Large B-cell Lymphoma-Associated Membranous Nephropathy With Positive PLA2R on Kidney Biopsy.

Large B-cell lymphoma associated with membranous nephropathy (MN) is a rare and complex medical condition that involves the simultaneous presence of two distinct diseases: a malignant lymphoma and a kidney disorder called membranous nephropathy. In this case, there is an additional element of interest, which is the presence of positive Phospholipase A2 Receptor (PLA2R) in the kidney. The case involves a 53-year-old Caucasian male with a three-week history of lower leg edema and a past medical history of recurrent upper respiratory infections. The upper respiratory infections were characterized by symptoms of fever, sore throat, and headache, and they required multiple rounds of antibiotics for treatment, including Augmentin and Keflex. A diagnosis of nephrotic syndrome was made based on proteinuria of fourteen grams with no RBC cast on urinalysis. Kidney biopsy stained positive for antiposophlipase A2 receptor on a frozen section. Thrombospondin type 1 domain-containing 7A (THSD7A) was not detected.  Given his biopsy and absence of clinical symptoms, he was treated as a case of primary membranous nephropathy with angiotensin-converting enzyme (ACE) inhibitors, steroids, and immunosuppressive. Three months following the treatment, his condition deteriorated, and after a thorough investigation, he appeared to have large B-cell lymphoma as a secondary cause of membranous glomerulopathy (MGN). When large B-cell lymphoma is associated with membranous nephropathy, it presents a unique clinical challenge. The interaction between these two conditions is not fully understood, but it is believed that the lymphoma may provoke an immune response that leads to the development of membranous nephropathy. Moreover, the presence of positive PLA2R in the kidney indicates a specific mechanism at play in this complex disease scenario. Treatment for this condition typically involves addressing both the lymphoma and the kidney disorder. This may include chemotherapy or other treatments to target the lymphoma and immunosuppressive therapy to manage the autoimmune response causing membranous nephropathy. Close monitoring and coordination between oncologists and nephrologists are essential for the best possible outcome in managing this rare and challenging condition.

Smart Approach for the Design of Highly Selective Aptamer-Based Biosensors.

Aptamers are chemically synthesized single-stranded DNA or RNA oligonucleotides widely used nowadays in sensors and nanoscale devices as highly sensitive biorecognition elements. With proper design, aptamers are able to bind to a specific target molecule with high selectivity. To date, the systematic evolution of ligands by exponential enrichment (SELEX) process is employed to isolate aptamers. Nevertheless, this method requires complex and time-consuming procedures. In silico methods comprising machine learning models have been recently proposed to reduce the time and cost of aptamer design. In this work, we present a new in silico approach allowing the generation of highly sensitive and selective RNA aptamers towards a specific target, here represented by ammonium dissolved in water. By using machine learning and bioinformatics tools, a rational design of aptamers is demonstrated. This "smart" SELEX method is experimentally proved by choosing the best five aptamer candidates obtained from the design process and applying them as functional elements in an electrochemical sensor to detect, as the target molecule, ammonium at different concentrations. We observed that the use of five different aptamers leads to a significant difference in the sensor's response. This can be explained by considering the aptamers' conformational change due to their interaction with the target molecule. We studied these conformational changes using a molecular dynamics simulation and suggested a possible explanation of the experimental observations. Finally, electrochemical measurements exposing the same sensors to different molecules were used to confirm the high selectivity of the designed aptamers. The proposed in silico SELEX approach can potentially reduce the cost and the time needed to identify the aptamers and potentially be applied to any target molecule.

An Aptasensor Based on a Flexible Screen-Printed Silver Electrode for the Rapid Detection of Chlorpyrifos.

In this work, we propose a novel disposable flexible and screen-printed electrochemical aptamer-based sensor (aptasensor) for the rapid detection of chlorpyrifos (CPF). To optimize the process, various characterization procedures were employed, including Fourier transform infrared spectroscopy (FT-IR), electrochemical impedance spectroscopy (EIS), and cyclic voltammetry (CV). Initially, the aptasensor was optimized in terms of electrolyte pH, aptamer concentration, and incubation time for chlorpyrifos. Under optimal conditions, the aptasensor showed a wide linear range from 1 to 105 ng/mL with a calculated limit of detection as low as 0.097 ng/mL and sensitivity of 600.9 µA/ng. Additionally, the selectivity of the aptasensor was assessed by identifying any interference from other pesticides, which were found to be negligible (with a maximum standard deviation of 0.31 mA). Further, the stability of the sample was assessed over time, where the reported device showed high stability over a period of two weeks at 4 °C. As the last step, the ability of the aptasensor to detect chlorpyrifos in actual samples was evaluated by testing it on banana and grape extracts. As a result, the device demonstrated sufficient recovery rates, which indicate that it can find application in the food industry.

