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Nuclear factor erythroid 2‐related factor 2 (Nrf2) is a transcriptional factor which acts as a regulator for cellular oxidative stress, and tightly regulated by Kelch‐like ECH‐associated protein 1 (Keap1). In this study, we found that auranofin and paclitaxel combination treatment increased TUNEL positive apoptotic cells and enhanced the DNA damage marker γ‐H2AX in MCF‐7 and MDA‐MB‐231 breast cancer cells. The immunoblotting analysis revealed the combination of auranofin and paclitaxel significantly increased the FOXO3 expression in a concentration dependent manner. Further we observed that auranofin and paclitaxel treatment prevents the translocation of Nrf2 in a concentration dependent manner. The increased FOXO3 expression might be involved in the cytoplasmic degradation of Nrf1‐Keap1 complex. Further, the molecular docking results confirm auranofin act as the agonist for Foxo3. Therefore, the present results suggest that auranofin sensitize the breast cancer cells to paclitaxel via regulating FOXO3/Nrf2/Keap1signaling pathway. Significance Statement: The present results show that auranofin enhances paclitaxel induced TUNEL positive apoptotic cells. Further, auranofin treatment increases FOXO3 which in turn inhibit the dissociation of Nrf2 and Keap1 in both MDA‐MB‐231 and MCF‐7 cell lines. Therefore, the present results clearly illustrate the chemosensitizing property of auranofin via regulating FOXO3/Nrf2/Keap1 signaling pathway in the breast cancer cells. Auranofin is already a Food and Drug administration approved drug and it could be considered for the clinical applications after preclinical experimentation. [ABSTRACT FROM AUTHOR]

The intrinsic redox status of cancer cells limits the efficacy of chemotherapeutic drugs. Auranofin, a Food and Drug Administration‐approved gold‐containing compound, documented with effective pharmacokinetics and safety profiles in humans, has recently been repurposed for anticancer activity. This study examined the paclitaxel‐sensitizing effect of auranofin by targeting redox balance in the MDA‐MB‐231 and MCF‐7 breast cancer cell lines. Auranofin treatment depletes the activities of superoxide dismutase, catalase, and glutathione peroxidase and alters the redox ratio in the breast cancer cell lines. Furthermore, it has been noticed that auranofin augmented paclitaxel‐mediated cytotoxicity in a concentration‐dependent manner in both MDA‐MB‐231 and MCF‐7 cell lines. Moreover, auranofin increased the levels of intracellular reactive oxygen species (observed using 2, 7‐diacetyl dichlorofluorescein diacetate staining) and subsequently altered the mitochondrial membrane potential (rhodamine‐123 staining) in a concentration‐dependent manner. Further, the expression of apoptotic marker p21 was found to be higher in auranofin plus paclitaxel‐treated breast cancer cells compared to paclitaxel‐alone treatment. Thus, the present results illustrate the chemosensitizing property of auranofin in MDA‐MB‐231 and MCF‐7 breast cancer cell lines via oxidative metabolism. Therefore, auranofin could be considered a chemosensitizing agent during cancer chemotherapy. Significance statement: In this study, auranofin, a Food and Drug Administration‐approved drug, has been repurposed for anticancer activity. The results illustrate that auranofin improved paclitaxel‐mediated cytotoxicity in breast cancer cell lines. The auranofin treatment altered the intracellular redox balance in the breast cancer cells, which contributes to paclitaxel‐mediated cell cycle arrest and subsequent apoptotic cell death. Thus, the present results illustrate the chemosensitizing property of auranofin in breast cancer cell lines via oxidative metabolism. Therefore, auranofin could be considered a chemosensitizing agent during cancer chemotherapy. [ABSTRACT FROM AUTHOR]

The article discusses the potential for targeting systemic inflammation in patients with heart failure through leucocyte immunomodulation. It highlights the high incidence of cardiovascular mortality and hospitalizations for heart failure despite current therapies. The role of inflammation in heart failure is explored, with a focus on the involvement of proinflammatory cytokines and biomarkers. The article introduces a novel approach using a selective cytopheretic device (SCD) to target activated neutrophils and monocytes, which has shown promise in reducing systemic inflammation and improving outcomes in other acute conditions. A case report is presented to demonstrate the potential effectiveness of the SCD in bridging patients to left ventricular assist device (LVAD) implantation. The article concludes by suggesting that further studies are needed to evaluate the use of the SCD and its potential to reduce cardiovascular mortality and hospitalizations in heart failure patients. [Extracted from the article]

