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ObjectiveCognitive and motor impairments are the key clinical manifestations of cerebral small vessel disease (SVD), but their interrelations and combined effects on functional outcome have not been elucidated. We investigated the associations between cognitive and motor functions and their interactions and mediating effects on instrumental activities of daily living (IADL) and quality of life in older individuals with various degrees of white matter hyperintensities (WMH).MethodsParticipants of the Helsinki Small Vessel Disease Study (n=152) were assessed according to an extensive clinical, neuropsychological and MRI protocol. Cognitive composite scores for global cognition, processing speed, executive functions and memory were constructed from multiple tests within each domain. Physical examination included measures of gait speed, balance (single-leg-stance) and functional mobility (timed-up-and-go test). IADL was evaluated with a proxy-based Amsterdam IADL questionnaire and quality of life with a self-report EUROHIS-Qol index. Volumes of WMH and gray matter (GM) were obtained with automated segmentation. Sets of linear regression analyses were used to model the associations between motor and cognitive performances, WMH and GM volumes, and IADL and quality of life.ResultsDomain-specific cognitive and motor functions had strong interrelations with each other, and they were significantly associated with IADL, quality of life as well as WMH and GM volumes. A consistent pattern on significant interactions between cognitive and motor functions was found on IADL, but not on quality of life. In particular, low cognitive scores together with decline in the timed-up-and-go test and gait speed were strongly related to impaired IADL. The association of WMH volume with IADL was mediated by global cognition, whereas the association of GM volume with IADL was mediated by global cognition and timed up-and-go performance.ConclusionThe results highlight the complex interplay and synergism between motor and cognitive abilities on functional outcome in SVD. The combined effect of motor and cognitive disturbances on IADL is likely to be greater than the individual effects of each of the two impairments. WMH and brain atrophy contribute to disability through cognitive and motor impairment.

DNA methylation shifts in Hypothalamic–pituitary–adrenal (HPA) axis related genes is reported in psychiatric disorders including hypersexual disorder. This study, comprising 20 dexamethasone suppression test (DST) non-suppressors and 73 controls, examined the association between the HPA axis dysregulation, shifts in DNA methylation of HPA axis related genes and importantly, gene expression. Individuals with cortisol level ≥ 138 nmol/l, after the low dose (0.5 mg) dexamethasone suppression test (DST) were classified as non-suppressors. Genome-wide methylation pattern, measured in whole blood using the EPIC BeadChip, investigated CpG sites located within 2000 bp of the transcriptional start site of key HPA axis genes, i.e.: CRH, CRHBP, CRHR-1, CRHR-2, FKBP5 and NR3C1. Regression models including DNA methylation M-values and the binary outcome (DST non-suppression status) were performed. Gene transcripts with an abundance of differentially methylated CpG sites were identified with binomial tests. Pearson correlations and robust linear regressions were performed between CpG methylation and gene expression in two independent cohorts. Six of 76 CpG sites were significantly hypermethylated in DST non-suppressors (nominal P CRH, CRHR1, CRHR2, FKBP5 and NR3C1. NR3C1 transcript AJ877169 showed statistically significant abundance of probes differentially methylated by DST non-suppression status and correlated with DST cortisol levels. Further, methylation levels of cg07733851 and cg27122725 were positively correlated with gene expression levels of the NR3C1 gene. Methylation levels of cg08636224 (FKBP5) correlated with baseline cortisol and gene expression. Our findings revealed that DNA methylation shifts are involved in the altered mechanism of the HPA axis suggesting that new epigenetic targets should be considered behind psychiatric disorders.

BACKGROUND: Gastrointestinal dysfunction is a frequent and disabling manifestation of autoimmune polyendocrine syndrome type 1 (APS-1), a rare monogenic multi-organ autoimmune disease caused by the loss of central AIRE-controlled immune tolerance. OBJECTIVE: We aimed to understand the role of the gut microbiome in APS-1 symptoms and potentially alleviate common gastrointestinal symptoms by probiotic intervention. METHODS: We characterized the fecal microbiomes of 28 APS-1 patients and searched for associations with gastrointestinal symptoms, circulating anti-cytokine autoantibodies and tryptophan-related metabolites. We additionally administered daily doses of the probiotic Lactobacillus rhamnosus GG for three months. RESULTS: Of 581 metagenomic operational taxonomic units (mOTUs) characterized in total, 14 were significantly associated with APS-1 compared to healthy controls, with six mOTUs depleted and eight enriched in APS-1 patients. Four overabundant mOTUs were significantly associated with severity of constipation. We observed phylogenetically conserved microbial associations with autoantibodies against cytokines. After the three-month intervention with the probiotic L. rhamnosus GG, a subset of gastrointestinal symptoms were alleviated. L. rhamnosus GG abundance was increased post-intervention and corresponded with decreased abundances of Alistipes onderdonkii and Collinsella aerofaciens, two species positively associated with severity of diarrhea in APS-1 patients. CONCLUSION: The APS-1 microbiome correlates with several APS-1 symptoms, some of which are alleviated after a three-month L. rhamnosus GG intervention. Autoantibodies against cytokines appear to shape the gut microbiome by positively correlating with a taxonomically consistent group of bacteria. CLINICAL IMPLICATIONS: Administration of L. rhamnosus GG appears to alleviate certain gastrointestinal symptoms of APS-1.

Purpose Automated analysis of neuroimaging data is commonly based on magnetic resonance imaging (MRI), but sometimes the availability is limited or a patient might have contradictions to MRI. Therefore, automated analyses of computed tomography (CT) images would be beneficial. Methods We developed an automated method to evaluate medial temporal lobe atrophy (MTA), global cortical atrophy (GCA), and the severity of white matter lesions (WMLs) from a CT scan and compared the results to those obtained from MRI in a cohort of 214 subjects gathered from Kuopio and Helsinki University Hospital registers from 2005 - 2016. Results The correlation coefficients of computational measures between CT and MRI were 0.9 (MTA), 0.82 (GCA), and 0.86 (Fazekas). CT-based measures were identical to MRI-based measures in 60% (MTA), 62% (GCA) and 60% (Fazekas) of cases when the measures were rounded to the nearest full grade variable. However, the difference in measures was 1 or less in 97–98% of cases. Similar results were obtained for cortical atrophy ratings, especially in the frontal and temporal lobes, when assessing the brain lobes separately. Bland–Altman plots and weighted kappa values demonstrated high agreement regarding measures based on CT and MRI. Conclusions MTA, GCA, and Fazekas grades can also be assessed reliably from a CT scan with our method. Even though the measures obtained with the different imaging modalities were not identical in a relatively extensive cohort, the differences were minor. This expands the possibility of using this automated analysis method when MRI is inaccessible or contraindicated.

