Secondary analyses of global datasets: do obesity and physical activity explain variation in diabetes risk across populations?

Copyright © 2021 The Author(s). Type 2 diabetes rates vary significantly across geographic regions. These differences are sometimes assumed to be entirely driven by differential distribution of environmental triggers, including obesity and insufficient physical activity (IPA). In this review, we discuss data which conflicts with this supposition. We carried out a secondary analysis of publicly available data to unravel the relative contribution of obesity and IPA towards diabetes risk across different populations. We used sex-specific, age-standardized estimates from Non-Communicable Disease Risk Factor Collaboration (NCD-RisC) on diabetes (1980–2014) and obesity (1975–2016) rates, in 200 countries, and from WHO on IPA rates in 168 countries in the year 2016. NCD-RisC and WHO organized countries into nine super-regions. All analyses were region- and sex-specific. Although obesity has been increasing since 1975 in every part of the world, this was not reflected in a proportional increase in diabetes rates in several regions, including Central and Eastern Europe, and High-income western countries region. Similarly, the association of physical inactivity with diabetes is not homogeneous across regions. Countries from different regions across the world could have very similar rates of diabetes, despite falling on opposite ends of IPA rate spectrum. The combined effect of obesity and IPA on diabetes risk was analyzed at the worldwide and country level. The overall findings highlighted the larger impact of obesity on disease risk; low IPA rates do not seem to be protective of diabetes, when obesity rates are high. Despite that, some countries deviate from this overall observation. Sex differences were observed across all our analyses. Overall, data presented in this review indicate that different populations, while experiencing similar environmental shifts, are apparently differentially subject to diabetes risk. Sex-related differences observed suggest that males and females are either subject to different risk factor exposures or have different responses to them.The work presented in this paper is part of a PhD project by the first author (Budour Alkaf); internal funding by Imperial College London Diabetes Centre is gratefully acknowledged. The authors are also grateful for The Medical Research Council, UK (grant numbers: MR/M013138/1, MRC/BBSRC MR/S03658X/1 (JPI HDHL H2020)) for their financial support during the authors time when conducting this piece of work and writing this paper

Local biases drive, but do not determine, the perception of illusory trajectories

When a dot moves horizontally across a set of tilted lines of alternating orientations, the dot appears to be moving up and down along its trajectory. This perceptual phenomenon, known as the slalom illusion, reveals a mismatch between the veridical motion signals and the subjective percept of the motion trajectory, which has not been comprehensively explained. In the present study, we investigated the empirical boundaries of the slalom illusion using psychophysical methods. The phenomenon was found to occur both under conditions of smooth pursuit eye movements and constant fixation, and to be consistently amplified by intermittently occluding the dot trajectory. When the motion direction of the dot was not constant, however, the stimulus display did not elicit the expected illusory percept. These findings confirm that a local bias towards perpendicularity at the intersection points between the dot trajectory and the tilted lines cause the illusion, but also highlight that higher-level cortical processes are involved in interpreting and amplifying the biased local motion signals into a global illusion of trajectory perception

Local biases drive, but do not determine, the perception of illusory trajectories

When a dot moves horizontally across a set of tilted lines of alternating orientations, the dot appears to be moving up and down along its trajectory. This perceptual phenomenon, known as the slalom illusion, reveals a mismatch between the veridical motion signals and the subjective percept of the motion trajectory, which has not been comprehensively explained. In the present study, we investigated the empirical boundaries of the slalom illusion using psychophysical methods. The phenomenon was found to occur both under conditions of smooth pursuit eye movements and constant fixation, and to be consistently amplified by intermittently occluding the dot trajectory. When the motion direction of the dot was not constant, however, the stimulus display did not elicit the expected illusory percept. These findings confirm that a local bias towards perpendicularity at the intersection points between the dot trajectory and the tilted lines cause the illusion, but also highlight that higher-level cortical processes are involved in interpreting and amplifying the biased local motion signals into a global illusion of trajectory perception

Toxin-Based Models to Investigate Demyelination and Remyelination.

Clinical myelin diseases, and our best experimental approximations, are complex entities in which demyelination and remyelination proceed unpredictably and concurrently. These features can make it difficult to identify mechanistic details. Toxin-based models offer lesions with predictable spatiotemporal patterns and relatively discrete phases of damage and repair: a simpler system to study the relevant biology and how this can be manipulated. Here, we discuss the most widely used toxin-based models, with a focus on lysolecithin, ethidium bromide, and cuprizone. This includes an overview of their respective mechanisms, strengths, and limitations and step-by-step protocols for their use

Why Self-Induced Pain Feels Less Painful than Externally Generated Pain: Distinct Brain Activation Patterns in Self- and Externally Generated Pain

Voluntary movement generally inhibits sensory systems. However, it is not clear how such movement influences pain. In the present study, subjects actively or passively experienced mechanical pain or pressure during functional MRI scanning. Pain and pressure were induced using two modified grip strengthener rings, each twined with four crystal bead strings, with polyhedral beads to induce pain, or spherical beads to induce pressure. Subjects held one ring in the left hand and were either asked to squeeze their left hand with their right hand (i.e., active pain or pressure), or to have their left hand squeezed by the experimenter (i.e., passive pain or pressure). Subjects rated the intensity and unpleasantness of the pain sensation lower in the active procedure than in the passive one. Correspondingly, pain-related brain areas were inhibited in the case of self-generated pain, including the primary somatosensory cortex (SI), anterior cingulate cortex (ACC), and the thalamus. These results suggest that active movement behaviorally inhibits concomitant mechanical pain, accompanied by an inhibition of pain response in pain-related brain areas such as the SI cortex. This might be part of the mechanisms underlying the kinesitherapy for pain treatment

