A family-based association analysis and meta-analysis of the reading disabilities candidate gene DYX1C1.

Reading disabilities (RD) have a significant genetic basis and have shown linkage to multiple regions including chromosome 15q. Dyslexia susceptibility 1 candidate gene 1 (DYX1C1) on chromosome 15q21 was originally proposed as a candidate gene with two potentially functional polymorphisms at the -3G/A and 1249G/T positions showing association with RD. However, subsequent studies have yielded mixed results. We performed a literature review and meta-analysis of the -3G/A and 1249G/T polymorphisms, including new unpublished data from two family-based samples. Ten markers in DYX1C1 were genotyped in the two independently ascertained samples. Single marker and -3G/A:1249G/T haplotype analyses were performed for RD in both samples, and quantitative trait analyses using standardized reading-related measures was performed in one of the samples. For the meta-analysis, we used a random-effects model to summarize studies that tested for association between -3G/A or 1249G/T and RD. No significant association was found between the DYX1C1 SNPs and RD or any of the reading-related measures tested after correction for the number of tests performed. The previously reported risk haplotype (-3A:1249T) was not biased in transmission. A total of 9 and 10 study samples were included in the meta-analysis of the -3G/A and 1249G/T polymorphisms, respectively. Neither polymorphism reached statistical significance, but the heterogeneity for the 1249G/T polymorphism was high. The results of this study do not provide evidence for association between the putatively functional SNPs -3G/A and 1249G/T and RD.

Ivor Lewis vs Mckeown esophagectomy: analysis of operative outcomes from the ACS NSQIP database.

OBJECTIVES: Ivor Lewis and McKeown esophagectomy are common techniques to treat esophageal cancer. In this study, we aim to compare these two approaches. METHOD: We used the American College of Surgeons National Surgical Quality Improvement Project database (2005-2017) to compare both techniques using bivariate analysis after propensity matching. RESULTS: We identified 6136 patients with esophagectomy and divided them into 2 groups based on whether they received a McKeown (1676; 27.31%) or an Ivor Lewis (4460; 70.14%) esophagectomy. McKeown esophagectomy was associated with higher rates of superficial surgical site infections (8.02% vs 3.67%, p < 0.001), anastomotic leaks (9.12% vs 7.71%, p = 0.02), prolonged intubation (15.06% vs 10.10%, p < 0.001), re-intubation (15.30% vs 10.34%, p ≤ 0.001), and return to the OR (16.46% vs 11.32%, p < 0.001). The McKeown esophagectomy patients also had longer hospital length of stay (14.5 ± 11.99 vs 13.37 ± 11.8, p = 0.002), higher re-admission rate (21.56% vs 16.87%, p = 0.002), and higher discharges to nursing/rehabilitation institutions (14.06% vs 11.99%, p = 0.004).The mortality rate and positive resection margins were not significantly different. There was a trend toward more utilization of Ivor Lewis esophagectomy over years. CONCLUSION: When compared to Ivor Lewis esophagectomy, McKeown esophagectomy is associated with more unplanned intubation, increased difficulty weaning from the ventilator, incisional surgical site infections, anastomotic leak, and higher length of stay.

Intergenerational transmission of adverse childhood experiences via maternal depression and anxiety and moderation by child sex.

Adverse childhood experiences (ACEs) of parents are associated with a variety of negative health outcomes in offspring. Little is known about the mechanisms by which ACEs are transmitted to the next generation. Given that maternal depression and anxiety are related to ACEs and negatively affect children's behaviour, these exposures may be pathways between maternal ACEs and child psychopathology. Child sex may modify these associations. Our objectives were to determine: (1) the association between ACEs and children's behaviour, (2) whether maternal symptoms of prenatal and postnatal depression and anxiety mediate the relationship between maternal ACEs and children's behaviour, and (3) whether these relationships are moderated by child sex. Pearson correlations and latent path analyses were undertaken using data from 907 children and their mothers enrolled the Alberta Pregnancy Outcomes and Nutrition study. Overall, maternal ACEs were associated with symptoms of anxiety and depression during the perinatal period, and externalizing problems in children. Furthermore, we observed indirect associations between maternal ACEs and children's internalizing and externalizing problems via maternal anxiety and depression. Sex differences were observed, with boys demonstrating greater vulnerability to the indirect effects of maternal ACEs via both anxiety and depression. Findings suggest that maternal mental health may be a mechanism by which maternal early life adversity is transmitted to children, especially boys. Further research is needed to determine if targeted interventions with women who have both high ACEs and mental health problems can prevent or ameliorate the effects of ACEs on children's behavioural psychopathology.