Background: Mulibrey nanism (MUL) is a rare condition with profound growth delay. Congestive heart failure is a major determinant of prognosis. The aim was to delineate pericardial constriction and myocardial functional abnormalities in a pediatric MUL sample. Methods: A total of 23 MUL patients and 23 individually sex- and age-matched healthy control subjects were prospectively assessed in a cross-sectional study with echocardiography. Results: Clinical signs of heart failure were present in 7 MUL patients, with severe congestive heart failure in 2. Significant diastolic dysfunction, mainly related to constriction, was found in MUL patients without pericardiectomy (N = 18)—septal bounce, pronounced hepatic vein atrial reversal and right heart inflow–outflow variations, and decreased inferior vena cava collapse during respiration. The appearance of the pericardium was not different from that of control subjects. Longitudinal diastolic myocardial velocities were similar to those in control subjects, suggesting an absence of significant myocardial restriction. Right ventricular free wall longitudinal systolic strain and bilateral longitudinal myocardial systolic velocities were decreased in MUL patients, indicating mild biventricular systolic dysfunction. Myocardial motion abnormalities and persistent congestive heart failure were common (in 3 of 6) in MUL patients with a history of pericardiectomy. Cardiac dimensions were similar between MUL patients and control subjects when adjusting for body size, except for smaller biventricular volumes. Conclusions: MUL disease presents with significant constriction-related diastolic dysfunction and mild bilateral systolic dysfunction. Constriction–restriction assessments during follow-up could be of benefit in decision-making regarding pericardiectomy in MUL disease. Myocardial abnormalities were prevalent among MUL patients who had undergone pericardiectomy and are consistent with progression of myocardial disease in a significant proportion of patients. Résumé: Contexte: Le nanisme Mulibrey (MUL) est une maladie rare qui donne lieu à un retard de croissance marqué. L’insuffisance cardiaque congestive est un déterminant majeur du pronostic. L’objectif de cette étude était de caractériser la constriction péricardique et les anomalies fonctionnelles myocardiques dans un échantillon de cas de MUL pédiatrique. Méthodologie: Au total, 23 patients atteints de MUL et 23 sujets témoins en bonne santé ont été appariés individuellement selon le sexe et l’âge et soumis à une évaluation prospective dans le cadre d’une étude transversale avec échocardiographie. Résultats: Sept patients atteints de MUL présentaient des signes cliniques d’insuffisance cardiaque, et deux, une insuffisance cardiaque congestive sévère. Une dysfonction diastolique significative, principalement liée à la constriction, a été observée chez les patients atteints de MUL n’ayant pas subi de péricardiectomie (N = 18) – rebond septal, inversion auriculaire marquée du flux de la veine hépatique, variations prononcées du flux entrant et sortant du cœur droit, diminution du collapsus de la veine cave inférieure pendant la respiration. L’apparence du péricarde n’était pas différente de celle notée chez les sujets témoins. Les vélocités myocardiques longitudinales pendant la diastole étaient similaires à celles relevées chez les sujets témoins, ce qui suggère l’absence de restriction myocardique significative. La déformation longitudinale de la paroi libre du ventricule droit et les vélocités myocardiques longitudinales bilatérales étaient diminuées pendant la systole chez les patients atteints de MUL, ce qui indique une dysfonction systolique biventriculaire légère. Les anomalies de la cinétique myocardique et la persistance de l’insuffisance cardiaque congestive étaient fréquentes (dans trois cas sur six) chez les patients atteints de MUL ayant des antécédents de péricardiectomie. Les dimensions cardiaques chez les patients atteints de MUL étaient similaires à celles observées chez les sujets témoins après les ajustements en fonction de la taille corporelle, à l’exception des volumes biventriculaires, qui étaient plus petits. Conclusions: Le MUL entraîne une dysfonction diastolique significative liée à la constriction et une légère dysfonction systolique bilatérale. Les évaluations axées sur la constriction et la restriction effectuées au cours du suivi pourraient être utiles pour la prise de décisions concernant le recours à la péricardiectomie dans les cas de MUL. Les anomalies myocardiques étaient fréquentes chez les patients atteints de MUL qui avaient subi une péricardiectomie et concordent avec la progression de la myocardiopathie dans une proportion significative de cas.

Background The Chihuahua dog breed is known for frequent occurrence of a bregmatic fontanelle on the dorsal skull. A common conception is that this skull defect is a clinically irrelevant finding. No studies, however, describe its prevalence or whether it is accompanied by other persistent fontanelles (PFs). Although Chihuahuas are predisposed to Chiari-like malformation (CM) and syringomyelia (SM), it is unknown whether PFs occur more commonly in dogs with clinical signs that are caused by CM or SM. Hypothesis/objectives To describe the number and location of PFs at cranial sutures (CSs) and to compare the occurrence of these PFs in dogs with and without CM/SM-related clinical signs. We hypothesized that PFs also occur commonly at lateral and caudal cranial surfaces, affect a higher number of CSs, and are larger in dogs with CM/SM-related clinical signs. Animals Fifty client-owned Chihuahuas with or without CM/SM-related clinical signs. Results Of the 50 dogs evaluated, 46 (92%) had either 1 or several PFs. The mean ± SD number of PFs was 2.8 ± 3.0 (range, 0-13). A total of 138 PFs occupied 118 CSs with 57 (48%) located dorsally, 44 (37%) caudally, and 17 (14%) laterally. The number of CSs affected by PFs was significantly higher (P ≤ .001) and total PF area was significantly larger (P = .003) in dogs with CM/SM-related clinical signs. Conclusions and clinical importance Persistent fontanelles are very common in this group of Chihuahuas and appear at dorsal, lateral, and caudal cranial surfaces. They are more numerous and larger in Chihuahuas with CM/SM-related clinical signs.

Background Influenza has been an acknowledged cause of respiratory disease for decades. However, considerable related, and often unappreciated, disease burden stems from cardiovascular complications, exacerbations of underlying medical conditions and secondary respiratory complications, with the highest burden in the elderly. This novel study combines the gold standard method of a randomized controlled trial with real-world data collection through national registries, to assess the relative effectiveness of high-dose (QIV-HD) vs standard-dose quadrivalent influenza vaccine (QIV-SD) in preventing cardio-respiratory hospitalizations in a large cohort of adults aged ≥65 years. Methods and results This trial (NCT04137887) is a Phase III/IV, modified double-blinded, randomized, registry-based trial, conducted by the Finnish Institute for Health and Welfare (THL). Participants (n>120 000) are being enrolled over multiple influenza seasons and randomized (1:1) to receive QIV-HD or QIV-SD. Participant follow-up is based on data collection up to 11 months post-vaccination using Finnish national health registries. The primary objective is to demonstrate the relative superior effectiveness of QIV-HD over QIV-SD in preventing cardio-respiratory hospitalizations up to 6 months post-vaccination. Safety will be assessed using automated online tools throughout the study, with causality assessed using statistical and probabilistic methods; serious adverse reactions and adverse events of special interest will be investigated individually. Conclusion This large, real-world, randomized study will provide valuable insight into the contribution of influenza in causing severe cardio-respiratory events, and the role of vaccination with QIV-HD in reducing these outcomes compared to the current standard of care. Funding Sanofi Pasteur

Background Modern multistrand repairs can withstand forces present in active flexion exercises, and this may improve the outcomes of flexor tendon repairs. We developed a simple home-based exercise regimen with free wrist and intrinsic minus splint aimed at facilitating the gliding of the flexor tendons and compared the outcomes with the modified Kleinert regimen used previously in the same institution. Methods We searched the hospital database to identify flexor tendon repair performed before and after the new regimen was implemented and invited all patients to participate. The primary outcome was total active range of motion, and secondary outcomes were Disabilities of Arm, Shoulder, and Hand; grip strength; globally perceived function; and the quality of life. Results The active range of motion was comparable between the groups (mean difference = 14; 95% confidence interval [CI], −8 to 36; P = .22). Disabilities of Arm, Shoulder, and Hand; grip strength; global perceived function; and health-related quality of life were also comparable between the groups. There was 1 (5.3%) rupture in the modified Kleinert group and 4 (15.4%) in the early active motion group (relative risk = 0.3; 95% CI, 0.04-2.5; P = .3). Conclusions Increasing active gliding with a free wrist and intrinsic minus splint did not improve the clinical outcomes after flexor tendon injury at a mean of 38-month follow-up.

