Throat related symptoms and voice: development of an instrument for self assessment of throat-problems

<p>Abstract</p> <p>Background</p> <p>Symptoms from throat (sensation of globus; frequent throat clearing; irritated throat) are common in patients referred to voice clinics and to ENT specialists. The relation to symptoms of voice discomfort is unclear and in some cases patients do not have voice problems at all. Instruments for patients' self-reporting of symptoms, and assessment of handicap, such as the Voice Handicap Index (VHI), are in common use in voice clinics. Symptoms from throat are however only marginally covered. Purpose: To develop and evaluate an instrument that could make the patients' estimation of symptoms from the throat possible. Further to facilitate the consideration of the relation between throat- and voice problems with the Throat subscale together with a Swedish translation of the Voice Handicap Index. Finally to try the VHI with the Throat subscale: the VHI-T, for test-retest reliability and validity.</p> <p>Methods</p> <p>A subscale with 10 throat related items was developed for appliance with the VHI. The VHI was translated to Swedish and retranslated to English. The questionnaire was tried in two phases on a total of 23+144 patients and 12+58 voice healthy controls. The reliability was calculated with Cronbach's alpha, ICC and Pearson's correlation coefficient. The validity was estimated by independent T-test.</p> <p>Results</p> <p>The difference in VHI-T scores between the patients and the voice-healthy controls was significant (<it>p </it>= < 0,01) and there was a good correlation of the test- retest occasions. The reliability testing of the entire questionnaire showed an alpha value of <it>r </it>= 0,90 and that for the Throat subscale separately a value of <it>r </it>= 0,87 which shows a high degree of reliability.</p> <p>Conclusions</p> <p>For the estimation of self-perceived throat and voice problems the scale on throat related problems together with the present Swedish translation of the Voice Handicap Index, (VHI) the VHI-Throat, proves to be a valid and reliable instrument. The throat subscale seems to help revealing a category of symptoms that are common in our patients. These are symptoms that have not earlier been possible to cover with the questionnaires designed for use in the voice clinic.</p

Is bigger always better? The importance of cortical configuration with respect to cognitive ability

General cognitive ability (GCA) has substantial explanatory power for behavioral and health outcomes, but its cortical substrate is still not fully established. GCA is highly polygenic and research to date strongly suggests that its cortical substrate is highly polyregional. We show in map-based and region-of-interest-based analyses of adult twins that a complex cortical configuration underlies GCA. Having relatively greater surface area in evolutionary and developmentally high-expanded prefrontal, lateral temporal, and inferior parietal regions is positively correlated with GCA, whereas relatively greater surface area in low-expanded occipital, medial temporal, and motor cortices is negatively correlated with GCA. Essentially the opposite pattern holds for relative cortical thickness. The phenotypic positive-to-negative gradients in our cortical-GCA association maps were largely driven by a similar pattern of genetic associations. The patterns are consistent with regional cortical stretching whereby relatively greater surface area is related to relatively thinner cortex in high-expanded regions. Thus, the typical "bigger is better" view does not adequately capture cortical-GCA associations. Rather, cognitive ability is influenced by complex configurations of cortical development patterns that are strongly influenced by genetic factors. Optimal cognitive ability appears to be driven both by the absolute size and the polyregional configuration of the entire cortex rather than by small, circumscribed regions.Peer reviewe

Contribution of brain or biological reserve and cognitive or neural reserve to outcome after TBI: a meta-analysis (prior to 2015)

