Diagnostic and Severity-Tracking Biomarkers for Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder afflicting about one in every 68 children. It is behaviorally diagnosed based on a triad of symptoms, including impairment in communication, impairment in sociability and abnormal and stereotypic behavior. The subjectivity of behavioral diagnosis urges the need for clinical biomarker tests to improve and complement ASD diagnosis and treatment. Over the past two decades, researchers garnered a broad range of biomarkers associated with ASD and often correlating with the severity of ASD, which includes metabolic and genetic biomarkers or neuroimaging abnormalities. Metabolic biomarkers are either involved in key pathways such as a trans-sulfuration pathway or produced due to the derangement of these pathways in the case of oxidative stress. Recent studies reported several genetic abnormalities related to ASD, encompassing various mechanisms, from copy number variations (CNVs) and single nucleotide polymorphisms (SNPs) to chromosomal anomalies. However, it is still premature to consider these genetic variants as true biomarkers for ASD, due to their low reproducibility and regional-specific nature. Herein, we comprehensively review state of the art about major biomarkers reported in ASD and the association of some biomarkers with ASD symptoms and severity. It is important to establish those biomarkers to be able to help in the diagnosis and to optimize the treatment of ASD.     

Autonomic and sensory symptoms and signs in incident,untreated Parkinson's disease: Frequent but mild

Although nonmotor symptoms are increasingly recognized as key features in Parkinson's disease (PD), the occurrence and severity of autonomic and sensory symptoms in patients with very early and untreated PD are poorly documented. Two hundred seven patients with newly diagnosed, untreated PD and 175 controls from the population‐based Norwegian ParkWest study were included. Postural blood pressure and olfactory function were measured and eight autonomic and sensory symptoms assessed using interview‐based rating scales. Autonomic and sensory symptoms were more frequent in patients compared with controls (mean number of symptoms 2.9 vs. 1.1; P < 0.001) and in the postural instability and gait difficulty motor‐subtype vs. tremor dominant subtype (mean 3.3 vs. 2.5; P = 0.008). In the patient group, reduced olfaction (59%), urinary problems (47%), increased saliva or drooling (42%), constipation (39%), and sensory complaints (34%) were the most frequent symptoms. Daily activities were not affected by these symptoms in 58% of the patients, and the influence on daily activities was rated as “mild” or less for all of these symptoms in 90%. A higher Hoehn and Yahr stage was associated with a higher number of autonomic and sensory symptoms and with the occurrence of gastrointestinal symptoms. Autonomic and sensory symptoms are common in patients with untreated, early PD although the severity of these symptoms is mild, with little or no influence on daily activities. The high prevalence of increased saliva or drooling close to the time of diagnosis is noteworthy and not described earlier. © 2010 Movement Disorder Society     

Targeted next-generation sequencing reveals MODY in up to 6.5% of antibody-negative diabetes cases listed in the Norwegian Childhood Diabetes Registry

Aims/hypothesis

MODY can be wrongly diagnosed as type 1 diabetes in children. We aimed to find the prevalence of MODY in a nationwide population-based registry of childhood diabetes.

Methods

Using next-generation sequencing, we screened the HNF1A, HNF4A, HNF1B, GCK and INS genes in all 469 children (12.1%) negative for both GAD and IA-2 autoantibodies and 469 antibody-positive matched controls selected from the Norwegian Childhood Diabetes Registry (3882 children). Variants were classified using clinical diagnostic criteria for pathogenicity ranging from class 1 (neutral) to class 5 (pathogenic).

Results

We identified 58 rare exonic and splice variants in cases and controls. Among antibody-negative patients, 6.5% had genetic variants of classes 3–5 (vs 2.4% in controls; p?=?0.002). For the stricter classification (classes 4 and 5), the corresponding number was 4.1% (vs 0.2% in controls; p?=?1.6?×?10^?5). HNF1A showed the strongest enrichment of class 3–5 variants, with 3.9% among antibody-negative patients (vs 0.4% in controls; p?=?0.0002). Antibody-negative carriers of variants in class 3 had a similar phenotype to those carrying variants in classes 4 and 5.

