A fast linkage method for population GWAS cohorts with related individuals.

Linkage analysis, a class of methods for detecting co-segregation of genomic segments and traits in families, was used to map disease-causing genes for decades before genotyping arrays and dense SNP genotyping enabled genome-wide association studies in population samples. Population samples often contain related individuals, but the segregation of alleles within families is rarely used because traditional linkage methods are computationally inefficient for larger datasets. Here, we describe Population Linkage, a novel application of Haseman-Elston regression as a method of moments estimator of variance components and their standard errors. We achieve additional computational efficiency by using modern methods for detection of IBD segments and variance component estimation, efficient preprocessing of input data, and minimizing redundant numerical calculations. We also refined variance component models to account for the biases in population-scale methods for IBD segment detection. We ran Population Linkage on four blood lipid traits in over 70,000 individuals from the HUNT and SardiNIA studies, successfully detecting 25 known genetic signals. One notable linkage signal that appeared in both was for low-density lipoprotein (LDL) cholesterol levels in the region near the gene APOE (LOD = 29.3, variance explained = 4.1%). This is the region where the missense variants rs7412 and rs429358, which together make up the ε2, ε3, and ε4 alleles each account for 2.4% and 0.8% of variation in circulating LDL cholesterol. Our results show the potential for linkage analysis and other large-scale applications of method of moments variance components estimation.

The natural history of progressive myoclonus ataxia.

Progressive myoclonus ataxia (PMA) is a rare clinical syndrome characterized by the presence of progressive myoclonus and ataxia, and can be accompanied by mild cognitive impairment and infrequent epileptic seizures. This is the first study to describe the natural history of PMA and identify clinical, electrophysiological, and genetic features explaining the variability in disease progression. A Dutch cohort of consecutive patients meeting the criteria of the refined definition of PMA was included. The current phenotype was assessed during in-person consultation by movement disorders experts, and retrospective data was collected to describe disease presentation and progression, including brain imaging and therapy efficacy. Extensive genetic and electrophysiological tests were performed. The presence of cortical hyperexcitability was determined, by either the identification of a cortical correlate of myoclonic jerks with simultaneous electromyography-electroencephalography or a giant somatosensory evoked potential. We included 34 patients with PMA with a median disease duration of 15 years and a clear progressive course in most patients (76%). A molecular etiology was identified in 82% patients: ATM, CAMTA1, DHDDS, EBF3, GOSR2, ITPR1, KCNC3, NUS1, POLR1A, PRKCG, SEMA6B, SPTBN2, TPP1, ZMYND11, and a 12p13.32 deletion. The natural history is a rather homogenous onset of ataxia in the first two years of life followed by myoclonus in the first 5 years of life. Main accompanying neurological dysfunctions included cognitive impairment (62%), epilepsy (38%), autism spectrum disorder (27%), and behavioral problems (18%). Disease progression showed large variability ranging from an epilepsy free PMA phenotype (62%) to evolution towards a progressive myoclonus epilepsy (PME) phenotype (18%): the existence of a PMA-PME spectrum. Cortical hyperexcitability could be tested in 17 patients, and was present in 11 patients and supported cortical myoclonus. Interestingly, post-hoc analysis showed that an absence of cortical hyperexcitability, suggesting non-cortical myoclonus, was associated with the PMA-end of the spectrum with no epilepsy and milder myoclonus, independent of disease duration. An association between the underlying genetic defects and progression on the PMA-PME spectrum was observed. By describing the natural history of the largest cohort of published patients with PMA so far, we see a homogeneous onset with variable disease progression, in which phenotypic evolution to PME occurs in the minority. Genetic and electrophysiological features may be of prognostic value, especially the determination of cortical hyperexcitability. Furthermore, the identification of cortical and non-cortical myoclonus in PMA helps us gain insight in the underlying pathophysiology of myoclonus.

Parental genetically predicted liability for coronary heart disease and risk of adverse pregnancy outcomes: a cohort study.

