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Kidney Transplantation Is Associated with Catastrophic Out of Pocket Expenditure in India
Raja Ramachandran, Vivekanand Jha
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0067812
Abstract: Kidney transplantation (KT) is only viable renal replacement option for most patients in India. Most patients do not have health insurance and meet treatment expenditure from their own resources. We prospectively evaluated the expenses associated with KT and its impact on the socioeconomic status of families in a public hospital. All direct and indirect expenses incurred by the patients from the time of diagnosis of chronic kidney disease to KT were recorded. Direct expenses included physician fees, cost of drugs and disposables, dialysis, and expenses on investigations and hospitalization. Indirect expenses included travel, food, stay, and loss of income suffered by the family. Educational dropout and financial loss were also recorded. There were 43 males and 7 females between the ages of 12 and 57 years. Direct expenses ranged from US$ 2,151–23,792 and accounted for two-thirds of the total expenses. Pre-referral hospitalization, dialysis and medication accounted for majority of direct expense. Indirect expenses ranged from US$ 226–15,283. Travel expenses and loss of income accounted for most of indirect expense. About 54%, 8%, and 10% of families suffered from severe, moderate, and some financial crisis respectively. A total of 38 families had job losses, and 1 patient and 12 caregivers dropped out of studies. To conclude, KT is associated with catastrophic out-of-pocket expenditure and pushes a majority of the patients who come for treatment to public hospitals into severe financial crisis. Educational dropout and loss of jobs are other major concerns. Systematic efforts are required to address these issues.
Association between Serum Neopterin and Inflammatory Activation in Chronic Kidney Disease
Ashok Kumar Yadav,Vinod Sharma,Vivekanand Jha
Mediators of Inflammation , 2012, DOI: 10.1155/2012/476979
Abstract: Background. The serum levels of neopterin, a marker associated with cell-mediated immunity are elevated in chronic kidney disease (CKD). We evaluated serum neopterin levels and investigated its association with markers of inflammation in a cross-section of CKD subjects without known cardiovascular disease. Methods. Serum neopterin levels were measured in 118 patients with stage 3–5 CKD and 41 healthy subjects with normal kidney function (HC). Patients with known cardiovascular disease were excluded. We also estimated highly sensitive CRP (hsCRP) and interluekin-6 (IL-6), tumor necrosis factor- (TNF-) and interferon- (IFN-) in the CKD subjects. All assays were done using commercially available ELISA kits. The correlation between neopterin and markers of inflammation were investigated. Results. Of the CKD population, 82 were in stage 5 (60 stage 5 D), 24 in stage 4, and 12 in stage 3. The mean age was 51.04±1.3 years and 66% were males. The commonest cause of CKD was diabetes (36%). Serum neopterin levels were 5-fold higher in CKD patients as compared to HC (74.8±3.6 versus 15.0±2.8 nmol/L, <0.0001). There was a graded increase of serum neopterin from stages 3 to 4 and 5. CKD 5 D patients exhibited significantly higher levels compared to nondialysis stage 5 patients (<0.0001). An inverse correlation was noted between serum neopterin and eGFR (=?0.359, <0.0001). Serum neopterin correlated with hsCRP (=0.285, =0.002), IL-6 (=0.212, =0.034), and IFN- (=0.32, =0.001) but not with TNF-. Conclusion. Serum neopterin level is elevated and correlates with the severity of CKD. The elevation correlates with elevation of most, but not all, inflammatory markers. Its role in future development of cardiovascular disease and modulation with anti-inflammatory therapies needs further studies.
