CNVs conferring risk of autism or schizophrenia affect cognition in controls.

In a small fraction of patients with schizophrenia or autism, alleles of copy-number variants (CNVs) in their genomes are probably the strongest factors contributing to the pathogenesis of the disease. These CNVs may provide an entry point for investigations into the mechanisms of brain function and dysfunction alike. They are not fully penetrant and offer an opportunity to study their effects separate from that of manifest disease. Here we show in an Icelandic sample that a few of the CNVs clearly alter fecundity (measured as the number of children by age 45). Furthermore, we use various tests of cognitive function to demonstrate that control subjects carrying the CNVs perform at a level that is between that of schizophrenia patients and population controls. The CNVs do not all affect the same cognitive domains, hence the cognitive deficits that drive or accompany the pathogenesis vary from one CNV to another. Controls carrying the chromosome 15q11.2 deletion between breakpoints 1 and 2 (15q11.2(BP1-BP2) deletion) have a history of dyslexia and dyscalculia, even after adjusting for IQ in the analysis, and the CNV only confers modest effects on other cognitive traits. The 15q11.2(BP1-BP2) deletion affects brain structure in a pattern consistent with both that observed during first-episode psychosis in schizophrenia and that of structural correlates in dyslexia.

Association of Genetically Predicted Lipid Levels With the Extent of Coronary Atherosclerosis in Icelandic Adults.

Importance: Genetic studies have evaluated the influence of blood lipid levels on the risk of coronary artery disease (CAD), but less is known about how they are associated with the extent of coronary atherosclerosis. Objective: To estimate the contributions of genetically predicted blood lipid levels on the extent of coronary atherosclerosis. Design, Setting, and Participants: This genetic study included Icelandic adults who had undergone coronary angiography or assessment of coronary artery calcium using cardiac computed tomography. The study incorporates data collected from January 1987 to December 2017 in Iceland in the Swedish Coronary Angiography and Angioplasty Registry and 2 registries of individuals who had undergone percutaneous coronary interventions and coronary artery bypass grafting. For each participant, genetic scores were calculated for levels of non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides, based on reported effect sizes of 345 independent, lipid-associated variants. The genetic scores' predictive ability for lipid levels was assessed in more than 87 000 Icelandic adults. A mendelian randomization approach was used to estimate the contribution of each lipid trait. Exposures: Genetic scores for levels of non-HDL-C, LDL-C, HDL-C, and triglycerides. Main Outcomes and Measures: The extent of angiographic CAD and coronary artery calcium quantity. Results: A total of 12 460 adults (mean [SD] age, 65.1 [10.7] years; 8383 men [67.3%]) underwent coronary angiography, and 4837 had coronary artery calcium assessed by computed tomography. A genetically predicted increase in non-HDL-C levels by 1 SD (38 mg/dL [to convert to millimoles per liter, multiply by 0.0259]) was associated with greater odds of obstructive CAD (odds ratio [OR], 1.83 [95% CI, 1.63-2.07]; P = 2.8 × 10-23). Among patients with obstructive CAD, there were significant associations with multivessel disease (OR, 1.26 [95% CI, 1.11-1.44]; P = 4.1 × 10-4) and 3-vessel disease (OR, 1.47 [95% CI, 1.26-1.72]; P = 9.2 × 10-7). There were also significant associations with the presence of coronary artery calcium (OR, 2.04 [95% CI, 1.70-2.44]; P = 5.3 × 10-15) and loge-transformed coronary artery calcium (effect, 0.70 [95% CI, 0.53-0.87]; P = 1.0 × 10-15). Genetically predicted levels of non-HDL-C remained associated with obstructive CAD and coronary artery calcium extent even after accounting for the association with LDL-C. Genetically predicted levels of HDL-C and triglycerides were associated individually with the extent of coronary atherosclerosis, but not after accounting for the association with non-HDL cholesterol. Conclusions and Relevance: In this study, genetically predicted levels of non-HDL-C were associated with the extent of coronary atherosclerosis as estimated by 2 different methods. The association was stronger than for genetically predicted levels of LDL-C. These findings further support the notion that non-HDL-C may be a better marker of the overall burden of atherogenic lipoproteins than LDL-C.

