Non-primary motor areas in the human frontal lobe are connected directly to hand muscles

Structural studies in primates have shown that, in addition to the primary motor cortex (M1), premotor areas are a source of corticospinal tracts. The function of these putative corticospinal neuronal tracts in humans is still unclear. We found frontal non-primary motor areas (NPMAs), which react to targeted non-invasive magnetic pulses and activate peripheral muscles as fast as or even faster than those in M1. Hand muscle movements were observed in all our subjects about 20 ms after transcranial stimulation of the superior frontal gyrus (Brodmann areas 6 and 8). Stimulation of NPMA could activate both proximal and distal upper limb muscles with the same delay as a stimulation of the M1, indicating converging motor representations with direct functional connections to the hand. We suggest that these non-primary cortical motor representations provide additional capacity for the fast execution of movements. Such a capacity may play a role in motor learning and in recovery from motor deficits.     

Maternal corticosterone but not testosterone level is associated with the ratio of second-to-fourth digit length (2D:4D) in field vole offspring (Microtus agrestis)

The steroid environment encountered by a foetus can strongly affect its post-natal physiology and behaviour. It has been proposed that steroid concentrations experienced in utero could be estimated from adults by measuring their second-to-fourth digit length ratio (2D:4D). However, there is still little direct evidence that intra-uterine steroid levels affect individual 2D:4D. We examined whether maternal pre-pregnancy testosterone and corticosterone levels (as estimates of intra-uterine testosterone and corticosterone exposure) affected the 2D:4D of pups in non-domesticated field voles (Microtus agrestis), measured by X-rays at the age of weaning (21 days). Furthermore, for the first time in a non-human species, we studied whether testosterone and corticosterone levels correlated with 2D:4D in adult females. We found that the maternal pre-pregnancy level of testosterone was not associated with offspring 2D:4D in either the left or the right paw. Instead, maternal pre-pregnancy corticosterone level was positively correlated with offspring 2D:4D in the right paw, but unrelated to 2D:4D in the left paw. In addition, the 2D:4D of adult females was not associated with either their circulating testosterone or corticosterone levels. Our results suggest that in field voles maternally administered testosterone is not a major determinant of offspring 2D:4D, whereas maternal stress appears to account for some of the variation in the 2D:4D of their offspring.     

Bayesian Latent Variable Collapsing Model for Detecting Rare Variant Interaction Effect in Twin Study

By analyzing more next‐generation sequencing data, researchers have affirmed that rare genetic variants are widespread among populations and likely play an important role in complex phenotypes. Recently, a handful of statistical models have been developed to analyze rare variant (RV) association in different study designs. However, due to the scarce occurrence of minor alleles in data, appropriate statistical methods for detecting RV interaction effects are still difficult to develop. We propose a hierarchical Bayesian latent variable collapsing method (BLVCM), which circumvents the obstacles by parameterizing the signals of RVs with latent variables in a Bayesian framework and is parameterized for twin data. The BLVCM can tackle nonassociated variants, allow both protective and deleterious effects, capture SNP‐SNP synergistic effect, provide estimates for the gene level and individual SNP contributions, and can be applied to both independent and various twin designs. We assessed the statistical properties of the BLVCM using simulated data, and found that it achieved better performance in terms of power for interaction effect detection compared to the Granvil and the SKAT. As proof of practical application, the BLVCM was then applied to a twin study analysis of more than 20,000 gene regions to identify significant RVs associated with low‐density lipoprotein cholesterol level. The results show that some of the findings are consistent with previous studies, and we identified some novel gene regions with significant SNP–SNP synergistic effects.     

Analyzing Citizens’ and Health Care Professionals’ Searches for Smell/Taste Disorders and Coronavirus in Finland During the COVID-19 Pandemic: Infodemiological Approach Using Database Logs

