Highly Specific Non-Enzymatic Electrochemical Sensor for the Detection of Uric Acid Using Carboxylated Multiwalled Carbon Nanotubes Intertwined with GdS-Gd2O3 Nanoplates in Human Urine and Serum.

Herein, the electrochemical sensing efficacy of carboxylic acid functionalized multiwalled carbon nanotubes (C-MWCNT) intertwined with coexisting phases of gadolinium monosulfide (GdS) and gadolinium oxide (Gd2O3) nanosheets is explored for the first time. The nanocomposite demonstrated splendid specificity for nonenzymatic electrochemical detection of uric acid (UA) in biological samples. It was synthesized using the coprecipitation method and thoroughly characterized. The presence of functional groups and disorder in the as-synthesized nanocomposite are confirmed using Fourier transform infrared spectroscopy and Raman spectroscopy. Furthermore, field emission scanning electron microscopy, high-resolution transmission electron microscope, X-ray powder diffraction, and X-ray photoelectron spectroscopy provides a clear understanding of the morphology, coexisting phases, and elemental composition of the as-synthesized nanocomposites. The differential pulse voltammetry technique was utilized to elaborate the electrochemical sensing of UA using a GdS-Gd2O3/C-MWCNT modified glassy carbon electrode (GCE), The sensor showed an enhanced current response by more than 2-fold compared to bare GCE. Also, the sensor's performance was further improved by dispersing the nanocomposite in an ionic liquid with the exceptional reproducibility (SD = 0.0025, n = 3). The fabricated UA sensor GdS-Gd2O3/C-MWCNT/IL/GCE demonstrated a wide linear detection range from 0.5-30 µM and 30-2000 µM, effectively covering the entire physiological range of UA in biological fluids with a limit of detection (LOD) of 0.380 µM (+3SD of blank) and a sensitivity of 356.125 µA mM-1 cm-2. Moreover, the electrodes exhibited storage stability for 2 weeks with decrease in zero-day current by only 4.5%. The sensor was validated by quantifying UA in 12 unprocessed clinical human urine and serum samples, and its comparison with the gold standard test yielded remarkable results (p < 0.05). Hence, the proposed nonenzymatic electrochemical UA sensor is selective, sensitive, reproducible, and stable, making it reliable for point-of-care diagnostics.

Design and simulation of a microfluidics-based artificial glomerular ultrafiltration unit to reduce cell-induced fouling.

BACKGROUND: The microfluidic-based Glomerulus-on-Chips (GoC) are mostly cell based, that is, 3D cell culture techniques are used to culture glomerular cells in order to mimic glomerular ultrafiltration. These chips require high maintenance to keep cell viability intact. There have been some approaches to build non-cell-based GoCs but many of these approaches have the drawback of membrane fouling. This article presents a structural design and simulation study of a dialysate free microfluidic channel for replicating the function of the human glomerular filtration barrier. The key advancement of the current work is addressing the fouling issue by combining a pre-filter to eliminate cellular components and performing filtration on the blood plasma. METHODS: The Laminar Flow Mixture Model in COMSOL Multiphysics 5.6 has been utilized to simulate the behavior of blood flow in the microchannels. The geometrical effect of microchannels on the separation of the filtrate was investigated. The velocity at the inlet of the microchannel and pore size of the filtration membrane are varied to see the change in outflow and filtration fraction. RESULTS: The efficiency of the device is calculated in terms of the filtration fraction (FF%) formed. Simulation results show that the filtrate obtained is ~20% of the plasma flow rate in the channel, which resembles the glomerular filtration fraction. CONCLUSION: Given that it is not dependent on the functionality of grown cells, the proposed device is anticipated to have a longer lifespan due to its non-cell-based design. The device's cost can be reduced by avoiding cell cultivation inside of it. It can be integrated as a glomerular functional unit with other units of kidney model to build a fully developed artificial kidney.