Heat Shock Proteins 60 and 70 Specific Proinflammatory and Cytotoxic Response of CD4+CD28null Cells in Chronic Kidney Disease
Ashok K. Yadav,Vinod Kumar,Vivekanand Jha
Mediators of Inflammation , 2013, DOI: 10.1155/2013/384807
Abstract: Background. CD4+CD28null T cells are expanded in peripheral blood of patients with chronic kidney disease and associated with subclinical atherosclerosis. However, triggers for the oligoclonal expansion and activation of these cells are not clear. Methods. We investigated twenty-five stage V-IV chronic kidney disease (CKD) patients and eight healthy subjects (HC). Peripheral mononuclear cells were isolated and incubated with heat shock protein- (HSP) 60 and 70. CD4+CD28null and CD4+CD28+ cells were sorted by flowcytometry and antigen specific response was assessed by the mRNA and protein expression of interferon (IFN)- , perforin, and granzyme B using qRT-PCR and Elispot. Results. The basal mRNA expression of IFN- , perforin, and granzyme B in CD4+CD28null cells was higher in subjects with CKD compared to that in HC ( ). Subjects with CKD also showed expression of IFN- , perforin, and granzyme B in the CD4+CD28+ subset, but this was much weaker than that seen in the CD4+CD28null population ( ). We did not note the expression of these molecules at mRNA or protein level in either subset of CD4 cells in HC. After incubation with HSP60 and HSP70, CD4+CD28null cells showed increased expression at mRNA ( ) and protein level ( ). CD4+CD28+ cells also showed a weak increase in expression. No antigen-specific response was noted in HC. Conclusion. These data show that CD4+CD28null cells in subjects with CKD react with HSP60 and HSP70 by upregulating the expression of IFN- , perforin and granzyme B. Increased circulating level of HSP60 and HSP70 might play a role in initiation and/or progression of atherosclerosis in CKD subjects through perturbation of CD4+CD28null cells. 1. Introduction Patients with chronic kidney disease (CKD) exhibit an expansion in the circulating CD4+CD28null cell population [1, 2]. In contrast to the classical CD4+ T helper cells, cells lacking CD28 molecule are cytotoxic and proinflammatory [3–5]. The ability of CD4+CD28null cells to interact with the endothelial cells through fractalkine-CX3CR interaction and the demonstration of these cells in atherosclerosis plaque, in combination with their ability to produce high level of IFN- and cytotoxic molecules leading to plaque destabilization, suggests their role in atherosclerotic disease [6]. The exact mechanism of their activation and expansion, however, is unclear. We have shown that this population is expanded in CKD even before development of clinically overt atherosclerotic coronary artery disease (CAD), and the degree of expansion correlates with common carotid artery intima media
PROCARB: A Database of Known and Modelled Carbohydrate-Binding Protein Structures with Sequence-Based Prediction Tools
Adeel Malik,Ahmad Firoz,Vivekanand Jha,Shandar Ahmad
Advances in Bioinformatics , 2010, DOI: 10.1155/2010/436036
Abstract: Understanding of the three-dimensional structures of proteins that interact with carbohydrates covalently (glycoproteins) as well as noncovalently (protein-carbohydrate complexes) is essential to many biological processes and plays a significant role in normal and disease-associated functions. It is important to have a central repository of knowledge available about these protein-carbohydrate complexes as well as preprocessed data of predicted structures. This can be significantly enhanced by tools de novo which can predict carbohydrate-binding sites for proteins in the absence of structure of experimentally known binding site. PROCARB is an open-access database comprising three independently working components, namely, (i) Core PROCARB module, consisting of three-dimensional structures of protein-carbohydrate complexes taken from Protein Data Bank (PDB), (ii) Homology Models module, consisting of manually developed three-dimensional models of N-linked and O-linked glycoproteins of unknown three-dimensional structure, and (iii) CBS-Pred prediction module, consisting of web servers to predict carbohydrate-binding sites using single sequence or server-generated PSSM. Several precomputed structural and functional properties of complexes are also included in the database for quick analysis. In particular, information about function, secondary structure, solvent accessibility, hydrogen bonds and literature reference, and so forth, is included. In addition, each protein in the database is mapped to Uniprot, Pfam, PDB, and so forth. 1. Introduction Carbohydrates play a key role in a variety of important biological recognition processes like infection, immune response, cell differentiation, and neuronal development. All of these biological phenomena may be regulated by the interaction of these carbohydrates with proteins [1–4]. One area of therapeutic significance in protein-carbohydrate interactions has relied on the role of carbohydrates as cell surface receptors enabling adherence of bacteria, parasites, and viruses by a process known as bioadhesion [5–10]. Bacteria are often competent enough to efficiently adhere to the surface membranes of the host cells via lectin binding, thus enabling subsequent colonization and progression of the disease [11]. Irregular structure and levels of certain tumor cell surface sugars may also present opportunities for therapeutic intervention [12]. On the other hand, the ubiquitous application of carbohydrates in nature potentially poses severe specificity issues. Understanding the molecular basis of carbohydrate recognition
CDKD: a clinical database of kidney diseases
Sanjay K Singh, Adeel Malik, Ahmad Firoz, Vivekanand Jha
BMC Nephrology , 2012, DOI: 10.1186/1471-2369-13-23
Abstract: Clinical database of kidney diseases (CDKD) has been developed with patient confidentiality and data security as a top priority. It can make comparative analysis of one or more parameters of patient’s record and includes the information of about whole range of data including demographics, medical history, laboratory test results, vital signs, personal statistics like age and weight.The goal of this database is to make kidney-related physiological data easily available to the scientific community and to maintain & retain patient’s record. As a Web based application it permits physician to see, edit and annotate a patient record from anywhere and anytime while maintaining the confidentiality of the personal record. It also allows statistical analysis of all data.
