17 research outputs found

    Tourettic OCD: Current understanding and treatment challenges of a unique endophenotype

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    Obsessive compulsive disorder (OCD) and chronic tic disorders (CTD) including Tourette Syndrome (TS) are often comorbid conditions. While some patients present with distinct symptoms of CTD and/or OCD, a subset of patients demonstrate a unique overlap of symptoms, known as Tourettic OCD (TOCD), in which tics, compulsions, and their preceding premonitory urges are overlapping and tightly intertwined. The specific behaviors seen in TOCD are typically complex tic-like behaviors although with a compulsive and partially anxious nature reminiscent of OCD. TOCD is not classified within the Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) as an independent diagnostic entity, but mounting evidence suggests that TOCD is an intermediate neuropsychiatric disorder distinct from either TS or OCD alone and as such represents a unique phenomenology. In this review of TOCD we discuss clinical, genetic, environmental, neurodevelopmental, and neurocircuit-based research to better characterize our current understanding of this disorder. TOCD is characterized by earlier age of onset, male predominance, and specific symptom clusters such as lower tendency toward compulsions related to checking, cleaning, and reassurance seeking and higher tendency toward compulsions such as rubbing, tapping, or touching associated with symmetry concerns or thoughts of exactness. Functional magnetic resonance imaging (fMRI) imaging suggests that TOCD symptoms may arise from involvement of an intermediate neurocircuitry distinct from classic OCD or classic CTD. Small cumulative contributions from multiple genetic loci have been implicated, as have environmental factors such as infection and perinatal trauma. In addition, this review addresses the treatment of TOCD which is especially complex and often treatment resistant and requires pharmacology and behavioral therapy in multiple modalities. Given the distressing impact of TOCD on patients’ functioning, the goal of this review is to raise awareness of this distinct entity toward the goal of improving standards of care

    Xlinked myotubular and centronuclear myopathies

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    Abstract Recent work has significantly enhanced our understanding of the centronuclear myopathies and, in particular, myotubular myopathy. These myopathies share similar morphologic appearances with other diseases, namely the presence of hypotrophic myofibers with prominent internalized or centrally placed nuclei. Early workers suggested that this alteration represented an arrest in myofiber maturation, while other hypotheses implicated either failure in myofiber maturation or neurogenic causes. Despite similarities in morphology, distinct patterns of inheritance and some differences in clinical features have been recognized among cases. A severe form, known as X-linked myotubular myopathy (XLMTM), presents at or near birth. Affected males have profound global hypotonia and weakness, accompanied by respiratory difficulties that often require ventilation. Most of these patients die in infancy or early childhood, but some survive into later childhood or even adulthood. The responsible gene (MTM1) has been cloned; it encodes a phosphoinositide lipid phosphatase known as myotubularin that appears to be important in muscle maintenance. In autosomal recessive centronuclear myopathy (AR CNM), the onset of weakness typically occurs in infancy or early childhood. Some investigators have divided AR CNM into 3 subgroups: 1) an early-onset form with ophthalmoparesis, 2) an early-onset form without ophthalmoparesis, and 3) a late-onset form without ophthalmoparesis. Clinically, autosomal dominant CNM (AD CNM) is relatively mild and usually presents in adults with a diffuse weakness that is slowly progressive and may be accompanied by muscle hypertrophy. Overall, the autosomal disorders are not as clinically uniform as XLMTM, which has made their genetic characterization more difficult. Currently the responsible gene(s) remain unknown. This review will explore the historical evolution in understanding of these myopathies and give an update on their histopathologic features, genetics and pathogenesis

    Why are western diet and western lifestyle pro-inflammatory risk factors of celiac disease?