Reading disability with motor problems may be an inherited subtype.

There is evidence from a number of studies that various forms of reading disability are inherited. The familial patterns of one specific type of reading disability that occurs together with impaired coordination and balance were evaluated. Ten reading-disabled children with these motor problems, ten children with only reading problems, and ten control children without reading disabilities were examined along with their siblings and parents. The control children were matched to the reading-disabled children for age, sex, and family socioeconomic status. A high prevalence of reading and motor problems was found in the relatives of the children with reading disability and motor problems, whereas a high prevalence of only reading problems was found in the relatives of the children with only reading disability. There were no differences among the three groups of children or their siblings on number of pregnancy and birth complications or prevalence of attention deficit disorder. It was concluded that reading disability with motor problems may be an inherited type of reading disability, distinct from reading disability without motor problems, which is also inherited.

Sleep disturbance in preschool-aged hyperactive and nonhyperactive children.

In spite of inadequate laboratory demonstrations of sleep problems in children with attention deficit disorder with hyperactivity, the belief persists that such problems exist. Sleep restlessness is, in fact, one of the criteria in the Diagnostic and Statistical Manual of Mental Disorders, ed 3, definition of attention deficit disorder with hyperactivity, and sleep problems are listed on two major checklists often used for describing the symptoms of this disorder. In a series of three studies, sleep problems were investigated in preschool-aged children with attention deficit disorder relative to control children without the disorder. Results of the first two studies demonstrated clearly that parents of hyperactive children considered their children to have many more sleep problems than did parents of the control children. Parental daily documentation, which is less likely to be affected by reporting bias, was used in the third study. Although the results of the third study supported the finding of increased frequency of night wakings in these children, there was no difference in total sleep time or sleep onset latency between the two groups. Two other significant group differences (enuresis and night sweats) were primarily due to subgroups of children with attention deficit disorder and hyperactivity. The greater number of sleep wakings, which disrupt parents' sleep, may be responsible for the clinical reports that these children are poor sleepers.

Dietary replacement in preschool-aged hyperactive boys.

A 10-week study was conducted in which all food was provided for the families of 24 hyperactive preschool-aged boys whose parents reported the existence of sleep problems or physical signs and symptoms. A within-subject crossover design was used, and the study was divided into three periods: a baseline period of 3 weeks, a placebo-control period of 3 weeks, and an experimental diet period of 4 weeks. The experimental diet was broader than those studied previously in that it eliminated not only artificial colors and flavors but also chocolate, monosodium glutamate, preservatives, caffeine, and any substance that families reported might affect their specific child. The diet was also low in simple sugars, and it was dairy free if the family reported a history of possible problems with cow's milk. According to the parental report, more than half of the subjects exhibited a reliable improvement in behavior and negligible placebo effects. In addition, several nonbehavioral variables tended to improve while the children received the experimental diet, particularly halitosis, night awakenings, and latency to sleep onset.

Evidence for a susceptibility locus on chromosome 6q influencing phonological coding dyslexia.

A linkage study of 96 dyslexia families containing at least two affected siblings (totaling 877 individuals) has found evidence for a dyslexia susceptibility gene on chromosome 6q11.2-q12 (assigned the name DYX4). Using a qualitative phonological coding dyslexia (PCD) phenotype (affected, unaffected, or uncertain diagnoses), two-point parametric analyses found highly suggestive evidence for linkage between PCD and markers D6S254, D6S965, D6S280, and D6S251 (LOD(max) scores = 2.4 to 2.8) across an 11 cM region. Multipoint parametric analysis supported linkage of PCD to this region (peak HLOD = 1.6), as did multipoint nonparametric linkage analysis (P = 0.012). Quantitative trait linkage analyses of four reading measures (phonological awareness, phonological coding, spelling, and rapid automatized naming speed) also provided evidence for a dyslexia susceptibility locus on chromosome 6q. Using a variance-component approach, analysis of phonological coding and spelling measures resulted in peak LOD scores at D6S965 of 2.1 and 3.3, respectively, under 2 degrees of freedom. Furthermore, multipoint nonparametric quantitative trait sibpair analyses suggested linkage between the 6q region and phonological awareness, phonological coding, and spelling (P = 0.018, 0.017, 0.0005, respectively, for unweighted sibpairs < 18 years of age). Although conventional significance thresholds were not reached in the linkage analyses, the chromosome 6q11.2-q12 region clearly warrants investigation in other dyslexia family samples to attempt replication and confirmation of a dyslexia susceptibility gene in this region.

