Hypo- and hyper- sensory processing heterogeneity in Autism Spectrum Disorder

Background. Sensory processing atypicalities are part of the core symptoms of autism spectrum disorder (ASD) and could result from an excitation/inhibition imbalance. Yet, the convergence level of phenotypic sensory processing atypicalities with genetic alterations in GABA-ergic and glutamatergic pathways remains poorly understood. This study aimed to characterize the distribution of hypo/hyper-sensory profile among individuals with ASD and investigate the role of deleterious mutations in GABAergic and glutamatergic pathways related genes in sensory processing atypicalities. Method. From the Short Sensory Profile (SSP) questionnaire, we defined and explored a score – the differential Short Sensory Profile (dSSP) - as a normalized and centralized hypo/hypersensitivity ratio for 1136 participants (533 with ASD, 210 first-degree relatives, and 267 controls) from two independent study samples (PARIS and LEAP). We also performed an unsupervised item-based clustering analysis on SSP items scores to validate this new categorization in terms of hypo and hyper sensitivity. We then explored the link between the dSSP score and the burden of deleterious mutations in a subset of individuals for which whole-genome sequencing data were available. Results. We observed a mean dSSP score difference between ASD and controls, driven mostly by a high dSSP score variability among groups (PARIS: p<0.0001, η2 = 0.0001, LEAP: p<0.0001, Cohen’s d=3.67). First-degree relatives were with an intermediate distribution variability profile (p<0.0001). We also reported a positive developmental trajectory of the dSSP score (PARIS: p=0.0006, η2 = 0.02; LEAP: p=0.01, η2 = 0.01). Clusters were similarly characterized by hypo- and hyper-sensitivity items in both study samples (Cramer's V from 0.64 to 0.69, p<0.05). Our genetic analysis showed a trend only for an association with mutations of the GABAergic pathway.Limitations. The major limitation was the dSSP score difficulty to discriminate subjects with a similar quantum of hypo- and hyper- sensory symptoms to those with no such symptoms, resulting both in a similar ratio score of 0.Conclusion. The dSSP score could be a relevant clinical score of the hypo/hyper-sensory individual profile in subjects with ASD. Combined with additional sensory domain characteristics, genetics and endophenotypic substrates, the dSSP score will offer new avenues to explore the underlying neurobiological mechanisms of sensory processing atypicalities in ASD.

Dopaminergic dysfunction in the 3xTg-AD mice model of Alzheimer’s disease

Alzheimer’s disease (AD) is characterized by amyloid (Aβ) protein aggregation and neurofibrillary tangles accumulation, accompanied by neuroinflammation. With all the therapeutic attempts targeting these biomarkers having been unsuccessful, the understanding of early mechanisms involved in the pathology is of paramount importance. Dopaminergic system involvement in AD has been suggested, particularly through the appearance of dopaminergic dysfunction-related neuropsychiatric symptoms and an overall worsening of cognitive and behavioral symptoms. In this study, we reported an early dopaminergic dysfunction in a mouse model presenting both amyloid and Tau pathology. 3xTg-AD mice showed an increase of postsynaptic D2/3R receptors density in the striatum and D2/3-autoreceptors in SN/VTA cell bodies. Functionally, a reduction of anxiety-like behavior, an increase in locomotor activity and D2R hyper-sensitivity to quinpirole stimulation have been observed. In addition, microglial cells in the striatum showed an early inflammatory response, suggesting its participation in dopaminergic alterations. These events are observed at an age when tau accumulation and Aβ deposits in the hippocampus are low. Thus, our results suggest that early dopaminergic dysfunction could have consequences in behavior and cognitive function, and may shed light on future therapeutic pathways of AD.

A Review on Recent Advances in Aloperine Research: Pharmacological Activities and Underlying Biological Mechanisms

Aloperine, a quinolizidine-type alkaloid, was first isolated from the seeds and leaves of herbal plant, Sophora alopecuroides L. Empirically, Sophora alopecuroides L. is appreciated for its anti-dysentry effect, a property that is commonly observed in other Sophora Genus phytomedicines. Following the rationale of reductionism, subsequent biochemical analyses attribute such anti-dysentry effect to the bactericidal activity of aloperine. From then on, the multiple roles of aloperine are gradually revealed. Accumulating evidence suggests that aloperine possesses multiple pharmacological activities and holds a promising potential in clinical conditions including skin hyper-sensitivity, tumor and inflammatory disorders etc.; however, the current knowledge on aloperine is interspersed and needs to be summarized. To facilitate further investigation, herein, we conclude the key pharmacological functions of aloperine, and most importantly, the underlying cellular and molecular mechanisms are clarified in detail to explain the functional mode of aloperine.

Oral Ornaments: An Overview

Nowadays, people desire to look attractive and have become very alert about their appearance and smile. Since the face is most exposed part of our body, and mouth a prominent feature, teeth are getting enormous share of attention. Intraoral jewellery has currently gained popularity and is slowly becoming a craze, but this fashion trend is also associated with some significant health issues. These ornaments though are said to enhance beauty cause problems such as increase pain, infection, scar formation, tooth fractures, metal hyper-sensitivity reactions, localized periodontal disease, speech impediment, and nerve damage. This review draws special attention to the prevalence, complications, and side effects of dental jewellery in humans. Here we suggest people must be aware of all the risks associated with wearing dental jewellery, and they should undergo dental check-ups regularly.