BACKGROUND: Adverse pregnancy outcomes (APO) may unmask or exacerbate a woman's underlying risk for coronary heart disease (CHD). We estimated associations of maternal and paternal genetically predicted liability for CHD with lifelong risk of APOs. We hypothesized that associations would be found for women, but not their male partners (negative controls). METHODS: We studied up to 83,969‬ women (and up to 55,568‬ male partners) from the Norwegian Mother, Father and Child Cohort Study or the Trøndelag Health Study with genotyping data and lifetime history of any APO in their pregnancies (1967-2019) in the Medical Birth Registry of Norway (miscarriage, stillbirth, hypertensive disorders of pregnancy, gestational diabetes, small for gestational age, large for gestational age, and spontaneous preterm birth). Maternal and paternal genetic risk scores (GRS) for CHD were generated using 148 gene variants (p-value < 5 × 10-8, not in linkage disequilibrium). Associations between GRS for CHD and each APO were determined using logistic regression, adjusting for genomic principal components, in each cohort separately, and combined using fixed effects meta-analysis. RESULTS: One standard deviation higher GRS for CHD in women was related to increased risk of any hypertensive disorders of pregnancy (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.05-1.10), pre-eclampsia (OR 1.08, 95% CI 1.05-1.11), and small for gestational age (OR 1.04, 95% CI 1.01-1.06). Imprecise associations with lower odds of large for gestational age (OR 0.98, 95% CI 0.96-1.00) and higher odds of stillbirth (OR 1.04, 95% CI 0.98-1.11) were suggested. These findings remained consistent after adjusting for number of total pregnancies and the male partners' GRS and restricting analyses to stable couples. Associations for other APOs were close to the null. There was weak evidence of an association of paternal genetically predicted liability for CHD with spontaneous preterm birth in female partners (OR 1.02, 95% CI 0.99-1.05), but not with other APOs. CONCLUSIONS: Hypertensive disorders of pregnancy, small for gestational age, and stillbirth may unmask women with a genetically predicted propensity for CHD. The association of paternal genetically predicted CHD risk with spontaneous preterm birth in female partners needs further exploration.

Cultural transmission, competition for prey, and the evolution of cooperative hunting.

Although cooperative hunting is widespread among animals, its benefits are unclear. At low frequencies, cooperative hunting may allow predators to escape competition and access bigger prey that could not be caught by a lone cooperative predator. Cooperative hunting is a more successful strategy when it is common, but its spread can result in overhunting big prey, which may have a lower per-capita growth rate than small prey. We construct a one-predator species, two-prey species model in which predators either learn to hunt small prey alone or learn to hunt big prey cooperatively. Predators first learn vertically from parents, then horizontally (i.e. socially) from random individuals or siblings. After horizontal transmission, they hunt with their learning partner if both are cooperative, and otherwise they hunt alone. Cooperative hunting cannot evolve when initially rare unless predators (a) interact with siblings, or (b) horizontally transmit the cooperative behavior to potential hunting partners. Whereas competition for small prey favors cooperative hunting when this cooperation is initially rare, the frequency of cooperative hunting cannot reach 100% unless big prey is abundant. Furthermore, a mutant that increases horizontal learning can invade if cooperative hunting is present, but not at 100%, because horizontal learning allows pairs of predators to have the same strategy. Our results reveal that the interactions between prey availability, social learning, and degree of cooperation among predators may have important effects on ecosystems.

Diabetes Mellitus and Acute Facial Palsy: A Nationwide Population-Based Study.

