Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome): defining and measuring functional impacts in pediatric patients

Background Research about pediatric patients’ perspective on mucopolysaccharidosis type VI (MPS VI) and its impact on daily life is limited. We aimed to identify the disease concepts of interest that most impact function and day-to-day life of pediatric patients with MPS VI, and to consider clinical outcome assessments (COAs) that may potentially measure meaningful improvements in these concepts. Methods Potential focus group participants were identified by the National MPS Society (USA) and invited to participate if they self-reported a clinician-provided diagnosis of MPS VI and were 4 to 18 years, receiving enzyme replacement therapy (ERT), and available to attend a 1-day focus group with their caregiver in Dallas, TX, USA. The focus group consisted of a series of polling and open-ended concept elicitation questions and a cognitive debriefing session. The discussion was audio recorded, transcribed verbatim, and analyzed to identify disease concepts of interest and functional impacts most relevant to participants. Results Overall, caregivers (n = 9) and patients with MPS VI (n = 9) endorsed that although their children/they receive ERT, residual symptoms exist and impact health-related quality of life. The key disease concepts of interest identified were impaired mobility, upper extremity and fine motor deficits, pain, and fatigue. Pain was unanimously reported by all patients across many areas of the body and impacted daily activity. Key disease concepts were mapped to a selection of pediatric COAs including generic measures such as PROMIS®, PODCI, CHAQ, and PedsQL™. Caregivers endorsed the relevance of PODCI and PROMIS Upper Extremity, Mobility, and Pain items and all patients completed the NIH Toolbox Pegboard Dexterity Test. Additional COAs that aligned with the disease concepts included range of motion, the 2- and 6-min walk tests, timed stair climbs, Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition, grip strength, pain visual analog scale, and the Faces Pain Scale-Revised. Conclusion An MPS VI focus group of pediatric patients and their caregivers identified impaired mobility, upper extremity and fine motor deficits, pain, and fatigue as key disease concepts of interest. These disease concepts were mapped to existing pediatric COAs, which were provided to the group for endorsement of their relevance.

Health and disease as practical concepts: exploring function in context-specific definitions

Despite the longstanding debate on definitions of health and disease concepts, and the multitude of accounts that have been developed, no consensus has been reached. This is problematic, as the way we define health and disease has far-reaching practical consequences. In recent contributions it is proposed to view health and disease as practical- and plural concepts. Instead of searching for a general definition, it is proposed to stipulate context-specific definitions. However, it is not clear how this should be realized. In this paper, we review recent contributions to the debate, and examine the importance of context-specific definitions. In particular, we explore the usefulness of analyzing the relation between the practical function of a definition and the context it is deployed in. We demonstrate that the variety of functions that health and disease concepts need to serve makes the formulation of monistic definitions not only problematic but also undesirable. We conclude that the analysis of the practical function in relation to the context is key when formulating context-specific definitions for health and disease. At last, we discuss challenges for the pluralist stance and make recommendations for future research.

«Health - disease» Conceptual Sphere: Cultural Code

The research is focused on the conceptual, figurative and value features of health - disease concepts due to their permanently growing importance, reflected in the language mindset. These processes are caused by various trends leading to the increasing danger to human health: epidemics, human-induced disasters, environment pollution. Due to the relevance of the issues, the authors aim to analyse the health - disease conceptual sphere as a strategy to changehuman mentality and the attitude to health as a norm and a value as well as to disease as a deviation from normal life, which implies observation of values and image characteristics of concepts, revealing and describing the cultural semantics of signs. The research is designed according to the original perceptive image that every concept is based on. This image represents a vector basis in a configuration of meanings inherent in the whole conceptual sphere. The analysis of the conceptual sphere using the corpus analysis tools allowed the authors comes to the conclusion that they vary and differ within cultural functionality determined by the conceptual characteristics. Actualization of a negative or positive attitude to health and disease caused by internal and external factors reveals the dominance of the signs motivated by the external events, such as the formation of the new human health-oriented mentality and the creation of a specified conceptual sphere. The description of ambivalent concepts provided in the axiological perspective provides an opportunity to learn more about complicated conceptual spheres and explore linguistic experience objectivation, experienced knowledge quantum as well as social and group specifics in the health - disease conceptual sphere.