Background Persistent fontanelles (PFs) are, in Chihuahuas, almost ubiquitous. Furthermore, Chihuahuas are predisposed to other craniomorphological abnormalities, including syringomyelia (SM), ventriculomegaly, and craniocervical junction (CCJ) overcrowding resulting in neural tissue deviation. It is, however, undetermined if PFs are more common in dogs with these structural abnormalities, and their etiology is unknown. Hypothesis/objectives Persistent fontanelles are more numerous and larger in Chihuahuas with low body weight, older age, SM, dilated fourth ventricle, ventriculomegaly, and CCJ overcrowding. Animals Fifty client-owned Chihuahuas. Methods Cross-sectional study evaluating the association of both the number of cranial sutures affected by PFs (NAS) and total fontanelle area (TFA), based on computed tomography with SM, fourth ventricle dilatation, lateral ventricle volume, and extent of neural tissue compression at the CCJ based on magnetic resonance images. Results The NASs was higher and TFA larger in dogs with low body weight (NAS: P = .007; 95% confidence interval [CI] = 0.384-0.861; TFA: P = .002; 95% CI = -1.91 to -0.478), larger lateral ventricles (NAS: P ≤ .001; 95% CI = 1.04-1.15; TFA: P ≤ .001; 95% CI = 0.099-0.363), and more severe neural tissue compression at the CCJ (NAS: P ≤ .001; 95% CI = 1.26-2.06; TFA: P = .03; 95% CI = 0.066-1.13). Similarly, dogs with SM (NAS: P = .004; 95% CI = 1.26-3.32; TFA: mean ± SD, 130 ± 217 mm2 ; P = .05) had higher NAS and larger TFA than did dogs without SM (43.7 ± 61.0 mm2 ). Age was not associated with NAS (P = .81; 95% CI = 0.989-1.01) or TFA (P = .33; 95% CI = -0.269 to 0.092). Conclusions and clinical importance Persistent fontanelles are associated with small size, SM, ventriculomegaly, and CCJ overcrowding.

We investigated the clinical, genetic, and pathological characteristics of a previously unknown severe juvenile brain disorder in several litters of Parson Russel Terriers. The disease started with epileptic seizures at 6 to 12 weeks of age and progressed rapidly to status epilepticus and death or euthanasia. Histopathological changes at autopsy were restricted to the brain. There was severe acute neuronal degeneration and necrosis diffusely affecting the grey matter throughout the brain with extensive intraneuronal mitochondrial crowding and accumulation of amyloid-β (Aβ). Combined homozygosity mapping and genome sequencing revealed an in-frame 6-bp deletion in the nuclear-encoded pitrilysin metallopeptidase 1 (PITRM1) encoding for a mitochondrial protease involved in mitochondrial targeting sequence processing and degradation. The 6-bp deletion results in the loss of two amino acid residues in the N-terminal part of PITRM1, potentially affecting protein folding and function. Assessment of the mitochondrial function in the affected brain tissue showed a significant deficiency in respiratory chain function. The functional consequences of the mutation were modeled in yeast and showed impaired growth in permissive conditions and an impaired respiration capacity. Loss-of-function variants in human PITRM1 result in a childhood-onset progressive amyloidotic neurological syndrome characterized by spinocerebellar ataxia with behavioral, psychiatric and cognitive abnormalities. Homozygous Pitrm1-knockout mice are embryonic lethal, while heterozygotes show a progressive, neurodegenerative phenotype characterized by impairment in motor coordination and Aβ deposits. Our study describes a novel early-onset PITRM1-related neurodegenerative canine brain disorder with mitochondrial dysfunction, Aβ accumulation, and lethal epilepsy. The findings highlight the essential role of PITRM1 in neuronal survival and strengthen the connection between mitochondrial dysfunction and neurodegeneration.

PLOS ONE 17(1), e0262110 (2022). doi:10.1371/journal.pone.0262110, Published by PLOS, San Francisco, California, US

Childhood exposure to alcohol misuse by household adults has been related to childhood developmental delay, cognitive impacts, mental illness, and problem behaviours. Most evidence comes from high income countries. This systematic review only included studies from low- and middle-income countries (LMICs). Five databases were searched from 1990–2020. Twenty-eight studies of children 0–12 years were included, with 42,599 participants from 11 LMICs. The most common outcome was behavioural problems/disorders (19 studies). Despite varying study designs, this review found that alcohol misuse by household members in LMICs is associated with adverse child neurodevelopmental outcomes, although casual inferences cannot be drawn in the absence of well conducted prospective studies. Statistically significant correlations were described between parental alcohol misuse and child emotional and behavioural difficulties, cognitive delay, and risky behaviours. In future, prospective cohort studies are recommended, with adjustment for confounders. Supplementary Information The online version contains supplementary material available at 10.1007/s10578-020-01112-3.

Background Increased left ventricular mass (LVM) predicts cardiovascular events and mortality. The objective of this study was to determine whether early-life exposures to body mass index (BMI) and systolic blood pressure (SPB) affects the left ventricular structure in adulthood. Methods We used longitudinal data from a 31-year follow-up to examine the associations between early-life (between ages 6-18) BMI and SPB on LVM in an adult population (N = 1864, aged 34-49). The burden of early-life BMI and SBP was defined as area under the curve. Results After accounting for contemporary adult determinants of LVM, early-life BMI burden associated significantly with LVM (3.61 g/SD increase in early-life BMI; [1.94 - 5.28], p 25 kg/m(2)) associated with 4.7% (2.5-6.9%, p 30kg/m(2)) resulted in a 21% (17.3-32.9%, p

Abstract In this work, deoxyribose-5-phosphate aldolase (Ec DERA, EC 4.1.2.4) from Escherichia coli was chosen as the protein engineering target for improving the substrate preference towards smaller, non-phosphorylated aldehyde donor substrates, in particular towards acetaldehyde. The initial broad set of mutations was directed to 24 amino acid positions in the active site or in the close vicinity, based on the 3D complex structure of the E. coli DERA wild-type aldolase. The specific activity of the DERA variants containing one to three amino acid mutations was characterised using three different substrates. A novel machine learning (ML) model utilising Gaussian processes and feature learning was applied for the 3rd mutagenesis round to predict new beneficial mutant combinations. This led to the most clear-cut (two- to threefold) improvement in acetaldehyde (C2) addition capability with the concomitant abolishment of the activity towards the natural donor molecule glyceraldehyde-3-phosphate (C3P) as well as the non-phosphorylated equivalent (C3). The Ec DERA variants were also tested on aldol reaction utilising formaldehyde (C1) as the donor. Ec DERA wild-type was shown to be able to carry out this reaction, and furthermore, some of the improved variants on acetaldehyde addition reaction turned out to have also improved activity on formaldehyde. Key points • DERA aldolases are promiscuous enzymes. • Synthetic utility of DERA aldolase was improved by protein engineering approaches. • Machine learning methods aid the protein engineering of DERA.

