Smouldering Myeloma: Chasing a Hyperviscous Sample.

Serum hyperviscosity is a rare laboratory finding. Amongst several causes of serum hyperviscosity, malignant disorders are quite common. Monoclonal gammopathy is a family of disorders in which monoclonal gammopathy of unknown significance (MGUS) and smoldering myeloma are the asymptomatic variants whereas multiple myeloma is the malignant variant showing different signs and symptoms related to bone lesions, renal failure and anemia. Initially during sample preparation, pipetting of a serum sample was found to be cumbersome. This sample during routine analysis in the automated analyser flagged repeated alarms for clot detection indicating a possibility of a hyper viscous sample. Serum was subjected to fibrinogen and D- dimer test. The D-Dimer levels were found to be normal and fibrinogen levels were mildly elevated. Routine biochemistry investigations were normal except grossly reversed A/G ratio. Due to gross reversal of A/G ratio, the possibility of Multiple myeloma was entertained. Physician's were alerted on telephone. Serum was sent for electrophoresis which showeda M spike. Bone marrow aspirate showed 13% plasma cells. Considering the above lab results the diagnosis of monoclonal gammopathy of smoldering type was considered. The sample was traced to a 77 years old male, who presented to Medicine OPD with the chief complaints of generalised weakness for two months without any history of fever. On physical examination pallor was evident but there was no icterus, cyanosis, clubbing, lymphadenopathy or edema. On haematological evaluation patient was found to be anemic. Careful tracking of hyperviscous patient's serum followed up by thorough investigation led us to the final conclusion that the case mentioned is a rare case of Smoldering type of multiple myeloma.

Association of circulatory Klotho levels and its expression with miRNA- 339 in patients with schizophrenia.

Schizophrenia is one of the major neuropsychiatric disorders affecting 1% of the population worldwide. Neuroinflammation, neurodevelopment, and oxidative stress are some of the crucial factors that can contribute to the pathogenesis of Schizophrenia. Klotho gene is an antiaging gene whose dysregulated expression can lead to Schizophrenia and aging-like symptoms in patients. Klotho gene expression is regulated by miRNA- 339, which might lead to expression changes of the klotho gene in schizophrenia patients. This study aimed to determine the Role of miRNA- 339-5p in the Regulation of Klotho Gene Expression and its Circulatory Levels in Schizophrenia. In this study total of 60 cases, schizophrenia patients and 30 healthy controls were recruited, and written informed consent was obtained from all the study subjects. The klotho gene and miRNA - 339-5p expressions were done using a reverse transcription polymerase chain reaction. And relative fold change expression was calculated by Livaak's method, that is 2^-double delta ct. It was found that the klotho gene is around 2.08 times upregulated as compared to healthy control, and miRNA- 339-5p was downregulated and showed an inverse relationship. The present study is the first to evaluate the klotho gene expression and correlate it with miRNA- 339-5p. Further confirmation of the results study should be planned with a large sample size and with drug naïve patients.

Role of Klotho Protein in Neuropsychiatric Disorders: A Narrative Review.

Neuropsychiatric disorders are comprised of diseases having both the neurological and psychiatric manifestations. The increasing burden of the disease on the population worldwide makes it necessary to adopt measures to decrease the prevalence. The Klotho is a single pass transmembrane protein that decreases with age, has been associated with various pathological diseases, like reduced bone mineral density, cardiac problems and cognitive impairment. However, multiple studies have explored its role in different neuropsychiatric disorders. A comprehensive search was undertaken in the Pubmed database for articles with the keywords "Klotho" and "neuropsychiatric disorders". The available literature, based on the above search strategy, has been compiled in this brief narrative review to describe the emerging role of Klotho in various neuropsychiatric disorders. The Klotho levels were decreased in various neuropsychiatric disorders except for bipolar disorder. A suppressed Klotho protein levels induced oxidative stress and incited pro-inflammatory conditions significantly contributing to the pathophysiology of neuropsychiatric disorder. The increasing evidence of altered Klotho protein levels in cognition-decrement-related disorders warrants its consideration as a biomarker in various neuropsychiatric diseases. However, further evidence is required to understand its role as a therapeutic target.

Klotho: A Possible Role in the Pathophysiology of Nephrotic Syndrome.