INTRODUCTION: Acute facial palsy, characterized by sudden hemifacial weakness, significantly impacts an individual's quality of life. Despite several predisposing factors identified for acute facial palsy, the specific relationship between diabetes mellitus (DM) and acute facial palsy has not been comprehensively explored in recent studies. The aim of the study was to assess the risk of acute facial palsy in patients with DM using a nationwide population sample cohort. METHODS: DM cohort and non-DM cohort were built using the Korean National Health Insurance Service-Sample Cohort which represents the entire population of the Republic of Korea from January 2002 to December 2019. The DM cohort comprised 92,872 patients with a record of medication and a diagnosis of DM. Individuals who had facial palsy before the diagnosis of DM were excluded. A comparison cohort comprised 1,012,021 individuals without DM matched sociodemographically in a 1:4 ratio. The incidence of Bell's palsy (BP) and Ramsay Hunt syndrome (RHS) were evaluated in both cohorts. The risk factors for acute facial palsy were also assessed. RESULTS: Among the 92,868 patients in the DM cohort, the incidence rate (IR) of BP and RHS were 31.42 (confidence interval [CI], 30.24-32.63) and 4.58 per 10,000 person-years (CI, 4.14-5.05), respectively. Among the 371,392 individuals in the non-DM cohort, the IR of BP was 22.11 per 10,000 person-years (CI, 21.62-22.59) and the IR of RHS was 2.85 per 10,000 person-years (CI, 2.68-3.02). IR ratios for BP and RHS were 1.42 (CI, 1.36-1.48) and 1.61 (CI, 1.43-1.80). In multivariate analysis, DM (hazard ratio [HR] 1.428), age (HR 1.008), and high comorbidity score (HR 1.051) were associated with increased risk of BP, and male (HR 0.803) and living in metropolis (HR 0.966) decreased the risk of BP. And DM (HR 1.615), high comorbidity score (HR 1.078), and living in metropolis (HR 1.201) were associated with increased risk for RHS. CONCLUSION: This study suggests that patients with DM had an increased risk of acute facial palsy including BP and RHS.

Insomnia symptoms and risk for atrial fibrillation - The HUNT study.

Studies on the effect of insomnia on atrial fibrillation risk in the general population are limited, therefore we investigated the association between insomnia and the risk of atrial fibrillation in a large-scale population-based study with valid atrial fibrillation measure. A total of 33,983 participants (55% women) reported their insomnia symptoms in the third wave of the HUNT study (between 2006 and 2008) in Norway, and they were followed for their first atrial fibrillation diagnosis until 2020 using hospital registers. Atrial fibrillation diagnoses were validated by physicians based on medical records and electrocardiograms. Insomnia symptoms were assessed by four questions, and analysed both individually and as cumulative symptoms. Cox regression, adjusted for age, sex, social and marital status, working in shiftwork, alcohol consumption, smoking, physical activity, body mass index, systolic blood pressure, and symptoms of anxiety and depression, was conducted. Overall, 1592 atrial fibrillation cases were identified during the follow-up and 31.6% of individuals reported at least one insomnia symptom. In our analysis, we did not detect meaningful associations between insomnia symptoms and the risk of atrial fibrillation. In conclusion, in this population there was no evidence for an association between insomnia symptoms and the risk of subsequent atrial fibrillation.

Moderate cardiac vagal tone predicts more cooperation in highly sensitive individuals.

Cooperation, as a mutual collaboration, is a defining feature of human social life. Individual characteristics can influence cooperation. Recent studies have shown a quadratic relationship between cardiac vagal tone (CVT), an index of self-regulation, and prosocial behaviors. Individual differences in cooperation might also vary as a function of people's environmental sensitivity (ES), i.e., may be influenced by individual differences in the perception and processing of inner and external stimuli. We tested the direct and interactive effect of CVT and ES on cooperative behaviors in two independent samples. We measured heart rate and engagement in cooperative acts in 80 young adults (M = 23.61; SD = 1.60) who were also asked to self-report on ES. We found an inverted-U relationship between CVT and cooperative behaviors. ES, on the other hand, did not predict differences in cooperative behaviors but moderated the relationships between CVT and cooperation, although the magnitude of this result was small. Specifically, only among individuals with higher ES cooperative behaviors change as a function of CVT. Highly sensitive individuals with lower or higher CVT, were less cooperative than low sensitive ones. Subsequently, we replicated the same study design in a second sample of 88 undergraduate students (M = 23.69; SD = 4.91). Once again, we found evidence supporting the presence of an inverted-U relationship between CVT and cooperative behaviors, and we also found that ES moderated the relationships between the quadratic CVT term and cooperation.

Preconception diet in adolescence and its association with hypertensive disorders of pregnancy and preterm birth. Results from the HUNT study.

