonatal complications are probably a nonshared environmental risk factor that may be pathogenic in children with ADHD. [ABSTRACT FROM AUTHOR]

We used a probability-based sampling scheme to survey the forested lands of 14 states in five regions in the US (California, Colorado, and parts of the Southeast, Mid-Atlantic, and Northeast) from 1990 to 1993. Using a nationally consistent plot design, we evaluated the local diversity of trees over 2.5 cm in diameter at breast height (dbh) at 780 1/15-ha plots nationwide by measuring the plot-level species richness (R). Visually evident anthropogenic disturbances (e.g. artificial regeneration, logging, grazing-by livestock, and prescribed burning), if any, were recorded on each plot. We classified plots with visually evident anthropogenic disturbance as 'disturbed' and the remaining plots as 'undisturbed'. In each of the five geopolitical regions,we quantified the difference in mean R between disturbed and undisturbed plots. With the exception of Colorado (5%), between 34 and 55% of forested lands in each region had recorded anthropogenic disturbances. Mean R was significantly higher for undisturbed areas than for disturbed areas in the Northeast and Southeast, with the largest differences occurring in the Southeast. Mean R was greater in undisturbed areas than in disturbed areas in most forest cover types for all regions. These differences were greatest in the loblolly pine (Pinus taeda), oak (Quercus spp.)-hickory (Carya spp.), and oak-pine forest typesof the Southeast. The only group for which mean R was significantly greater in disturbed areas was the mixed western hardwoods in California. As expected from previous studies, significant differences between regions in mean R were observed, in both disturbed and undisturbedareas. This study bridges an important gap between site-specific forest studies and remote-sensing studies of the forests of a region. Wediscuss (1) why combining site-specific studies is not appropriate in most cases for rigorous testing at the regional level and (2) how data for some important site-specific variables are not available frommost [ABSTRACT FROM AUTHOR]

Using a pre/posttest design, with a nine-month follow-up, a new, "modified" social skills training program, which incorporates the concept of self/other perspective-taking, was evaluated and compared to a traditional social skills program in a sample of 36 children. Students in the modified group showed more short- and long-term improvement in behavior than did those in the traditional social skills training group. Implications for practice and research are discussed. [ABSTRACT FROM AUTHOR]

Background: Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent childhood disorder. Maternal smoking during pregnancy is a replicated environmental risk factor for this disorder. It is also a robust modifier of gene methylation during the prenatal developmental period. In this study, we sought to identify loci differentially methylated by maternal smoking during pregnancy and relate their methylation levels to various behavioural and physical outcomes relevant to ADHD., Methods: We extracted DNA from blood samples from children diagnosed with ADHD and deeply phenotyped. Genome-wide DNA methylation was assessed using Infinium MethylationEPIC BeadChip. Maternal smoking during pregnancy was self-declared and assessed retrospectively., Results: Our sample included 231 children with ADHD. Statistically significant differences in DNA methylation between children exposed or not to maternal smoking during pregnancy were detected in 3457 CpGs. We kept 30 CpGs with at least 5% of methylation difference between the 2 groups for further analysis. Six genes were associated with varied phenotypes of clinical relevance to ADHD. The levels of DNA methylation in RUNX1 were positively correlated with the CBCL scores, and DNA methylation in MYO1G correlated positively with the score at the Conners rating scale. Methylation level in a CpG located in GFI1 correlated with birthweight, a risk factor for ADHD. Differentially methylated regions were also identified and confirmed the association of RUNX1 methylation levels with the CBCL score., Limitations: The study has several limitations, including the retrospective recall with self-report of maternal smoking during pregnancy as well as the grouping of individuals of varying age and developmental stage and of both males and females. In addition, the correlation design prevents the building of causation models., Conclusion: This study provides evidence for the association between the level of methylation at specific loci and quantitative dimensions highly relevant for ADHD as well as birth weight, a measure that has already been associated with increased risk for ADHD. Our results provide further support to public health educational initiatives to stop maternal smoking during pregnancy., Competing Interests: Competing interests: B. Chaumette has received research funding from the Fondation Bettencourt Schueller (180 000€/4 yr) and speaking fees from Janssen-Cilag, Lundbeck and Eisai, outside the submitted work. He has no direct employment in profit organizations nor consultancies. N. Grizenko reports receiving research funding from the Canadian Institutes of Health Research (CIHR) and is a member of the advisory board for Purdue and Shire. A. Labbe is an associate editor of JPN. She was not involved in the review or decision to accept this manuscript for publication. R. Joober reports having received research funding from CIHR. He is on the advisory boards and speakers’ bureaus of Pfizer, Janssen Ortho, BMS, Sunovion, Otsuka, Lundbeck, Perdue and Myelin. He has received grant funding from them and from AstraZeneca and HLS. He has received honoraria from Janssen Canada, Shire, Lundbeck, Otsuka, Pfizer and from Perdue for CME presentations and royalties for Henry Stewart talks. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