Brain/biological (BR) and cognitive/neural reserve (CR) have increasingly been used to explain some of the variability that occurs as a consequence of normal ageing and neurological injuries or disease. However, research evaluating the impact of reserve on outcomes after adult traumatic brain injury (TBI) has yet to be quantitatively reviewed. This meta-analysis consolidated data from 90 studies (published prior to 2015) that either examined the relationship between measures of BR (genetics, age, sex) or CR (education, premorbid IQ) and outcomes after TBI or compared the outcomes of groups with high and low reserve. The evidence for genetic sources of reserve was limited and often contrary to prediction. APOE ∈4 status has been studied most, but did not have a consistent or sizeable impact on outcomes. The majority of studies found that younger age was associated with better outcomes, however most failed to adjust for normal age-related changes in cognitive performance that are independent of a TBI. This finding was reversed (older adults had better outcomes) in the small number of studies that provided age-adjusted scores; although it remains unclear whether differences in the cause and severity of injuries that are sustained by younger and older adults contributed to this finding. Despite being more likely to sustain a TBI, males have comparable outcomes to females. Overall, as is the case in the general population, higher levels of education and pre-morbid IQ are both associated with better outcomes.Jane L. Mathias, Patricia Wheato

Brain cortical characteristics of lifetime cognitive ageing

Regional cortical brain volume is the product of surface area and thickness. These measures exhibit partially distinct trajectories of change across the brain’s cortex in older age, but it is unclear which cortical characteristics at which loci are sensitive to cognitive ageing differences. We examine associations between change in intelligence from age 11 to 73 years and regional cortical volume, surface area, and thickness measured at age 73 years in 568 community-dwelling older adults, all born in 1936. A relative positive change in intelligence from 11 to 73 was associated with larger volume and surface area in selective frontal, temporal, parietal, and occipital regions (r &lt; 0.180, FDR-corrected q &lt; 0.05). There were no significant associations between cognitive ageing and a thinner cortex for any region. Interestingly, thickness and surface area were phenotypically independent across bilateral lateral temporal loci, whose surface area was significantly related to change in intelligence. These findings suggest that associations between regional cortical volume and cognitive ageing differences are predominantly driven by surface area rather than thickness among healthy older adults. Regional brain surface area has been relatively underexplored, and is a potentially informative biomarker for identifying determinants of cognitive ageing differences

Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation

Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets

Genome-Wide Association Study of Circulating Interleukin 6 Levels Identifies Novel Loci

Interleukin-6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery, and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (n{discovery} = 52 654 and n_{replication} = 14 774) individuals of European ancestry. The inverse variance fixed-effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on Chromosome (Chr) 2q14, (pcombined = 1.8 × 10^{−11}), HLA-DRB1/DRB5 rs660895 on Chr6p21 (p_{combined} = 1.5 × 10^{−10}) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (p_{combined} = 1.2 × 10^{−122}). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology

Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Illness perceptions mediate the relationship between bowel symptom severity and health-related quality of life in IBS patients

PURPOSE: Irritable bowel syndrome (IBS) is a functional bowel disorder with a large negative impact on HRQOL. The present study examines whether severity of bowel symptoms is directly related to HRQOL, and/or indirectly, mediated by the patients’ illness perceptions. METHODS: Patients were recruited from an IBS support group (N = 123), and data were collected online. HRQOL was measured with the Quality of Life Measure for Persons with IBS and illness perceptions with the brief Illness Perception Questionnaire. Mediation models were tested using the bootstrapping procedure developed by Hayes. RESULTS: Irritable bowel syndrome symptom severity is directly related to total HRQOL and its subscales; after entering the mediator variables (i.e. the patients’ illness perceptions) into the model, this direct association remained only significant for total HRQOL. The relationship between bowel symptom severity and total HRQOL was partially mediated by illness perceptions, and its relationship with each of the HRQOL subscales was fully mediated by the patients’ illness perceptions. Perceived consequences were a mediator of the relationship between bowel symptom severity, total HRQOL as well as its subscales, with the exception of Sexuality. CONCLUSIONS: Bowel symptom severity not only has a direct relationship with HRQOL, but also an indirect relationship via the patients’ cognitive and emotional representations of their illness. In order to better understand this relationship, future research should not only include illness perceptions but also assess cognitive and behavioural coping responses. Clinicians wanting to improve patients’ HRQOL should not only focus on the patients’ symptoms, but also on their illness beliefs and coping responses