International audience; Different types of carbon materials are biocompatible with neural cells and can promote maturation. The mechanism of this effect is not clear. Here we have tested the capacity of a carbon material composed of amorphous sp 3 carbon backbone, embedded with a percolating network of sp 2 carbon domains to sustain neuronal cultures. We found that cortical neurons survive and develop faster on this novel carbon material. After 3 days in culture, there is a precocious increase in the frequency of neuronal activity and in the expression of maturation marker KCC2 on carbon films as compared to a commonly used glass surface. Accelerated development is accompanied by a dramatic increase in neuronal dendrite arborization. The mechanism for the precocious maturation involves the activation of intracellular calcium oscillations by the carbon material already after 1 day in culture. Carbon-induced oscillations are independent of network activity and reflect intrinsic spontaneous activation of developing neurons. Thus, these results reveal a novel mechanism for carbon material-induced neuronal survival and maturation. Brain trauma as well as neurodegenerative diseases are the leading cause of irreversible disability and low quality of life in the elderly population 1. A way to combat neurodegeneration is to promote reparation of neuronal networks, rewiring of neuronal connections, and eventual restoration or substitution of the lost functionality 2. One putative therapeutic avenue is providing scaffolds-special materials that support targeted differentiation of neuronal stem cells and neurite outgrowth of regenerating neurons. Carbon-derived materials possess numerous properties that make them usable as scaffolds 3. Carbon nanotubes (CNTs) and graphene are among the most studied carbon materials for biological applications. These materials enhance neuronal stem cell differentiation 4-6 , as well as promote neuronal survival, neuronal activity, and neuronal process outgrowth 7-13. Neurons cultured on CNTs have increased levels of neuronal K +-Cl − cotransporter KCC2, a key component in the functional maturation of inhibitory synaptic 14 and glutamatergic 15-17 transmission. Downregulation of this protein is also implicated in reactive plasticity following brain trauma 18. CNTs have been suggested to improve the electrical responsiveness of neurons by facilitating local electronic shortcuts between somas and dendrites 19. The ability of CNTs to form tight contacts with neurons is beneficial for neuron-electrode interfaces 20-24. 3D gra-phene substrates support growth and differentiation of neurons 25-27 that in combination with anti-inflammatory properties 28,29 makes graphene a next-generation neuronal tissue scaffold. Despite the importance of novel carbon materials for future engineering, we do not fully understand the mechanisms underlining the trophic action of carbon scaffolds. In this work, we propose a novel mechanism by which a new type of sputtered carbon material accelerates neuronal maturation. The carbon film material consists of conducting nanoscale sp 2 carbon islands embedded in a diamond-like sp 3 carbon matrix. We demonstrate OPEN

Exposure to alcohol misuse is considered an adverse childhood experience impacting on neurodevelopmental and behavioural outcomes in adolescents including substance use, mental illness, problem behaviours, suicidality, and teenage pregnancy. Most research on this issue has focussed on higher income countries, whereas patterns of alcohol use and related factors may be different in low- and middle-income countries (LMICs). This systematic review therefore seeks to collate all published studies from 1990–2020 on the topic set in LMICs. 43 studies were included, totalling 70,609 participants from 18 LMICs. Outcomes assessed included: substance use; depression/anxiety; suicidal ideation; problem behaviour; emotional dysfunction; teenage pregnancy; and self-harm. Despite heterogeneity in the studies identified, this review documented some association between exposure to household alcohol misuse and adverse adolescent outcomes in LMICs, including mental health problems, problem behaviours, and suicidality. The mechanisms leading to these outcomes are likely varied, and further research in different socio-economic and cultural contexts, particularly in the form of longitudinal studies, is called for. Electronic supplementary material The online version of this article (10.1007/s10578-020-01038-w) contains supplementary material, which is available to authorized users.

Perioperative dysglycaemia is associated with deleterious outcomes but guidelines to improve glucose management are poorly or inconsistently adhered to. We evaluated glucose management among diabetic and non-diabetic patients undergoing elective hip or knee arthroplasty.Capillary plasma glucose (CPG) was measured prospectively four times daily of 209 patients undergoing elective hip or knee surgery. Actions of the attending teams to CPG values and detection of patients at risk were analysed.A total of 209 patients were enrolled. All diabetic patients on insulin (6/6) had hyperglycaemia (≥7.8 mmol/l) more than twice and severe hyperglycaemia (10 mmol/l) at least once. Of the 27 diabetic patients not on insulin 26 (96.3%) had CPG ≥ 7.8 mmol/l ≥ 2 times and 17 (63%)10 mmol/l. The corresponding figures of the 176 non-diabetic patients were 137 (77.8%) and 61 (34.7%). Severe hyperglycaemia occurred in 54/176 (30.1%) of the non-diabetic patients with pre-operative HbA1c 42 mmol/mol and random plasma glucose 7.8 mmol/l. Of the 84 hyperglycaemic episodes 10 mmol/l, none was treated. Patients with a FINDRISC score ≥ 12 (corresponding to moderate to high risk of diabetes) and hyperglycaemia went unnoticed.Hyperglycaemia is common among elective orthopaedic surgery patients with or without diabetes. More than 80% of the 209 patients had hyperglycaemia and 40% had severe hyperglycaemia. None of the patients was treated according to guidelines and none of the patients at risk of hyperglycaemia or diabetes was noticed. There is an obvious need for further education and support by diabetes specialists.Clinical trials, gov. NCT03306810.

Completeness of adverse event (AE) reports is an important component of quality for good pharmacovigilance practices. We aimed to evaluate the impact of incorporating a measure of completeness of AE reports on quantitative signal detection. An internal safety database from a global pharmaceutical company was used in the analysis. vigiGrade, an index score of completeness, was derived for each AE report. Data from various patient support programs (PSPs) were categorized based on average vigiGrade score per PSP. Performance of signal detection was compared between: (1) weighting and not weighting by vigiGrade score; and, (2) well documented and poorly documented PSPs using sensitivity, specificity, area under the receiver operating characteristics curve (AUC) and time-to-signal detection. The ability to detect signals did not differ significantly when weighting by vigiGrade score [sensitivity (50% vs. 45%, p = 1), specificity (82.8% vs. 82.8%, p = 1), AUC (0.66 vs. 0.63, p = 0.051) or time-to-signal detection (HR 0.81, p = 0.63)] compared to not weighting. Well documented PSPs were better at detecting signals than poorly documented PSPs (AUC 0.66 vs. 0.52; p = 0.041) but time-to-signal detection did not differ significantly (HR 1.54, p = 0.42). Completeness of AE reports did not significantly impact the ability to detect signals when weighting by vigiGrade score or restricting the database based on the level of completeness. While the vigiGrade helps provide quality assessments of AE reports and prioritize cases for review, our findings indicate the tool might not be useful for quantitative signal detection when used by itself.