Our aim was to estimate associations of adolescent dietary patterns and meal habits with hypertensive disorders of pregnancy (HDP) and preterm birth. We used data from a prospective cohort study (Norwegian Young-HUNT1) where dietary information was collected during adolescence and pregnancy outcomes were obtained through record linkage to the Norwegian national birth registry. The outcomes were HDP, hypertension, pre-eclampsia/eclampsia, and preterm birth in the first pregnancy and in any pregnancy. Diet was self-reported from validated questionnaires, and exposures were dietary indexes (healthy; unhealthy; fruit and vegetable; fibre index) and meal habits. Recruitment took place in schools. Eligible participants were females aged 13-19 years at the time of dietary assessment with a subsequent singleton pregnancy (n 3622). Women who reported a higher fibre intake in adolescence had a lower risk of pre-eclampsia in the first pregnancy (Relative Risk: 0·84; 95 % CI 0·7, 1·0), although this was weaker in sensitivity analyses. Regular meal habits in mid-adolescence (aged 13-15 years), particularly breakfast and lunch, were weakly associated with a lower risk of hypertension in pregnancy. Our results are the first to indicate an association between aspects of diet and dietary behaviour in mid-adolescence and subsequent HDP. More evidence is needed from larger studies to replicate the results and from alternative study designs to disentangle causality.

Episodic memory during middle childhood: What is developing?

Whereas previous research has concentrated on the emergence of episodic memory during the early years, fewer investigations have explored the details of this development through middle and late childhood. Considerable variation in task demands and testing methodologies have rendered the trajectory of episodic memory during this period unclear, particularly with regard to which elements are in a state of change at which time. This study separately assessed memory for item, location, and temporal order, as well as integrated what-where-when (WWW) information using a WWW memory test (the Treasure Hunt task), with 84 children aged 6 to 12 years. Two versions of the task were used, varying in the degree of retrieval support while keeping encoding constant. Results show that episodic memory continued to develop across this period, with individual item, spatial, temporal, and WWW memory all improving relatively linearly with age. These improvements were underpinned by both the associative binding and strategic control processes. These findings suggest that it is not any one element of episodic memory that is driving development during this period but that all aspects are continuing to mature in parallel.

Electrocardiographic abnormalities are prognostic of the clinical outcomes and mortality of patients with subarachnoid hemorrhages.

PURPOSE: We explored the relationships between electrocardiographic (ECG) abnormalities and the clinical outcomes and mortality of patients with non-traumatic aneurysmal subarachnoid hemorrhages (SAHs). METHODS: This retrospective cohort study enrolled consecutive adult patients who presented to emergency departments with non-traumatic aneurysmal SAHs. We recorded their demographics, clinical characteristics, and ECG findings, and explored the relationships between ECG abnormalities, on the one hand, and 28-day mortality and prognosis, on the other. RESULTS: We enrolled 158 patients, 76 females (48.10%) and 82 males (51.90%) of average age 54.70 ± 7.07 years. A total of 107 patients (67.72%) exhibited at least one ECG abnormality, most commonly a T-wave change (n = 54, 34.18%). Such patients evidenced significantly higher Hunt-Hess and Fisher scale scores than those without abnormalities (both p < 0.001). Patients with abnormal ECG findings experienced more unfavorable outcomes and higher mortality than others (both p < 0.001). ECG abnormalities, including PR prolongation, pathological Q waves, QRS widening, left bundle branch blocks, premature ventricular contractions, ST segment changes, and T-wave changes, were more common in non-survivors and patients with Hunt-Hess scores of 4-5 compared to survivors and those with Hunt-Hess scores <4, respectively. Moreover, increased age and presence of abnormal ECG findings were independent predictors of mortality in aneurysmal SAHs. CONCLUSIONS: Patients with abnormal ECG findings exhibited unfavorable clinical outcomes and increased mortality rates. Abnormal ECG findings combined with higher Hunt-Hess or Fischer grade scores usefully predict adverse clinical outcomes in and mortality of SAH patients.

Health-promoting behaviors in older adulthood and intrinsic capacity 10 years later: the HUNT study.