Integration of Gravitational Torques in Cerebellar Pathways Allows for the Dynamic Inverse Computation of Vertical Pointing Movements of a Robot Arm

Several authors suggested that gravitational forces are centrally represented in the brain for planning, control and sensorimotor predictions of movements. Furthermore, some studies proposed that the cerebellum computes the inverse dynamics (internal inverse model) whereas others suggested that it computes sensorimotor predictions (internal forward model).This study proposes a model of cerebellar pathways deduced from both biological and physical constraints. The model learns the dynamic inverse computation of the effect of gravitational torques from its sensorimotor predictions without calculating an explicit inverse computation. By using supervised learning, this model learns to control an anthropomorphic robot arm actuated by two antagonists McKibben artificial muscles. This was achieved by using internal parallel feedback loops containing neural networks which anticipate the sensorimotor consequences of the neural commands. The artificial neural networks architecture was similar to the large-scale connectivity of the cerebellar cortex. Movements in the sagittal plane were performed during three sessions combining different initial positions, amplitudes and directions of movements to vary the effects of the gravitational torques applied to the robotic arm. The results show that this model acquired an internal representation of the gravitational effects during vertical arm pointing movements.This is consistent with the proposal that the cerebellar cortex contains an internal representation of gravitational torques which is encoded through a learning process. Furthermore, this model suggests that the cerebellum performs the inverse dynamics computation based on sensorimotor predictions. This highlights the importance of sensorimotor predictions of gravitational torques acting on upper limb movements performed in the gravitational field

I Feel what You Feel if You Are Similar to Me

Social interactions are influenced by the perception of others as similar or dissimilar to the self. Such judgements could depend on physical and semantic characteristics, such as membership in an ethnic or political group. In the present study we tested whether social representations of the self and of others could affect the perception of touch. To this aim, we assessed tactile perception on the face when subjects observed a face being touched by fingers. In different conditions we manipulated the identity of the shown face. In a first experiment, Caucasian and Maghrebian participants viewed a face belonging either to their own or to a different ethnic group; in a second experiment, Liberal and Conservative politically active participants viewed faces of politicians belonging to their own or to the opposite political party. The results showed that viewing a touched face most strongly enhanced the perception of touch on the observer's face when the observed face belonged to his/her own ethnic or political group

Screening for HIV-Associated Tuberculosis and Rifampicin Resistance before Antiretroviral Therapy Using the Xpert MTB/RIF Assay: A Prospective Study

In a prospective study, Stephen Lawn and colleagues find that pre-ART screening with Xpert MTB/RIF increased tuberculosis case detection by 45% compared to smear microscopy in HIV-positive patients at high risk of TB risk. AE competing interests must also pull through to the proof. “The Academic Editor, Madhukar Pai, declares that he consults for the Bill & Melinda Gates Foundation (BMGF). The BMGF supported FIND which was involved in the development of the Xpert MTB/RIF assay. He also co-chairs the Stop TB Partnership's New Diagnostics Working Group that was involved in the WHO endorsement of the Xpert assay.” Linked: Scott pmed.1001061; Evans pmed.1001064; Dowdy pmed.100106

Regeneration of myelin sheaths of normal length and thickness in the zebrafish CNS correlates with growth of axons in caliber

Demyelination is observed in numerous diseases of the central nervous system, including multiple sclerosis (MS). However, the endogenous regenerative process of remyelination can replace myelin lost in disease, and in various animal models. Unfortunately, the process of remyelination often fails, particularly with ageing. Even when remyelination occurs, it is characterised by the regeneration of myelin sheaths that are abnormally thin and short. This imperfect remyelination is likely to have implications for the restoration of normal circuit function and possibly the optimal metabolic support of axons. Here we describe a larval zebrafish model of demyelination and remyelination. We employ a drug-inducible cell ablation system with which we can consistently ablate 2/3rds of oligodendrocytes in the larval zebrafish spinal cord. This leads to a concomitant demyelination of 2/3rds of axons in the spinal cord, and an innate immune response over the same time period. We find restoration of the normal number of oligodendrocytes and robust remyelination approximately two weeks after induction of cell ablation, whereby myelinated axon number is restored to control levels. Remarkably, we find that myelin sheaths of normal length and thickness are regenerated during this time. Interestingly, we find that axons grow significantly in caliber during this period of remyelination. This suggests the possibility that the active growth of axons may stimulate the regeneration of myelin sheaths of normal dimensions

Top-down social modulation of interpersonal observation-execution.

Cyclical upper limb movement can involuntarily deviate from its primary movement axis when the performer concurrently observes incongruent biological motion (i.e. interpersonal observation-execution). The current study examined the social modulation of such involuntary motor interference using a protocol that reflected everyday social interactions encountered in a naturalistic social setting. Eighteen participants executed cyclical horizontal arm movements during the observation of horizontal (congruent) or curvilinear (incongruent) biological motion. Both prior to, and during the interpersonal observation-execution task, participants also received a series of social words designed to prime a pro-social or anti-social attitude. The results showed greater orthogonal movement deviation, and thus interference, for the curvilinear compared to horizontal stimuli. Importantly, and opposite to most of the previous findings from work on automatic imitation and mimicry, there was a greater interference effect for the anti-social compared to pro-social prime condition. These findings demonstrate the importance of interpreting the context of social primes, and strongly support predictions of a comparison between the prime construct and the self-concept/-schema and the top-down response modulation of social incentives