Identifying Challenges and Potential Solutions for Sustainable Kidney Nutrition Care Delivery in Selected Asian Countries.

BACKGROUND: Recent surveys highlight gross workforce shortage of dietitians in global kidney health and significant gaps in renal nutrition care, with disparities greater in low/low-middle income countries. OBJECTIVE: This paper narrates ground experiences gained through the Palm Tocotrienols in Chronic Hemodialysis (PaTCH) project on kidney nutrition care scenarios and some Asian low-to-middle-income countries namely Bangladesh, India, and Malaysia. METHOD: Core PaTCH investigators from 3 universities (USA and Malaysia) were supported by their postgraduate students (n = 17) with capacity skills in kidney nutrition care methodology and processes. This core team, in turn, built capacity for partnering hospitals as countries differed in their ability to deliver dietitian-related activities for dialysis patients. RESULTS: We performed a structural component analyses of PaTCH affiliated and nonaffiliated (Myanmar and Indonesia) countries to identify challenges to kidney nutrition care. Deficits in patient-centered care, empowerment processes and moderating factors to nutrition care optimization characterized country comparisons. Underscoring these factors were some countries lacked trained dietitians whilst for others generalist dietitians or nonclinical nutritionists were providing patient care. Resolution of some challenges in low-to-middle-income countries through coalition networking to facilitate interprofessional collaboration and task sharing is described. CONCLUSIONS: We perceive interprofessional collaboration is the way forward to fill gaps in essential dietitian services and regional-based institutional coalitions will facilitate culture-sensitive capacity in building skills. For the long-term an advanced renal nutrition course such as the Global Renal Internet Course for Dietitians is vital to facilitate sustainable kidney nutrition care.

Comparative Study to Evaluate the Effect of Low-Protein Diet Supplementation with Taurine and N-Acetylcysteine, N-Acetylcysteine and Pyridoxamine Dihydrochloride in Preventing the Progression of Chronic Renal Failure in Patients with Non-Diabetic Kidney Disease.

Chronic Kidney Disease(CKD) has multifactorial etiology and there are lots of grey zone in understanding its complex pathophysiology. There is no silver bullet for optimal care of CKD. Oxidative stress being well understood and considered as an important common progressive factor for CKD of different etiology. Several research studies focused on reducing oxidative stress and have shown diverse outcomes. In this randomized, open-label, three arms, controlled, single center study we evaluated the role of N acetylcysteine which is a direct scavenger of free radical, in combination with taurine and pyridoxamine in retarding the progression of non-diabetic kidney disease. METHODS: 69 non-dialysis, non-diabetic patients diagnosed with chronic renal failure with GFR more than 15 ml/min/1.73m2 and less than 60ml/min/1.73m2 receiving standard of care were enrolled in the study, of which 22 were in the placebo arm, 23 treated with NT (500 mg Taurine + 150 mg NAC) arm and 24 in the NP (300mg NAC+ 50mg pyridoxamine di-hydrochloride) arm. The subjects in the treatment arm received the study drug twice a day along with low protein (0.6gm protein per Kg body weight) isocaloric diet with 25-30 Kcal/Kg/D and were evaluated monthly up to 6 months. Change in eGFR accorss 3 groups over 6 months were compared. RESULT: Mean age of the subjects was 57 ± 13 years of 56.25% were male and 43.75% were female. 69 patients completed the study. The Empirical Distribution Function (EDF) of NP group was dominant over control and NT group indicating a positive effect of NT on non-diabetic CKD at 10% level of significance. In the subgroup analysis a significant effect was observed in the cases of patients receiving NP with baseline eGFR more than 45 ml/min. The mean increase in eGFR readings over six months was 8.15 units higher in the NP group than in the control group. The two-sided p-values of the t-test, the Wilcoxon test and the Kolmogorov-Smirnov test were 0.0496, 0.0316 and 0.0354, respectively. Thus, all the three tests reject the hypothesis of identical changes in eGFR at the 5% level. In subjects with bicarbonate more than 22 mg/dl, the mean increase in eGFR over six months was 10.86 units higher in the NP group than in the control group indicating NP has a positive effect on increasing eGFR over 6 months, in patients without the presence of any metabolic acidosis. The two-sided p-vales of the t-test, the Wilcoxon test and the Kolmogorov-Smirnov test were 0.0325, 0.0205 and 0.1495, respectively. Thus, two of the three tests reject the hypothesis of identical changes in eGFR at the 5% level which clearly indicates that NP had better efficacy than other groups. CONCLUSION: N-acetyl cysteine along with pyridoxine may be a useful intervention along with a low protein diet in retarding progression of CKD in the nondiabetic population in early CKD.