BACKGROUND: With the global population growing older, there is a need for more knowledge of how to improve and/or maintain functional capacities to promote healthy ageing. In this study we aimed to assess the effect of several known health-promoting behaviors in old age with intrinsic capacity ten years later. METHODS: This was a prospective cohort study looking at participants that were ≥ 65 years at the time of the third wave of the Trøndelag Health Study (HUNT3, 2006-2008) who also took part in the 70 + sub-study of the fourth wave (HUNT4 70+, 2017-2019). Self-reported behavior data from short questionnaires, including diet and physical activity, were collected in HUNT3, and data on the five domains of intrinsic capacity defined by the World Health Organization were collected in HUNT4 70+. A composite index was created for both healthy life and intrinsic capacity, awarding points for how well participants adhered to guidelines for healthy living and their level of functional impairment, respectively. Ordinal logistic regression was used to assess the relationship between health-promoting behaviors and intrinsic capacity. RESULTS: Of 12,361 participants in HUNT3 ≥ 65 years, 4699 (56.5% women) also participated in HUNT4 70+. On the health-promoting behaviors, lowest adherence to healthy living guidelines were seen for fruit and vegetables intake (47.2%), milk intake (46.7%) and physical activity (31.1%). On intrinsic capacity domains, highest impairment was seen in the domains of locomotion (29.7%), hearing (11.1%) and vitality (8.3%). A higher adherence to guidelines for healthy living was associated with higher intrinsic capacity 10 years later. A one-point increase in the healthy life index was associated with a 1.15 (95% confidence interval 1.10-1.21) times increased odds of being in a higher intrinsic capacity category. CONCLUSION: Health-promoting behaviors in old age are associated with better intrinsic capacity ten years later. In clinical settings assessment of health-promoting behaviors could potentially be done using short questionnaires.

The Impact of the COVID-19 Pandemic on Bell's Palsy and Ramsay-Hunt Syndrome: A Multicenter Retrospective Study.

BACKGROUND: This article presents a comprehensive review of data on the impact of facial palsy during the coronavirus disease 2019 (COVID-19) pandemic. The possible causes and pathophysiological mechanisms of changes in the epidemiology of facial palsy during the COVID-19 pandemic are also discussed. METHODS: This multicenter retrospective cohort study included 943 patients diagnosed with Bell's palsy or Ramsay Hunt syndrome. This study compared patient demographics, comorbidities, symptoms, and treatments before the COVID-19 pandemic (from 2017 to 2019) and during the COVID-19 pandemic, from 2020 to 2022). RESULTS: Following the COVID-19 outbreak, there has been a significant increase in the number of cases of Bell's palsy, particularly among elderly individuals with diabetes. Bell's palsy increased after the COVID-19 outbreak, rising from 75.3% in the pre-COVID-19 era to 83.6% after the COVID-19 outbreak. The complete recovery rate decreased from 88.2% to 73.9%, and the rate of recurrence increased from 2.9% to 7.5% in patients with Bell's palsy. Ramsay Hunt syndrome showed fewer changes in clinical outcomes. CONCLUSION: This study highlights the impact of the COVID-19 pandemic on the presentation and management of facial palsy, and suggests potential associations with COVID-19. Notably, the observed increase in Bell's palsy cases among elderly individuals with diabetes emphasizes the impact of the pandemic. Identifying the epidemiological changes in facial palsy during the COVID-19 pandemic has important implications for assessing its etiology and pathological mechanisms of facial palsy disease.

Secular trends in risk factors for adolescent anxiety and depression symptoms: the Young-HUNT studies 1995-2019, Norway.

In recent decades, increases in mental health problems in adolescents have been reported from several large population-based surveys. This raises questions about changes in underlying risk and protective factors that can inform future intervention strategies. Population data were collected from 1995 to 2019 in three waves of the Young-HUNT studies in Norway to map decennial trends in the prevalence of established risk factors for, and their associations with, adolescent mental health problems. All adolescents (aged 13-19 years) attending lower and upper secondary school in the county of Trøndelag were invited, representing three historical cohorts of 25,245 unique adolescents. Mental health problems (HSCL-5) and established mental health risk factors were self-reported. Using a generalized linear model and linear regression, we calculated changes in relative and absolute differences between risk factors and mental health problems. Overall, the prevalence of established risk factors for mental health problems in adolescence increased markedly between 1995 and 2019, especially in girls. Prominent increases were observed for fatigue, bullying, musculoskeletal pain and migraine, loneliness, and overweight. Furthermore, with the exception of excess alcohol use and family economy, associations between each risk factor and adolescent mental health problems strengthened over the same time span in girls, but less among boys. Our findings suggest that several modifiable risk factors for poor mental health in adolescence are increasing, especially among girls, and should be targeted in community, school, and in clinical settings.