The neural orphan G protein coupled receptor GPR88 is predominant in the striatum and cortex of both rodents and humans, and considered a potential target for brain disorders. Previous studies have shown multiple behavioral phenotypes in Gpr88 knockout mice, and human genetic studies have reported association with psychosis. Here we tested the possibility that GPR88 contributes to Attention Deficit Hyperactivity Disorder (ADHD). In the mouse, we tested Gpr88 knockout mice in three behavioral paradigms, best translatable between rodents and humans, and found higher motor impulsivity and reduced attention together with the reported hyperactivity. Atomoxetine, a typical ADHD drug, reduced impulsivity in mutant mice. Conditional Gpr88 knockout mice in either D1R-type or D2R-type medium spiny neurons revealed distinct implications of the two receptor populations in waiting and stopping impulsivity. Thus, animal data demonstrate that deficient GPR88 activity causally promotes ADHD-like behaviors, and identify circuit mechanisms underlying GPR88-regulated impulsivity. In humans, we performed a family-based genetic study including 567 nuclear families with DSM-IV diagnosis of ADHD. There was a minor association for SNP rs2036212 with diagnosis, treatment response and cognition. A stronger association was found for SNP rs2809817 upon patient stratification, suggesting that the T allele is a risk factor when prenatal stress is involved. Human data therefore identify GPR88 variants associated with the disease, and highlight a potential role of life trajectories to modulate GPR88 function. Overall, animal and human data concur to suggest that GPR88 signaling should be considered a key factor for diagnostic and treatment of ADHD., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: The aetiology of ADHD is complex, with genetic and environmental factors both implicated in the disorder. The most recent ADHD genome-wide association study identified 12 loci that showed significant association with the disorder. However, as highlighted by the authors, these loci "only capture a tiny fraction" of the risk for ADHD. It has been suggested that it may be important to disentangle: (1) the clinical complexity of the disorder, and (2) the complex interaction between genetic and environmental factors, in order to better dissect the aetiology of the disorder., Method: We have conducted a clinically-relevant Pharmaco-Behavioural Genetic study in a large group of children with ADHD (~850 families) over the last 15 years. The study includes detailed evaluation of quantitative behavioural and neuropsychological phenotypes, as well as short-term response of these phenotypes to treatment with a fixed dose of methylphenidate (0.5mg/kg in a b.i.d. dose). Specific genetic markers and environmental factors were examined for their association with these dimensions., Results: Here we present results that highlight the importance of examining genetic association with quantitative traits, including those constructs having relevance to Research Domain Criteria (RDoC). Further, we demonstrate that by conducting association analysis in groups of children stratified based on exposure to key environmental exposure (maternal smoking or stress during pregnancy), we are able to increase the sensitivity for finding genes involved in the disorder., Conclusion: These results suggest that deep phenotyping and heterogeneity reduction may be imperative in order to uncover the "missing heritability" of the disorder., (Copyright © 2020 Canadian Academy of Child and Adolescent Psychiatry.)