Flexible Screen-Printed Electrochemical Sensors Functionalized with Electrodeposited Copper for Nitrate Detection in Water.

Nitrate (NO3 -) contamination is becoming a major concern due to the negative effects of an excessive NO3 - presence in water which can have detrimental effects on human health. Sensitive, real-time, low-cost, and portable measurement systems able to detect extremely low concentrations of NO3 - in water are thus becoming extremely important. In this work, we present a novel method to realize a low-cost and easy to fabricate amperometric sensor capable of detecting small concentrations of NO3 - in real water samples. The novel fabrication technique combines printing of a silver (Ag) working electrode with subsequent modification of the electrode with electrodeposited copper (Cu) nanoclusters. The process was tuned in order to reach optimized sensor response, with a high catalytic activity toward electroreduction of NO3 - (sensitivity: 19.578 µA/mM), as well as a low limit of detection (LOD: 0.207 nM or 0.012 µg/L) and a good dynamic linear concentration range (0.05 to 5 mM or 31 to 310 mg/L). The sensors were tested against possible interference analytes (NO2 -, Cl-, SO4 2-, HCO3 -, CH3COO-, Fe2+, Fe3+, Mn2+, Na+, and Cu2+) yielding only negligible effects [maximum standard deviation (SD) was 3.9 µA]. The proposed sensors were also used to detect NO3 - in real samples, including tap and river water, through the standard addition method, and the results were compared with the outcomes of high-performance liquid chromatography (HPLC). Temperature stability (maximum SD 3.09 µA), stability over time (maximum SD 3.69 µA), reproducibility (maximum SD 3.20 µA), and repeatability (maximum two-time useable) of this sensor were also investigated.

Deletion of newly described pro-survival molecule Pellino-1 increases oxidative stress, downregulates cIAP2/NF-κB cell survival pathway, reduces angiogenic response, and thereby aggravates tissue function in mouse ischemic models.

INTRODUCTION: In the present study, we aimed to explore the functional role of Pellino-1 (Peli1) in inducing neovascularization after myocardial infarction (MI) and hindlimb ischemia (HLI) using Peli1 global knockout mice (Peli1-/-). Recently we have shown that Peli1, an E3 ubiquitin ligase, induce angiogenesis and improve survivability, with decreased necrosis of ischemic skin flaps. METHODS: Peli1fl/fl and Peli1-/- mice were subjected to either permanent ligation of the left anterior descending coronary artery (LAD) or sham surgery (S). Tissues from the left ventricular risk area were collected at different time points post-MI. In addition, Peli1fl/fl and Peli1-/- mice were also subjected to permanent ligation of the right femoral artery followed by motor function scores, Doppler analysis for blood perfusion and immunohistochemical analysis. RESULTS: Global Peli1 knockout exacerbated myocardial dysfunction, 30 and 60 days after MI compared to wild type (WT) mice as measured by echocardiogram. In addition, Peli1-/- mice also showed decreased motor function scores and perfusion ratios compared with Peli1fl/fl mice 28 days after the induction of HLI. The use of Peli1 in adenoviral gene therapy following HLI in CD1 mice improved the perfusion ratio at 28 days compared to Ad.LacZ-injected mice. CONCLUSION: These results suggest new insights into the protective role of Peli1 on ischemic tissues and its influence on survival signaling.

Overexpression of Thioredoxin1 enhances functional recovery in a mouse model of hind limb ischemia.