Klotho, encoded by the klotho gene, is associated with phosphate homeostasis. Klotho acts as a co-receptor for FGF23 for binding to its receptors. With FGF23, klotho regulates the systemic mineral homeostasis by regulation of vitamin D and parathyroid hormone. The anti-inflammatory, antifibrotic and antioxidant properties of klotho give it a cardinal role in the development of various renal diseases. The protective effect of klotho has been evident in different types of nephropathy, including diabetic nephropathy, cyclosporine A-induced nephropathy, Calcineurin inhibitors-induced nephropathy, and renal ischemic-reperfusion injury. Nephrotic syndrome is distinguished by hypoproteinemia, proteinuria, and hypercholesterolemia as a result of the aberration of the glomerular filtration barrier. The various factors and pathways associated with the pathophysiology of the nephrotic syndrome have similarities with other types of nephropathy. Despite these similarities, the role of klotho in the pathology of nephrotic syndrome remains still unexplored. This minireview builds the case for the possible role of klotho in nephrotic syndrome. The review explores the possible pathways where klotho can play a major role by identifying the similarities in the pathophysiology of nephrotic syndrome and other types of nephropathy.

Trace Elements as Immunoregulators in SARS-CoV-2 and Other Viral Infections.

Nutritional deficiency is associated with impaired immunity and increased susceptibility to infections. The complex interactions of trace elements with the macromolecules trigger the effective immune response against the viral diseases. The outcome of various viral infections along with susceptibility is affected by trace elements such as zinc, selenium, iron, copper, etc. due to their immuno-modulatory effects. Available electronic databases have been comprehensively searched for articles published with full text available and with the key words "Trace elements", "COVID-19", "Viral Infections" and "Immune Response" (i.e. separately Zn, Se, Fe, Cu, Mn, Mo, Cr, Li, Ni, Co) appearing in the title and abstract. On the basis of available articles we have explored the role of trace elements in viral infections with special reference to COVID-19 and their interactions with the immune system. Zinc, selenium and other trace elements are vital to triggerTH1 cells and cytokine-mediated immune response for substantial production of proinflammatory cytokines. The antiviral activity of some trace elements is attributed to their inhibitory effect on viral entry, replication and other downstream processes. Trace elements having antioxidants activity not only regulate host immune responses, but also modify the viral genome. Adequate dietary intake of trace elements is essential for activation, development, differentiation and numerous functions.

Association of Vitamin D Status with COVID-19 Infection and Mortality in the Asia Pacific region: A Cross-Sectional Study.

COVID-19 has been declared a global pandemic by WHO on 11 March 2020. Still, very little is known about the potential protective dietary factors for the prevention of infection and mortality due to COVID-19. Keeping in view the scarcity of literature/studies available, in this regards present study was undertaken to assess if there is any correlation between mean levels of Vitamin D in various Asia Pacific countries with the infection and mortality caused by COVID-19. We collected data for mean levels of Vitamin D for 37 Asia Pacific countries for which we have also got the data regarding the morbidity and mortality of COVID-19. The mean levels of Vitamin D were found to have a significant association with the number of cases/million(r = - 0.394, p value = 0.016) and a weak association with the number of deaths/ million (r = - 0.280, p value = 0.093) due to COVID-19. In conclusion, we found a significant relationship between Vitamin D levels with the number of COVID-19 cases. So further clinical trial/study with a large sample size is needed to elucidate the protective role of Vitamin D in COVID-19.

A Framework Model for a Contextualized and Integrated Warfarin Therapy Case in a Master of Pharmacy Program.

Objective. To develop and integrate a case study on warfarin into a clinical pharmacy workshop. Methods. A framework model was designed and used to create a case study on warfarin therapy. The case study was implemented in a third-year Master of Pharmacy course. Student feedback was obtained using an online questionnaire and two focus groups. Results. All students agreed that the case study successfully integrated the science of warfarin and concepts of pharmacy practice. The majority of students (94%) agreed that this approach helped them to understand the science of warfarin more than a traditional lecture would have. Students felt the time allocated to the workshop was too short. Conclusion. An integrated case study provides a learning environment that emphasizes the contextualization of chemistry and pharmacology into a clinical pharmacy setting.