Fonds de Recherche du Québec - Santé

BACKGROUND: A population-based phylogenetic approach was used to characterize human immunodeficiency virus (HIV)-transmission dynamics in Quebec. METHODS: HIV-1 pol sequences included primary HIV infections (PHIs; <6 months after seroconversion) from the Quebec PHI cohort (1998-2005; n=215) and the provincial genotyping program (2001-2005; n=481). Phylogenetic analysis determined sequence interrelationships among unique PHIs (n=593) and infections from untreated (n=135) and treated (n=660) chronically infected (CI) potential transmitter populations (2001-2005). Clinical features, risk factors, and drug resistance for clustered and nonclustered transmission events were ascertained. RESULTS: Viruses from 49.4% (293/593) of PHIs cosegregated into 75 transmission chains with 2-17 transmissions/cluster. Half of the clusters included 2.7+/-0.8 (mean+/-SD) transmissions, whereas the remainder had 8.8+/-3.5 transmissions. Maximum periods for onward transmission in clusters were 15.2+/-9.5 months. Coclustering of untreated and treated CIs with PHIs were infrequent (6.2% and 4.8%, respectively). The ages, viremia, and risk factors were similar for clustered and nonclustered transmission events. Low prevalence of drug resistance in PHI supported amplified transmissions at early stages. CONCLUSIONS: Early infection accounts for approximately half of onward transmissions in this urban North American study. Therapy at early stages of disease may prevent onward HIV transmission.

Why are some less solidly supported health care innovations widely adopted while others with apparently stronger scientific support remain underused? Drawing on four case studies, the authors argue that the way in which the distribution of benefits and risks map onto the interests, values, and power distribution of the adopting system is critical to understanding how innovations diffuse.

RATIONALE: Dexmedetomidine is associated with less delirium than benzodiazepines and better sleep architecture than either benzodiazepines or propofol; its effect on delirium and sleep when administered at night to patients requiring sedation remains unclear. OBJECTIVES: To determine if nocturnal dexmedetomidine prevents delirium and improves sleep in critically ill adults. METHODS: This two-center, double-blind, placebo-controlled trial randomized 100 delirium-free critically ill adults receiving sedatives to receive nocturnal (9:30 p.m. to 6:15 a.m.) intravenous dexmedetomidine (0.2 μg/kg/h, titrated by 0.1 μg /kg/h every 15 min until a goal Richmond Agitation and Sedation Scale score of -1 or maximum rate of 0.7 μg/kg/h was reached) or placebo until ICU discharge. During study infusions, all sedatives were halved; opioids were unchanged. Delirium was assessed using the Intensive Care Delirium Screening Checklist every 12 hours throughout the ICU admission. Sleep was evaluated each morning by the Leeds Sleep Evaluation Questionnaire. MEASUREMENTS AND MAIN RESULTS: Nocturnal dexmedetomidine (vs. placebo) was associated with a greater proportion of patients who remained delirium-free during the ICU stay (dexmedetomidine [40 (80%) of 50 patients] vs. placebo [27 (54%) of 50 patients]; relative risk, 0.44; 95% confidence interval, 0.23-0.82; P = 0.006). The average Leeds Sleep Evaluation Questionnaire score was similar (mean difference, 0.02; 95% confidence interval, 0.42-1.92) between the 34 dexmedetomidine (average seven assessments per patient) and 30 placebo (six per patient) group patients able to provide one or more assessments. Incidence of hypotension, bradycardia, or both did not differ significantly between groups. CONCLUSIONS: Nocturnal administration of low-dose dexmedetomidine in critically ill adults reduces the incidence of delirium during the ICU stay; patient-reported sleep quality appears unchanged. Clinical trial registered with www.clinicaltrials.gov (NCT01791296).

OBJECTIVES: To document the frequency of insomnia (according to DSM-IV and ICSD criteria), to describe its sociodemographic and clinical characteristics, and to identify potential predictors of insomnia in persons with traumatic brain injury (TBI). PARTICIPANTS AND PROCEDURE: Four hundred fifty-two participants aged 16 years and older with minor to severe TBI answered a questionnaire pertaining to quality of sleep and fatigue. MAIN OUTCOME MEASURES: Proportion of participants fulfilling criteria for insomnia symptoms or syndrome. Validated measures of insomnia severity, fatigue level, and psychologic distress. Results of a logistic regression analysis. RESULTS: Overall, 50.2% of the sample reported insomnia symptoms and 29.4% fulfilled the diagnostic criteria for an insomnia syndrome. For the latter participants, insomnia was a severe and chronic condition remaining untreated in almost 60% of cases. Risk factors associated with insomnia were milder TBIs, and higher levels of fatigue, depression, and pain. CONCLUSION: Insomnia is a prevalent condition after TBI requiring more clinical and scientific attention as it may have important repercussions on rehabilitation.