Recreating the size-dependent reabsorption function of proximal convoluted tubule towards artificial kidney applications: Structural analysis and computational study.

Human kidneys tend to be affected adversely and fail to function more often than any other organ in the body because of diet, heredity, and lifestyle of a person. Dialysis is the technique presently in use for replacing the failed kidney function but it is packed with painfulness, bulkiness, and is costly also. There is a growing need for development of an artificial kidney that eradicates the problems associated with dialysis. This article proposes a structure that mimics the most important aspect of the human kidney: the size-dependent reabsorption of endothelial cells in the proximal convoluted tubule (PCT). The proposed structure consists of transporting channels connecting blood tubules surrounded on both sides of a main tubule. Geometries of the channels are analyzed for optimum flow by varying angles with respect to the main tubule. The analytical formulae have been developed by considering proper boundary conditions governing the flow in the structure, which makes the model as robust, concise, and realistic as the actual PCT. The mathematical model is validated against the benchmark FEM tool COMSOL Multiphysics and the results seem to be satisfactory. This article concludes, that slant channels possess a considerably higher average flow velocity of 5.39 × 10-5  m/s (≈52% reabsorption rate) than straight channels with 4.77 × 10-5  m/s (≈46% reabsorption rate) which is closer to the actual PCT reabsorption rate of 60%. The proposed model is first of its kind in nature among the reported works which creates and exhibits simulation environment of PCT reabsorption function supported by mathematical formulation and also can be useful to study and develop artificial kidney in near future.

Passenger Lymphocyte Syndrome in a Renal Transplant Recipient.

New onset anaemia within three months after renal transplantation though not very common sometimes present as diagnostic challenge to the renal physicians. Understanding the etiology is necessary for correct management and avoiding adverse graft outcome. Passenger lymphocyte syndrome (PLS) is a rare entity of immune haemolytic anaemia that sometimes occurs in recipient of minor ABO mismatched renal transplantation. In this case report we present an AB positive renal allograft recipient who received organ from an O positive donor and developed acute haemolytic anaemia and jaundice, 19 days after renal transplantation due to PLS.

Unusual presentation post renal transplant lymphocele.

Retroperitoneal lymphocele is one of the common complications following renal transplantation, and usually present with persistent lymphatic drain in immediate post transplant period or perigraft collection in post transplant routine ultrasound. In this case report, we present a renal transplant recipient who presented with acute urinary retention and right sided lower limb swelling mimicking deep vein thrombosis (DVT), due to a large lymphocele behind the bladder compressing bladder neck and common iliac vessels, approximately 2 months after renal transplant. Though lymphocele is not uncommon post transplant complication, the presentation of lymphocele after 2 months post transplant with pressure effect of this type is uncommon. In this case, pressure on common iliac vessels mimicking DVT and on bladder neck, leading to acute retention of urine and leading to hydronephrotic graft; which occurred in CNI (Cyclosporine) based regimen is extremely rare.

Design and Modeling of Bioreactor Utilizing Electrophoresis and Di-Electrophoresis Techniques for Regenerating Reabsorption Function of Human Kidney PCT in Microfluidics Environment.