The performance of the flange joint depends on the relaxation of load in bolts. This in turn affects the gasket stress and control of leakage. A finite element model of flange joint with threaded bolt‐nut fastener having zero helix angle is developed and analyzed for stress distribution in the threaded bolt. The stress concentration factor at the thread root region is observed to be non‐uniform along the circumference due to the bending behavior of the bolt in the flange joint. The maximum stress is observed in the first engaged thread. The variation in bolt load due to internal fluid, thermal and external loads are also investigated for both single and twin‐gaskets (two concentric half‐sized single gaskets). The gasket material and gasket configuration are observed to be potential factors causing variation in the distribution of load in the flange joint. In a flange joint subjected to external bending load, the maximum stress concentration in the bolt is observed to be in the first thread, instead of the first engaged thread. Under external bending load, the flange joint loses its structural integrity before the traces of leakage occur in the joint. [ABSTRACT FROM AUTHOR]

Currently described hyperkalemia (HK) animal models are typically acute and cause significant distress and mortality to the animals, warranting new approaches for studying chronic HK in a more appropriate clinical setting. Using the spontaneously hypertensive rat (SHR) model as a more relevant disease template, as well as surgical (unilateral nephrectomy), dietary (3% potassium [K+] supplementation), and pharmacological (amiloride) interventions, we were able to stably induce HK on a chronic basis for up to 12 weeks to serum K+ elevations between 8 and 9 mmol/L, with minimal clinical stress to the animals. Short‐term proof‐of‐concept and long‐term chronic studies in hyperkalemic SHRs showed concomitant increases in serum aldosterone, consistent with the previously reported relationship between serum K+ and aldosterone. Treatment with the K+ binder patiromer demonstrated that the disease model was responsive to pharmacological intervention, with significant abrogation in serum K+, as well as serum aldosterone to levels near baseline, and this was consistent in both short‐term and long‐term 12‐week chronic studies. Our results demonstrate the feasibility of establishing a chronic HK disease state, and this novel HK animal model may be suitable for further evaluating the effects of long‐term, K+‐lowering therapies on effects such as renal fibrosis and end‐organ damage. [ABSTRACT FROM AUTHOR]

Signal transducers and activators of transcription 3 ( STAT3) play a critical role in inflammation, proliferation and carcinogenesis. Inhibition of JAK- STAT3 signaling is proved to be a novel target for prevention of UVB-induced skin carcinogenesis. In this study, chronic UVB irradiation (180 mJ cm−2; weekly thrice for 30 weeks) induces the expression of IL-10 and JAK1 that eventually activates the STAT3 which leads to the transcription of proliferative and antiapoptotic markers such as PCNA, Cyclin-D1, Bcl2 and Bcl-xl, respectively. Caffeic acid ( CA) inhibits JAK- STAT3 signaling, thereby induces apoptotic cell death by upregulating Bax, Cytochrome-C, Caspase-9 and Caspase-3 expression in mouse skin. Furthermore, TSP-1 is an antiangiogeneic protein, which is involved in the inhibition of angiogenesis and proliferation. Chronic UVB exposure decreased the expression of TSP-1 and pretreatment with CA prevented the UVB-induced loss of TSP-1 in UVB-irradiated mouse skin. Thus, CA offers protection against UVB-induced photocarcinogenesis probably through modulating the JAK- STAT3 in the mouse skin. [ABSTRACT FROM AUTHOR]