Motor learning changes the activity of cortical motor and subcortical areas of the brain, but does learning affect sensory systems as well? We examined in humans the effects of motor learning using fMRI measures of functional connectivity under resting conditions and found persistent changes in networks involving both motor and somatosensory areas of the brain. We developed a technique that allows us to distinguish changes in functional connectivity that can be attributed to motor learning from those that are related to perceptual changes that occur in conjunction with learning. Using this technique, we identified a new network in motor learning involving second somatosensory cortex, ventral premotor cortex, and supplementary motor cortex whose activation is specifically related to perceptual changes that occur in conjunction with motor learning. We also found changes in a network comprising cerebellar cortex, primary motor cortex, and dorsal premotor cortex that were linked to the motor aspects of learning. In each network, we observed highly reliable linear relationships between neuroplastic changes and behavioral measures of either motor learning or perceptual function. Motor learning thus results in functionally specific changes to distinct resting-state networks in the brain.

Glaucoma, a major cause of blindness worldwide, is a neurodegenerative optic neuropathy in which vision loss is caused by loss of retinal ganglion cells (RGCs). To better define the pathways mediating RGC death and identify targets for the development of neuroprotective drugs, we developed a high-throughput RNA interference screen with primary RGCs and used it to screen the full mouse kinome. The screen identified dual leucine zipper kinase (DLK) as a key neuroprotective target in RGCs. In cultured RGCs, DLK signaling is both necessary and sufficient for cell death. DLK undergoes robust posttranscriptional up-regulation in response to axonal injury in vitro and in vivo. Using a conditional knockout approach, we confirmed that DLK is required for RGC JNK activation and cell death in a rodent model of optic neuropathy. In addition, tozasertib, a small molecule protein kinase inhibitor with activity against DLK, protects RGCs from cell death in rodent glaucoma and traumatic optic neuropathy models. Together, our results establish a previously undescribed drug/drug target combination in glaucoma, identify an early marker of RGC injury, and provide a starting point for the development of more specific neuroprotective DLK inhibitors for the treatment of glaucoma, nonglaucomatous forms of optic neuropathy, and perhaps other CNS neurodegenerations.

The recovery of locomotion, following interactive training with graded weight support, in the adult spinal cat has led to the proposal that removal of body weight may be a therapeutic tool in human gait retraining. There would be benefits, however, in knowing normal responses of humans to partial weight bearing before applying this strategy to patients. In this study, 10 nondisabled male subjects walked on a treadmill while 0%, 30%, 50%, and 70% of their body weight was supported by a modified climbing harness. To dissociate the changes attributable to walking speed from those attributable to body weight, each subject walked at the specified body-weight-support (BWS) levels and at full weight bearing (FWB) at the same speed. Simultaneously, electromyographic data from the right leg muscles, footswitch signals, and video recording of joint motion were collected. The FWB and BWS gaits appeared similar, except at the highest level of BWS studied (ie, 70% of BWS). Significant differences among other BWS and FWB trials at comparable speeds included decreases in percentage of stance, percentage of total double-limb support time, and maximum hip and knee flexor swing angle. Other adaptations to BWS were a reduction in the mean burst amplitude of the muscles that are active during stance and an increase in the mean burst amplitude of the tibialis anterior muscle. The possible implications of this new gait retraining strategy for patients with neurological impairment are discussed. [Finch L, Barbeau H, Arsenault B. Influence of body weight support on normal human gait: development of a gait retraining strategy.