Objective: To identify risk factors for suicide after bariatric surgery.Summary background data: Bariatric surgery reduces obesity-related mortality. However, it is for unclear reasons is associated with an increased risk of suicide.Methods: This population-based cohort study included patients having undergone bariatric surgery in 1982 to 2012 in any of the 5 Nordic countries, with follow-up through 2012. Eleven potential risk factors of suicide (sex, age, comorbidity, surgery type, surgical approach, calendar year of surgery, history of depression or anxiety, psychosis, schizophrenia, mania, or bipolar disorder, personality disorder, substance use, and number of previously documented psychiatric diagnoses) were analyzed using Cox regression.Results: Of 49,977 bariatric surgery patients, 98 (0.2%) committed suicide during follow-up. Women had a decreased risk of suicide compared to men (hazard ratio [HR] = 0.48, 95% confidence interval [CI] 0.33–0.77), although age and comorbidity did not influence this risk. Compared to gastric bypass, other types of bariatric surgery had lower risk of suicide (HR = 0.44, 95%CI 0.27–0.99). There was no difference in suicide risk between laparoscopic and open surgical approach. A history of depression or anxiety (HR = 6.87, 95%CI 3.97–11.90); mania, bipolar disorder, psychosis, or schizophrenia (HR = 2.70, 95%CI 1.14–6.37); and substance use (HR = 2.28, 95%CI 1.08–4.80), increased the risk of suicide. More of the above psychiatric diagnoses increased the risk of suicide (HR = 22.59, 95%CI 12.96–39.38 for ≥2 compared to 0 diagnoses).Conclusions: Although the risk of suicide is low, psychiatric disorders, male sex, and gastric bypass procedure seem to increase the risk of suicide after bariatric surgery, indicating a role for tailored preoperative psychiatric evaluation and postoperative surveillance.

Abnormal vasculature in tumors leads to poor tissue perfusion and cytostatic drug delivery. Although drugs inducing vascular normalization, for example, angiopoietin-2 (Ang2)-blocking antibodies, have shown promising results in preclinical tumor models, clinical studies have so far shown only little efficacy. Because Ang2 is known to play a protective role in stressed endothelial cells, we tested here whether Ang2 blocking could enhance radiation-induced tumor vascular damage. Tumor-bearing mice were treated with anti-Ang2 antibodies every 3 or 4 days starting 3 days before 3 × 2 Gy or 4 × 0.5 Gy whole-body or tumor-focused radiation. Combination treatment with anti-Ang2 and radiation improved tumor growth inhibition and extended the survival of mice with melanoma or colorectal tumors. Single-cell RNA-sequencing revealed that Ang2 blocking rescued radiation-induced decreases in T cells and cells of the monocyte/macrophage lineage. In addition, anti-Ang2 enhanced radiation-induced apoptosis in cultured endothelial cells. In vivo, combination treatment decreased tumor vasculature and increased tumor necrosis in comparison with tumors treated with monotherapies. These results suggest that a combination of Ang2-blocking antibodies with radiation increases tumor growth inhibition and extends the survival of tumor-bearing mice. Significance: These findings offer a preclinical rationale for further testing of the use of radiation in combination with Ang2-blocking antibodies to improve the overall outcome of cancer treatment.

Background Compulsive sexual behavior disorder (CSBD) is a common disorder affecting different areas of life, although studies focusing on pharmacological treatment are sparse. Aim To investigate whether the opioid receptor antagonist naltrexone is feasible and tolerable and can provide symptom reduction in CSBD. Methods Twenty men aged 27–60 years (mean = 38.8 years, standard deviation = 10.3) with CSBD seeking treatment in an outpatient nonforensic clinic received four weeks of naltrexone 25–50 mg. Measurements were made before, during, and four weeks after treatment. Outcomes The self-assessment Hypersexual Disorder: Current Assessment Scale (HD: CAS) score was the primary outcome measure, and secondary outcomes were the Hypersexual Behavior Inventory (HBI) score, reported adverse effects, adherence to treatment, and dropouts. Results There was significant decrease on both HD: CAS and HBI scores during treatment with naltrexone. Even though some of the effects remained after treatment, the increased scores on HD: CAS indicated worsening of CSBD symptoms. The most reported side effects were fatigue (55%), nausea (30%), vertigo (30%), and abdominal pain (30%). However, there were no serious adverse effects leading to discontinuation of naltrexone. Clinical Implications Despite side effects being common, naltrexone seems to be feasible in the treatment of CSBD. Strengths & Limitations Being the first nonforensic prospective trial on naltrexone in CSBD, this study provides novel insights on a pharmacological intervention. However, owing to the small sample size and the lack of a control group, conclusions of effectiveness should be interpreted with caution. Conclusion Naltrexone is feasible and tolerable and may reduce symptoms of CSBD; nevertheless, future studies should ensure a randomized controlled procedure to evaluate possible effectiveness.

Objective:Both clinically observable and subclinical hemispatial neglect are related to functional disability. The aim of the present study was to examine whether increasing task complexity improves sensitivity in assessment and whether it enables the identification of subclinical neglect.Method:We developed and compared two computerized dual-tasks, a simpler and a more complex one, and presented them on a large, 173 × 277 cm screen. Participants in the study included 40 patients with unilateral stroke in either the left hemisphere (LH patient group, n = 20) or the right hemisphere (RH patient group, n = 20) and 20 healthy controls. In addition to the large-screen tasks, all participants underwent a comprehensive neuropsychological assessment. The Bells Test was used as a traditional paper-and-pencil cancellation test to assess neglect.Results:RH patients made significantly more left hemifield omission errors than controls in both large-screen tasks. LH patients’ omissions did not differ significantly from those of the controls in either large-screen task. No significant group differences were observed in the Bells Test. All groups’ reaction times were significantly slower in the more complex large-screen task compared to the simpler one. The more complex large-screen task also produced significantly slower reactions to stimuli in the left than in the right hemifield in all groups.Conclusions:The present results suggest that dual-tasks presented on a large screen sensitively reveal subclinical neglect in stroke. New, sensitive, and ecologically valid methods are needed to evaluate subclinical neglect.