EXPRESS: Frailty and Cerebrovascular Disease: Concepts and Clinical Implications for Stroke Medicine

Frailty is a distinctive health state in which the ability of older people to cope with acute stressors is compromised by an increased vulnerability brought by age-associated declines in physiological reserve and function across multiple organ systems. Although closely associated with age, multimorbidity, and disability, frailty is a discrete syndrome that is associated with poorer outcomes across a range of medical conditions. However, its role in cerebrovascular disease and stroke has received limited attention. The estimated rise in the prevalence of frailty associated with changing demographics over the coming decades makes it an important issue for stroke practitioners, cerebrovascular research, clinical service provision, and stroke survivors alike. This review will consider the concept and models of frailty, how frailty is common in cerebrovascular disease, the impact of frailty on stroke risk factors, acute treatments, and rehabilitation, and considerations for future applications in both cerebrovascular clinical and research settings.  

A Knowledge Graph of Mechanistic Associations Between COVID-19, Diabetes Mellitus and Kidney Diseases

This paper proposes an automated knowledge synthesis and discovery framework to analyze published literature to identify and represent underlying mechanistic associations that aggravate chronic conditions due to COVID-19. We present a literature-based discovery approach that integrates text mining, knowledge graphs and ontologies to discover semantic associations between COVID-19 and chronic disease concepts that were represented as a complex disease knowledge network that can be queried to extract plausible mechanisms by which COVID-19 may be exacerbated by underlying chronic conditions.

Emerging Dynamics of Macrophage Cellular Senescence and Immunosenescence in Governing Organismal Aging and Disease: Concepts and Opportunities

An intricate relationship between impaired immune functions and the age-related accumulation of tissue senescent cells (SC) is rapidly emerging. The immune system is unique as it undergoes mutually inclusive and deleterious processes of immunosenescence and cellular senescence with advancing age. While factors inducing immunosenescence and cellular senescence may be shared, however, both these processes are fundamentally different which holistically influence the aging immune system. Immunosenescence is a well-characterized phenomenon, but our understanding and biological impact of cellular senescence in immune cells, especially in the innate immune cells such as macrophages, is only beginning to be understood. Tissue-resident macrophages are long-lived, and while functioning in tissue-specific and niche-specific microenvironments, senescence in macrophages can be directly influenced by senescent host cells which may impact organismal aging. In addition, evidence of age-associated immunometabolic changes as drivers of altered macrophage phenotype and functions such as inflamm-aging is also emerging. The present review describes the emerging impact of cellular senescence vis-à-vis immunosenescence in aging macrophages, its biological relevance with other senescent non-immune cells, and known immunometabolic regulators. Gaps in our present knowledge, as well as strategies aimed at understanding cellular senescence and its therapeutics in the context of macrophages, have been reviewed.

The Progenetix oncogenomic resource in 2021

In cancer, copy number aberrations (CNA) represent a type of nearly ubiquitous and frequently extensive structural genome variations. To disentangle the molecular mechanisms underlying tumorigenesis as well as identify and characterize molecular subtypes, the comparative and meta-analysis of large genomic variant collections can be of immense importance. Over the last decades, cancer genomic profiling projects have resulted in a large amount of somatic genome variation profiles, however segregated in a multitude of individual studies and datasets. The Progenetix project, initiated in 2001, curates individual cancer CNA profiles and associated metadata from published oncogenomic studies and data repositories with the aim to empower integrative analyses spanning all different cancer biologies.During the last few years, the fields of genomics and cancer research have seen significant advancement in terms of molecular genetics technology, disease concepts, data standard harmonization as well as data availability, in an increasingly structured and systematic manner. For the Progenetix resource, continuous data integration, curation and maintenance have resulted in the most comprehensive representation of cancer genome CNA profiling data with 138’663 (including 115’357 tumor) CNV profiles. In this article, we report a 4.5-fold increase in sample number since 2013, improvements in data quality, ontology representation with a CNV landscape summary over 51 distinctive NCIt cancer terms as well as updates in database schemas, and data access including new web front-end and programmatic data access. Database URL:progenetix.org

Resources of IlmulAmraz during early Abbasid caliph (7th-9th C.E) up to the work of Al-Razi

Aim and Objective:The literature of Ilmul Amraz occupies a pedestal position in Unani medicine.The literature, however, is scattered among many manuscripts and requires being collected and compiled for better understanding and comprehension of disease concepts of Unani medicine. The material has been collected from the original resourcesof early Abbasid caliph (from7th-9thC.E) till the period of Al-Razi and briefly introduced in this article. Material and Methodology: The proposed literary research is conducted through ‘input-processing-output’ approach. The literature has been collected from different classical texts, reference books and various digitalized mode. Conclusion: The present review article underlines the contributions of Arab physicians, their original works, innovations, and practical experiences. The impact of theoretical contribution of Al Razi manifests in ancient Greco-Roman theory of diseases. Bangladesh Journal of Medical Science Vol.20(2) 2021 p.228-233