The high levels of comorbidity between oppositional/conduct problems and hyperactivity/attention problems underscore the need for assessing how vulnerability for peer victimization is shaped by overlap among these behavior problems. Children (mean age 8.39, SD = 0.93) participating in a longitudinal study of the development of conduct problems (N = 744; 348 girls) in Quebec, Canada, were evaluated by their teachers regarding experiences of peer verbal and physical victimization every year for 6 years. Parent and teacher ratings of clinically significant oppositional/conduct problems, and hyperactivity/attention problems, as well as cormorbid opposition defiant/conduct problems and hyperactivity/attention problems were regressed onto trajectories of verbal and physical victimization. While behavior problems (both alone and together) were associated with higher levels of verbal and physical victimization, some variation was observed across rater and type of victimization. Ultimately, these findings suggest the importance of adapting programming for reducing victimization to children with oppositional and conduct problems.

Several epidemiological and genetic studies have provided evidence of an overlap between neurodevelopmental disorders. However, the details of the etiological pathways remain to be elucidated. In this study, we garnered the findings of previous GWAS, conducted with schizophrenia and bipolar disorder. We conducted an exploratory study to examine the association between these SNPs and quantitative clinical/ behavioural/ cognitive/ structural brain parameters, as well as response to treatment with a fixed dose of methylphenidate, in a relatively large sample of children with ADHD. Family-based association tests were conducted with nine tag SNPs with 602 nuclear families. In addition, structural magnetic resonance imaging (sMRI) was conducted in a subset of children with ADHD (n = 76). Of the 9 tag SNPs examined, rs1602565 showed a significant association with ADHD, several dimensional measures and response to treatment. An association was also observed between rs1006737 (CACNA1C) and performance IQ. In addition, significant reductions in cortical thickness measurements were observed with the risk allele in rs1006737. These results provide preliminary evidence for putative shared genetic vulnerability between childhood ADHD and other neurodevelopmental disorders., (Copyright © 2018. Published by Elsevier B.V.)

Objective: The goal of this study was to examine the relationship between comorbid disorders and executive function (EF) in children diagnosed with Attention Deficit/Hyperactivity Disorder (ADHD)., Methods: Three hundred and fifty-five, 6-12 year old children clinically diagnosed with ADHD were included in the study. Comorbid anxiety disorders, Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD) were examined. The EF domains were assessed using the Conners' Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), Tower of London (ToL), Finger Windows (FW) and Self Ordered Pointing Test (SOPT)., Results: The findings indicate that children with comorbid anxiety disorders performed worse in domains measured by CPT and prior to controlling for age and sex, by FW. However, once sex was controlled for the results for FW were no longer significant. Children with CD obtained lower scores on WCST. Furthermore, a significant sex by CD interaction was observed., Conclusion: These results indicate that comorbid disorders should be carefully examined as they play a significant role in EF performance and subsequently in day-to-day functioning of children with ADHD.

Vitamin A has biological functions as diverse as sensing light for vision, regulating stem cell differentiation, maintaining epithelial integrity, promoting immune competency, regulating learning and memory, and acting as a key developmental morphogen. Vitamin A derivatives have also been used in treating human diseases. If vitamin A is considered a drug that everyone needs to take to survive, evolution has come up with a natural drug delivery system that combines sustained release with precise and controlled delivery to the cells or tissues that depend on it. This "drug delivery system" is mediated by plasma retinol binding protein (RBP), the principle and specific vitamin A carrier protein in the blood, and STRA6, the cell-surface receptor for RBP that mediates cellular vitamin A uptake. The mechanism by which the RBP receptor absorbs vitamin A from the blood is distinct from other known cellular uptake mechanisms. This review summarizes recent progress in elucidating the fundamental molecular mechanism mediated by the RBP receptor and multiple newly discovered catalytic activities of this receptor, and compares this transport system with retinoid transport independent of RBP/STRA6. How to target this new type of transmembrane receptor using small molecules in treating diseases is also discussed.