The advantages of a multiplier-less architecture are reduction in hardware and latency. This paper proposes multiplier-less architectures for the implementation of radix-22 folded pipelined complex FFT core based on coordinate rotation digital computer (CORDIC) and new distributed arithmetic (NEDA). The number of points considered in the work is sixteen and the folding is done by a factor of four. The proposed designs have been implemented on Xilinx XC5VSX240T-2FF1738 FPGA and also have been synthesized using the Synopsys design compiler. Proposed designs based on NEDA have reduced area over 83% and based on CORDIC have a reduced area over 78%. The observed slice-delay product for NEDA based designs are 2.196 and 5.735, and for CORDIC based design is 2.369. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Dengue virus infection is an emerging global threat caused by Arbovirus, a virus from Flaviridiae family, which is transmitted by mosquitoes, Aedes aegypti and Aedes albopictus. Renal transplant recipients who live in the endemic zones of dengue infection or who travel to an endemic zone could be at risk of this infection. Despite multiple epidemics and a high case fatality rate in the Southeast Asian region, only a few cases of dengue infection in renal transplant recipients have been reported. Here, we report a case series of 8 dengue viral infection in renal transplant recipients. Of the 8 patients, 3 developed dengue hemorrhagic shock syndrome and died. [ABSTRACT FROM AUTHOR]

1. Despite considerable theoretical work, the evolution of population stability has rarely been investigated empirically. Moreover, it is not clear whether different stability properties of a population evolve together, or independently. 2. We investigate the evolution of two aspects of population stability using laboratory populations of Drosophila melanogaster selected for faster preadult development and early reproduction, and their matched controls. 3. We show that the constancy stability of the selected populations is significantly higher than their controls, confirming a previous observation that population stability can evolve as a by-product of life-history evolution. This enhanced constancy stability is due to a reduced maximal per capita growth rate, brought about by a reduction in fecundity of the selected populations as a result of the trade-off between developmental rate and fecundity. 4. Persistence stability, as reflected by the probability of extinction, does not differ significantly between selected and control populations. 5. We also show how seemingly trivial experimental details, such as the protocol for restarting extinct populations, can interact with life-history traits to alter the manifestation of the stability properties of a population. [ABSTRACT FROM AUTHOR]

The 1B isoforms of the divalent metal transporter (DMT1) have recently been shown to be regulated transcriptionally via NF-κB but whether other regulatory elements are present on this promoter, however, have not been determined. Accordingly, studies were performed to delineate a minimal promoter region responsible for basal expression of these isoforms of DMT1. Promoter analysis has established that the 1B promoter is a TATA-less promoter containing a common CCAAT-box element conserved in mouse, rat, and human. Using luciferase reporter assays, it was found that mutation of this sequence leads to more than 95% reduction in the basal activity in mouse P19 cells. Using EMSA and ChIP assay, it was confirmed that NF-YA protein subunit can bind specifically to this site. Transfecting these cells with a dominant negative (DN) form of NF-YA leads to ∼60% decrease in luciferase activity and ∼65% decrease in 1B form of mRNA. To determine the location of the CCAAT-box in relation to the transcription start site, 5′ RACE was performed. Results of these studies reveal that the CCAAT-box resides at position -6 to -2 upstream from the transcriptional start site. These data demonstrate that binding of NF-Y to this CCAAT-box domain is responsible for the basal regulation of 1B isoforms of DMT1 mRNA. J. Cell. Physiol. 211: 183–188, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Mucormycosis is historically associated with substantial morbidity and carries a very high mortality in renal transplant patients. The common sites of involvement include cerebral, pulmonary, gastrointestinal, or disseminated lesions. We report the successful outcome of gastric mucormycosis along with Strongyloides stercoralis infection in a renal transplant patient, who has survived for 5 years. We also review the literature. [ABSTRACT FROM AUTHOR]

Studies were performed to examine the affect of nitric oxide (NO) on expression of the divalent metal transporter (DMT1) in undifferentiated P19 embryonic carcinoma cells. DMT1 has four known isoforms which differ in both the N- and C-terminals. Results demonstrate that exposure of P19 cells to the NO precursor, sodium nitro-prusside (SNP), resulted in a decrease in expression of both positive (+) and negative (–) IRE isoforms of DMT1 with no change in the 1A species. Regulation was not as a result of decreased stability of message but was caused by reduction in transcription of the DMT1 1B isoforms. Similar results were observed in other cell lines, including PC12 and SH-SY5Y cells and rat primary sympathetic neurons. Nuclear NF-κB was decreased after SNP treatment, suggesting that NF-κB may mediate this response. Luciferase reporter assays with normal and NF-κB mutated constructs of the 1B promoter confirm that the NF-κB site between −23 to −19 upstream from the transcription start site was responsible for regulating expression. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays further demonstrate that the p65 subunit of NF-κB and not p50 binding is specifically decreased by NO treatment. Results of these studies provide a general mechanism responsible for regulating DMT1 expression induced by stress-related signaling processes in vivo. [ABSTRACT FROM AUTHOR]