Increasing sex difference in bone strength in old age: The Age, Gene/Environment Susceptibility-Reykjavik study (AGES-REYKJAVIK).

INTRODUCTION: It is important to identify possible pathological mechanisms that underlie the known sexual dimorphism in bone fragility in old age. In this cross-sectional population-based study, we use data from three different skeletal sites to examine sex differences in volumetric bone density, geometry and strength indices and determine whether sex differences in these bone strength measures continue to increase into very old age. MATERIALS AND METHODS: A total of 1715 elderly individuals (807 men and 908 women) age 67-93 years, participants in a population-based study, the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-REYKJAVIK) and not taking medications affecting bone metabolism, were studied. Quantitative computed tomography (QCT) was performed in the lumbar spine, hip and mid-femoral shaft to estimate volumetric trabecular, cortical and integral BMD, bone geometry and bone strength indices. Regression models were used to assess the effects of age and gender-adjustment for standing midlife height and current weight. RESULTS: At age 67-69 years, men had 24.9-31.7% larger cross-sectional bone size at measured sites than women. At all bone sites, women had two- to fivefold diminution in net bone mass with age compared to men but had comparable increments in bone size (1.8-6.0% per 10 years). This was reflected in significantly worse (more than twofold) bone strength measures with age in women, including compressive strength indices at the spine, femoral neck and trochanter and bending strength indices at the femoral neck. CONCLUSION: With the limitations of a cross-sectional study, our data support the hypothesis that sex differences in bone strength continue into old age. These sex differences appear to be due to greater net bone loss in women rather than due to greater bone gain in men.

Associations of visceral and liver fat with the metabolic syndrome across the spectrum of obesity: the AGES-Reykjavik study.

Visceral adipose tissue (VAT) is a key pathogenic fat depot in the metabolic syndrome (MetS), but liver fat (LF) may also play an important role. We evaluated associations of VAT and LF with MetS in normal weight, overweight, and obese men and women (BMI <25, 25-29.9, and ≥30 kg/m2, respectively). This analysis included 2,495 participants from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik study with computed tomography measurements for VAT and LF. MetS was defined by ≥3 of the following: larger abdominal circumference, hypertension, elevated triglyceride (TG), low high-density lipoprotein (HDL), impaired fasting glucose (IFG), and microalbuminuria. We estimated the odds of MetS per 1-s.d. increase in VAT and LF, adjusting for key covariates. VAT was associated with an increased odds of MetS in normal weight, overweight, and obese women (odds ratios (OR) = 2.78, 1.63, and 1.43, respectively; all P < 0.01) that diminished in magnitude with increasing BMI (VAT × BMI class interaction P < 0.001). In men, VAT was related to MetS only among the overweight (OR = 1.69, P < 0.01). LF was associated with MetS in the overweight and obese groups in women (OR = 1.38 and 1.45; both P < 0.001) and in men (OR = 1.38, P = 0.01; and OR = 1.27, P = 0.10), but not in the normal weight groups. These BMI-specific relationships persisted when both fat depots were included in the model. VAT and LF were associated with MetS independently of each other, and these relationships were modified by BMI class such that, VAT was the more important depot at lower levels of obesity and LF at higher levels. Importantly, fatty liver may be a novel metabolic risk factor in overweight and obese individuals.

Diagnostic accuracy of 64-slice multidetector CT for detection of in-stent restenosis in an unselected, consecutive patient population.

OBJECTIVES: To investigate the diagnostic accuracy of 64-slice multidetector computed tomography (64-CT) for detection of in-stent restenosis (ISR) in an unselected, consecutive patient population. BACKGROUND: Detection of in-stent restenosis by cardiac CT would be a major advance for the evaluation of patients suspected of having ISR. However, the diagnostic accuracy of current generation 64-CT in this context is not fully established. METHODS: We conducted a prospective study on patients with stable angina or acute coronary syndrome with no prior history of coronary artery disease. Six months after percutaneous coronary intervention (PCI) with stent placement they underwent a 64-CT scan (Toshiba Multi-Slice Aquilion 64) and consequently a repeat coronary angiography for comparison. Cardiac CT data sets were analyzed for the presence of in-stent restenosis by two independent expert readers blinded to the coronary angiographic data. RESULTS: Ninety-three patients with a total of 140 stents were evaluated. Males comprised 82% of the study group and the mean age was 63±10 years. The mean time from PCI to the repeat coronary angiography was 208±37 days and the mean time from 64-CT to repeat coronary angiography was 3.7±4.9 days. The restenosis rate according to coronary angiography was 26%. Stent diameter, strut thickness, heart rate and body mass index (BMI) significantly affected image quality. The sensitivity, specificity, positive and negative predictive values of 64-CT for detection of in-stent restenosis were 27%, 95%, 67% and 78%, respectively. CONCLUSIONS: Current generation, 64-slice CT, remains limited in its ability to accurately detect in-stent restenosis.