Pigment Epithelium Derived Factor (PEDF) is a secreted factor that has broad biological activities. It was first identified as a neurotrophic factor and later as the most potent natural antiangiogenic factor, a stem cell niche factor, and an inhibitor of cancer cell growth. Numerous animal models demonstrated its therapeutic value in treating blinding diseases and diverse cancer types. A long-standing challenge is to reveal how PEDF acts on its target cells and the identities of the cell-surface receptors responsible for its activities. Here we report the identification of transmembrane proteins PLXDC1 and PLXDC2 as cell-surface receptors for PEDF. Using distinct cellular models, we demonstrate their cell type-specific receptor activities through loss of function and gain of function studies. Our experiments suggest that PEDF receptors form homooligomers under basal conditions, and PEDF dissociates the homooligomer to activate the receptors. Mutations in the intracellular domain can have profound effects on receptor activities.

Vitamin A and its derivatives (retinoids) play diverse and crucial functions from embryogenesis to adulthood and are used as therapeutic agents in human medicine for eye and skin diseases, infections and cancer. Plasma retinol binding protein (RBP) is the principal and specific vitamin A carrier in the blood and binds vitamin A at 1:1 ratio. STRA6 is the high-affinity membrane receptor for RBP and mediates cellular vitamin A uptake. STRA6 null mice have severely depleted vitamin A reserves for vision and consequently have vision loss, even under vitamin A sufficient conditions. STRA6 null humans have a wide range of severe pathological phenotypes in many organs including the eye, brain, heart and lung. Known membrane transport mechanisms involve transmembrane pores that regulate the transport of the substrate (e.g., the gating of ion channels). STRA6 represents a new type of membrane receptor. How this receptor interacts with its transport substrate vitamin A and the functions of its nine transmembrane domains are still completely unknown. These questions are critical to understanding the molecular basis of STRA6's activities and its regulation. We employ acute chemical modification to introduce chemical side chains to STRA6 in a site-specific manner. We found that modifications with specific chemicals at specific positions in or near the transmembrane domains of this receptor can almost completely suppress its vitamin A transport activity. These experiments provide the first evidence for the existence of a transmembrane pore, analogous to the pore of ion channels, for this new type of cell-surface receptor.

Objective: Examine the short-term (acute) effects of methylphenidate (MPH) on math performance in children with attention-deficit hyperactivity disorder (ADHD) and what factors predict improvement in math performance., Method: One hundred ninety-eight children with ADHD participated in a double-blind, placebo-controlled, randomized crossover MPH trial. Math response to MPH was determined through administration of math problems adjusted to their academic level during the Restricted Academic Situation Scale (RASS). Student t tests were conducted to assess change in math performance with psychostimulants. Correlation between change on the RASS and change on the math performance was also examined. Linear regression was performed to determine predictor variables., Results: Children with ADHD improved significantly in their math with MPH (P < 0.001). The degree of improvement on the RASS (which evaluates motor activity and orientation to task) and on math performance on MPH was highly correlated. A child's age at baseline and Wechsler Individual Achievement Test (WIAT)-Numerical Operations standard scores at baseline accounted for 15% of variances for acute math improvement., Conclusions: MPH improves acute math performance in children with ADHD. Younger children with lower math scores (as assessed by the WIAT) improved most on math scores when given psychostimulants., Clinical Trial Registration Number: NCT00483106.

Retinoids are vitamin A derivatives with diverse biological functions. Both natural and artificial retinoids have been used as therapeutic reagents to treat human diseases, but not all retinoid actions are understood mechanistically. Plasma retinol binding protein (RBP) is the principal and specific carrier of vitamin A in the blood. STRA6 is the membrane receptor for RBP that mediates cellular vitamin A uptake. The effects of retinoids or related compounds on the receptor's vitamin A uptake activity and its catalytic activities are not well understood. In this study, we dissected the membrane receptor-mediated vitamin A uptake mechanism using various retinoids. We show that a subset of retinoids strongly stimulates STRA6-mediated vitamin A release from holo-RBP. STRA6 also catalyzes the exchange of retinol in RBP with certain retinoids. The effect of retinoids on STRA6 is highly isomer-specific. This study provides unique insights into the RBP receptor's mechanism and reveals that the vitamin A transport machinery can be a target of retinoid-based drugs.