The need for innovation in medical device technology is immense; especially to replace dialysis techniques the necessity is extremely high. Available techniques that promised to replace dialysis have not yet geared up to the marketization level. The utilization of live kidney cells makes these devices costly, delicate, and unreliable. This paper aims to design a bioreactor to mimic the reabsorption function of the kidney that is fully artificial and highly controllable, which can be one step forward to the emerging Kidney-on-Chip (KOC) technology. The additional benefit of the proposed design is that it utilizes size-dependent reabsorption along with charge-dependent reabsorption phenomena to make it more compatible with human kidney function. The electrophoresis (EP), and di-electrophoresis (DEP) techniques are utilized to mimic the reabsorption function in this report. The structure utilized in the present design exactly replicates the proximal convoluted tubule (PCT) dimensions and functions as well. The whole setup is implemented in the COMSOL Multiphysics FEM benchmark tool for simulation, and analysis with appropriate boundary conditions. The device when excited by an electric field, Electrophoresis has produced a maximum velocity of 1.07 m/s for DC excitation and di-electrophoresis has produced a maximum flow velocity of 1.23 m/s, where both the offset voltages are the same (0.7 V). The flow velocity obtained utilizing both EP and DEP produced a reabsorption rate of 50-58% depending on the voltage applied and dimensions considered which is close to 60% reabsorption rate of the normal human kidney PCT. In accordance with the outcomes produced, the di-electrophoresis technique proved to be more efficient in realizing bioreactor as compared to electrophoresis. The novelty of the present work lies in the creation of a simulation environment, rigorous analysis, and optimization of the bioreactor supported by compact mathematical model.

A comprehensive review on advancements in tissue engineering and microfluidics toward kidney-on-chip.

This review provides a detailed literature survey on microfluidics and its road map toward kidney-on-chip technology. The whole review has been tailored with a clear description of crucial milestones in regenerative medicine, such as bioengineering, tissue engineering, microfluidics, microfluidic applications in biomedical engineering, capabilities of microfluidics in biomimetics, organ-on-chip, kidney-on-chip for disease modeling, drug toxicity, and implantable devices. This paper also presents future scope for research in the bio-microfluidics domain and biomimetics domain.

Hepatitis E-Induced Acute Myocarditis in an Elderly Woman.

Hepatitis E is a common, mainly water-borne hepatotropic virus prevalent mainly in Southeast Asia, Africa, the Middle East, and Central America. In the eastern part of India epidemics of acute hepatitis E are well reported. Hepatitis E commonly presents as self-limiting acute viral hepatitis among young adults, except for some critical clinical complications during pregnancy. In epidemiological research, subclinical acute hepatitis E infection is also reported from different parts of the world, including developed nations such as the USA (predominantly in the population aged >60 years). Though primarily hepatotropic, in the literature there are reports of rare extrahepatic manifestation of acute hepatitis E. Here we present an elderly lady with acute hepatitis E who primarily presented with acute myocarditis.

Colistin-induced myasthenic syndrome in a patient with end-stage renal disease.

With resurgence of multidrug resistance (MDR) bacteria and no new novel broad-spectrum antibiotic in research pipeline, usage of older generation antibiotics, once discarded due to their toxicity profile are becoming popular again. Often these drugs are the only option left in managing MDR bacteria-related sepsis. Colistin is one of such antibiotic which is often used in recent times after decades of its avoidance due to its diverse toxicity profile. In this case report, we present a rare myasthenic syndrome like neuromuscular complication developed in a patient after receiving colistin for treatment of MDR Klebsiella-related urosepsis.

Dialysis disequilibrium leading to posterior reversible encephalopathy syndrome in chronic renal failure.

Dialysis disequilibrium syndrome is a neurological adverse effect of acute hemodialysis in advanced uremic patients. Dialysis disequilibrium has a wide spectrum of clinical manifestations starting from subtle uneasiness, confusion, to florid and complex life threatening neurological deficit. In this case study, we present a patient who developed sudden cortical blindness following hemodialysis due to posterior reversible encephalopathy, which is a rare presentation of dialysis disequilibrium syndrome.