BackgroundThe COVID-19 pandemic has prevailed over a year, and log and register data on coronavirus have been utilized to establish models for detecting the pandemic. However, many sources contain unreliable health information on COVID-19 and its symptoms, and platforms cannot characterize the users performing searches. Prior studies have assessed symptom searches from general search engines (Google/Google Trends). Little is known about how modeling log data on smell/taste disorders and coronavirus from the dedicated internet databases used by citizens and health care professionals (HCPs) could enhance disease surveillance. Our material and method provide a novel approach to analyze web-based information seeking to detect infectious disease outbreaks.ObjectiveThe aim of this study was (1) to assess whether citizens’ and professionals’ searches for smell/taste disorders and coronavirus relate to epidemiological data on COVID-19 cases, and (2) to test our negative binomial regression modeling (ie, whether the inclusion of the case count could improve the model).MethodsWe collected weekly log data on searches related to COVID-19 (smell/taste disorders, coronavirus) between December 30, 2019, and November 30, 2020 (49 weeks). Two major medical internet databases in Finland were used: Health Library (HL), a free portal aimed at citizens, and Physician’s Database (PD), a database widely used among HCPs. Log data from databases were combined with register data on the numbers of COVID-19 cases reported in the Finnish National Infectious Diseases Register. We used negative binomial regression modeling to assess whether the case numbers could explain some of the dynamics of searches when plotting database logs.ResultsWe found that coronavirus searches drastically increased in HL (0 to 744,113) and PD (4 to 5375) prior to the first wave of COVID-19 cases between December 2019 and March 2020. Searches for smell disorders in HL doubled from the end of December 2019 to the end of March 2020 (2148 to 4195), and searches for taste disorders in HL increased from mid-May to the end of November (0 to 1980). Case numbers were significantly associated with smell disorders (P<.001) and taste disorders (P<.001) in HL, and with coronavirus searches (P<.001) in PD. We could not identify any other associations between case numbers and searches in either database.ConclusionsNovel infodemiological approaches could be used in analyzing database logs. Modeling log data from web-based sources was seen to improve the model only occasionally. However, search behaviors among citizens and professionals could be used as a supplementary source of information for infectious disease surveillance. Further research is needed to apply statistical models to log data of the dedicated medical databases.     

Gas‐foamed poly(lactide‐co‐glycolide) and poly(lactide‐co‐glycolide) with bioactive glass fibres demonstrate insufficient bone repair in lapine osteochondral defects

Deep osteochondral defects may leave voids in the subchondral bone, increasing the risk of joint structure collapse. To ensure a stable foundation for the cartilage repair, bone grafts can be used for filling these defects. Poly(lactide‐co‐glycolide) (PLGA) is a biodegradable material that improves bone healing and supports bone matrix deposition. We compared the reparative capacity of two investigative macroporous PLGA‐based biomaterials with two commercially available bone graft substitutes in the bony part of an intra‐articular bone defect created in the lapine femur. New Zealand white rabbits (n = 40) were randomized into five groups. The defects, 4 mm in diameter and 8 mm deep, were filled with neat PLGA; a composite material combining PLGA and bioactive glass fibres (PLGA–BGf); commercial beta‐tricalcium phosphate (β‐TCP) granules; or commercial bioactive glass (BG) granules. The fifth group was left untreated for spontaneous repair. After three months, the repair tissue was evaluated with X‐ray microtomography and histology. Relative values comparing the operated knee with its contralateral control were calculated. The relative bone volume fraction (?BV/TV) was largest in the β‐TCP group (p ≤ 0.012), which also showed the most abundant osteoid. BG resulted in improved bone formation, whereas defects in the PLGA–BGf group were filled with fibrous tissue. Repair with PLGA did not differ from spontaneous repair. The PLGA, PLGA–BGf, and spontaneous groups showed thicker and sparser trabeculae than the commercial controls. We conclude that bone repair with β‐TCP and BG granules was satisfactory, whereas the investigational PLGA‐based materials were only as good as or worse than spontaneous repair.     

Cardioversion for atrial fibrillation – how to prevent thromboembolic complications?

Abstract

Cardioversion is an essential component of rhythm control strategy for atrial fibrillation. The thromboembolic risk of cardioversion is well established and the mechanisms behind the phenomenon have been comprehensively described. There are several clinical aspects that are important to take into consideration when assessing the safety of cardioversion. Before proceeding to cardioversion, the probability of early treatment failure and antiarrhythmic treatment options to prevent recurrences should be carefully evaluated to avoid the risks of repeated futile cardioversions. Effective periprocedural anticoagulation is the mainstay in thromboembolic complication prevention and the first week after rhythm conversion is the most vulnerable period in this respect. Early timing of cardioversion appears to be another important measure to decrease the risk of thromboembolic complications. Transoesophageal echocardiography is useful in clinical scenarios where early cardioversion is desirable due to debilitating clinical symptoms and a short duration of arrhythmia or the adequacy of preceding anticoagulation is uncertain. However, it does not lessen the need for effective anticoagulation after cardioversion. This review summarizes the recent scientific discoveries to improve the safety of cardioversion for atrial fibrillation.

• Key messages

• Cardioversion for atrial fibrillation entails a significant risk of thromboembolic complications, especially during the first week after the procedure.

• The intensity of periprocedural anticoagulation and the timing of cardioversion appear to be significant determinants of the risk of thromboembolism.

