Membranous Nephropathy With Crescents in a Patient With Hashimoto’s Thyroiditis: A Case Report

Membranous nephropathy is a common cause of nephrotic syndrome in adults. It usually occurs secondary to underlying disease processes such as autoimmune disorders, malignancy, infection, and drugs. The presentation of nephrotic syndrome with concomitant precipitous decline in renal function warrants investigation of a coexistent disorder.We report the case of a 30-year-old male who presented with symptoms and signs of hypothyroidism.A diagnosis of Hashimoto’s thyroiditis was contemplated based on the presence of high serum levels of antithyroglobulin and antithyroid peroxidase antibodies. Upon initiation of treatment with levothyroxine, patient symptomatology improved; however, the laboratory studies demonstrated continued elevated creatinine, hematuria, and proteinuria, which had not been addressed. Two months following treatment initiation, he had progressive deterioration in renal function and proteinuria. A renal biopsy revealed coexistent necrotizing and crescentic glomerulonephritis and membranous nephropathy.The final diagnosis was necrotizing, crescentic glomerulonephritis with superimposed membranous nephropathy likely secondary to Hashimoto’s thyrodiitis.Induction treatment with oral cyclophosphamide and prednisone was started.At the end of 6 months of treatment, there was improvement in renal function and proteinuria and maintenance treatment with azathioprine and low-dose prednisone was initiated. This case highlights the importance of precise and detailed evaluation of patients with autoimmune diseases such as Hashimoto’s thyroiditis particularly in the presence of active urine sediment. Proper evaluation and diagnosis of such patients has implications on the prognosis and response to treatment.     

Docking Based Screening of Potent Flavonoids as CHK2 Inhibitors from Genus Miliusa

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Annonaceae plants play significant role in ethanopharmacology due to their medicinal properties and...     

Evaluation of efficacy,biodistribution and safety of antibiotic-free plasmid encoding somatostatin genes delivered by attenuated Salmonella enterica serovar Choleraesuis

We describe here a balanced-lethal system using an Asd⁺ expression plasmid pVGS/2SS-asd encoding two copies of somatostatin (SS) genes carried by Δasd/Δcrp double mutant Salmonella enterica serovar Choleraesuis (named C501). The advantage of this novel system is the use of asd (aspartate-semialdehyde dehydrogenase) gene as selection marker to replace the antibiotic resistance markers, thus eliminating the industrial cultivation and environmental problems. We then evaluated the efficacy, biodistribution and safety of antibiotic-free plasmid delivered by strains C501. Mice orally immunized with C501 (pVGS/2SS-asd) had significantly higher levels of anti-SS total IgG and IgA antibodies than control mice and demonstrated a bias toward Th2-associated responses (IgG1/IgG2a ratio > 1). Safety evaluation indicated that vaccinated mice displayed no abnormal clinical signs and histological changes. Biodistribution result revealed that the GS/2SS message was detected in several examined tissues with the exception of ovary and brain, but was rapidly cleared from the body (approximately 10 days). Furthermore, the risk of integration of plasmid pVGS/2SS-asd into the host cellular genome was considered to be negligible. These results may have important implications for the use of vaccine strain C501 (pVGS/2SS-asd) in domestic animals and prompt new perspectives on the safety of DNA vaccines delivered by attenuated bacteria.     

Genetic polymorphisms in the Toll-like receptor signalling pathway in Helicobacter pylori infection and related gastric cancer

Background

Gastric cancer (GC) is a progressive process initiated by Helicobacter pylori-induced inflammation. Initial recognition of H. pylori involves Toll-like receptors (TLRs), central molecules in the host inflammatory response. Here, we investigated the association between novel polymorphisms in genes involved in the TLR signalling pathway, including TLR2, TLR4, LBP, MD-2, CD14 and TIRAP, and risk of H. pylori infection and related GC.

Methods

A case-control study comprising 310 ethnic Chinese individuals (87 non-cardia GC cases and 223 controls with functional dyspepsia) was conducted. Twenty-five polymorphisms were detected by MALDI-TOF mass spectrometry, PCR, PCR–RFLP and real-time PCR.

Results

Seven polymorphisms showed significant associations with GC (TLR4 rs11536889, TLR4 rs10759931, TLR4 rs1927911, TLR4 rs10116253, TLR4 rs10759932, TLR4 rs2149356 and CD14 −260 C/T). In multivariate analyses, TLR4 rs11536889 remained a risk factor for GC (OR: 3.58, 95% CI: 1.20–10.65). TLR4 rs10759932 decreased the risk of H. pylori infection (OR: 0.59, 95% CI: 0.41–0.86). Statistical analyses assessing the joint effect of H. pylori infection and the selected polymorphisms revealed strong associations with GC (TLR2, TLR4, MD-2, LBP and TIRAP polymorphisms).

Conclusions

Novel polymorphisms in TLR2, TLR4, MD-2, LBP, CD14 and TIRAP, genes encoding important molecules of the TLR signalling pathway, showed clear associations with H. pylori-related GC in Chinese.     

Does Self-Selection Affect Samples’ Representativeness in Online Surveys? An Investigation in Online Video Game Research

Background

The number of medical studies performed through online surveys has increased dramatically in recent years. Despite their numerous advantages (eg, sample size, facilitated access to individuals presenting stigmatizing issues), selection bias may exist in online surveys. However, evidence on the representativeness of self-selected samples in online studies is patchy.

Objective

Our objective was to explore the representativeness of a self-selected sample of online gamers using online players’ virtual characters (avatars).

