Inflammation in Asthma Pathogenesis: Role of T cells, Macrophages, Epithelial Cells and Type 2 Inflammation

: Asthma is a chronic disease with abnormal inflammatory and immunological responses. The disease initiated by antigens in subjects with genetic susceptibility. However, environmental factors play a role in the initiation and exacerbation of asthma attack. Asthma is T helper 2 (Th2)-cell-mediated disease. Recent studies indicated that asthma is not a single disease entity, but it is with multiple phenotypes and endotypes. The pathophysiological changes in asthma included a series of subsequent continuous vicious circle of cellular activation contributed to induction of chemokines and cytokines that potentiate inflammation. The heterogeneity of asthma influenced the treatment response. The asthma pathogenesis driven by varied set of cells such as eosinophils, basophils, neutrophils, mast cells, macrophages, epithelial cells and T cells. In this review the role of T cells, macrophage, and epithelial cells are discussed.

Fifteen-minute guide to managing oligoarticular juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease affecting children and young people today. However, it is not a single disease entity, but an umbrella term that gathers together a heterogeneous collection of complex, chronic inflammatory conditions with oligoarticular JIA the most common form in both Europe and North America. Due to its relative rarity in daily practice and potential to mimic other conditions, oligoarticular JIA can present a diagnostic and management challenge to healthcare professionals in both primary care and general paediatrics. The aim of this article is to provide a summary of the key aspects of diagnosis, investigation and management of this condition, with the hopes of building clinicians’ confidence when facing a possible case of oligoarticular JIA.

LGG-15. COMPREHENSIVE ANALYSIS OF MYB/MYB1-ALTERED GLIOMAS: A MULTI-INSTITUTIONAL EXPERIENCE OF 33 GLIOMAS

Background Pediatric diffuse gliomas harbor recurrent genetic alterations, including those in MYB and MYBL1. Regardless of histopathologic classification, low-grade diffuse gliomas with MYB/MYBL1 alterations represent a single disease entity. Additional insight is needed to define optimal therapeutic strategies for these tumors. Methods We retrospectively reviewed gliomas with MYB or MYB1L alterations treated or referred for pathologic review at St. Jude Children’s Research Hospital (St. Jude). Tumor specimens were centrally reviewed. Molecular characterization and clinical data were collated from St. Jude and referring institutions. Results Thirty-three patients were identified. Two tumors had MYBL1 alterations, while 31 had MYB alterations. MYB-QKI fusion was the most common alteration. Eighteen (55%) were male. The median age at diagnosis was 5 years (range, 0–40 years). Most tumors were in the cerebral cortex (22/33), and the most common presentation was seizures (16/33). Three patients (9%) presented with hydrocephalus and required cerebrospinal fluid diversion. Two patients (6%) presented with metastatic disease. Gross-total resection was achieved in 15 patients (45%). Of the 7 patients receiving cytotoxic chemotherapy, no substantial response was observed. Of the 6 patients who received RT, one had disease progression. The median follow-up was 5.9 years. The 5-year event-free survival was 88.1%, while the 5-year overall survival was 96.3%. Two patients died, one of unclear cause and one of treatment-related acute myelogenous leukemia. Using log-rank tests, no difference in outcomes was observed based on molecular characteristics, degree of resection, metastatic status, or treatment modality. Conclusions Although tumors with MYB and MYBL1 alterations present with varying molecular and clinical features, they represent a group of tumors with favorable outcomes. Further characterization is required to identify the subgroup of tumors with a higher propensity for progression.

Interstitial lung disease (ILD)

The interstitial lung diseases (ILDs), are an extensive range of lung diseases, rather than a single disease entity. These diseases are often grouped together because they have similarities in clinical presentation, radiographic changes, physiological features, and symptoms. Despite their similarities, these diseases have a variety of aetiologies, treatments, and prognoses. The rate of onset of symptoms is very variable. Some patients present with long-standing radiological symptoms, often found opportunistically. Other patients present with acute onset symptoms, rapidly developing respiratory failure and ultimately progressing to death. This chapter covers the presentation, clinical findings, diagnosis, common causes, and associated investigations. Common ILDs are also described.

Autoimmunity in Focal Segmental Glomerulosclerosis: A Long-Standing Yet Elusive Association

Focal segmental glomerulosclerosis (FSGS) is a histological term that describes a pathologic renal entity affecting both adults and children, with a wide array of possible underlying etiologies. Podocyte damage with scarring, the hallmark of this condition, leads to altered permeability of the glomerular barrier, which may result in massive proteinuria and relentless renal function deterioration. A definite cause of focal segmental glomerulosclerosis can be confirmed in a minority of cases, while most forms have been traditionally labeled as primary or idiopathic. Despite this definition, increasing evidence indicates that primary forms are a heterogenous group rather than a single disease entity: several circulating factors that may affect glomerular permeability have been proposed as potential culprits, and both humoral and cellular immunity have been implicated in the pathogenesis of the disease. Consistently, immunosuppressive drugs are considered as the cornerstone of treatment for primary focal segmental glomerulosclerosis, but response to these agents and long-term outcomes are highly variable. In this review we provide a summary of historical and recent advances on the pathogenesis of primary focal segmental glomerulosclerosis, focusing on implications for its differential diagnosis and treatment.