The significance of shooting angle in seal shooting.

The present study aimed to investigate the relationship between shooting angle to the head and animal welfare outcomes in the hunt of young harp seals (Pagophilus groenlandicus). The study population consisted of young harp seals belonging to the Greenland Sea harp seal population. A sample of 171, 2-7 weeks old, weaned harp seals of both sexes were included. The study was conducted as an open, randomised parallel group designed trial during the regular hunt. The animals were allocated into four groups, A-D, according to the observed shooting angle to the head, defined as the angle between the direction of the shot and the longitudinal axis of the animal's head: (A) directly from the front; (B) obliquely from the front; (C) directly from the side; and (D) obliquely or directly from behind. Instantaneous death rate (IDR) and time to death (TTD) were the main variables. The mean IDR differed significantly between groups and was highest in group B (96.8%) and lowest in group C (66.7%). For all groups combined it was 84.2%. The mean TTD for seals not rendered instantaneously unconscious or dead (n = 27) differed significantly between groups and was shortest in group A (16 s) and longest in group C (85 s). However, the number of animals included in the TTD analysis was limited. In conclusion, based on the significantly higher IDR, the shooting angle obliquely from the front is recommended to help achieve the best animal welfare outcomes during the hunt of young harp seals.

Loneliness increases the risk of type 2 diabetes: a 20 year follow-up - results from the HUNT study.

AIMS/HYPOTHESIS: Type 2 diabetes is one of the leading causes of death globally and its incidence has increased dramatically over the last two decades. Recent research suggests that loneliness is a possible risk factor for type 2 diabetes. This 20 year follow-up study examined whether loneliness is associated with an increased risk of type 2 diabetes. As both loneliness and type 2 diabetes have been linked to depression and sleep problems, we also investigated whether any association between loneliness and type 2 diabetes is mediated by symptoms of depression and insomnia. METHODS: We used data from the Trøndelag Health Study (HUNT study), a large longitudinal health study based on a population from central Norway (n=24,024). Self-reports of loneliness (HUNT2 survey, 1995-1997) and data on HbA1c levels (HUNT4 survey, 2017-2019) were analysed to evaluate the associations between loneliness and incidence of type 2 diabetes. Associations were reported as ORs with 95% CIs, adjusted for sex, age and education. We further investigated the role of depression and insomnia as potential mediating factors. RESULTS: During the 20 year follow-up period, 4.9% of the study participants developed type 2 diabetes. Various degrees of feeling lonely were reported by 12.6% of the participants. Individuals who felt most lonely had a twofold higher risk of developing type 2 diabetes relative to those who did not feel lonely (adjusted OR 2.19 [95% CI 1.16, 4.15]). The effect of loneliness on type 2 diabetes was weakly mediated by one subtype of insomnia but not by symptoms of depression. CONCLUSIONS/INTERPRETATION: This study suggests that loneliness may be one factor that increases the risk of type 2 diabetes; however, there is no strong support that the effect of loneliness on type 2 diabetes is mediated by depression or insomnia. We recommend that loneliness should be included in clinical guidelines on consultations and interventions related to type 2 diabetes.

Exploring shared genetics between maximal oxygen uptake and disease: the HUNT study.