Methods

All avatars belonged to individuals playing World of Warcraft (WoW), currently the most widely used online game. Avatars’ characteristics were defined using various games’ scores, reported on the WoW’s official website, and two self-selected samples from previous studies were compared with a randomly selected sample of avatars.

Results

We used scores linked to 1240 avatars (762 from the self-selected samples and 478 from the random sample). The two self-selected samples of avatars had higher scores on most of the assessed variables (except for guild membership and exploration). Furthermore, some guilds were overrepresented in the self-selected samples.

Conclusions

Our results suggest that more proficient players or players more involved in the game may be more likely to participate in online surveys. Caution is needed in the interpretation of studies based on online surveys that used a self-selection recruitment procedure. Epidemiological evidence on the reduced representativeness of sample of online surveys is warranted.     

The synthesis and application of (E)-N′-(benzo[d]dioxol-5-ylmethylene)-4-methyl-benzenesulfonohydrazide for the detection of carcinogenic lead

In this study, noble ligands of (E)-N′-(benzo[d]dioxol-5-ylmethylene)-4-methyl-benzenesulfonohydrazide (BDMMBSH) were prepared via a simple condensation method using benzo-[d][1,3]-dioxole carbaldehyde, benzenesulfonylhydrazine (BSH), and 4-methyl-benzenesulphonylhydrazine (4-MBSH) in good yield, which were crystallized in acetone, EtOAc, and EtOH. The BDMMBSH derivatives were characterized using different spectroscopic techniques, such as ¹H-NMR, ¹³C-NMR, FTIR, and UV-Vis spectroscopy, and their crystal structures were analyzed using the single crystal X-ray diffraction method (SCXRDM). Subsequently, the BDMMBSH compounds were used for the significant detection of the carcinogenic heavy metal ion, lead (Pb²⁺), via a reliable electrochemical approach. A sensitive and selective Pb²⁺ sensor was developed via the deposition of a thin layer of BDMMBSH on a GCE with the conducting polymer matrix Nafion (NF). The sensitivity, LOQ, and LOD of the proposed sensor towards Pb²⁺ were calculated from the calibration curves to be 2220.0 pA μM⁻¹ cm⁻², 320.0 mM, and 96.0 pM, respectively. The validation of the BDMMBSH/GCE/NF sensor probe was performed via the selective determination of Pb²⁺ in spiked natural samples with a satisfactory and rational outcome.

A sensitive cationic sensor was developed by BDMMBSH onto GCE with 5% Nafion using electrochemical method, which was validated with the selective determination of Pb²⁺ in spiked samples and found satisfactory results.     

Copper oxide integrated perylene diimide self-assembled graphitic pencil for robust non-enzymatic dopamine detection

Exploring a robust, extremely sensitive, cost-effective and reliable assay platform for the precise analysis of dopamine (DA) has become a big challenge predominantly at the clinical level. To participate in this quest, herein, we fabricated a perylene diimide (PDI) self-assembled graphitic surface of the graphitic pencil electrode (GPE) anchored copper oxide (CuO). The self-assembled N-rich PDI led to the fast movement of ions by decreasing the bandgap and improved the electron transport kinetics with more exposed catalytic active sites, thus resulting in the robust electrochemical sensing of DA. The designed sensor exhibited good sensitivity (4 μM⁻¹ cm⁻²), high structural stability, repeatability and excellent reproducibility with an RSD value of 2.9%. Moreover, the developed system showed a wide linear range (5 μM to 500 μM) and reliable selectivity even in the presence of co-existing interferants, such as ascorbic acid and uric acid. The fabricated nanohybrid was eventually employed to analyze DA in spiked physiological fluids and provided satisfactory recoveries. The designed PDI-CuO based interface also showed a very low detection limit of 6 nM (S/N = 3), consequently confirming its suitability for clinical and biological applications.

Exploring a robust, extremely sensitive, cost-effective and reliable assay platform for the precise analysis of dopamine (DA) has become a big challenge predominantly at the clinical level.     

Eye bank versus surgeon prepared Descemet stripping automated endothelial keratoplasty tissues: Influence on adhesion force in a pilot study

Purpose:To evaluate and compare the biomechanical properties of the eye bank-prepared and surgeon prepared Descemet stripping automated endothelial keratoplasty (DSAEK) tissues.Methods:In this laboratory study, corneal tissues for research were randomly allocated in the following groups: a) surgeon-cut DSAEK and b) eye bank-prepared (pre-cut and pre-loaded) DSAEK. Endothelial cell loss (ECL), immunostaining for tight junction protein ZO-1, elastic modulus, and adhesion force were investigated.Results:ECL was not found to be significantly different between surgeon-cut DSAEK (7.8% ±6.5%), pre-cut DSAEK (8.6% ±2.3%), and pre-loaded DSAEK (11.1% ±4.8%) (P = 0.5910). ZO-1 was expressed equally across all groups. Surgeon-cut DSAEK grafts showed a significantly higher elastic modulus compared to pre-cut and pre-loaded DSAEK groups (P = 0.0047 and P < 0.0001, respectively). Adhesion force was significantly greater in the surgeon-cut DSAEK compared to pre-cut (P < 0.0001) or pre-loaded DSAEK groups (P = 0.0101).Conclusion:The laboratory data on the biomechanics of DSAEK grafts suggests that surgeon-cut DSAEK grafts present higher elastic modulus and adhesion force compared to eye bank-prepared DSAEK grafts.