Brain metastases (BM) are the most frequent intracranial SOL and extremely heterogeneous group of tumours from morphological point of view. Nevertheless, studies devoted to BM up to now paid little attention to the histogenesis of the primary tumour. Lung carcinoma is the most common source of BM; morpologically this is a very heterogeneous group of tumors, and they demostrate different clinical pathway and outcome. The aim of present study was to evaluate clinical and morphological prognostic factors in 126 patients with lung carcinoma metastases to the brain, operated in 2004-2010 at Burdenko Neurosurgical Institute. Statistical analysis demonstrated that age, gender, amount and location of BM, primary operation and even histological tumour type were not significant prognostic factors, meanwhile absence of extracranial metastases and Karnofsky index above 70 were significant factors of the favorable prognosis.

Metastatic tumours of the optic nerve are extremely rare. The review of literature revealed only 12 cases of breast carcinoma metastasis to the optic nerve. All patients survived less then 6 month after surgical treatment. We describe a case of metastatic breast carcinoma to the optic nerve that occurred 8 years after radical mastectomy followed by chemotherapy. The metastasis manifested with progressive decrease in visual acuity in the right eye during 3 month. CT and MRI demostrated enhancing lesion in the muscle cone apex of the right orbit with an extension to the optic canal. The presumable diagnosis was optic nerve sheath meningioma, and surgical resection was performed. The tumour involved the optic nerve and has been resected togeher with the nerve. Histology report confirmed metastatic tumour. Postoperatively, the patient received additional stereotactic radiotherapy. Patient died of tumour dissemination 2,5 years after surgery. Breast carcinoma metastases to the optic nerve usually have unfavorable prognosis both for survival and for visual acuity. Isolated metastatic tumors of the optic nerve remain a diagnostic challenge because of their clinical and radiological similarities to more common primary tumors of the optic nerve.

Unlabelled: The aim of the present study was to evaluate and compare diagnostic/and treatment modalities of primary and metastatic Ewing sarcoma (ES) of the skull base., Material and Methods: We analyzed nine cases of the skull base ES patients operated in Burdenko Neurosurgical Institute from 2003 to 2011. Among them there were five cases of primary ES, the other four were of metastatic origin. Clinical history, neuroimaging and pathology data together with IHC are presented. Treatment options and results are discussed. Seven patients were operated transcranially, in the other two cases endoscopic endonsnasal operations/were performed. Mean follow up was 11-92 months., Results: We did not reveal arW pathological or IHC differences between primary and metastatic tumors. The labeling index Ki-67 was insignificantly higher in the metastatic tumors gro'Vip. In one case the patient developed relapse of the metastatic tumour in the temporal bone; he underwent second surgery and died 7 months after the operation., Conclusion: Despite both metastatic and primary ES of the skull base are of maMignant behavior, the long-term relatively good prognosis can be achieved when combined treatment, including surgery, chemotherapy and radiation is applied.

Vitamin A has diverse biological functions and is essential for human survival. STRA6 is the high-affinity membrane receptor for plasma retinol binding protein (RBP), the principle and specific carrier of vitamin A (retinol) in the blood. It was previously shown that STRA6 couples to lecithin retinol acyltransferase (LRAT) and cellular retinol binding protein I (CRBP-I), but poorly to CRBP-II, for retinol uptake from holo-RBP. STRA6 catalyzes both retinol release from holo-RBP, which is responsible for its retinol uptake activity, and the loading of free retinol into apo-RBP, which can cause retinol efflux. Although STRA6-catalyzed retinol efflux into apo-RBP can theoretically deplete cells of retinoid, it is unclear to what extent this efflux happens and in what context. We show here that STRA6 can couple strongly to both CRBP-I and CRBP-II for retinol efflux to apo-RBP. Strikingly, pure apo-RBP can cause almost complete depletion of retinol taken up by CRBP-I in a STRA6-dependent manner. However, if STRA6 encounters both holo-RBP and apo-RBP (as in blood), holo-RBP blocks STRA6-mediated retinol efflux by competing with apo-RBP's binding to STRA6 and by counteracting retinol efflux with influx. We also found that STRA6 catalyzes efficient retinol exchange between intracellular CRBP-I and extracellular RBP, even in the presence of holo-RBP. STRA6's retinol exchange activity may serve to refresh the intracellular retinoid pool. This exchange is also a previously unknown function of CRBP-I and distinguishes CRBP-I from LRAT.