OBJECTIVE: The purpose of this study was to determine whether the New Injury Severity Score (NISS) is a better predictor of mortality than the Injury Severity Score (ISS) in general and in subgroups according to age, penetrating trauma, and body region injured. METHODS: The study population consisted of 24,263 patients from three urban Level I trauma centers in the province of Quebec, Canada. Discrimination and calibration of NISS and ISS models were compared using receiver operator characteristic (ROC) curves and Hosmer-Lemeshow statistics. RESULTS: NISS showed better discrimination than ISS (area under the ROC curve = 0.827 vs. 0.819; p = 0.0006) and improved calibration (Hosmer-Leme-show = 62 vs. 112). The advantage of the NISS over the ISS was particularly evident among patients with head/neck injuries (area under the ROC curve = 0.819 vs. 0.784; p < 0.0001; Hosmer-Lemeshow = 59 vs. 350). CONCLUSION: The NISS is a more accurate predictor of in-hospital death than the ISS and should be chosen over the ISS for case-mix control in trauma research, especially in certain subpopulations such as head/neck-injured patients.

BACKGROUND: While minimalist running shoes may have an influence on running biomechanics and on the incidence of overuse injuries, the term "minimalist" is currently used without standardisation. The objectives of this study were to reach a consensus on a standard definition of minimalist running shoes, and to develop and validate a rating scale that could be used to determine the degree of minimalism of running shoes, the Minimalist Index (MI). METHODS: For this modified Delphi study, 42 experts from 11 countries completed four electronic questionnaires on an optimal definition of minimalist shoes and on elements to include within the MI. Once MI was developed following consensus, 85 participants subjectively ranked randomly assigned footwear models from the most to the least minimalist and rated their degree of minimalism using visual analog scales (VAS), before evaluating the same footwear models using MI. A subsample of thirty participants reassessed the same shoes on another occasion. Construct validity and inter- and intra-rater reliability (intraclass correlation coefficients [ICC]; Gwet's AC1) of MI were evaluated. RESULTS: The following definition of minimalist shoes was agreed upon by 95 % of participants: "Footwear providing minimal interference with the natural movement of the foot due to its high flexibility, low heel to toe drop, weight and stack height, and the absence of motion control and stability devices". Characteristics to be included in MI were weight, flexibility, heel to toe drop, stack height and motion control/stability devices, each subscale carrying equal weighing (20 %) on final score. Total MI score was highly correlated with VAS (r = 0.91). A significant rank effect (p < 0.001) confirmed the MI's discriminative validity. Excellent intra- and inter-rater reliability was found for total MI score (ICC = 0.84-0.99) and for weight, stack height, heel to toe drop and flexibility subscales (AC1 = 0.82-0.99), while good inter-rater reliability was found for technologies (AC1 = 0.73). CONCLUSION: This standardised definition of minimalist shoes developed by an international panel of experts will improve future research on minimalist shoes and clinical recommendations. MI's adequate validity and reliability will allow distinguishing running shoes based on their degree of minimalism, and may help to decrease injuries related to footwear transition.

The provocative concentrations of inhaled methacholine that cause 6% (PC6) and 20% (PC20) falls in forced expiratory volume in one second (FEV1) were assessed in a population of 100 nonsmoking persons, equally distributed for sex, who ranged uniformly from 20 to 60 yr of age. These subjects had no respiratory symptoms, rhinitis, atopic history, or familial history of asthma. Single twofold dilutions of methacholine from 2 to 128 mg/ml were used; 81 and 34 subjects, respectively, showed PC6 and PC20 values less than 128 mg/ml. Eight subjects had PC20 values less than 16 mg/ml. In these subjects, the test had a good reproducibility (r = 0.92) when we repeated it, and serial measurements of peak expiratory flow rates did not suggest asthma. The fact that PC6 was related, although loosely, to baseline FEV, FEV/FVC, and forced expiratory flow during the middle half of the FVC (FEF) and that 4 of the 8 subjects with PC20 values less than 16 mg/ml had lower values of FEF might suggest that responsiveness to methacholine is partially linked with baseline airway caliber.