Gluten hyper sensitivity: an unseen storm of neurological spectrum disorders

Gluten sensitivity, an autoimmune systemic disease with its protean manifestation occur in genetically susceptible individuals with gluten in their diet. Coeliac disease is the intestinal form of disease mostly seen in children with predominant gastrointestinal manifestations. The neurological presentation of gluten sensitivity mostly without enteropathy are also frequent and affect adult population in contrast. The most common presentation includes cerebellar ataxia, peripheral neuropathy and seizure followed by encephalopathy, schizoaffective and movement related manifestations. These varied clinical presentations are attributed to an immune related attack on central and peripheral nervous system involving both adaptive and innate immunity. Early suspicion, prompt diagnosis and institution of gluten free diet provides remarkable benefits to these patients with amelioration of troublesome symptoms. A better understanding of disease etiopathogenesis is likely to add more therapeutic options.

Lynne Tillman's Literary Ecologies: Affect, Cognition, and Signification in American Genius, A Comedy

Attuned to the need for ecologically informed criticism addressing the ‘affective turn’ in contemporary fiction, and following upon psychoanalytic critiques of the fantasies underlying neoliberal ideology, this article engages critically with questions concerning affect and meaning through a deliberate reading of Lynne Tillman's American Genius, A Comedy (2006). Tillman's encyclopaedic novel – narrated by an erudite, obsessive woman, Helen, afflicted with an irritating skin condition – is read as a cognitive-affective fiction that provides an oblique psychoanalysis of post-9/11 America: a neoliberal culture of would-be victims where the ascendant sensibility is hyper-sensitivity. While some literary theorists have recently advocated for phenomenological approaches less focused on interpretation and critique and more receptive to corporeal experiences, Helen's digressive, repetitive, skin-fixated narration reminds readers just how irritating, and funny, tangibility and ‘presence effects’ can be – precisely because of the curious way affects inevitably generate meaningful thinking. Tillman's artful syntax registers a heightened sensitivity to how affective forces in the environment, including language, stimulate our embodied minds and shape our thinking, feeling, and interactions. Much affect-studies scholarship claims affect circumvents semantics and resists being captured in language. But Tillman's writing, this article argues, contests notions of ineffable affect. Tillman's investment in transcribing affective phenomena, it is claimed, belies neither an individualistic or a solipsistic concern with subjective response, nor a radical materialist commitment to pushing the materialities of communication to the brink of meaninglessness. Affect, American Genius ingeniously demonstrates, is integral to eco-critical thinking. This account of affective circulations in American Genius demonstrates how Tillman successfully takes up the challenge of conveying, in prose, the complex, infra-linguistic affective processes underlying embodied communication and cognition. After introducing the novel, Section Two, ‘Ambivalent Belief’ explains how its opening prepares readers to confront what Slavoj Žižek calls the contemporary crisis of belief. Section Three tests and ultimately rejects the hypothesis that American Genius expresses a meaningless posthistoricist aesthetic; rather, Tillman's ecological aesthetic entails a meticulous staging of how imbricated cognitive processes are within the biological human body and political social body. Through her recursive prose, Tillman creates a mediating space for staging affectively inflected meta-cognitions. Section Four analyses passages where these meta-cognitions involve ecological perceptions. The critical focus throughout is on form. Deliberate readings reveal how, sentence by sentence, Tillman's ‘skintax’ evokes multidimensional corporeal processes that constitute the affective dimension of thinking. ‘Sensitivity and Making Sense’, the Fifth Section, identifies the ethical core of Tillman's eco-aesthetic and unpacks passages that expand the concept of sensitivity in ways that attune readers to affective modulations of the social that are potentially transformative.

The Prevalence of People With Restricted Access to Work in Man-Made Electromagnetic Environments

Some surveys have identified people who have restricted access to work in environments with man-made electromagnetic exposures. This study attempts to determine their prevalence, an aspect not previously investigated in its own right. It is based on analyses of the two different types of surveys of people with Idiopathic Environmental Intolerance attributed to Electromagnetic Fields (IEI-EMF), or Electromagnetic Hyper-Sensitivity (EHS), either of the general population or of people with IEI-EMF/EHS. In addition, there are different definitions of IEI-EMF/EHS, with a range of subconscious, mild, moderate or severe symptoms, potentially leading in three stages to hyper-sensitivity. The current evidence is assessed as indicating that, in addition to subconscious sensitivity, the prevalence of IEI-EMF/EHS is between about 5.0 and 30 per cent of the general population for mild cases, 1.5 and 5.0 per cent for moderate cases and < 1.5 per cent for severe cases. The prevalence of people restricted in their access to work in a man-made electromagnetic environment is estimated at 0.65 per cent of the general population, at about 18% of the general population with moderate IEI-EMF/EHS. The estimate of 0.65% equates to 435,500 people in the UK’s population of 67 million. Some reasons for possible under-reporting are discussed. Adjustments can enable some people with this disability to remain in employment, suggesting that rates of restriction in access to work may fall as employers become aware of what adjustments are needed.

Hyper-Sensitivity in Global Virtual Teams

This chapter broadens the understanding of global virtual teams by integrating two theoretical approaches—the hyper-personal perspective and the social constructionist theory—to examine how members of global virtual teams develop relational interactions and outcomes. Specifically, the integrated research model presented here suggests that global virtual team members are hyper-sensitive to their computer-mediated interpersonal interactions in that individuals' socially constructed perceptions of the context influence their relational development and judgments much more intensively than those of collocated members. The chapter offers managerial suggestions and research directions.