Extending the Enterovirus Lead: Could a Related Picornavirus be Responsible for Diabetes in Humans?

We found an association between the abundance of rodents in the wild and onset of type 1 diabetes (T1D) in humans. A picornavirus named Ljungan virus (LV) was subsequently isolated from wild bank voles. Both picornavirus-like particles detected by electron microscopy and LV antigen visualized by immunohistochemistry was seen in islets of Langerhans in diabetic wild bank voles. LV antigen has also been found in islets of Langerhans in a patient with recent onset of T1D and in the commonly used Bio Breeding (BB) T1D rat model. We discuss the possibility of T1D and type 2 diabetes (T2D) as parts of a single disease entity. Antiviral compounds directed against picornavirus have been found to be an effective treatment of diabetes in BB rats. We propose using the same currently available antiviral compounds in clinical trials in humans. Antiviral treatment would have the potential to be both proof of concept for involvement of a picornavirus in diabetes pathogenesis and also present a first-generation therapy.

Reviewing the genetics of heterogeneity in depression: operationalizations, manifestations and etiologies

With progress in genome-wide association studies of depression, from identifying zero hits in ~16 000 individuals in 2013 to 223 hits in more than a million individuals in 2020, understanding the genetic architecture of this debilitating condition no longer appears to be an impossible task. The pressing question now is whether recently discovered variants describe the etiology of a single disease entity. There are a myriad of ways to measure and operationalize depression severity, and major depressive disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders-5 can manifest in more than 10 000 ways based on symptom profiles alone. Variations in developmental timing, comorbidity and environmental contexts across individuals and samples further add to the heterogeneity. With big data increasingly enabling genomic discovery in psychiatry, it is more timely than ever to explicitly disentangle genetic contributions to what is likely ‘depressions’ rather than depression. Here, we introduce three sources of heterogeneity: operationalization, manifestation and etiology. We review recent efforts to identify depression subtypes using clinical and data-driven approaches, examine differences in genetic architecture of depression across contexts, and argue that heterogeneity in operationalizations of depression is likely a considerable source of inconsistency. Finally, we offer recommendations and considerations for the field going forward.

To split or to lump? Classifying the central disorders of hypersomnolence

The classification of the central disorders of hypersomnolence has undergone multiple iterations in an attempt to capture biologically meaningful disease entities in the absence of known pathophysiology. Accumulating data suggests that further refinements may be necessary. At the 7th International Symposium on Narcolepsy, a group of clinician-scientists evaluated data in support of keeping or changing classifications, and as a result suggest several changes. First, idiopathic hypersomnia with long sleep durations appears to be an identifiable and meaningful disease subtype. Second, idiopathic hypersomnia without long sleep time and narcolepsy without cataplexy share substantial phenotypic overlap and cannot reliably be distinguished with current testing, and so combining them into a single disease entity seems warranted at present. Moving forward, it is critical to phenotype patients across a wide variety of clinical and biological features, to aid in future refinements of disease classification.

Genetics of Type 2 Diabetes: A Review

Diabetes Mellitus (DM), one of the most non-communicable diseases, is increasing day by day in an alarming way. More than 140 million people are suffering from diabetes throughout the world. It is not a single disease entity, but rather a group of metabolic disorders sharing the common underlying feature of hyperglycemia. Hyperglycemia in diabetes results from defects in insulin secretion, insulin action, or, most commonly, both. The chronic hyperglycemia and attendant metabolic deregulation may be associated with secondary damage in multiple organ systems, especially the kidneys, eyes, nerves, and blood vessels. The pathophysiology of diabetes is not fully elucidated. Insulin secretory dysfunction and insulin resistance or both is main candidate for this metabolic disorder, moreover various genetic and environmental factors may also involve in this process. Racial variations play also an important role as evidenced by various studies. However, the interrelationships between the molecular and metabolic mechanisms in these parameters contributing this life threatening disease still remain a mystery to the scientists. Journal of Current and Advance Medical Research 2019;6(1):59-63

Lupus Nephritis

Lupus nephritis (LN) is common manifestation of systemic lupus erythematosus and is associated with significant morbidity and mortality. LN is a not a single-disease entity; on the contrary, it encompasses a wide array of renal histological patterns. The treatment options and outcomes vary with the type of renal histology. Proliferative LN remains the most aggressive histological form of LN and requires aggressive treatment. The goal of therapy for LN is to achieve clinical and histological remission and avoid progression to chronic kidney disease. Remission of LN not only improves renal outcomes but also results in significant improvement in overall patient mortality. Though much progress has been made in this arena, there is still a need for therapeutic agents that are less toxic and more effective than the currently available therapies.