BACKGROUND: There is keen interest in finding nonsurgical treatments for peripheral vascular disease (PVD). Previously, we demonstrated that selective activation of Thioredoxin1 (Trx1), a 12-kDa cytosolic protein, initiates redox-dependent signaling and promotes neovascularization after ischemic heart disease. Therefore, Trx1 might possess immense potential to not only treat murine hind limb ischemia (HLI) through effective angiogenesis but also provide PVD patients with nonsurgical therapy to enhance neovascularization and improve blood perfusion. METHODS: To determine whether activation of Trx1 increases blood perfusion in HLI, two different strategies were used-gene therapy and transgenic model system. In adenoviral-mediated gene therapy, 8- to 12-wk-old mice were divided into two groups: (1) control Adeno-LacZ (Ad-LacZ) and (2) Adeno-Thiroedoxin1 (Ad-Trx1). The mice underwent surgical intervention to induce right HLI followed by injection with Ad-LacZ or Ad-Trx1, respectively. In the second strategy, we used wild-type and transgenic mice overexpressing Trx1 (Trx1Tg/+). All the animals underwent Doppler imaging for the assessment of limb perfusion followed by immunohistochemistry and Western blot analysis. RESULTS: Significant increases in perfusion ratio were observed in all the Trx1 overexpressed groups compared with their corresponding controls. Expressions of heme oxygenase-1, vascular endothelial growth factor, and the vascular endothelial growth factor receptors Flk-1 and Flt-1 were increased in Trx1 overexpressed mice compared with their respective controls. Blood perfusion in the ischemic limb gradually improved and significantly recovered in Trx1Tg/+ and Ad-Trx1 groups compared with their corresponding controls. The capillary and arteriolar density in the ischemic zone were found to be higher in Trx1Tg/+ group compared with wild type. CONCLUSIONS: The overall outcomes of our study demonstrate that Trx1 enhances blood perfusion and increases angiogenic protein expression in a rodent HLI model. These results suggest that Trx1 is a potential target for clinical trials and drug therapy for the treatment of PVD.

Deletion of prolyl hydroxylase domain proteins (PHD1, PHD3) stabilizes hypoxia inducible factor-1 alpha, promotes neovascularization, and improves perfusion in a murine model of hind-limb ischemia.

BACKGROUND: There is an emerging focus on investigating innovative therapeutic molecules that can potentially augment neovascularization in order to treat peripheral arterial disease (PAD). Although prolyl hydroxylase domain proteins 1 and 3 (PHD1 and PHD3) may modulate angiogenesis via regulation of hypoxia inducible factor-1α (HIF-1α), there has been no study directly addressing their roles in ischemia-induced vascular growth. We hypothesize that PHD1(-/-) or PHD3(-/-) deficiency might promote angiogenesis in the murine hind-limb ischemia (HLI) model. STUDY DESIGN: Wild type (WT), PHD1(-/-) and PHD3(-/-) male mice aged 8-12weeks underwent right femoral artery ligation. Post-procedurally, motor function assessment and laser Doppler imaging were periodically performed. The mice were euthanized after 28days and muscles were harvested. Immunohistochemical analysis was performed to determine the extent of angiogenesis by measuring capillary and arteriolar density. VEGF expression was quantified by enzyme-linked immunosorbent assay (ELISA). Bcl-2 and HIF-1α were analyzed by immunofluorescence. Fibrosis was measured by picrosirius red staining. RESULTS: PHD1(-/-) and PHD3(-/-) mice showed significantly improved recovery of perfusion and motor function score when compared to WT after femoral artery ligation. These mice also exhibited increased capillary and arteriolar density, capillary/myocyte ratio along with decreased fibrosis compared to WT. VEGF, Bcl-2 and HIF-1α expression increased in PHD1(-/-) and PHD3(-/-) mice compared to WT. CONCLUSIONS: Taken together these results suggest that PHD1 and PHD3 deletions promote angiogenesis in ischemia-injured tissue, and may present a promising therapeutic strategy in treating PAD.

Tick-borne trauma: an unusual presentation of anaplasmosis.

INTRODUCTION: Tick-borne diseases present a special problem in Connecticut and the Northeastern United States. The tick species Ixodes scapularis known for Lyme disease may also infect humans with anaplasmosis, while other tick species [Amblyomma spp.] may transmit ehrlichiosis. These illnesses may present in various ways depending on the virulence of the organism and variable host factors. CASE PRESENTATION: Our patient presented as a motor vehicle trauma presumably from encephalopathy secondary to anaplasmosis. Unusual features of the patient's case led to the causative diagnosis on peripheral blood smear examination. CONCLUSION: Tick-borne diseases are endemic in Connecticut. The astute clinician should maintain a healthy vigilance for these illnesses. Although our patient presented as a trauma, the presumed precipitating disease could have been treated. Physician awareness and patient education may lessen the impact of these diseases.

Computed tomographic modeling before and after treatment for posttraumatic empyema: early decortication is superior to catheter drainage.