The crystallization kinetics in the glass system (100-x) LiBO2-xNb2O5 (5≤x≤20, in molar ratio) prepared via the conventional metal-plate quenching technique have been studied by isothermal and non-isothermal methods using differential thermal analysis. X-ray powder diffraction studies carried out on heat-treated (500°C) glasses reveal the evolution of lithium niobate crystalline phase along with a minor phase of LiBO2. The exponent n in the Jhonson-Mehl-Avrami (JMA) equation applied to the isothermal process is 2.62, which is in excellent agreement with that obtained under the non-isothermal process (2.67). The activation energies for crystal growth obtained from JMA equation under isothermal condition, modified Ozawa and Kissinger equations under non-isothermal conditions, are 293, 311, and 306 kJ/mol, respectively. [ABSTRACT FROM AUTHOR]

Les grandes enquětes gouvernementales permettent généralement de produire des statistiques précises au plan national. Pour décroǐtre l'erreur quadratique moyenne des estimations pour les petites régions, c'est-à-dire les secteurs pour lesquels la taille d'échantillon est faible, on a souvent recours à des variables auxiliaires extraites de fichiers administratifs, lesquelles servent de covariables dans un modèle linéaire mixte. On suppose d'habitude que cette information auxiliaire est disponible pour toutes les petites régions. Dans plusieurs cas, toutefois, on ne dispose de tels renseignements que pour certaines d'entre elles, soit par l'intermédiaire d'une autre enquěte ou d'une édition précédente de la měme enquěte. Les auteurs proposent et étudient des estimateurs pour petites régions qui font appel à des modèles multivariés permettant de combiner les données provenant de plusieurs enquětes. Ils présentent des algorithmes de calcul et font état d'une étude de simulation montrant que si les variables des différentes enquětes sont suffisamment corrélées, de substantiels gains d'efficacité sont possibles. [ABSTRACT FROM AUTHOR]

The bacterial transposon Tn7 utilizes four Tn7-encoded proteins, TnsA, TnsB, TnsC and TnsD, to make insertions at a specific site termed attTn7. This target is selected by the binding of TnsD to attTn7 in a sequence-specific manner, followed by the binding of TnsC and activation of the transposase. We show that TnsD binding to attTn7 induces a distortion at the 5' end of the binding site and TnsC contacts the region of attTn7 distorted by TnsD. Previous work has shown that a target site containing triplex DNA, instead of TnsD-attTn7, can recruit TnsABC and effect sitespecific insertion of Tn7. We propose that the DNA distortion imposed by TnsD on attTn7, like the altered DNA structure via triplex formation, serves as a signal to recruit TnsC. We also show that TnsD primarily contacts the major groove of DNA, whereas TnsC is a minor groove binding protein. The footprint of the TnsC-TnsD-attTn7 nucleoprotein complex includes and extends beyond the Tn7 insertion site, where TnsC forms a platform to receive and activate the transposase to carry out recombination. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) is a major obstacle in cancer chemotherapy. P‐glycoprotein (P‐gp) one of the ATP‐binding cassette (ABC) transporters plays an important role in MDR. In this study, we examined the sensitizing property of andrographolide (Andro) to reverse MDR in the drug‐resistant KBChR 8‐5 cells. Andro exhibited increased cytotoxicity in a concentration‐dependent manner in the P‐gp overexpressing KBChR 8‐5 cells. Furthermore, Andro showed synergistic interactions with PTX and DOX in this drug‐resistant cells. Andro co‐administration enhanced PTX‐ and DOX‐induced cytotoxicity and reduced cell proliferation in the MDR cancer cells. Moreover, reactive oxygen species (ROS) were elevated with a decrease in the mitochondrial membrane potential (MMP) during Andro and chemotherapeutic drugs combination treatment in the drug‐resistant cells. Furthermore, Andro and PTX‐induced cell cycle arrest was observed in the drug‐resistant cell. We also noticed that the expression of ABCB1 and AKT were downregulated during Andro (4 µM) treatment. Furthermore, Andro treatment enhanced the expression of caspase 3 and caspase 9 in the combinational groups that support the enhanced apoptotic cell death in drug‐resistant cancer cells. Therefore, the results reveal that Andro plays a role in the reversal of P‐gp‐mediated MDR in KBChR 8‐5 cells which might be due to regulating ABCB1/AKT signaling pathway. Significance statement: ATP‐binding cassette (ABC) transporters‐mediated multidrug resistance (MDR) is a major hindrance during cancer treatment. Efflux mechanism of P‐glycoprotein (P‐gp) decreases bioavailability and efficacy of chemotherapeutic drugs. Already known inhibitors of P‐gp exhibit higher toxicity to the untargeted cells. Phytochemicals have great potential to reverse the MDR mechanism in cancer cells with less toxicity. Andrographolide (Andro), a phytochemical of Andrographis paniculata, enhanced the efficacy of the chemotherapeutic drugs and reverses drug resistance in MDR cancer cells. Therefore, Andro can be considered as a potent candidate to overcome MDR after preclinical and clinical validations. [ABSTRACT FROM AUTHOR]