ContPro: A web tool for calculating amino acid contact distances in protein from 3D -structures at different distance threshold
Ahmad Firoz,Adeel Malik,Obaid Afzal,Vivekanand Jha
Bioinformation , 2010,
Abstract: To investigate the functional sites on a protein and the prediction of binding sites (residues) in proteins, it is often required to identify the binding site residues at different distance threshold from protein three dimensional (3D) structures. For the study of a particular protein chain and its interaction with the ligand in complex form, researchers have to parse the output of different available tools or databases for finding binding-site residues. Here we have developed a tool for calculating amino acid contact distances in proteins at different distance threshold from the 3D-structure of the protein. For an input of protein 3D-structure, ContPro can quickly find all binding-site residues in the protein by calculating distances and also allows researchers to select the different distance threshold, protein chain and ligand of interest. Additionally, it can also parse the protein model (in case of multi model protein coordinate file) and the sequence of selected protein chain in Fasta format from the input 3D-structure. The developed tool will be useful for the identification and analysis of binding sites of proteins from 3D-structure at different distance thresholds.
The Legislative Push to Mandate Rules-Based Monetary Policymaking in the US: The Latest Salvo in the Long-Running “Rules versus Discretion” Debate  [PDF]
Vivekanand Jayakumar
Theoretical Economics Letters (TEL) , 2016, DOI: 10.4236/tel.2016.66122
Abstract: US Congressional leaders have recently proposed legislation aimed at forcing the Federal Reserve to implement an instrument rule based monetary policy regime. The avowed rationale is to increase transparency and reduce uncertainty associated with monetary policymaking, and to impose constraints on the US central bank. The proposed legislation would require the Federal Reserve to adopt an interest rate setting rule, preferably a rule based on the standard Taylor Rule. This article examines the theoretical rationale for considering monetary policy rules and provides a critique of the move to legislate the adoption of interest rate setting rules in the US. Specifically, the challenges that the Federal Reserve would encounter if it were required to follow an instrument rule, and the shortcomings of any monetary regime based on the standard Taylor Rule, are detailed in this study. This article also considers the merits of basing a monetary policy regime on a targeting rule instead of an instrument rule, and argues that US policymakers would be better served if they shift their focus towards establishing a clearly defined nominal GDP targeting rule and abandon their efforts to impose operational constraints on the Federal Reserve.
UK Current Account Sustainability in the Post-Brexit Era: Insights from an Intertemporal Current Account Framework  [PDF]
Vivekanand Jayakumar
Theoretical Economics Letters (TEL) , 2017, DOI: 10.4236/tel.2017.72020
Abstract: British voters decided in a June 2016 referendum that they wanted the UK to leave the European Union (EU). The Brexit referendum result represents a critical turning point for the UK and the EU alike, and the decision to exit the bloc is bound to have far-reaching consequences. UK’s persistent current account deficits and its outsized external assets and external liabilities reflect Britain’s deep economic and financial integration with the European Single Market System, and highlight London’s central role as Europe’s financial capital. Unraveling of the symbiotic relationship between the UK and the EU will profoundly impact Britain’s ability to entice foreign investors to fund its current account deficits. Using a rich intertemporal current account framework that incorporates valuation effects, this study examines the potential impact of Brexit on UK’s current account sustainability and on UK’s net foreign debt position. It argues that a “hard Brexit” outcome would imperil UK’s ability to sustain current account deficits. UK’s role as a gateway for non-EU states looking to invest inside EU, and the benefits enjoyed by UK-based financial institutions from the European financial passport system would both be endangered if UK is shutout of the European Single Market system. UK is bound to become far less attractive to foreign investors in such a scenario, and a rapid and painful current account deficit reduction is probable. On the other hand, the study shows that a “soft Brexit” outcome in conjunction with a sustained and orderly depreciation of the pound would actually improve UK’s current account balance and its net foreign debt position.