Low cardiorespiratory fitness, measured as maximal oxygen uptake (V̇o2max), is associated with all-cause mortality and disease-specific morbidity and mortality and is estimated to have a large genetic component (∼60%). However, the underlying mechanisms explaining the associations are not known, and no association study has assessed shared genetics between directly measured V̇o2max and disease. We believe that identifying the mechanisms explaining how low V̇o2max is related to increased disease risk can contribute to prevention and therapy. We used a phenome-wide association study approach to test for shared genetics. A total of 64,479 participants from the Trøndelag Health Study (HUNT) were included. Genetic variants previously linked to V̇o2max were tested for association with diseases related to the cardiovascular system, diabetes, dementia, mental disorders, and cancer as well as clinical measurements and biomarkers from HUNT. In the total population, three single-nucleotide polymorphisms (SNPs) in and near the follicle-stimulating hormone receptor gene (FSHR) were found to be associated (false discovery rate < 0.05) with serum creatinine levels and one intronic SNP in the Rap-associating DIL domain gene (RADIL) with diabetes type 1 with neurological manifestations. In males, four intronic SNPs in the PBX/knotted homeobox 2 gene (PKNOX2) were found to be associated with endocarditis. None of the association tests in the female population reached overall statistical significance; the associations with the lowest P values included other cardiac conduction disorders, subdural hemorrhage, and myocarditis. The results might suggest shared genetics between V̇o2max and disease. However, further effort should be put into investigating the potential shared genetics between inborn V̇o2max and disease in larger cohorts to increase statistical power.NEW & NOTEWORTHY To our knowledge, this is the first genetic association study exploring how genes linked to cardiorespiratory fitness (CRF) relate to disease risk. By investigating shared genetics, we found indications that genetic variants linked to directly measured CRF also affect the level of blood creatinine, risk of diabetes, and endocarditis. Less certain findings showed that genetic variants of high CRF might cause lower body mass index, healthier HDL cholesterol, and lower resting heart rate.

The causal role of C-reactive protein and interleukin-6 on anxiety and depression symptoms and life satisfaction: Mendelian randomisation analyses in the HUNT study.

BACKGROUND: Serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) have been associated with anxiety and depression in cross-sectional and Mendelian randomisation studies, but results regarding the effect size and direction have been mixed. A recent Mendelian Randomisation (MR) study suggested that CRP may decrease and IL-6 may increase anxiety and depression symptoms. METHODS: Among 68 769 participants of the population-based Trøndelag Health Study (HUNT), we performed cross-sectional observational and one-sample MR analyses of serum CRP and two-sample MR analysis of serum IL-6. The main outcomes were symptoms of anxiety and depression assessed using the Hospital Anxiety and Depression Scale (HADS) and life satisfaction assessed using a seven-level ordinal questionnaire where higher scores indicate lower life satisfaction. RESULTS: In cross-sectional observational analyses, a doubling in serum CRP level was associated with 0.27% (95% CI -0.20 to 0.75) difference in HADS depression score (HADS-D), -0.77% (95% CI -1.24 to -0.29) difference in HADS anxiety score (HADS-A) and -0.10% (95% CI -0.41 to 0.21) difference in life satisfaction score. In one-sample MR analyses, a doubling in serum CRP was associated with 2.43% (95% CI -0.11 to 5.03) higher HADS-D, 1.94% (95% CI -0.58 to 4.52) higher HADS-A, and 2.00% (95% CI 0.45 to 3.59) higher life satisfaction score. For IL-6, causal point estimates were in the opposite direction, but imprecise and far from conventional criteria for statistical significance. CONCLUSIONS: Our results do not support a major causal role of serum CRP on anxiety and depression symptoms and life satisfaction, but provides weak evidence that serum CRP may modestly increase anxiety and depression symptoms and reduce life satisfaction. Our findings do not support the recent suggestion that serum CRP may lower anxiety and depression symptoms.

Insomnia and risk of dementia in a large population-based study with 11-year follow-up: The HUNT study.

Despite evidence suggesting that insomnia is associated with the risk of dementia and cognitive dysfunction, studies have shown mixed results. Dementia has a long prodromal phase, and studies with long follow-up are required to avoid reverse causality. In our 11-year follow-up study, we assessed whether probable insomnia disorder (PID) based on diagnostic criteria, and insomnia symptoms were associated with risk of all-cause dementia, Alzheimer's disease (AD) and cognition, measured with the Montreal Cognitive Assessment scale. We also examined if Apolipoprotein E genotype modified any associations with dementia through interaction. We analysed data from 7492 participants in the Norwegian Trøndelag Health Study. PID was not associated with all-cause dementia (odds ratio = 1.03, 95% confidence interval = 0.74-1.43), AD (odds ratio = 1.07, 95% confidence interval = 0.71-1.60) or Montreal Cognitive Assessment score (regression coefficient = 0.37, 95% confidence interval = -0.06 to 0.80). The insomnia symptom "difficulties maintaining sleep" was associated with a lower risk of all-cause dementia (odds ratio = 0.81, 95% confidence interval = 0.67-0.98), AD (odds ratio = 0.73, 95% confidence interval = 0.57-0.93), and better Montreal Cognitive Assessment score, mean 0.40 units (95% confidence interval = 0.15-0.64). No interaction with Apolipoprotein E genotype was found. PID and insomnia symptoms did not increase the risk of dementia in our study. More research with longer follow-up is needed, and future studies should explore if the associations to dementia risk vary across insomnia subtypes.