Summary Background Primordial and primary prevention is the cornerstone for cardiometabolic health. In the randomised, controlled Special Turku Coronary Risk Factor Intervention Project (STRIP; n=1116), a 20-year dietary counselling intervention was given to children biannually from infancy, and cardiometabolic health benefits had been observed among the participants in the intervention group. Here, we report on the key results of the first follow-up done 6 years after the end of the intervention, at age 26 years. Methods The randomised controlled STRIP study recruited children at age 5 months from well-baby clinics in Turku, Finland, and randomly assigned them to either an intervention or control group; group allocation was unmasked. The intervention introduced participants to a heart-healthy diet, characterised by low proportional intake of saturated fat and cholesterol, by dietary counselling and nutrition education sessions to parents and children from the age of 7 months to 20 years. Children in the control group received only the basic health education given at Finnish well-baby clinics and school health care. We assessed diet, lifestyle, and cardiometabolic risk factor data, including blood pressure, anthropometry, serum biochemistry (lipids, apolipoproteins, glucose, and insulin), and homoeostatic model assessment of insulin resistance (HOMA-IR) in the participants at age 26 years. Findings 1116 children were included in the original STRIP study, of whom 551 provided data at the age 26 years follow-up, and data for 507 participants were analysed (243 in the intervention group and 264 in the control group). At follow-up, those who had been in the intervention group had slightly lower mean intake of saturated fat as a proportion of total energy intake than the control group (13·0% [SD 3·3] vs 13·7% [3·6], p=0·049). A higher proportion of participants in the intervention group achieved the targeted monounsaturated and polyunsaturated fat to saturated fat ratio of more than 2:1 than the control group (78 [39%] of 200 vs 70 [30%] of 235; risk ratio [RR] 1·16 [95% CI 1·01–1·33]; p=0·035). A higher proportion of intervention group participants met the ideal total cholesterol concentration of less than 5·17 mmol/L (194 [81%] of 240 vs 187 [72%] of 261; RR 1·45 [1·05–2·01], p=0·024) and optimal LDL cholesterol concentration of less than 3·0 mmol/L (166 [69%] of 240 vs 158 [61%] of 251; RR 1·30 [1·03–1·66], p=0·031). Those who received the intervention had lower glucose (5·00 mmol/L [SD 0·43] vs 5·07 mmol/L [0·46], p=0·040) and HOMA-IR (median 1·44 [IQR 1·09–1·91] vs 1·62 [1·22–2·09], p=0·037) than the participants in the control group. Interpretation Previously observed intervention effects during the 20-year counselling were largely maintained into adulthood 6 years after the withdrawal of the intervention. Dietary counselling introduced in infancy thus provided a sustained benefit to diet quality and cardiometabolic risk factor levels. Funding Academy of Finland, Juho Vainio Foundation, Finnish Foundation for Cardiovascular Research, Finnish Ministry of Education and Culture, Finnish Cultural Foundation, Sigrid Juselius Foundation, Special Governmental grants for Health Sciences Research (Turku University Hospital), Yrjo Jahnsson Foundation, Finnish Medical Foundation, and Turku University Foundation.

Objective: Addiction comorbidity is an important clinical challenge in mood disorders, but the best way of pharmacologically treating people with mood disorders and addictions remains unclear. The aim of this study was to assess the efficacy of pharmacological treatments for mood and addiction symptoms in people with mood disorders and addiction comorbidity. Methods: A systematic search of placebo-controlled randomized controlled trials investigating the effects of pharmacological treatments in people with bipolar disorder (BD) or major depressive disorder (MDD), and comorbid addictions was performed. Treatment-related effects on mood and addiction measures were assessed in a meta-analysis, which also estimated risks of participant dropout and adverse effects. Results: A total of 32 studies met systematic review inclusion criteria. Pharmacological therapy was more effective than placebo for improving manic symptoms (standardized mean difference [SMD] = −0.15; 95% confidence interval [95% CI], −0.29 to −0.02; P = 0.03) but not BD depressive symptoms (SMD = −0.09; 95% CI, −0.22 to 0.03; P = 0.15). Quetiapine significantly improved manic symptoms (SMD = −0.23; 95% CI, −0.39 to −0.06; P = 0.008) but not BD depressive symptoms (SMD = −0.07; 95% CI, −0.23 to 0.10; P = 0.42). Pharmacological therapy was more effective than placebo for improving depressive symptoms in MDD (SMD = −0.16; 95% CI, −0.30 to −0.03; P = 0.02). Imipramine improved MDD depressive symptoms (SMD = −0.58; 95% CI, −1.03 to −0.13; P = 0.01) but Selective serotonin reuptake Inhibitors (SSRI)-based treatments had no effect (SMD = −0.06; 95% CI, −0.30 to 0.17; P = 0.60). Pharmacological treatment improved the odds of alcohol abstinence in MDD but had no effects on opiate abstinence. Conclusions: Pharmacological treatments were significantly better than placebo in improving manic symptoms, MDD depressive symptoms, and alcohol abstinence but were not better for bipolar depression symptoms. Importantly, quetiapine was not more effective than placebo in improving bipolar depression symptoms nor were SSRI’s for the treatment of MDD depression. Our findings highlight the need for further high-quality clinical trials of treatments for mood disorders and comorbid addictions.

Purpose Severity of white matter lesion (WML) is typically evaluated on magnetic resonance images (MRI), yet the more accessible, faster, and less expensive method is computed tomography (CT). Our objective was to study whether WML can be automatically segmented from CT images using a convolutional neural network (CNN). The second aim was to compare CT segmentation with MRI segmentation. Methods The brain images from the Helsinki University Hospital clinical image archive were systematically screened to make CT-MRI image pairs. Selection criteria for the study were that both CT and MRI images were acquired within 6 weeks. In total, 147 image pairs were included. We used CNN to segment WML from CT images. Training and testing of CNN for CT was performed using 10-fold cross-validation, and the segmentation results were compared with the corresponding segmentations from MRI. Results A Pearson correlation of 0.94 was obtained between the automatic WML volumes of MRI and CT segmentations. The average Dice similarity index validating the overlap between CT and FLAIR segmentations was 0.68 for the Fazekas 3 group. Conclusion CNN-based segmentation of CT images may provide a means to evaluate the severity of WML and establish a link between CT WML patterns and the current standard MRI-based visual rating scale.

We studied whether exposure to parental smoking in childhood/adolescence is associated with midlife cognitive function, leveraging data from the Cardiovascular Risk in Young Finns Study. A population-based cohort of 3,596 children/adolescents aged 3–18 years was followed between 1980 and 2011. In 2011, cognitive testing was performed on 2,026 participants aged 34–49 years using computerized testing. Measures of secondhand smoke exposure in childhood/adolescence consisted of parental self-reports of smoking and participants’ serum cotinine levels. Participants were classified into 3 exposure groups: 1) no exposure (nonsmoking parents, cotinine

Introduction Hypersexual disorder as suggested to be included in the Diagnostic and Statistical Manual of Mental Disorders-5 integrates aspects of sexual desire deregulation, impulsivity, and compulsivity. However, it is unknown how it affects gonadal activity and the function of the hypothalamus-pituitary-gonadal (HPG) axis. Aim The aim of this study was to investigate testosterone and luteinizing hormone (LH) levels in hypersexual men compared with healthy controls. Furthermore, we investigated associations between epigenetic markers and hormone levels. Methods Basal morning plasma levels of testosterone, LH, and sex hormone–binding globulin (SHBG) were assessed in 67 hypersexual men (mean age: 39.2 years) compared with 39 age-matched healthy controls (mean age: 37.5 years). The Sexual Compulsivity Scale and the Hypersexual Disorder: Current Assessment Scale were used for assessing hypersexual behavior, the Montgomery-Åsberg Depression Scale-self rating was used for depression severity, and the Childhood Trauma Questionnaire (CTQ) was used for assessing history of childhood adversity. The genome-wide methylation pattern of more than 850 K CpG sites was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip. CpG sites located within 2,000 bp of the transcriptional start site of hypothalamus pituitary adrenal (HPA) and HPG axis–coupled genes were included. Main Outcome Measures Testosterone and LH plasma levels in association with clinical rating and a secondary outcome was the epigenetic profile of HPA and HPG axis–coupled CpG sites with testosterone and LH levels. Results LH plasma levels were significantly higher in patients with hypersexual disorder than in healthy volunteers. No significant differences in plasma testosterone, follicle stimulating hormone, prolactin, and SHBG levels were found between the groups. There were no significant associations between DNA methylation of HPA and HPG axis–coupled genes and plasma testosterone or LH levels after multiple testing corrections. Conclusions Subtle dysregulation of the HPG axis, with increased LH plasma levels but no difference in testosterone levels may be present in hypersexual men. Chatzittofis A, Boström AE, Öberg KG, et al. Normal Testosterone but Higher Luteinizing Hormone Plasma Levels in Men With Hypersexual Disorder. Sex Med 2020;8:243–250.