[Diagnostic accuracy of 64-slice computed tomography compared with coronary angiography]. / Greiningarhaefni 64 sneida tövusneidmyndataekni til samanburdar vid hefdbundna kransaedapraedingu.

OBJECTIVE: The aim of this study was to evaluate the diagnostic accuracy (sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV)) of 64-slice multidetector computed tomography (MDCT) compared with quantitative coronary angiography (QCA) for detection of coronary artery disease (CAD). MATERIAL AND METHODS: Sixty-nine patients participating in a study of coronary in-stent restenosis were investigated. After a 64-slice MDCT scan patients were evaluated by QCA. The coronary arteries were divided into 15 segments and stenosis was graded for each segment by both methods. The diagnostic accuracy of 64-slice MDCT was evaluated using the QCA as the gold standard. RESULTS: Among the 69 patients included in the study 13 (19%) were female and 56 male. The mean age was 63 (SD 10) years. The following risk factors were present: high blood pressure 67%, elevated blood cholesterol 54%, diabetes 12% and family history of CAD 71%. Current smokers were 22% and previous smokers were 48%. Altogether 663 segments were examined. Of those 221 (33%) segments were excluded; 103 because of stents, 48 because of heavy calcification, 41 because of motion artifacts and 29 because the segments were less than 1.5 mm in diameter. The mean time between MDCT and QCA was 6.3 (SD 12.1) days. The sensitivity of 64-slice MDCT for diagnosing significant stenosis (>or= 50% according to QCA) was 20%, the specificity was 94%, PPV was 16%, NPV was 95% and the accuracy was 89%. CONCLUSION: High NPV and specificity indicates that MDCT is useful for accurately excluding significant CAD but the low sensitivity and low PPV indicate that the method is not accurate in diagnosing coronary artery stenosis of 50% or more according to QCA.

[Not all wheezing is asthma. Case report]. / Ekki er allt astmi sem hvaesir. Sjúkratilfelli.

UNLABELLED: A fifty six year old woman with history of asthma visited a respiratory specialist. She had been diagnosed with asthma more than a year previously in a primary care clinic. She was treated with inhaled medications without good response. A respiratory specialist diagnosed tracheal narrowing secondary to thyroid enlargement that was pushing the trachea together. She was cured with a thyroid operation. Discussed are differential diagnosis of asthma and causes of airway narrowing and the importance of spirometry in diagnosing asthma. KEYWORDS: case report, asthma, airway narrowing, spirometry.

Inaccuracy in self-report of fractures may underestimate association with health outcomes when compared with medical record based fracture registry.

INTRODUCTION AND OBJECTIVE: Misreporting fractures in questionnaires is known. However, the effect of misreporting on the association of fractures with subsequent health outcomes has not been examined. METHODS: Data from a fracture registry (FR) developed from an extensive review of radiographic and medical records were related to self-report of fracture for 2,255 participants from the AGES Reykjavik Study. This data was used to determine false negative and false positive rates of self-reported fractures, correlates of misreporting, and the potential effect of the misreporting on estimates of health outcomes following fractures. RESULTS: In women, the false positive rate decreased with age as the false negative rate increased with no clear trend with age in men. Kappa values for agreement between FR and self-report were generally higher in women than men with the best agreement for forearm fracture (men 0.64 and women 0.82) and the least for rib (men 0.28 and women 0.25). Impaired cognition was a major factor associated with discordant answers between FR and self-report, OR 1.7 (95% CI: 1.3-2.1) (P < 0.0001). We estimated the effect of misreporting on health after fracture by comparison of the association of the self-report of fracture and fracture from the FR, adjusting for those factors associated with discordance. The weighted attenuation factor measured by mobility and muscle strength was 11% (95% CI: 0-24%) when adjusted for age and sex but reduced to 6% (95% CI: -10-22%) when adjusted for cognitive impairment. CONCLUSION: Studies of hip fractures should include an independent ascertainment of fracture but for other fractures this study supports the use of self-report.