BACKGROUND: Posttraumatic empyema is relatively unusual. There are little data comparing the results of various interventions, and no data that have documented the restoration of lung volumes. METHODS: We compared patients with posttraumatic empyema who were treated with catheter drainage or decortication. Computed tomographic scans of the chest were obtained before and after treatment, and computed tomographic modeling was used to determine the change in lung volumes after each intervention. RESULTS: From 2006 to 2010 there were 478 patients admitted after sustaining chest trauma and 25 (5%) developed an empyema. The definitive treatment was decortication in 15 patients (60%) and chest tube or catheter drainage in 10 (40%). Four patients (16%) initially treated with chest tubes later required decortication. The overall complication rate was 33% for decortication and 100% for catheters. There was no significant difference in days of mechanical ventilation (catheter-median 0, SD±13 days; decortication-median 10, SD±12 days; p=0.6), total length of stay (catheter-median 15, SD±36 days; decortication-median 27, SD±17 days; p=0.9), and intensive care unit days (catheter-median 6, SD±19 days; decortication-median 15, SD±17 days; p=0.5). After chest tube drainage, the lung volume increased on average by 751 cubic centimeters (range, 99 to 1,982 cc). After decortication, the lung volume increased on average by 1,519 cc (range, 616 to 2,916, p=0.02). CONCLUSIONS: Decortication for posttraumatic empyema results in higher postoperative lung volumes than catheter drainage and has a lower complication rate. Decortication is more effective in restoring full pulmonary capacity in the treatment of posttraumatic empyema.

Response of sugarcane to treated wastewater of oil refinery.

The crop of sugarcane (Saccharum officinarum) was grown at the agricultural farm of the Mathura Oil Refinery in a simple randomized block design. The experimental plots were irrigated with ground water (GW) or treated wastewater (TW) as and when required The plants gave better response to the latter than the former. The quantity of the required nutrients was comparatively more in TW than GW. The soil receiving wastewater did not show any significant change in its physico-chemical characteristics. The soil accumulated all the heavy metals but the plant samples receiving TW only exhibited the presence of Ni, Pb and Zn whose values are far below the permissible limits.

Effect of long-term application of oil refinery wastewater on soil health with special reference to microbiological characteristics.

The ground water (GW), treated wastewater (TW) and the soil at the agricultural farm in the premises of the Mathura Oil Refinery have been monitored for various physico-chemical characteristics, over the last 12 years (1987-1998). It was noted that the heavy metal content in the soil, repeatedly irrigated with TW, was increasing because the wastewater itself was a better source of these metals than GW. However, the level of these metals, both in the wastewater and the soil, was very much below the permissible limits. The quantitative analysis of various functional groups of microorganism and their interaction with metals revealed that the viable count of aerobic heterotrophs, asymbiotic nitrogen fixers, actinomycetes and fungi were in the ranges of 2.6 x 10(6)-7.2 x 10(7), 5.0 x 10(4)-6.8 x 10(5), 2.0 x 10(4)-2.8 x 10(5) and 2.5 x 10(4)-7.5 x 10(5), respectively. The presence of Rhizobium spp. in the soil was shown by the nodulation in the leguminous crops cultivated in the experimental field. The significant viable counts of above functional groups of bacteria on each heavy metal supplemented plate indicated that these populations could tolerate high levels (> or = 200 microg/ml) of metal. Among them, nitrogen fixers and aerobic heterotrophs (largely, Gram-negative) had a higher degree of resistance to heavy metals than actinomycetes. Similarly, the strains of Rhizobium, isolated from the experimental field, showed a higher degree of resistance under in vitro conditions and the minimum inhibitory concentration (MIC) was in the range of 50-800 microg/ml, determined by a plate dilution method. It may, therefore, be deduced that 12 years repeated application of treated wastewater had not significantly changed the microbial dynamics of the soil and possibly the bacteria had adapted to the changed soil environment by developing various levels of metal resistance.

Epitaxial cuprate superconductor/ferroelectric heterostructures.

Thin-film heterostructures of Bi(4)Ti(3)O(12)Bi(2)Sr(2)CuO(6+x), have been grown on single crystals of SrTiO(3), LaAlO(3), and MgAl(2)O(4) by pulsed laser deposition. X-ray diffraction studies show the presence of c-axis orientation only; Rutherford backscattering experiments show the composition to be close to the nominal stoichiometry. The films are ferroelectric and exhibit a symmetric hysteresis loop. The remanent polarization was 1.0 microcoulomb per square centimeter, and the coercive field was 2.0 x 10(5) volts per centimeter. Similar results were obtained with YBa(2)Cu(3)O(7-x) and Bi(2)Sr(2)CaCu(2)O(8+x), and single-crystal Bi(2)Sr(2)CuO(6+x)as the bottom electrodes. These films look promising for use as novel, lattice-matched, epitaxial ferroelectric film/electrode heterostructures in nonvolatile memory applications.