Conclusions/interpretation

This is the first study screening for MODY in all antibody-negative children in a nationwide population-based registry. Our results suggest that the prevalence of MODY in antibody-negative childhood diabetes may reach 6.5%. One-third of these MODY cases had not been recognised by clinicians. Since a precise diagnosis is important for treatment and genetic counselling, molecular screening of all antibody-negative children should be considered in routine diagnostics.

     

Sense of coherence as a resource in relation to health-related quality of life among mentally intact nursing home residents – a questionnaire study

Background  

Sense of coherence (SOC) is a strong determinant of positive health and successful coping. For older people living in the community or staying in a hospital, SOC has been shown to be associated with health-related quality of life (HRQOL). Studies focusing on this aspect among nursing home (NH) residents have been limited. This study investigated the relationship between SOC and HRQOL among older people living in NHs in Bergen, Norway.     

Retinal vascular calibres are significantly associated with cardiovascular risk factors: the Tromsø Eye Study

Purpose: To describe the association between retinal vascular calibres and cardiovascular risk factors. Methods: Population‐based cross‐sectional study including 6353 participants of the Tromsø Eye Study in Norway aged 38–87 years. Retinal arteriolar calibre (central retinal artery equivalent) and retinal venular calibre (central retinal vein equivalent) were measured computer‐assisted on retinal photographs. Data on blood pressure, body mass index (BMI), high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) cholesterol, glycosylated haemoglobin (HbA1c) and smoking were collected. Association between retinal vessel calibre and the cardiovascular risk factors was assessed by multivariable linear and logistic regression analyses. Results: Retinal arteriolar calibre was independently associated with age, blood pressure, HbA1c and smoking in women and men, and with HDL cholesterol in men only. Blood pressure had the strongest effect on arteriolar calibre, with a decrease in calibre of 3.6 μm (women)/4.1 μm (men) per standard deviation increase in mean arterial blood pressure. Retinal venular calibre was independently associated with age, blood pressure, BMI, HDL and LDL cholesterol and smoking in men and women. The effect of BMI and HDL cholesterol on venular calibre was significantly stronger in men than in women. Current smoking was the most important factor for venular calibre, where smokers had 13.2 μm (women)/15.2 μm (men) wider calibre than nonsmokers. Conclusion: All the explored cardiovascular risk factors were independently associated with retinal vascular calibre, with stronger effect of HDL cholesterol and BMI in men than in women. Blood pressure and smoking contributed most to the explained variance.     

Bradykinin induced sustained anti-adrenergic actions in guinea pig heart muscle involves PKC

OBJECTIVES: Adenosine attenuates the effect of beta-adrenergic stimulation upon contractile force, both when present during beta-adrenergic stimulation and for a period after washout of adenosine. Protein kinase C (PKC) mediates the sustained effect. The present study investigated if bradykinin (500 nM) could induce anti-beta-adrenergic actions. DESIGN: Guinea pig papillary muscles (36.5 degrees C, 1 Hz) were subjected to 15 min exposure to and 20 min washout of bradykinin. Isoproterenol 100 nM was added for 3 min at the end of test exposure and at the end of washout. The PKC-inhibitor bisindolylmaleimide (20 nM) was given to investigate the importance of PKC. RESULTS: Bradykinin significantly reduced the increase in contractile force in response to isoproterenol, both when present and after washout of test substance. Inhibition of PKC abolished the sustained effect, while inhibition of PI3-kinase with wortmannin did not seem to affect the results. CONCLUSIONS: Anti-beta-adrenergic effects of bradykinin on contractile force and action potential duration were demonstrated. PKC was important for the sustained effect on contractile force, but not for the acute effect and the effect on action potential duration.     