[Comparison between coronary angiography with multislice computed tomography and by cardiac catheterisation for assessing atherosclerotic lesions and stenosis]. / Samanburethur á mati kransaeethathornrengsla meeth tölvusneiethmyndataekni og hjartathornraeethingu.

AIM OF STUDY: To compare the utility and reliability of coronary angiography with multislice computed tomography (MSCT) and by cardiac catheterisation in assessing atherosclerotic lesions and stenosis. MATERIAL AND METHODS: Data were assessed from 44 subjects (25 men, 19 women) (mean age 63 years; range 34-80 years) referred to MSCT who also had undergone invasive coronary angiography within a time frame of one year. Coronary angiograms from both studies were assessed by segmental analysis and the atherosclerotic severity graded. The frequency of coronary calcification on MSCT was separately assessed in 150 subjects. RESULTS: By retrospective evaluation, 29 segments were found to have significant stenosis (> or = 50%) on the invasive coronary angiogram. Of these 17 had a diameter over 2.0 mm and 14 (83%) thereof were correctly diagnosed by MSCT. On the other hand, MSCT assessed four stenosis to be significant that were not judged so on the invasive angiogram. On MSCT, the frequency of coronary calcifications increased with age and in those 60 years and older it was 96% in males and 71% in females (p=0.025). CONCLUSION: Good agreement was found between MSCT and invasive coronary angiography in assessing significant stenosis in vessel segments over 2.0 mm. In older subjects coronary calcification on MSCT is frequent and diminishes its accuracy. MSCT seems most useful in relatively young subjects in whom the coronary arteries need to be evaluated to avoid unnecessary cardiac catheterisation.

[Farmer's lung disease caused by straw or hay? Case report]. / Hálmsótt eda heysótt?

A young woman was admitted to Akranes Regional Hospital because of dyspnea, fatigue and fever. She was found to have bilateral pneumonia but etiology was not found. She was treated with antibiotics with good resolution and was discharged after eight days from the hospital. Four weeks later she noticed rapidly progressive dyspnea and was found to be hypoxemic, and to have restrictive spirometry and diffuse interstitial changes on chest radiography. Computerized tomography of the lungs showed diffuse ground glass changes. Transbronchial biopsies from the lungs showed numerous small granulomas. She was treated with prednisolone for a short time with excellent recovery. She stall-fed horses and underneath them was straw containing organic dust. This is important to keep in mind as a differential diagnosis to farmers lung disease that is caused by hay.

Probable destructive meningioma in an archaeological adult male skull from Alaska.

Several intracranial pathological conditions can affect the bones of the skull. The most common cause of these conditions is tumor, but infection and other diseases are also known to affect the bones of the skull. Distinguishing between the various causes of intracranial skeletal pathology in archaeological human remains is usually a challenging exercise, and a specific diagnosis will often be impossible. Meningiomas are tumors that arise in arachnoid tissues embedded in the outer layer of the dura. Because of this association, they occur almost exclusively in the skull and vertebral column. Usually meningiomas are slow-growing tumors that do not metastasize to other organs and tissues of the body. However, rare cases can be malignant and, even when meningiomas are benign, their presence and growth can adversely affect the nervous and vascular supply to other tissues in the skull and vertebral column. Their effect on adjacent bone tissue varies from stimulating bone-forming lesions to causing highly destructive lesions. A few examples of meningioma have been described in the paleopathological literature. Most of these cases are bone-stimulating meningiomas. The case presented here is a probable example of a highly destructive meningioma of the skull base, with unilateral extension into the left side of the cranium. This case is compared with a modern clinical case of destructive intracranial meningioma that was documented both radiographically and pathologically. Destructive meningiomas can be confused with other pathological conditions, including benign and malignant tumors. Criteria for differentiating the diagnostic options are reviewed.