High-density SNP association study of the 17q21 chromosomal region linked to autism identifies CACNA1G as a novel candidate gene.

Chromosome 17q11-q21 is a region of the genome likely to harbor susceptibility to autism (MIM(209850)) based on earlier evidence of linkage to the disorder. This linkage is specific to multiplex pedigrees containing only male probands (MO) within the Autism Genetic Resource Exchange (AGRE). Earlier, Stone et al.(1) completed a high-density single nucleotide polymorphism association study of 13.7 Mb within this interval, but common variant association was not sufficient to account for the linkage signal. Here, we extend this single nucleotide polymorphism-based association study to complete the coverage of the two-LOD support interval around the chromosome 17q linkage peak by testing the majority of common alleles in 284 MO trios. Markers within an interval containing the gene, CACNA1G, were found to be associated with Autism Spectrum Disorder at a locally significant level (P=1.9 × 10(-5)). While establishing CACNA1G as a novel candidate gene for autism, these alleles do not contribute a sufficient genetic effect to explain the observed linkage, indicating that there is substantial genetic heterogeneity despite the clear linkage signal. The region thus likely harbors a combination of multiple common and rare alleles contributing to the genetic risk. These data, along with earlier studies of chromosomes 5 and 7q3, suggest few if any major common risk alleles account for Autism Spectrum Disorder risk under major linkage peaks in the AGRE sample. This provides important evidence for strategies to identify Autism Spectrum Disorder genes, suggesting that they should focus on identifying rare variants and common variants of small effect

Randomised comparison of primary stent placement versus primary angioplasty followed by selective stent placement in patients with iliac-artery occlusive disease

Background Percutaneous transluminal angioplasty (PTA) is a safe, simple, and successful treatment for intermittent claudication caused by iliac-artery occlusive disease. Primary stent placement has been proposed as more effective than PTA. We compared the technical results and clinical outcomes of two treatment strategies-primary placement of a stent across the stenotic segment of the iliac artery, or primary PTA followed by selective stent placement when haemodynamic results were inadequate. Methods We randomly assigned 279 patients with intermittent claudication, recruited from departments of vascular surgery, either to direct stent placement (group I, n=143) or primary angioplasty (group II, n=136), with subsequent stent placement in case of a residual mean pressure gradient greater than 10 mm Hg across the treated site. The main inclusion criterion was intermittent claudication on the basis of iliac-artery stenosis of more than 50%, proven by angiography. All patients had a clinical assessment before intervention and at 3, 12, and 24 months. Clinical success was defined as improvement of at least one clinical category. Secondary endpoints were initial technical results, procedural complications, cumulative patency as assessed by duplex ultrasonography, and quality of life. Findings In group II, selective stent placement was done in 59 (43%) of the 136 patients. The mean follow-up was 9.3 months (range 3-24). Initial haemodynamic success and complication rates were 119 (81%) of 149 limbs and 6 (4%) of 143 limbs (group I) versus 103 (82%) of 126 limbs and 10 (7%) of 136 limbs (group II), respectively. Clinical success rates at 2 years were 29 (78%) of 37 patients and 26 (77%) of 34 patients in groups I and II, respectively (p=0.6); however, 43% and 35% of the patients, respectively, still had symptoms. Quality of life improved significantly after intervention (p Interpretation There were no substantial differences in technical results and clinical outcomes of the two treatment strategies both at short-term and long-term follow-up. Since angioplasty followed by selective stent placement is less expensive than direct placement of a stent, the former seems to be the treatment of choice for lifestyle-limiting intermittent claudication caused by iliac artery occlusive disease

Randomised comparison of primary stent placement versus primary angioplasty followed by selective stent placement in patients with iliac-artery occlusive disease