OBJECTIVE: To investigate pain perception and the potential analgesic effects of mindful states in experienced Zen meditators. METHODS: Highly trained Zen meditators (n = 13; >1000 hours of practice) and age/gender-matched control volunteers (n = 13) received individually adjusted thermal stimuli to elicit moderate pain on the calf. Conditions included: a) baseline-1: no task; b) concentration: attend exclusively to the calf; c) mindfulness: attend to the calf and observe, moment to moment, in a nonjudgmental manner; and d) baseline-2: no task. RESULTS: Meditators required significantly higher temperatures to elicit moderate pain (meditators: 49.9 degrees C; controls: 48.2 degrees C; p = .01). While attending "mindfully," meditators reported decreases in pain intensity whereas control subjects showed no change from baseline. The concentration condition resulted in increased pain intensity for controls but not for meditators. Changes in pain unpleasantness generally paralleled those found in pain intensity. In meditators, pain modulation correlated with slowing of the respiratory rate and with greater meditation experience. Covariance analyses indicated that mindfulness-related changes could be partially explained by changes in respiratory rates. Finally, the meditators reported higher tendencies to observe and be nonreactive of their own experience as measured on the Five Factor Mindfulness Questionnaire; these factors correlated with individual differences in respiration. CONCLUSIONS: These results indicated that Zen meditators have lower pain sensitivity and experience analgesic effects during mindful states. Results may reflect cognitive/self-regulatory skills related to the concept of mindfulness and/or altered respiratory patterns. Prospective studies investigating the effects of meditative training and respiration on pain regulation are warranted.

OBJECTIVE: Osteoarthritis (OA) is accompanied by subchondral bone sclerosis. The present study was undertaken to determine whether osteoblast-like cells in patients with OA show an abnormal phenotype that could contribute to this sclerosis. METHODS: Explants and primary in vitro osteoblast-like cell cultures were prepared from subchondral bone specimens from OA patients or from bone removed at autopsy from individuals showing no signs of OA or metabolic bone disease. We measured the abundance and activity of urokinase plasminogen activator (uPA), and the levels of PA inhibitor (PAI-1) and insulin-like growth factor 1 (IGF-1) in conditioned media from both explants and osteoblast-like cells. The expression of osteoblast phenotypic biomarkers was also evaluated. RESULTS: OA explants showed increased levels and activity of uPA, no changes in PAI-1 abundance, and increases in IGF-1 release, as compared with preparations from normal individuals. In vitro primary osteoblast-like cells showed results similar to the ex vivo findings for uPA, PAI-1, and IGF-1. Primary OA osteoblast-like cells also expressed higher alkaline phosphatase activity and osteocalcin release than normal cells, both under basal conditions and with 1,25(OH)2D3 (1,25-dihydroxyvitamin D) stimulation. Conversely, OA osteoblast-like cells showed blunted cAMP synthesis in response to human parathyroid hormone and prostaglandin E2 in contrast to the finding with normal osteoblast-like cells, a result that could not be attributed to altered adenylate cyclase activity. CONCLUSION: Ex vivo and in vitro results indicate similar altered activities of OA osteoblasts as compared with normal cells. This suggests that an altered phenotype of subchondral osteoblasts may be a contributing factor in human OA.

PURPOSE: This study was undertaken to evaluate the presence of the metabolic syndrome in COPD patients who participated in a cardiopulmonary rehabilitation program. The metabolic syndrome is characterized by the presence of abdominal obesity, atherogenic dyslipidemia, raised blood pressure, presence of insulin resistance, and prothrombotic and inflammatory states that predispose to cardiovascular diseases. METHODS: Thirty-eight COPD patients (age: 66 +/- 7 years, [mean +/- SD], FEV1: 43 +/- 16% predicted) and 34 control participants matched for age and gender are included in this study. The criteria for the identification of the metabolic syndrome include 3 or more of the following features: abdominal obesity (waist circumference: > 102 cm in men, > 88 cm in women), triglycerides levels (>or= 1.69 mmol/L), high-density lipoprotein cholesterol levels (< 1.0 mmol/L in men, < 1.3 mmol/L in women), blood pressure (>or= 130/ >or= 85 mm Hg), and fasting glucose levels (>or= 6.1 mmol/L). RESULTS: Forty-seven percent of COPD patients and 21% of control participants presented 3 or more determinants of the metabolic syndrome. CONCLUSIONS: The presence of metabolic syndrome is frequent in patients with COPD who participated in a cardiopulmonary program. Hence, this population should be considered for screening for the metabolic syndrome.