Background: The use of percutaneous coronary intervention (PCI) in patients with ST‐segment elevation myocardial infarction (STEMI) is associated with a mortality rate of 5%–7%. It is clear that there is an urgent need to develop new drugs that can effectively prevent cardiac reperfusion injury. ATP‐sensitive K+ (KATP) channel openers (KCOs) can be classified as such drugs. Results: KCOs prevent irreversible ischemia and reperfusion injury of the heart. KATP channel opening promotes inhibition of apoptosis, necroptosis, pyroptosis, and stimulation of autophagy. KCOs prevent the development of cardiac adverse remodeling and improve cardiac contractility in reperfusion. KCOs exhibit antiarrhythmic properties and prevent the appearance of the no‐reflow phenomenon in animals with coronary artery occlusion and reperfusion. Diabetes mellitus and a cholesterol‐enriched diet abolish the cardioprotective effect of KCOs. Nicorandil, a KCO, attenuates major adverse cardiovascular event and the no‐reflow phenomenon, reduces infarct size, and decreases the incidence of ventricular arrhythmias in patients with acute myocardial infarction. Conclusion: The cardioprotective effect of KCOs is mediated by the opening of mitochondrial KATP (mitoKATP) and sarcolemmal KATP (sarcKATP) channels, triggered free radicals' production, and kinase activation. [ABSTRACT FROM AUTHOR]

Ultraviolet radiation induces oxidative photoaging in the skin cells. In this study, we investigated the ability of andrographolide (ADP) to protect human dermal fibroblasts (HDFa) from UVB radiation‐induced oxidative stress and apoptosis. The HDFa cells were exposed to UVB (19.8 mJ/cm2) radiation in the presence or absence of ADP (7 μM) and then oxidative stress and apoptotic protein expression were analyzed. UVB exposure resulted in a significant decline in the activity of antioxidant enzymes and altered mitochondrial membrane potential (MMP). Furthermore, UVB‐irradiation causes increased intracellular reactive oxygen species (ROS) production, apoptotic morphological changes, and lipid peroxidation levels in the HDFa. Moreover, the pretreatment with ADP reduced the UVB‐induced cytotoxicity, ROS production, and increased antioxidant enzymes activity. Further, the ADP pretreatment prevents the UVB‐induced loss of MMP and apoptotic signaling in HDFa cells. Therefore, the present results suggest that ADP protects HDFa cells from UVB‐induced oxidative stress and apoptotic damage. Significance statement: Andrographolide (ADP) exhibits potent antioxidant in the in vitro free radical scavenging activity and it prevents UVB‐induced oxidative stress and apoptotic signaling in human dermal fibroblasts. Further, we suggest that the ADP pretreatment predominantly protects against UVB‐induced cytotoxicity, lipid peroxidation, antioxidant depletion, and apoptotic molecules. In this study, ADP possesses antioxidant effects; it could help to develop photoprotective and new sunscreen agents. [ABSTRACT FROM AUTHOR]

A response by N. Prasad to a letter to the editor regarding their article "Dengue virus infection in renal allograft recipients: a case series during 2010 outbreak" in the December 28, 2011 issue is presented.

