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Genomic Informatics in the Healthcare System
Published in Salvatore Volpe, Health Informatics, 2022
Another possible explanation for the phenotypic heterogeneity among cases is epigenetic differences. Epigenetic processes such as DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs can alter the activity of a gene without changing the DNA sequence. To further understand and identify the detail of the heterogeneity, a strategy such as the chromatin immunoprecipitation sequencing (ChIP-Seq) or RNA-Seq can be used. Exploring factors that can account for the phenotypic variability may provide insight into the pathways involved in disease. Furthermore, the comprehensive genetic evaluation and investigation of various individuals with these conditions will likely enlighten the fields of genomic locus heterogeneity and allelic heterogeneity of the genes with a broad spectrum of detected variants.
Epidemiology of COVID-19
Published in Srijan Goswami, Chiranjeeb Dey, COVID-19 and SARS-CoV-2, 2022
Rehab A. Rayan, Christos Tsagkaris, Imran Zafar, Aikaterini Tata
The global expertise in the care of patients with COVID-19 with ARDS is booming by adopting mechanical processes and the ventilation of respiratory organs (Pan et al., 2020). In the last two decades, the variance in ARDS has risen. In an explanatory endeavor, subgroups of people with various biological, behavioral, psychiatric, and attentive characteristics have been established (Fan et al., 2018). An increased hospital burden on COVID-19 patients and healthcare staff, also with inadequate services to rescue ARDS patients, led to the revelation that the variability results in all medical characteristics of patients with COVID-19. The findings were presented with heterogeneity. Phenotypic heterogeneity is an important principle, but it may be overused or abused by certain principles, which may adversely affect the efficiency of ventilation management. Given the importance of lung defense in ARDS, ventilation techniques in this area have been explored in recent studies addressing the phenotypic heterogeneity of COVID-19 ARDS patients (Gattinoni et al., 2020). We highly advocate the implementation of evidence-driven management (Phua et al., 2020) based on clinical physiology and supported by current results, with a clear evidence base that can drive a transition from the existing patient care paradigm.
Ayurveda Renaissance – Quo Vadis?
Published in D. Suresh Kumar, Ayurveda in the New Millennium, 2020
Identifying phenotypic and genetic heterogeneity, gene–gene interactions and allelic spectrum is a major challenge in understanding complex diseases. Of the several factors which contribute to this, phenotypic heterogeneity is a serious limitation encountered in modern medicine (Manchia et al. 2013). Juyal et al. (2012) opine that conditioning association studies on prior risk, predictable in Ayurveda, will uncover much more variation and advance diagnostics and therapeutics. They attempted identification of genetic susceptibility markers in a rheumatoid arthritis (R.A.) cohort by combining the prakṛti-based grouping of individuals with genetic analysis tools. Association of 21 markers from commonly implicated inflammatory and oxidative stress pathways was tested using a case-control approach in a total cohort comprising 325 cases, 356 controls and the three subgroups separately. A few postulates of Ayurveda on the disease characteristics were also tested in the various prakṛti groups using clinico-genetic data (Juyal et al. 2012).
An evaluation of mepolizumab for the treatment of severe asthma
Published in Expert Opinion on Biological Therapy, 2019
Jaymin B Morjaria, Rosalia Emma, Virginia Fuochi, Riccardo Polosa, Massimo Caruso
Asthma has long been recognized as a heterogeneous condition, both in terms of clinical outcomes and response to therapy. Various phenotypes have been identified based on asthma control and severity, age of onset of disease, obesity, smoking status, and sputum eosinophil counts [7,8,70]. Different molecular pathways underlying asthma inflammation may support this phenotypic heterogeneity. Consequently, intensive research in severe asthma has led to the development of specific biological agents that target specific pathological pathways, such as anti-IgE, anti-IL5, anti-IL4 and anti-IL13, anti-prostaglandin D2 (PGD2) receptor [71,72], and anti-thymic stromal lymphopoietin (TSLP) [73]. Currently, three biologic drugs targeting the IL-5 signaling pathway are approved as an add-on therapy for severe eosinophilic asthma, including mepolizumab (Nucala®, GlaxoSmithKline, UK), reslizumab (CINQAIR®; Teva, Israel) and benralizumab (FASENRATM, AstraZeneca, UK).
New drugs in preclinical and early stage clinical development in the treatment of heart failure
Published in Expert Opinion on Investigational Drugs, 2019
Juan Tamargo, Ricardo Caballero, Eva Delpón
Evaluation of new drugs in the heterogeneous HF population is challenging and the old strategy of treating HF as a single entity (‘one-size-fits-all approach’) is doomed to failure [11,12]. Furthermore, because of the multiple signaling pathways involved in the different HF phenotypes, it is possible that some new drugs were studied in the wrong population or the wrong endpoints were selected based on the underlying pathophysiological mechanisms and/or the MOA of the drug. Improved phenotypic characterization of the HF syndromes based on pathophysiology, clinical/etiologic subtype, type of clinical presentation, and comorbidities would allow to select specific patient phenotypes whose underlying pathophysiological mechanisms can be targeted by the MOA of evaluated drug. This will allow to limit excessive phenotypic heterogeneity and maximize the expected therapeutic benefit by selecting the patients that most likely can benefit. A major limitation is our limited ability to identify the primary mechanism underlying HF and to identify such homogeneous subsets of patients. The development of population-based disease registries collecting clinical, imaging, laboratory, and genetic data, treatment patterns, and causes of death and hospitalizations may facilitate the identification of the right populations and represent the most efficient way for improving the treatment of HF [13].
The spermatogenesis-associated protein-7 (SPATA7) gene – an overview
Published in Ophthalmic Genetics, 2020
SPATA7-associated phenotypes, which are categorized as ciliopathies based on the location of the SPATA7 gene product, may develop at birth or in early childhood. Patients with a diagnosis of LCA are reported with poor visual function at birth, nystagmus, hyperopia, and non-recordable or extinguished electroretinograms (ERGs). Other features of SPATA7-associated LCA are enophthalmos and midfacial hypoplasia (2). The patients affected with early-onset RP on the other hand, have some degree of useful vision at birth and do not have nystagmus, may have good visual acuity despite a severe constriction of visual fields, and nyctalopia. They present with increasing loss of visual acuity in the first decade of life or later (4). The retinal appearance in these patients whether with LCA or early-onset RP shows certain features common to both types of disease. These include disc pallor, atrophy of the retinal pigment epithelium, presence of pigmentary deposits and narrowing of the retinal vasculature. However, the phenotypes may be variable between patients. Electroretinography shows extinguished rod and cone responses (3,12,19). Phenotypic heterogeneity is evident even among patients with the same mutation. Variant phenotypes such as cone-rod dystrophy (CRD) are associated to a SPATA7 mutation of Arg85Ter (13), in addition to LCA (12). Phenotypes in SPATA7-associated disease may resemble both RP and CRD, changing over time as the disease progresses (16). Unusual phenotypic features have been documented in certain cases. These include RP with asymmetrical progression of the disease between both eyes and choroidal sclerosis in the areas of RPE loss (20).