Residue propensities, discrimination and binding site prediction of adenine and guanine phosphates
Ahmad Firoz, Adeel Malik, Karl H Joplin, Zulfiqar Ahmad, Vivekanand Jha, Shandar Ahmad
BMC Biochemistry , 2011, DOI: 10.1186/1471-2091-12-20
Abstract: Residue preferences for AMP, GMP, ADP, GDP, ATP and GTP have been investigated in details with additional comparison with cyclic variants cAMP and cGMP. We also attempt to predict residues interacting with these nucleotides using information derived from local sequence and evolutionary profiles. Results indicate that subtle differences exist between single residue preferences for specific nucleotides and taking neighbor environment and evolutionary context into account, successful models of their binding site prediction can be developed.In this work, we explore how single amino acid propensities for these nucleotides play a role in the affinity and specificity of this set of nucleotides. This is expected to be helpful in identifying novel binding sites for adenine and guanine phosphates, especially when a known binding motif is not detectable.Adenine triphosphate (ATP) is widely known to be energy currency of biological molecules as its conversion to corresponding di- and mono-phosphate leads to energy release, commonly used in conformational changes required for many biological interactions [1,2]. Closely related molecules such as guanidine triphosphate (GTP) also have similar metabolic implications [3,4]. Use of GTP versus ATP is highly specific to organisms as well as pathways [5]. Since, adenine and guanine have similar structures (both are purines) and essentially differ from each other by a nitrogenous versus oxygen group [5], (See Figure 1), a high degree of specificity between them is quite surprising and not well understood. A thorough understanding of this specificity therefore has wide biological implications, including discovery of metabolic drug targets as well as inhibitor design. There are other areas of biological research, where these molecules play a role such as cell-signaling and cofactor activity [6-11]. Thus, adenine and guanine phosphates form an important group of molecules, whose interactions with proteins at single residue as well as sequen
Deferred Pre-Emptive Switch from Calcineurin Inhibitor to Sirolimus Leads to Improvement in GFR and Expansion of T Regulatory Cell Population: A Randomized, Controlled Trial
Dinesh Bansal, Ashok K. Yadav, Vinod Kumar, Mukut Minz, Vinay Sakhuja, Vivekanand Jha
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0075591
Abstract: Background Measures to prevent chronic calcineurin inhibitor (CNI) toxicity have included limiting exposure by switching to sirolimus (SIR). SIR may favorably influence T regulator cell (Treg) population. This randomized controlled trial compares the effect of switching from CNI to SIR on glomerular filtration rate (GFR) and Treg frequency. Methods In this prospective open label randomized trial, primary living donor kidney transplant recipients on CNI-based immunosuppression were randomized to continue CNI or switched to sirolimus 2 months after surgery; 29 were randomized to receive CNI and 31 to SIR. All patients received mycophenolate mofetil and steroids. The main outcome parameter was estimated GFR (eGFR) at 180 days. Treg population was estimated by flowcytometry. Results Baseline characteristics in the two groups were similar. Forty-eight patients completed the trial. At six months, patients in the SIR group had significantly higher eGFR as compared to those in the CNI group (88.94±11.78 vs 80.59±16.51 mL/min, p = 0.038). Patients on SIR had a 12 mL/min gain of eGFR of at the end of six months. Patients in the SIR group showed significant increase in Treg population at 30 days, which persisted till day 180. There was no difference in the adverse events in terms of number of acute rejection episodes, death, infections, proteinuria, lipid profile, blood pressure control and hematological parameters between the two groups. Four patients taking SIR developed enthesitis. No patient left the study or switched treatment because of adverse event. Conclusions A deferred pre-emptive switch over from CNI to SIR safely improves renal function and Treg population at 6 months in living donor kidney transplant recipients. Registered in Clinical Trials Registry of India (CTRI/2011/091/000034)
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