OBJECTIVE: First, to validate an ultrasonographic measure of the acromio-humeral distance (AHD); second, to compare the AHD variation during active abduction in patients with shoulder impingement syndrome (SIS) and healthy subjects; and third, to evaluate the relationship between functional status and AHD variations before and after rehabilitation in SIS subjects. DESIGN: This study has 3 components: (1) a reliability study, (2) a case-control study, and (3) a preliminary pretreatment/posttreatment clinical trial. SETTING: Primary care hospital setting. PARTICIPANTS: Seven SIS patients and 13 healthy subjects. INTERVENTIONS: For the clinical trial, the SIS subjects participated in 12 sessions of a rehabilitation program over 4 weeks. MAIN OUTCOME MEASURES: First, intraclass correlation coefficient for interobserver reliability; second, AHD measured at 0 degrees, 45 degrees, and 60 degrees of active abduction; and third, Western Ontario Rotator Cuff Index. RESULTS: Intraclass correlation coefficient for interobserver reliability ranged from 0.86 to 0.92 for the 3 shoulder positions. A significant reduction of the AHD was found within groups between rest and active abduction (P < 0.05). Comparison of AHD between groups was not statistically different (P = 0.06; beta < 0.80). In pre-post rehabilitation analysis, improvement of the Western Ontario Rotator Cuff Index score was positively correlated to the reduction of the AHD narrowing as the arm was abducted (r = 0.86; P = 0.01). CONCLUSIONS: The ultrasound measure of AHD is reliable and sensitive. Although a distinct pattern of AHD variation in SIS patients could not be confirmed, a strong positive relationship was found between the reduction of AHD narrowing and functional improvement following rehabilitation. Ultrasound measurement of AHD might help identify SIS patients who will benefit from rehabilitation.

The routine use of antibiotics in agriculture has contributed to an increase in drug-resistant bacterial pathogens in animals that can potentially be transmitted to humans. In 2000, the World Health Organization identified resistance to antibiotics as one of the most significant global threats to public health and recommended that the use of antibiotics as additives in animal feed be phased out or terminated, particularly those used to treat human infections. Research is currently being carried out to identify alternative antimicrobial compounds for use in animal production. A number of studies, mostly in vitro, have provided evidence indicating that bacteriocins, which are antimicrobial peptides of bacterial origin, may be promising alternatives to conventional antibiotics in poultry and swine production. This review provides an update on bacteriocins and their potential for use in the poultry and swine industries.

Enamelin is critical for proper dental enamel formation, and defects in the human enamelin gene cause autosomal dominant amelogenesis imperfecta. We used gene targeting to generate a knock-in mouse carrying a null allele of enamelin (Enam) that has a lacZ reporter gene replacing the Enam translation initiation site and gene sequences through exon 7. Correct targeting of the transgene was confirmed by Southern blotting and PCR analyses. No enamelin protein could be detected by Western blotting in the Enam-null mice. Histochemical 5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside (X-gal) staining demonstrated ameloblast-specific expression of enamelin. The enamel of the Enam(+/-) mice was nearly normal in the maxillary incisors, but the mandibular incisors were discolored and tended to wear rapidly where they contacted the maxillary incisors. The Enam(-/-) mice showed no true enamel. Radiography, microcomputed tomography, and light and scanning electron microscopy were used to document changes in the enamel of Enam(-/-) mice but did not discern any perturbations of bone, dentin, or any other tissue besides the enamel layer. Although a thick layer of enamel proteins covered normal-appearing dentin of unerupted teeth, von Kossa staining revealed almost a complete absence of mineral formation in this protein layer. However, a thin, highly irregular, mineralized crust covered the dentin on erupted teeth, apparently arising from the formation and fusion of small mineralization foci (calcospherites) in the deeper part of the accumulated enamel protein layer. These results demonstrate ameloblast-specific expression of enamelin and reveal that enamelin is essential for proper enamel matrix organization and mineralization.