Graft function 1 year after pregnancy in an islet‐transplanted patient

Pancreatic islet transplantation is a treatment option for patients with type 1 diabetes (T1D), but pregnancy has generally not been advised for women after receiving an islet allograft. We hereby describe what is to our knowledge the first successful pregnancy and persistent graft function in a woman 4 years after her initial islet transplantation. A 37‐year‐old woman with brittle type 1 diabetes was transplanted with two separate islet graft infusions, eventually becoming insulin independent. Ten months after her second transplantation, her immunosuppression was switched from tacrolimus and sirolimus to tacrolimus, azathioprine, and prednisolone, due to her wish to become pregnant. She became pregnant one year later, and after 38 weeks of uncomplicated pregnancy, she gave birth to a healthy child by C‐section. The current report suggests that pregnancy and childbirth can be accomplished after islet transplantation without loss of islet graft function.     

Distribution patterns of muscle fibre types in major muscles of the bull (Bos taurus).

Summary The study describes the variations in distribution and cross-sectional area (fibre size) of three muscle fibre types (I, IIA, IIB) in 34 of the largest muscles of the bull (Bos taurus). The animals had been kept strictly unexercised for one year before slaughter. Representative sampling was done at 15 positions within each muscle, and from 2700 to 4500 fibres were analysed in each muscle. Different intermuscular patterns are described. The overall volume fraction (%) of type I fibres was about 10% higher in the forepart muscles than in the hindpart muscles (41% and 31%, respectively), while the mean content of type IIB fibres was similar. Type I fibres were particularly abundant in antigravity muscles. Of these, the hindlimb muscles contained 50% more type I fibres (by weight) than those of the forelimb. Typical antigravity antagonists contained very few type I fibres. In the thigh cross-section the proportion of type I fibres was highest in the anterior and medial parts, while the IIB fibres tended to be concentrated in the superficial and posterior parts. Intramuscular patterns were revealed, with type I fibres becoming gradually more abundant from superficial to deep regions, while IIB fibres had an opposite distribution. This was particularly evident in the thigh proper and in the scapular region. Within each fasciculus of all the muscles, the I fibres in the muscles of the forepart were on average about 15% larger than those of the muscles in the hindpart. The IIB fibres were on average about 10% larger in the hindpart than in the forepart muscles. A covariation between the proportion of type I and IIB fibres and their cross-sectional area was indicated.     

Validation of the Dental Fear Scale and the Dental Belief Survey in a Norwegian sample

Abstract –The aim of this study was to validate the Kleinknecht's Dental Fear Scale and the Getz's Dental Belief Survey in a Norwegian sample by 1) testing their ability to discriminate between fearful (n= 151) and regular (n= 160) patients, and 2) correlating them. Both instruments were highly reliable (Cronbach's alpha >0.90). Between 81% and 95% of the fearful and regular patients were correctly assigned to their appropriate groups with both instruments. It may thus be concluded that both instruments are valid. Also, the correlation between the instruments was 0.68, indicating that they to a large extent seem to measure the same concept. The most important predictor items for both instruments were related to avoidance of dental treatment.     

Psychometric evaluation of a Norwegian version of the Communication Strategies Scale of the Communication Profile for the Hearing Impaired

Aim. To evaluate the Communication Strategies Scale (CSS) in an adult Norwegian sample with hearing loss.

Subjects and methods. Of 474 invited patients, a total of 337 consecutive adults admitted to the outpatient Unit of Audiology, ENT Department of a university hospital answered the CSS of the Communication Profile for the Hearing Impaired. The inventory assesses the use of three specific coping strategies; Maladaptive Behaviour, Verbal and Nonverbal Communication Strategies. The psychometric evaluation included construct validity by corrected item-total correlation, the internal consistency reliability by coefficient alpha (Cronbach's) and standard error of the measurement (SEM). Internal structure was evaluated by factor analyses using principal factors followed by a varimax rotation.

Results. CSS showed good psychometric properties with acceptable and good internal consistency reliability for the subscales. The internal structure of the entire scale gave main loadings at 24 of 25 items at the same factor as the original one.

Conclusion. CSS may well be used as a clinical tool in the routine assessment of maladaptive and adaptive communication strategies in an unselected adult population of hearing impaired outpatients.