• Awareness of the clinical aspects influencing cardioversion safety should be raised.

     

Occurrence of vesicoureteral reflux in children

Aim: The reported low occurrence of vesicoureteral reflux in the general population seems implausible. We wanted to test the hypothesis that reflux is more common and more independent of urinary‐tract infection than has previously been thought. Methods: We tested our hypothesis by analysing the characteristics of 406 consecutive children aged <5 years who had been referred for consultation because of urinary‐tract infection. Using data on their urine samples, we evaluated the reliability of the urinary‐tract infection diagnosis and analysed the frequencies of vesicoureteral reflux and abnormal ultrasound findings in three reliability groups (A: certain urinary‐tract infection, B: possible and C: improbable). Results: The occurrence of reflux was the same irrespective of the diagnostic reliability of urinary‐tract infection (A: 98/276 [36%] versus B: 13/46 [28%] versus C: 9/25 [36%]). Most of the abnormal ultrasound findings (58/71, 80%) were found among patients with a certain diagnosis (Group A). Conclusion: We suggest that vesicoureteral reflux is more common in children even without urinary‐tract infection than has been thought previously. The guidelines recommending a search for reflux by means of voiding cystourethrography should be reconsidered.     

Health-related services on the internet

The primary objective of this study is to evaluate a sample of health-related services available on the internet. In addition, types of new services and service qualities that may be required in the future were estimated. A registered nurse using a questionnaire containing items about usability, quality, and other characteristics related to the subject carried out an evaluation of 100 health-related internet sites, and the results were processed to determine average qualities and graphical presentations for the studied parameters. The services studied differed greatly from each other both in terms of content and quality. A general observation was that sites of larger organizations were, typically, both in terms of presentation and content, more sophisticated than sites of smaller producers. A typical characteristic was the superficiality of the information presented. In conclusion, the internet is an emerging medium for health-related information, and standards for the production and presentation of health content for the internet are still in development. However, even at this early stage, the internet represents a valuable source of information for those in need of health-related information for both health care professionals and consumers.     

Joint Modeling of Genetic Association and Population Stratification Using Latent Class Models

We show how latent class log‐linear models can be used to test for an association between a candidate gene and a disease phenotype in a stratified population when the stratification is unobserved. The stratification may arise because of several ethnic groups or immigration and may lead to spurious associations between several loci and the disease. The information about the stratification is drawn from additional markers that are chosen to be independent of the disease and unlinked to the candidate gene and to each other within each population stratum. We use the EM algorithm to simultaneously estimate all the model parameters, including proportions of individuals in the latent population strata. The latent class model is used to test the phenotype association of single nucleotide polymorphism markers in four candidate regions in population‐based case‐control data selected from simulated Genetic Analysis Workshop (GAW) 12 population isolate 30. The analysis clearly demonstrates how the number of false positive associations can be reduced when the model accounts for population stratification. © 2001 Wiley‐Liss, Inc.     

Effects of stimulation of alpha1-adrenergic and NMDA/glycine-B receptors on learning defects in aged rats

The present study was designed to investigate the efficacy of stimulation of alpha₁-adrenoceptors and the strychnine insensitive glycine-B binding sites of the N-methyl-D-aspartate (NMDA) receptor complex to alleviate the age-related defect in water maze (WM) spatial (hidden platform) navigation. We found that daily pretraining IP treatment with 2-(2-chloro-5-trifluoromethylphenylamino) imidazole nitrate (ST 587), an alpha₁-adrenoceptor agonist, at 3000 μg/kg, but not at 1000 μg/kg, facilitated acquisition of water maze spatial navigation in aged rats. However, ST 587 3000 μg/kg (IP) did not stimulate WM spatial reversal learning or cue navigation to a visible platform in aged rats. A partial strychnine insensitive glycine-B binding site agonist, D-cycloserine (DCS) at 10000 μg/kg stimulated acquisition of WM navigation, but had no effect on reversal learning or cue navigation. DCS at 1000 or 3000 μg/kg (IP) had no marked effect on WM spatial navigation, and did not enhance the WM performance improving effect of ST 587 in aged rats. A subthreshold dose of ST 587 1000 μg/kg did not enhance the therapeutic effect of DCS 10000 μg/kg. The present results indicate that activation of alpha₁-adrenoceptors and glycine binding sites of NMDA receptor may to some extent alleviate the age-related defect in spatial navigation. DCS treatment does not enhance the therapeutic effects of ST 587 and vice versa. Received: 20 August 1996/Final version: 21 November 1996