Effective mood stabilization with a chelated mineral supplement: an open-label trial in bipolar disorder.

BACKGROUND: To determine in open trials the therapeutic benefit of a nutritional supplement for bipolar disorder. METHOD: The sample consisted of 11 patients with DSM-IV-diagnosed bipolar disorder aged 19 to 46 years, who were taking a mean of 2.7 psychotropic medications each at study entry. Three additional patients dropped out prematurely. The intervention is a broad-based nutritional supplement of dietary nutrients, primarily chelated trace minerals and vitamins, administered in high doses. At study entry and periodically thereafter, patients were assessed with the Hamilton Rating Scale for Depression (HAM-D), the Brief Psychiatric Rating Scale (BPRS), and the Young Mania Rating Scale (YMRS). RESULTS: For those who completed the minimum 6-month open trial, symptom reduction ranged from 55% to 66% on the outcome measures; need for psychotropic medications decreased by more than 50%. Paired t tests revealed treatment benefit on all measures for patients completing the trial: HAM-D mean score at entry = 19.0, mean score at last visit = 5.4, t = 5.59, df = 9, p < 01; BPRS mean score at entry = 35.3, mean score at last visit = 7.4, t = 2.57, df = 9, p <.05; YMRS mean score at entry = 15.1, mean score at last visit = 6.0, t = 4.11, df = 9, p < .01. The effect size for the intervention was large (> .80) for each measure. The number of psychotropic medications decreased significantly to a mean +/- SD of 1.0+/-1.1 (t = 3.54, df = 10, p < .01). In some cases, the supplement replaced psychotropic medications and the patients remained well. The only reported side effect (i.e., nausea) was infrequent, minor, and transitory. CONCLUSION: Some cases of bipolar illness may be ameliorated by nutritional supplementation. A randomized, placebo-controlled trial in adults with bipolar I disorder is currently underway, as well as open trials in children.

Intracortical evoked potentials of cats elicited by punctate visual stimuli in receptive field peripheries.

Intracortical visual evoked potentials, related to stimulus eccentricity from receptive field center, were investigated as a possible measure of interaction among adjacent populations of cortical neurons. Displacement of the stimuli from field center resulted in (1) a progressive decline in amplitude of the primary potential and (2) an enhancement or development of longer latency (60-100 ms) 'secondary' potentials often not apparent with field center stimulation.

Cerebral blood volume in a rat model of ischemia by MR imaging at 4.7 T.

Perturbation of the cerebral circulation by occlusion of the vertebral arteries and a carotid artery can be visualized by using MR imaging and the intravascular contrast agent Gd-DTPA complexed to albumin. This tracer consistently reduced the T1 relaxation time in the brain and blood. The difference between hemispheres was revealed by less T1 reduction in the occluded hemisphere and by an adjustment in the display contrast of images that revealed the territory of decreased perfusion. These results were confirmed by comparing them with cerebral blood flow using radioactive microspheres and the intravascular blood volume tracer 51Cr-EDTA. This method, combined with high-resolution MR imaging, can be applied to serial noninvasive studies of cerebral blood volume in ischemia and other conditions.

Morphological evidence that reline SMR and human mu are analogous rhythms.

In cats implanted with epidural screw electrodes over sensorimotor cortex, various recording montages were used to observe the waveform of the sensorimotor rhythm (SMR). It was found that in bipolar recordings spanning the crus, SMR exhibited a wicket-shaped waveform comparable in shape and polarity to the human mu rhythm. Based on previously reported topographic and functional similarities of feline SMR and human mu, and on the present data demonstrating morphological similarities, it appears that feline SMR is the first proven feline model of a spontaneous human ieeg rhythm.

The effects of parental immunoreactivity on pregnancy, birth, and cognitive development: maternal immune attack on the fetus?

The effects of parental immunoreactivity were tested in two ways on questionnaire data collected from 468 children and their families. (1) It was found that the presence of learning difficulties in boys was associated with pregnancy and birth complications, as well as with maternal immunoreactivity. Paternal immunoreactivity did not appear to be related to any of the variables in question. (2) The antecedent brother effect, that children, particularly males, with older brothers have higher rates of the same set of variables, was not found. Maternal immunoreactivity emerges as a risk factor for pregnancy, birth, and cognitive development, but not exclusively by the proposed mechanism of maternal immune attack on the fetus.

Are families of children with reading difficulties at risk for immune disorders and nonrighthandedness?