Background and aims Carotid plaque is a specific sign of atherosclerosis and adults with carotid plaque are at increased risk for cardiovascular outcomes. Atherosclerosis has roots in childhood and pediatric guidelines provide cut-off values for cardiovascular risk factors. However, it is unknown whether these cut-offs predict adulthood advanced atherosclerosis. Methods The Cardiovascular Risk in Young Finns Study is a follow-up of children that begun in 1980 when 2653 participants with data for the present analyses were aged 3–18 years. In 2001 and 2007 follow-ups, in addition to adulthood cardiovascular risk factors, carotid ultrasound data was collected. Long-term burden, as the area under the curve, was evaluated for childhood (6–18 years) risk factors. To study the associations of guideline-based cut-offs with carotid plaque, both childhood and adult risk factors were classified according to clinical practice guidelines. Results Carotid plaque, defined as a focal structure of the arterial wall protruding into lumen >50% compared to adjacent intima-media thickness, was present in 88 (3.3%) participants. Relative risk for carotid plaque, when adjusted for age and sex, was 3.03 (95% CI, 1.76–5.21) for childhood dyslipidemia, 1.51 (95% CI, 0.99–2.32) for childhood elevated systolic blood pressure, and 1.93 (95% CI, 1.26–2.94) for childhood smoking. Childhood dyslipidemia and smoking remained independent predictors of carotid plaque in models additionally adjusted for adult risk factors and family history of coronary heart disease. Carotid plaque was present in less than 1% of adults with no childhood risk factors. Conclusions Findings reinforce childhood prevention efforts and demonstrate the utility of guideline-based cut-offs in identifying children at increased risk for adulthood atherosclerosis.

We explored opportunities for personalized and predictive health care by collecting serial clinical measurements, health surveys, genomics, proteomics, autoantibodies, metabolomics, and gut microbiome data from 96 individuals who participated in a data-driven health coaching program over a 16-month period with continuous digital monitoring of activity and sleep. We generated a resource of >20,000 biological samples from this study and a compendium of >53 million primary data points for 558,032 distinct features. Multiomics factor analysis revealed distinct and independent molecular factors linked to obesity, diabetes, liver function, cardiovascular disease, inflammation, immunity, exercise, diet, and hormonal effects. For example, ethinyl estradiol, a common oral contraceptive, produced characteristic molecular and physiological effects, including increased levels of inflammation and impact on thyroid, cortisol levels, and pulse, that were distinct from other sources of variability observed in our study. In total, this work illustrates the value of combining deep molecular and digital monitoring of human health. A record of this paper's transparent peer review process is included in the supplemental information.

Aerosol particles form in the atmosphere via the clustering of certain atmospheric vapors. After growing into larger particles by the condensation of low-volatility gases, they can affect the Earth's climate by scattering light and acting as cloud condensation nuclei (CCN). Observations of low-volatility aerosol precursor gases have been reported around the world, but longer-term measurement series and any Arctic data sets showing seasonal variation are close to nonexistent. Here, we present ∼7 months of aerosol precursor gas measurements performed with a nitrate-based chemical ionization atmospheric pressure interface time-of-flight (CI-APi-TOF) mass spectrometer. We deployed our measurements ∼150 km north of the Arctic Circle at the SMEAR I (Station for Measuring Ecosystem–Atmosphere Relations) continental Finnish subarctic field station, located in the Värriö strict nature reserve. We report concentration measurements of the most common compounds related to new particle formation (NPF): sulfuric acid (SA), methane sulfonic acid (MSA), iodic acid (IA) and the total concentration of highly oxygenated organic molecules (HOMs). At this remote measurement site, SA originates from both anthropogenic and biological sources and has a clear diurnal cycle but no significant seasonal variation. MSA shows a more distinct seasonal cycle, with concentrations peaking in the summer. Of the measured compounds, IA concentrations are the most stable throughout the measurement period, except in April during which time the concentration of IA is significantly higher than during the rest of the year. Otherwise, IA has almost identical daily maximum concentrations in spring, summer and autumn, and on NPF event or non-event days. HOMs are abundant during the summer months and low in the autumn months. Due to their low autumn concentrations and high correlation with ambient air temperature, we suggest that most HOMs are products of biogenic emissions, most probably monoterpene oxidation products. NPF events at SMEAR I happen under relatively low-temperature (1–8 ∘C) conditions, with a fast temperature rise in the early morning hours as well as lower and decreasing relative humidity (RH, 55 % vs. 80 %) during NPF days compared with non-event days. NPF days have clearly higher global irradiance values (∼450 m−2 vs. ∼200 m−2) and about 10 ppbv higher ozone concentrations than non-event days. During NPF days, we have, on average, higher SA concentrations, peaking at noon; higher MSA concentrations in the afternoon; and slightly higher IA concentration than during non-event days. In summary, these are the first long-term measurements of aerosol-forming vapors from SMEAR I in the subarctic region, and the results of this work will help develop an understanding of atmospheric chemical processes and aerosol formation in the rapidly changing Arctic.

Funding Information: This research was supported by Academy of Finland project “Silicon mushrooms: microengineered liquid repellency (# 297360). This work utilized the OtaNano research infrastructure and the cleanroom facilities of Micronova. Publisher Copyright: © 2021, The Author(s). A polydimethylsiloxane (PDMS)/Cu superhydrophobic composite material is fabricated by wet etching, electroless plating, and polymer casting. The surface topography of the material emerges from hierarchical micro/nanoscale structures of etched aluminum, which are rigorously copied by plated copper. The resulting material is superhydrophobic (contact angle > 170°, sliding angle < 7° with 7 µL droplets), electrically conductive, elastic and wear resistant. The mechanical durability of both the superhydrophobicity and the metallic conductivity are the key advantages of this material. The material is robust against mechanical abrasion (1000 cycles): the contact angles were only marginally lowered, the sliding angles remained below 10°, and the material retained its superhydrophobicity. The resistivity varied from 0.7 × 10–5 Ωm (virgin) to 5 × 10–5 Ωm (1000 abrasion cycles) and 30 × 10–5 Ωm (3000 abrasion cycles). The material also underwent 10,000 cycles of stretching and bending, which led to only minor changes in superhydrophobicity and the resistivity remained below 90 × 10–5 Ωm.