We present a case of a rare tumor--melanotic schwannoma of trigeminal nerve root and gasserian ganglion. Differential diagnosis between metastatic melanoma and melanotic schwannoma (MS) is associated with serious difficulties and high responsibility. Metastatic melanoma is a high grade tumor while most MS are benign lesions with good outcome. By the date 105 cases of these tumors are described in the world literature, 3 of them originated from trigeminal nerve root and gasserian ganglion. MS predominantly occur in relatively young patients, they are characterized by presence of Carney's complex and psammomatous bodies and absence of primary focus. MS and metastatic melanoma have similar appearance on MRI due to presence of melanin granules. Indirect signs evident for MS include cystic structure and dumbbell-shaped growth. Metastatic melanoma of cranial nerves is more typical in people older than 40, primary focus in the face in the zone of innervation of affected nerve is common. In case of absence of the listed features differential diagnosis is based on immunohistochemical analysis and electron microscopy of tissue samples.

Malignant peripheral nerve sheath tumor (MPNST) is a rare entity with only 18 cases of trigeminal nerve MPNST described by now and only one report of malignant transformation of trigeminal nerve tumor into MPNST published up to date. One more case of malignant transformation of trigeminal nerve (1st division) tumor into MPNST is demonstrated.

During recent decade development of frameless techniques of fixation enabled introduction of stereotactic radiation therapy in metastatic brain lesions and made possible irradiation of large foci involving or proximal to eloquent and critical brain areas. This paper focuses on comparative analysis of effectiveness of hypofractionation (HRST) and radiosurgery (SRS) using CyberKnife system in cerebral metastases. Since November 2009 till June 2011 54 patients with cerebral metastases were treated using CyberKnife system. Age of patients ranged between 25 and 77 years (mean 54 years). 16 patients received radiosurgical treatment (mean total dose was 22.5-35 Gy, number of fractions varied from 2 to 7, mean volume of irradiation was 22.69 cm3) and 8 patients were treated by HRST with RS of selected foci (mean total dose reached 23 and 30 Gy, mean volume of irradiation was 1.02 cm3 and 11.19 cm3, respectively). Indices of overall regression and stabilization of disease for HRST and SRS groups were 81% and 79%, respectively. With mean follow-up period of 12.3 (1-16.1) months median survival for SRS and HRST reached 6.38 (1-15.8) and 6.2 (0.2-16.1) months and median recurrence-free survival was 3.6 (1-13.6) and 5.5 (2-14.2) months, respectively. Obtained results confirmed biological advantages of fractionated stereotactic radiotherapy of large cerebral tumors in comparison with radiosurgery. Prospective studies with rigid criteria of inclusion are required to determine optimal dose/volume/fractionation interrelations in stereotactic radiation treatment of cerebral metastases.