This study used questionnaire data to examine immune disorders and nonrighthandedness in the families of children enrolled in a learning disabilities school and children attending regular classrooms in public schools. Groups were organized according to their performance on a standardized test of reading comprehension to avoid overlap. In total, 468 questionnaires were returned, from which we were able to derive a final sample of carefully matched subjects: 55 subjects undergoing remediation for reading problems and 55 age- and sex-matched control subjects. The results indicated that children with reading problems and their families more frequently suffered from some immune and autoimmune disorders, particularly those involving the gastrointestinal tract and the thyroid gland. In addition, symptoms of attention deficit hyperactivity disorder were associated with Crohn's disease and migraine headache in the families. There was no evidence of an elevated prevalence of nonrighthandedness in the children with reading problems and their families.

Cervical carotid artery dissection secondary to malignant fibrous histiocytoma.

A rare case of malignant fibrous histiocytoma of the cervical carotid artery is presented. Erosion of the vessel wall by this neoplasm resulted in dissection and pseudoaneurysm formation. The etiology and diagnosis of and the therapeutic alternatives for this unique disorder are discussed briefly.

Effects of aortic occlusion on regional spinal cord blood flow and somatosensory evoked potentials in sheep.

Somatosensory evoked potentials (SEPs) were recorded continuously during aortic occlusion in sheep, with simultaneous measurement of spinal cord blood flow (SCBF) by radiolabeled microspheres. Aortic occlusion was associated with disappearance of the SEPs in seven of nine sheep in 7.8 +/- 4.1 (SD) minutes. SCBF at the time of initial cross clamping and 30 minutes after the onset of ischemia revealed a severe reduction in white and gray matter flow in the thoracolumbar cord. Release of the aortic clamp was associated with reactive hyperemia in these ischemic regions. In two animals, the SEP persisted during aortic cross clamping. The total SCBF in the thoracic and lumbar regions of these two animals exceeded 20 ml/100 g/min after 30 minutes of ischemia and was significantly greater than the flow recorded in sheep whose evoked response disappeared. The relation between spinal cord ischemia and evoked potential alterations is discussed in detail.

Effects of induced hypotension during experimental vasospasm: a neurological, electrophysiological, and pathological analysis.

Vasospasm of the vertebrobasilar system was induced in seven dogs by the intracisternal injection of autologous blood. Somatosensory and brain stem auditory evoked potentials were recorded before and after the induction of angiographically confirmed vasospasm. Additionally, somatosensory evoked potentials were monitored during graded hypotension to 40 mm Hg. There was no significant alteration in the evoked potentials by vasospasm or hypotension. Detailed clinical examination and postmortem histopathological studies did not demonstrate any focal neurological deficit or infarction attributable to vasospasm. Previous studies have noted close correlations between decreased cerebral blood flow and evoked potential alterations. Induced hypotension to a mean arterial pressure of 40 mm Hg in the presence of documented vasospasm was not sufficient to cause evoked potential changes, focal neurological deficit, or pathological evidence of infarction in the canine model.

Somatosensory evoked potential monitoring of spinal cord ischemia during aortic operations.

Somatosensory evoked potentials were monitored in 22 consecutive patients undergoing surgical correction of an aortic coarctation. Induction of spinal cord ischemia by cross clamping of the aorta elicited a change in the evoked potential in 9 patients (41%). These alterations occurred within 5 minutes of aortic clamping in 3 cases and after 18 to 21 minutes in the remaining 6 cases. Loss of the somatosensory evoked potential for more than 14 minutes was associated with postoperative neurological deficit. Alteration of the evoked potential within 5 minutes of aortic cross clamping was significantly related to poor collateral circulation shown on the preoperative aortogram. The pathophysiology of evoked potential changes in spinal ischemia is discussed in detail.

Intraoperative brain-stem auditory evoked potentials during posterior fossa microvascular decompression.

Recent technological advances have led to increased interest in intraoperative evoked potential monitoring. Although theoretically valuable, its precise role remains to be defined, and useful criteria for predicting neurological deficit are not well established. The authors used brain-stem auditory evoked potential (BAEP) monitoring during 21 posterior fossa microvascular decompression procedures to assess the value of this technique in predicting postoperative deficit. The surgeon was notified only if there was complete disappearance of wave V. Although no patients had postoperative deafness, BAEP latencies changed significantly in all cases. In four patients, wave V totally disappeared during cerebellar retraction. The BAEP appears to be a very sensitive monitor of auditory function, such that "false positive" results will be frequent if latency criteria alone are used to trigger alterations in surgical technique.