Identifying middle school students' challenges in computational thinking-based science learning.

Computational thinking (CT) parallels the core practices of science, technology, engineering, and mathematics (STEM) education and is believed to effectively support students' learning of science and math concepts. However, despite the synergies between CT and STEM education, integrating the two to support synergistic learning remains an important challenge. Relatively, little is known about how a student's conceptual understanding develops in such learning environments and the difficulties they face when learning with such integrated curricula. In this paper, we present a research study with CTSiM (Computational Thinking in Simulation and Modeling)-computational thinking-based learning environment for K-12 science, where students build and simulate computational models to study and gain an understanding of science processes. We investigate a set of core challenges (both computational and science domain related) that middle school students face when working with CTSiM, how these challenges evolve across different modeling activities, and the kinds of support provided by human observers that help students overcome these challenges. We identify four broad categories and 14 subcategories of challenges and show that the human-provided scaffolds help reduce the number of challenges students face over time. Finally, we discuss our plans to modify the CTSiM interfaces and embed scaffolding tools into CTSiM to help students overcome their various programming, modeling, and science-related challenges and thus gain a deeper understanding of the science concepts.

Assessment of insulin resistance in non-diabetic hypertensives in Eastern India.

To assess prevalence of insulin resistance in non-diabetic hypertensive patients in eastern part of India, a case-control study was undertaken among 112 patients of hypertension without diabetes mellitus or ischaemic heart disease and 76 age and sex matched controls. Anthropometric measurements (height, weight, waist circumference) were done and fasting blood sugar and fasting insulin levels were estimated. Among 112 patients, 50.9% (n = 57) have fasting hyperinsulinaemia, whereas in control population 12% had hyperinsulinemia (p < 0.001). Mean waist circumference was higher in hypertensive patients compared to control. No statistical difference of body mass index between cases and control found. In this study prevalence of fasting hyperinsulinaemia, considered as a surrogate marker for insulin resistance, was 50% in hypertensives. Body mass index was not associated with insulin resistance or hypertension.

Surgical outcome in thymic tumors with myasthenia gravis after plasmapheresis--a comparative study.

Plasmapheresis has been used widely in the treatment of myasthenia gravis and also in symptomatic thymectomized patients with short-term clinical improvement. But the utility of preoperative plasmapheresis in the outcome has not been widely studied. The authors analyzed its impact in the surgical outcome of thymic tumors with myasthenia gravis. We studied a total of 19 patients, who were operated on in the period from January 2000 to July 2006 for thymic tumors with myasthenia gravis. Of these 19 patients, preoperative plasmapheresis was performed in 10 patients (group B) and the remaining nine patients (group A) had no preoperative plasmapheresis based on risk factors for requirement of postoperative ventilation. Outcome in the form of requirement of ventilation, symptomatic improvement, hospital stay and requirement of drugs were assessed at the end of one year and compared between the two groups. Six out of nine patients (67%) in group A required ventilatory support in the immediate postoperative period, whereas two out of ten patients (20%) in group B required it. Significant and sustained symptomatic improvement was noted in group B as compared with group A (P<0.01). Preoperative plasmapheresis in the patients of thymic tumors with myasthenia gravis is beneficial and can cause a significant difference in the postoperative outcome.

Heart failure and acquired immune deficiency syndrome: report of 2 cases.

Acquired immune deficiency syndrome (AIDS) patients usually present with prolonged fever, chronic diarrhoea, weight loss and other opportunistic infections. Congestive heart failure is not a usual presentation of AIDS. Here two cases, one a female of 38 years and another a male of 22 years presented with fever and breathlessness. On examination they were found to have features of congestive heart failure. Echocardiography revealed dilated cardiomyopathy. Laboratory investigations suggested human immunodeficiency virus was reactive in both cases with immune deficiencies of different degrees. The first patient expired during hospital stay, but the second one is progressing well with antiretroviral therapy.