Cells are known to take up molecules through membrane transport mechanisms such as active transport, channels, and facilitated transport. We report here a new membrane transport mechanism that employs neither cellular energy like active transport nor a preexisting electrochemical gradient of the free substrate like channels or facilitated transport. Through this mechanism, cells take up vitamin A bound with high affinity to retinol binding protein (RBP) in the blood. This mechanism is mediated by the RBP receptor STRA6, which defines a new type of cell-surface receptor. STRA6 is essential for the proper functioning of multiple human organs, but the mechanisms that enable and control its cellular vitamin A uptake activity are unknown. We found that STRA6-mediated vitamin A uptake is tightly coupled to specific intracellular retinoid storage proteins, but no single intracellular protein is absolutely required for its transport activity. By developing sensitive real-time monitoring techniques, we found that STRA6 is not only a membrane receptor but also catalyzes vitamin A release from RBP. However, vitamin A released from RBP by STRA6 inhibits further vitamin A release by STRA6 unless specific intracellular retinoid storage proteins relieve this inhibition. This mechanism is responsible for its coupling to intracellular storage proteins. The coupling of uptake to storage provides high specificity in cellular uptake of vitamin A and prevents the excessive accumulation of free vitamin A. We have also identified a robust small-molecule-based technique to specifically stimulate cellular vitamin A uptake. This technique has implications in treating human diseases.

Metastatic skull base tumors are rare and complicated lesions. They involve cranial nerves and craniobasal vascular structures causing multiform clinical presentation. Despite modern neurovisualization techniques, risk of preoperative diagnostic pitfall remains high. Final diagnosis and planning of further treatment are possible only after surgical removal of tumor with subsequent immunohistochemical verification.

Combination of trigeminal neuralgia and tentorial dural arteriovenous malformation is extremely rare. The authors present a case of 72-year-old male patient who suffered from left-side trigeminal neuralgia. MRI revealed numerous tortuous vessels in the left parapontine region. The trigeminal root entry zone was explored via retrosigmoid approach. Tentorial dural arteriovenous malformation localized in proximity to superior petrosal sinus with significant enlargement of leptomeningeal cerebellar vessels (Borden type III) was demonstrated. The fistula was clipped and transsected with immediate restoration of bluish color of cerebellar veins. The trigeminal root entry zone was compressed by the loop of superior cerebellar artery and vascular decompression was performed. After surgery patient became pain-free without any neurological complications. This case clearly demonstrated that trigeminal neuralgia associated with tentorial dural atreriofenous malformation may occur not only due to dilated arterialized cerebellar veins but also can be caused by tortuous loop of superior cerebellar artery.

Physical activity experiences of 12 age-matched boys with and without attention-deficit hyperactivity disorder (ADHD) were explored by converging information from Test of Gross Motor Development-2 assessments and semistructured interviews. The knowledge-based approach and the inhibitory model of executive functions, a combined theoretical lens, enabled the description of similarities and differences in experiences that emerged during interviews. Skill assessments indicated boys with ADHD were not as proficient movers as their peers without ADHD. Thematic analysis revealed that boys with ADHD reported playing with friends, paid little attention to detail, possessed superficial knowledge about movement skills, and expressed many negative feelings about physical activity. Task-specific interventions and a wider range of mixed methods research are recommended for future research studies in ADHD.

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a heterogeneous disorder from both clinical and pathogenic viewpoints. Executive function deficits are considered among the most important pathogenic pathways leading to ADHD and may index part of the heterogeneity in this disorder., Methods: To investigate the relationship between the dopamine transporter gene (SLC6A3) 3'-UTR VNTR genotypes and executive function in children with ADHD, 196 children diagnosed with ADHD were sequentially recruited, genotyped, and tested using a battery of three neuropsychological tests aimed at assessing the different aspects of executive functioning., Results: Taking into account a correction for multiple comparisons, the main finding of this study is a significant genotype effect on performances on the Tower of London (F = 6.902, p = 0.009) and on the Wechsler Intelligence Scale for Children, Third Edition (WISC-III) Freedom From Distractibility Index (F = 7.125, p = 0.008), as well as strong trends on Self Ordered Pointing Task error scores (F = 4,996 p = 0.026) and WISC-III Digit Span performance (F = 6.28, p = 0.023). Children with the 9/10 genotype exhibited, on average, a poorer performance on all four measures compared to children with the 10/10 genotype. No effect of genotype on Wisconsin Card Sorting Test measures of performance was detected., Conclusion: Results are compatible with the view that SLC6A3 genotype may modulate components of executive function performance in children with ADHD.