Background Percutaneous transluminal angioplasty (PTA) is a safe, simple, and successful treatment for intermittent claudication caused by iliac-artery occlusive disease. Primary stent placement has been proposed as more effective than PTA. We compared the technical results and clinical outcomes of two treatment strategies-primary placement of a stent across the stenotic segment of the iliac artery, or primary PTA followed by selective stent placement when haemodynamic results were inadequate. Methods We randomly assigned 279 patients with intermittent claudication, recruited from departments of vascular surgery, either to direct stent placement (group I, n=143) or primary angioplasty (group II, n=136), with subsequent stent placement in case of a residual mean pressure gradient greater than 10 mm Hg across the treated site. The main inclusion criterion was intermittent claudication on the basis of iliac-artery stenosis of more than 50%, proven by angiography. All patients had a clinical assessment before intervention and at 3, 12, and 24 months. Clinical success was defined as improvement of at least one clinical category. Secondary endpoints were initial technical results, procedural complications, cumulative patency as assessed by duplex ultrasonography, and quality of life. Findings In group II, selective stent placement was done in 59 (43%) of the 136 patients. The mean follow-up was 9.3 months (range 3-24). Initial haemodynamic success and complication rates were 119 (81%) of 149 limbs and 6 (4%) of 143 limbs (group I) versus 103 (82%) of 126 limbs and 10 (7%) of 136 limbs (group II), respectively. Clinical success rates at 2 years were 29 (78%) of 37 patients and 26 (77%) of 34 patients in groups I and II, respectively (p=0.6); however, 43% and 35% of the patients, respectively, still had symptoms. Quality of life improved significantly after intervention (p Interpretation There were no substantial differences in technical results and clinical outcomes of the two treatment strategies both at short-term and long-term follow-up. Since angioplasty followed by selective stent placement is less expensive than direct placement of a stent, the former seems to be the treatment of choice for lifestyle-limiting intermittent claudication caused by iliac artery occlusive disease

Gender Specific Brood Cells in the Solitary Bee Colletes halophilus (Hymenoptera; Colletidae)

We studied the reproductive behaviour of the solitary bee Colletes halophilus based on the variation in cell size, larval food amount and larval sex in relation to the sexual size dimorphism in this bee. Brood cells with female larvae are larger and contain more larval food than cells with males. Occasionally males are reared in female-sized cells. We conclude that a female C. halophilus in principal anticipates the sex of her offspring at the moment brood cell construction is started. Additionally a female is able to ‘change her mind’ about the sex of her offspring during a single brood cell cycle. We present a model that can predict the sex of the larvae in an early stage of development

Design and validation of the 1-week memory battery for assessing episodic memory and accelerated long-term forgetting in cognitively unimpaired subjects

Subtle decline in memory is thought to arise in the preclinical phase of Alzheimer's disease (AD). However, detecting these initial cognitive difficulties cross-sectionally has been challenging, and the exact nature of the decline is still debated. Accelerated long-term forgetting (ALF) has been recently suggested as one of the earliest and most sensitive indicators of memory dysfunction in subjects at risk of developing AD. The objective of this study was to design and validate the 1-week memory battery (1WMB) for assessing episodic memory and ALF in cognitively unimpaired individuals.The 1WMB is unique in that it assesses multimodal memory and measures recall at both short delay (20 min) and at long term (1 week). Forty-five cognitively unimpaired subjects were assessed with 1WMB and standardized neuropsychological tests. Subjective cognitive decline (SCD), levels of anxiety and depression, and cognitive reserve were also measured.The tests of 1WMB showed a high internal consistency, and concurrent validity was observed with standard tests of episodic memory and executive functions. The analysis revealed a greater loss of information at 1 week compared to short-term forgetting (20 min). Performance in the 1WMB was affected by age and educational level, but was not associated with levels of anxiety and depression. Unlike standard tests, performance in the 1WMB correlated with measures of SCD.Our findings indicate that the 1WMB has good psychometric properties, and future studies are needed to explore its potential usefulness to assess cognitively unimpaired subjects at increased risk of developing AD. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Parenting a child with phenylketonuria or galactosemia: implications for health-related quality of life

Parents of children with chronic disorders have an impaired health-related quality of life (HRQoL) compared to parents of healthy children. Remarkably, parents of children with a metabolic disorder reported an even lower HRQoL than parents of children with other chronic disorders. Possibly, the uncertainty about the course of the disease and the limited life expectancy in many metabolic disorders are important factors in the low parental HRQoL. Therefore, we performed a cross-sectional study in parents of children with phenylketonuria (PKU, OMIM #261600) and galactosemia (OMIM #230400), metabolic disorders not affecting life expectancy, in order to investigate their HRQoL compared to parents of healthy children and to parents of children with other metabolic disorders. A total of 185 parents of children with PKU and galactosemia aged 1-19 years completed two questionnaires. Parents of children with PKU or galactosemia reported a HRQoL comparable to parents of healthy children and a significantly better HRQoL than parents of children with other metabolic disorders. Important predictors for parental mental HRQoL were the psychosocial factors emotional support and loss of friendship. As parental mental functioning influences the health, development and adjustment of their children, it is important that treating physicians also pay attention to the wellbeing of the parents. The insight that emotional support and loss of friendship influence the HRQoL of the parents enables treating physicians to provide better support for these parents