A hybrid precursor protein constructed by fusing the mitochondrial matrix-targeting signal of rat preornithine carbamyl transferase to murine cytosolic dihydrofolate reductase (designated pO-DHFR) was expressed in Escherichia coli. Following purification under denaturing conditions, pO-DHFR was capable of membrane translocation when diluted directly into import medium containing purified mitochondria but lacking cytosolic extracts. This import competence was lost with time, however, when the precursor was diluted and preincubated in medium lacking mitochondria, unless cytosolic proteins (provided by rabbit reticulocyte lysate) were present. Identical results were obtained for purified precursor made by in vitro translation. The ability of the cytosolic proteins to maintain the purified precursor in an import-competent state was sensitive to protease, N-ethylmaleimide (NEM), and was heat labile. Further, this activity appeared to be signal sequence dependent. ATP was not required for the maintenance of pO-DHFR competence, nor did purified 70-kDa heat shock protein (the constitutive form of Hsp70) substitute for this activity. Interestingly, however, purified Hsp70 prevented aggregation of the precursor in an ATP-dependent manner and, as well, retarded the apparent rate and extent of pO-DHFR folding. Partial purification of reticulocyte lysate proteins indicated that competence activity resides within a large mass protein fraction (200-250 kDa) that contains Hsp70. Sucrose density gradient analysis revealed that pO-DHFR reversibly interacts with components of this fraction. Pretreatment of the fraction with NEM, however, significantly stabilized the subsequent formation of a complex with the precursor. The results indicate that Hsp70 can retard precursor polypeptide folding and prevent precursor aggregation; however, by itself, Hsp70 cannot confer import competence to pO-DHFR. Maintenance of import competence correlates with interactions between the precursor and an NEM-sensitive cytosolic protein fraction. Efficient dissociation of the precursor from this complex appears to require a reactive thiol moiety on the cytosolic protein(s).

OBJECTIVE: To record the prevalence, extent, cost, and satisfaction with use of alternative medicine practices by patients with fibromyalgia syndrome (FMS), compared to control rheumatology patients. METHODS: An interviewer-based questionnaire was administered to 221 consecutive rheumatology patients and 80 FMS patients. RESULTS: Alternative medicine interventions were currently being used extensively by rheumatology patients overall, and by FMS patients in particular. All categories of alternative practices were used more often by FMS patients, compared to controls, including overall use 91% versus 63% (P = 0.0001), over-the-counter products 70% versus 54% (NS), spiritual practices 48% versus 37% (NS), and alternative practitioners 26% versus 12% (P = 0.003), respectively. Two-thirds of patients using alternative medicine practices were concurrently using multiple interventions. Patient satisfaction ratings were highest for spiritual interventions. CONCLUSIONS: Alternative medicine practices were currently being used by almost all FMS patients. This observation might indicate that traditional medical therapies are inadequate in providing symptomatic relief to FMS patients.

OBJECTIVE: To determine the prevalence and clinical correlations of an anomaly consisting of electroencephalographic (EEG) waves within the alpha frequency band during non-rapid eye movement (NREM) sleep in patients with fibromyalgia, and to evaluate the alpha NREM sleep anomaly as a predictor of response to amitriptyline. METHODS: Twenty-two patients with fibromyalgia were studied in a 2-month, double-blind, crossover trial of amitriptyline (25 mg/day) versus placebo. Nocturnal EEGs were conducted on 2 consecutive nights at baseline and at the end of each 2-month treatment period. RESULTS: Six patients (27%) had a clinical response to amitriptyline, while none responded to placebo (P = 0.02). Treatment with amitriptyline or placebo did not result in any changes in the alpha ratings during NREM sleep. Only 8 patients (36%) exhibited the alpha NREM sleep anomaly at baseline. Those patients reported more sleep difficulty, but otherwise were clinically indistinguishable from those without this EEG sleep anomaly. Lower baseline alpha NREM sleep ratings were seen in responders to amitriptyline than in nonresponders, but these differences did not reach statistical significance. CONCLUSION: The alpha NREM sleep anomaly is present in only a small proportion of patients with fibromyalgia. It does not correlate with disease severity nor is it affected by treatment with amitriptyline. A larger sample size will be needed to adequately assess the value of this sleep anomaly in predicting the response to amitriptyline.

We sequenced genes coding for components of the SNARE complex (STX1A, VAMP2, SNAP25) and their regulatory proteins (STXBP1/Munc18-1, SYT1), which are essential for neurotransmission, in 95 patients with idiopathic mental retardation. We identified de novo mutations in STXBP1 (nonsense, p.R388X; splicing, c.169+1G>A) in two patients with severe mental retardation and nonsyndromic epilepsy. Reverse transcriptase polymerase chain reaction and sequencing showed that the splicing mutation creates a stop codon downstream of exon-3. No de novo or deleterious mutations in STXBP1 were found in 190 control subjects, or in 142 autistic patients. These results suggest that STXBP1 disruption is associated with autosomal dominant mental retardation and nonsyndromic epilepsy.