A case report on recurrent alternating Tolosa-Hunt syndrome due to bacterial sphenoid sinusitis: rediscussing the diagnostic terminology and classification.

BACKGROUND: Tolosa-Hunt syndrome (THS) is characterized by painful ophthalmoplegia caused by idiopathic granulomatous inflammation involving the cavernous sinus region. Patients respond well to steroid therapy. THS is included in the differential diagnosis of cavernous sinus syndrome, so it is important to fully exclude other lesions in this area before treatment, otherwise steroid treatment may lead to fatal outcomes. Here we describe a patient who initially presented with symptoms that simulated THS symptoms and developed recurrent alternating painful ophthalmoplegia during follow-up, and the patient was finally diagnosed with cavernous sinusitis caused by bacterial sphenoid sinusitis. CASE PRESENTATION: A 34-year-old woman presented with left painful ophthalmoplegia. Magnetic resonance imaging (MRI) revealed abnormal signals in the left cavernous sinus area, and these abnormal signals were suspected to be THS. After steroid treatment, the patient obtained pain relief and had complete recovery of her ophthalmoplegia. However, right painful ophthalmoplegia appeared during the follow-up period. MRI showed obvious inflammatory signals in the right cavernous sinus and right sphenoid sinus. Then nasal sinus puncture and aspiration culture were performed, and the results showed a coagulase-negative staphylococcus infection. After antibiotic treatment with vancomycin, the painful ophthalmoplegia completely resolved, and the neurological examination and MRI returned to normal. CONCLUSION: Some other causes of painful ophthalmoplegia also fulfill the diagnostic criteria for THS in the International Classification of Headache Disorders third edition (ICHD-3) and respond well to steroid therapy. Early diagnosis of THS may be harmful to patients, and clinicians should exercise great caution when dealing with similar cases without a biopsy. Using "cavernous sinus syndrome" instead of "Tolosa-Hunt syndrome" as a diagnostic category may provide a better clinical thinking for etiological diagnosis.

Two cases of Ramsay-Hunt syndrome following varicella zoster viral meningitis in young immunocompetent men: case reports.

BACKGROUND: Ramsay-Hunt syndrome (RHS) due to varicella zoster virus (VZV) infection is commonly reported in individuals aged at least 50 years or immunocompromised individuals. VZV infection may invade the central nervous system (CNS) and cause meningitis or encephalitis, which are more likely to occur in patients with chronic diseases such as diabetes and chronic renal failure. However, cases with VZV-induced concurrent RHS and CNS infections are rare. CASE PRESENTATION: Two young male patients, aged 32 and 43 years, with no underlying disease developed VZV meningitis, followed by RHS involving cranial nerves VII and VIII. Both patients presented with symptoms of peripheral facial palsy, and dizziness accompanied by tinnitus and hearing loss, which appeared several days after the onset of fever and headache. These symptoms were documented as facial neuropathy and sensorineural hearing loss in the electrophysiologic studies. Lymphocyte-dominant pleocytosis and VZV positivity were confirmed from cerebrospinal fluid examination and polymerase chain reaction, respectively. The patients were treated with intravenous acyclovir and oral steroids simultaneously. Following the treatment completion, both patients were relieved of their headaches and fever; however, facial palsy, dizziness, and tinnitus persisted. They were followed up at the outpatient clinic. CONCLUSION: These cases confirmed that RHS and CNS infections can co-exist even in young adults with normal immune function and more importantly, that CNS infection can precede RHS. Since early detection and treatment of RHS improve the prognosis, it is critical to closely monitor patients with VZV meningitis or encephalitis considering the possible superimposition of RHS.