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    The prevalence of celiac disease increased in recent years. In addition to the genetic and immunological factors, it appears that environmental determinants are also involved in the pathophysiology of celiac disease. Gastrointestinal infections impact the development of celiac disease. Current research does not directly confirm the protective effect of natural childbirth and breastfeeding on celiac disease. However, it seems that in genetically predisposed children, the amount of gluten introduced into the diet may have an impact on celiac disease development. Also western lifestyle, including western dietary patterns high in fat, sugar, and gliadin, potentially may increase the risk of celiac disease due to changes in intestinal microbiota, intestinal permeability, or mucosal inflammation. Further research is needed to expand the knowledge of the relationship between environmental factors and the development of celiac disease to define evidence-based preventive interventions against the development of celiac disease. The manuscript summarizes current knowledge on factors predisposing to the development of celiac disease including factors associated with the western lifestyle

    We Do Not Like It: A Likert-Type Scale Survey on the Attitudes of a Young Population towards the Transhumanistic Theory of Education

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    Transhumanists assume that future education may be purely based on technological stimulation. The question is: Do potential clients of education “like” such vision? In order to check this, we asked over one thousand two hundred young Poles to evaluate their identification with the transhumanistic theory of education. The results are quite surprising: its show that they disagree with the assumptions of this theory, while they rather agree with the postulates of more traditional (and no technology-based) concepts of education

    Is There an Ideal Diet to Protect against Iodine Deficiency?

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    Iodine deficiency is a global issue and affects around 2 billion people worldwide, with pregnant women as a high-risk group. Iodine-deficiency prevention began in the 20th century and started with global salt iodination programmes, which aimed to improve the iodine intake status globally. Although it resulted in the effective eradication of the endemic goitre, it seems that salt iodination did not resolve all the issues. Currently, it is recommended to limit the consumption of salt, which is the main source of iodine, as a preventive measure of non-communicable diseases, such as hypertension or cancer the prevalence of which is increasing. In spite of the fact that there are other sources of iodine, such as fish, seafood, dairy products, water, and vegetables, the high consumption of processed food with a high content of unionised salt, alternative diets or limited salt intake can still lead to iodine deficiency. Thus, iodine deficiency remains a relevant issue, with new, preventive solutions necessary. However, it appears that there is no diet which would fully cover the iodine requirements, and iodine food supplementation is still required

    Why Does Obesity as an Inflammatory Condition Predispose to Colorectal Cancer?

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    Obesity is a complex and multifactorial problem of global importance. Additionally, obesity causes chronic inflammation, upregulates cell growth, disturbs the immune system, and causes genomic instability, increasing the risk of carcinogenesis. Colorectal cancer is one of the most common cancers, and it has become a global problem. In 2018, there were around 1.8 million new cases and around 881,000 deaths worldwide. Another risk factor of colorectal cancer associated with obesity is poor diet. A Western diet, including a high intake of red and processed meat and a low consumption of whole grains, fruits, vegetables, and fiber, may increase the risk of both colorectal cancer and obesity. Moreover, the Western diet is associated with a proinflammatory profile diet, which may also affect chronic low-grade inflammation. In fact, people with obesity often present gut dysbiosis, increased inflammation, and risk of colorectal cancer. In this article, the association between obesity and colorectal cancer is discussed, including the most important mechanisms, such as low-grade chronic inflammation, gut dysbiosis, and poor diet

    Myotubularin controls desmin intermediate filament architecture and mitochondrial dynamics in human and mouse skeletal muscle

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    Muscle contraction relies on a highly organized intracellular network of membrane organelles and cytoskeleton proteins. Among the latter are the intermediate filaments (IFs), a large family of proteins mutated in more than 30 human diseases. For example, mutations in the DES gene, which encodes the IF desmin, lead to desmin-related myopathy and cardiomyopathy. Here, we demonstrate that myotubularin (MTM1), which is mutated in individuals with X-linked centronuclear myopathy (XLCNM; also known as myotubular myopathy), is a desmin-binding protein and provide evidence for direct regulation of desmin by MTM1 in vitro and in vivo. XLCNM-causing mutations in MTM1 disrupted the MTM1-desmin complex, resulting in abnormal IF assembly and architecture in muscle cells and both mouse and human skeletal muscles. Adeno-associated virus–mediated ectopic expression of WT MTM1 in Mtm1-KO muscle reestablished normal desmin expression and localization. In addition, decreased MTM1 expression and XLCNM-causing mutations induced abnormal mitochondrial positioning, shape, dynamics, and function. We therefore conclude that MTM1 is a major regulator of both the desmin cytoskeleton and mitochondria homeostasis, specifically in skeletal muscle. Defects in IF stabilization and mitochondrial dynamics appear as common physiopathological features of centronuclear myopathies and desmin-related myopathies
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