Objective:Patients with unilateral stroke commonly show hemispatial neglect or milder contralesional visuoattentive deficits, but spatially non-lateralized visuoattentive deficits have also been reported. The aim of the present study was to compare spatially lateralized (i.e., contralesional) and non-lateralized (i.e., general) visuoattentive deficits in left and right hemisphere stroke patients.Method:Participants included 40 patients with chronic unilateral stroke in either the left hemisphere (LH group, n = 20) or the right hemisphere (RH group, n = 20) and 20 healthy controls. To assess the contralesional deficits, we used a traditional paper-and-pencil cancellation task (the Bells Test) and a Lateralized Targets Computer Task. To assess the non-lateralized deficits, we developed a novel large-screen (173 × 277 cm) computer method, the Ball Rain task, with moving visual stimuli and fast-paced requirements for selective attention.Results:There were no contralesional visuoattentive deficits according to the cancellation task. However, in the Lateralized Targets Computer Task, RH patients missed significantly more left-sided than right-sided targets in bilateral trials. This omission distribution differed significantly from those of the controls and LH patients. In the assessment of non-lateralized attention, RH and LH patients missed significantly more Ball Rain targets than controls in both the left and right hemifields.Conclusions:Computer-based assessment sensitively reveals various aspects of visuoattentive deficits in unilateral stroke. Patients with either right or left hemisphere stroke demonstrate non-lateralized visual inattention. In right hemisphere stroke, these symptoms can be accompanied by subtle contralesional visuoattentive deficits that have remained unnoticed in cancellation task.

Objective: To determine the association of number of siblings on cardiovascular risk factors in childhood and in adulthood. Study design: In total, 3554 participants (51% female) from the Cardiovascular Risk in Young Finns Study with cardiovascular disease risk factor data at baseline 1980 (age 3-18 years) and 2491 participants with longitudinal risk factor data at the 2011 follow-up. Participants were categorized by number of siblings at baseline (0, 1, or more than 1). Risk factors (body mass index, physical activity, hypertension, dyslipidemia, and overweight, and metabolic syndrome) in childhood and in adulthood were used as outcomes. Analyses were adjusted for age and sex. Results: In childhood, participants without siblings had higher body mass index (18.2 kg/m2, 95% CI 18.0-18.3) than those with 1 sibling (17.9 kg/m2, 95% CI 17.8-18.0) or more than 1 sibling (17.8 kg/m2, 95% CI 17.7-17.9). Childhood physical activity index was lower among participants without siblings (SD -0.08, 95% CI -0.16-0.00) compared with participants with 1 sibling (SD 0.06, 95%CI 0.01-0.11) or more than 1 sibling (SD -0.02, 95% CI -0.07-0.03). OR for adulthood hypertension was lower among participants with 1 sibling (OR 0.73, 95% CI 0.54-0.98) and more than 1 sibling (OR 0.71, 95% CI 0.52-0.97) compared with participants with no siblings. OR for obesity was lower among participants with 1 sibling (OR 0.72, 95% CI 0.54-0.95) and more than 1 sibling (OR 0.75, 95% CI 0.56-1.01) compared with those with no siblings. Conclusions: Children without siblings had poorer cardiovascular risk factor levels in childhood and in adulthood. The number of siblings could help identify individuals at increased risk that might benefit from early intervention. publishedVersion

Background and purpose: Cerebral small vessel disease is characterized by progressive white matter hyperintensities (WMH) and cognitive decline. However, variability exists in how individuals maintain cognitive capabilities despite significant neuropathology. The relationships between individual cognitive reserve, psychological resilience and cognitive functioning were examined in subjects with varying degrees of WMH. Methods: In the Helsinki Small Vessel Disease Study, 152 subjects (aged 65–75 years) underwent a comprehensive neuropsychological assessment, evaluation of subjective cognitive complaints and brain magnetic resonance imaging with volumetric WMH evaluation. Cognitive reserve was determined by education (years) and the modified Cognitive Reserve Scale (mCRS). Psychological resilience was evaluated with the Resilience Scale 14. Results: The mCRS total score correlated significantly with years of education (r = 0.23, p

Embigin (gp70), a transmembrane glycoprotein, has been shown to regulate hematopoietic stem cell and progenitor cell niche. Still, little is known about its expression and function in other organ systems during development or adulthood. By combining immunofluorescence, RNA sequencing, and in vivo mouse models, we show that embigin is highly expressed during development and in adult lung, kidney, epididymis, skin, and testis. Adult Emb-/- mice have a normal lifespan and fertility without apparent pathologies. In contrast, the Emb-/- embryos are significantly smaller than their WT littermates. Markedly increased mortality of the Emb-/- embryos is seen especially during the neonatal period. Embigin is present in the placenta, but placental morphology and gene expression patterns stay unaltered. At E17.5, Emb-/- mice show defective morphogenesis of the lung, low alkaline phosphatase activity in amniotic fluid, and remarkable activation of genes involved in cell proliferation in the lungs. Thus, lung underdevelopment explains the high neonatal mortality. Our work demonstrates the crucial role of embigin during development, and it paves the way to further characterization of embigin in specific organ systems in development and homeostasis.Summary statementEmbigin is a basigin-group transmembrane glycoprotein. In vivo mouse model shows that embigin is crucial for embryonic lung development and neonatal survival.

Background Many studies of epilepsy in veterinary medicine use subjective data (eg, caregiver-derived histories) to determine seizure frequency. Conversely, in people, objective data from electroencephalography (EEG) are mainly used to diagnose epilepsy, measure seizure frequency and evaluate efficacy of antiseizure drugs. These EEG data minimize the possibility of the underreporting of seizures, a known phenomenon in human epileptology. Objective To evaluate the correlation between reported seizure frequency and EEG frequency of ictal paroxysmal discharges (PDs) and to determine whether seizure underreporting phenomenon exists in veterinary epileptology. Animals Thirty-three ambulatory video-EEG recordings in dogs showing >= 1 ictal PD, excluding dogs with status epilepticus. Methods Retrospective observational study. Ictal PDs were counted manually over the entire recording to obtain the frequency of EEG seizures. Caregiver-reported seizure frequency from the medical record was categorized into weekly, daily, hourly, and per minute seizure groupings. The Spearman rank test was used for correlation analysis. Results The coefficient value (r(s)) comparing reported seizure to EEG-confirmed ictal PD frequencies was 0.39 (95% confidence interval [CI] = 0.048-0.64, P = .03). Other r(s) values comparing history against various seizure types were: 0.36 for motor seizures and 0.37 for nonmotor (absence) seizures. Conclusions and Clinical Importance A weak correlation was found between the frequency of reported seizures from caregivers (subjective data) and ictal PDs on EEG (objective data). Subjective data may not be reliable enough to determine true seizure frequency given the discrepancy with EEG-confirmed seizure frequency. Confirmation of the seizure underreporting phenomenon in dogs by prospective study should be carried out.

“Toba Tek Singh,” which describes the exchange of mental asylum inmates between India and Pakistan in the wake of partition, was perhaps Saadat Hasan Manto’s most well-known short story. Manto’s work was coloured by his experience of mental illness, including alcohol addiction and possible depressive disorder. This essay attempts to use “Toba Tek Singh” as a lens through which to shine an integrative light on the role of mental illness in Manto’s work and life, by discussing his personal experiences, themes of mental illness in the story, and the implications of his writing in the historical context of post-partition South Asia.