STRA6 is a multitransmembrane domain protein not homologous to any other proteins with known function. It functions as the high-affinity receptor for plasma retinol binding protein (RBP) and mediates cellular uptake of vitamin A from the vitamin A-RBP complex. Consistent with the diverse roles of vitamin A and the wide tissue expression pattern of STRA6, mutations in STRA6 are associated with severe pathological phenotypes in humans. The structural basis for STRA6's biochemical function is unknown. Although computer programs predict 11 transmembrane domains for STRA6, its topology has never been studied experimentally. Elucidating the transmembrane topology of STRA6 is critical for understanding its structure and function. By inserting an epitope tag into all possible extracellular and intracellular domains of STRA6, we systematically analyzed the accessibility of each tag on the surface of live cells, the accessibility of each tag in permeabilized cells, and the effect of each tag on RBP binding and STRA6-mediated vitamin A uptake from the vitamin A-RBP complex. In addition, we used a new lysine accessibility technique combining cell-surface biotinylation and tandem-affinity purification to study a region of the protein not revealed by the epitope tagging method. These studies not only revealed STRA6's extracellular, transmembrane, and intracellular domains but also implicated extracellular regions of STRA6 in RBP binding.

The authors present the results of microsurgical anterior cervical foraminotomy used in unilateral cervical radiculopathy caused by lateral disc herniation or foraminal stenosis. In 2000 to 2006, anterior cervical foraminotomy was performed at one or two adjacent levels in 44 patients (27 males and 17 females aged 18 to 64 years (mean age 43 years)) with cervical radiculopathy and myelopathy. All the patients underwent pre- and postoperative computed tomography, magnetic resonance imaging, and functional X-ray study. The surgical technique permitted anterior decompression of the affected nerve root from the site of its formation to the vertebral artery, by maintaining the stability and mobility of the involved vertebral segments. The immediate postoperative period was marked by excellent results with regression of radicular syndrome in 84% of the patients and by good results in 16%. A late (6-month-to-6-year) follow-up showed excellent (78%) and good (22%) results without additional surgery. The findings indicate that anterior cervical foraminotomy is an effective technique of nerve root decompression in patients with lateral disc herniation or foraminal stenosis.

Objective: There is considerable evidence that maternal stress is associated with behavioural disturbances in offspring. The objective of this study was to examine whether there is an association between the severity of maternal stress during pregnancy and the severity of symptoms of attention-deficit hyperactivity disorder (ADHD). A second objective was to examine whether there is an association between maternal stress and children's response to methylphenidate (MPH)., Methods: Using the Kinney Medical and Gynecological Questionnaire, we assessed 203 children with ADHD, aged between 6 and 12 years, regarding maternal stress during pregnancy. We assessed symptom severity with the Child Behavior Checklist (CBCL) and Conners' Global Index for Parents (CGI-P) and Teachers (CGI-T). Subjects were recruited from the ADHD clinic and the day-treatment program of the Child Psychiatry Department of the Douglas Hospital, Montréal, Quebec. The quality of their therapeutic response was assessed in a double-blind, placebo-controlled randomized 2-week crossover trial of MPH., Results: The most severe symptoms as assessed by the CBCL were found in the moderate stressor group, (p < 0.002), whereas, according to the CGI-P (emotional liability), the most severe symptoms were found in the severe stressor group (p < 0.029). There was no statistically significant difference between degree of response to MPH and level of maternal stress., Conclusion: Children with ADHD whose mothers were exposed to moderate and severe stress during pregnancy tend to develop more severe symptoms than children with ADHD whose mothers were not exposed to prenatal stress. It is therefore important to minimize stress in pregnant women.

The purpose of this study was to compare the fundamental movement skills of 22 children with attention-deficit hyperactivity disorder (ADHD), from 6 to 12 years of age, to gender- and age-matched peers without ADHD and assess the effects of stimulant medication on the movement skill performance of the children with ADHD. Repeated measures analyses revealed significant skill differences between children with and without ADHD (p