In experimental evolutionary studies, altering sex ratio in populations imposes sex‐biased intrasexual and intersexual interactions, which is useful to study the effect of sexual selection and sexual conflict in such populations. We studied cuticular hydrocarbon (CHC) patterns of 170 generations‐old operational sex ratio‐altered Drosophila melanogaster population to investigate the evolutionary outcomes of such selection lines. Our results indicate that the competing sex in each of the selection lines has less variable CHC profile than the less abundant sex, potentially due to sexual selection. The intensity of sexual selection is possibly influenced by intense competition among the abundant sex as well as potential mate choice due to easy availability of mates for the rarer sex in the population. This result is even more striking since the male‐biased replicates were previously shown to have diverged in terms of mate preferences due to sexually antagonistic coevolution (SAC). The precopulatory isolating mechanism underlying such divergent mate preference could be sexual signals such as CHCs since they evolve rapidly and are involved in D. melanogaster mate recognition. Therefore, we also investigate whether CHC profiles diverged in male‐biased replicates in comparison to female‐biased replicates. We found no evidence that cuticular hydrocarbon profiles of male‐biased and female‐biased populations have evolved due to SAC. This study indicates that the differentiation of sexual traits may not be credited to sexual conflict despite populations isolated due to high sexual conflict evolve divergent cuticular hydrocarbon profiles. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a frequent infectious complication in patients on renal replacement therapy, as a result of immunosuppression from uremia and drugs in the post-transplantation period. A retrospective study of all renal transplantation patients from 1989 to date was conducted. This study tried to examine the prevalence, course, and outcome of TB in renal transplant recipients. A comparison with the occurrence of TB in other modalities of renal replacement therapy was also made. We also discussed the treatment protocols for TB in this group of patients. No difference in the prevalence, age, or male/female ratio of TB was seen among the 3 modes of renal replacement therapy. TB of the lung was the more favored site of infection in patients on hemodialysis (77.3%), when compared with those on CAPD (30%) and renal transplant recipients (33.3%). In renal transplant recipients, no deaths occurred due to TB. In 7 patients there was co-infection with cytomegalovirus and in 3 patients there was Aspergillus lung infection. [ABSTRACT FROM AUTHOR]

Background Cryptosporidium is one of the common causes of infective diarrhea in post-transplant patients in endemic areas. However, data are limited on Cryptosporidium infection in recipients of solid organ transplantation. The aim of this study was to determine the incidence, disease manifestation, management, and outcome of Cryptosporidium infection in living-donor renal transplant recipients ( RTR). Methods We performed a detailed retrospective review of the data on all RTR who had diarrheal illness requiring evaluation and hospitalization, and Cryptosporidium infection. Results During the study period, 119/1235 (8.98%) RTR developed diarrhea, and Cryptosporidium was found in 34/119 (28.5%). Nine of 680 (1.3%) patients were on a cyclosporine ( CSA)-based regimen, and 25/643 (3.8%) patients were on a tacrolimus (Tac)-based regimen. The relative risk of developing Cryptosporidium infection was lower on the CSA-based regimen, compared with the Tac-based regimen (odds ratio [ OR]: 0.35, 95% confidence interval [ CI]: 0.17-0.72, P = 0.003). Twelve of the 34 patients had acute graft dysfunction, mainly caused by combined Tac toxicity and dehydration. Mean serum creatinine and trough Tac level were 2.04 ± 0.65 mg/dL and 8.24 ± 1.19 ng/dL, respectively. Nitazoxanide alone was used in 13 patients, and nitazoxanide in combination with fluoroquinolone in 21 patients, with duration of treatment ranging from 16 to 60 days. Tac was changed to CSA in 8/11 patients. The clearance of cysts and response to nitazoxanide alone were significantly lower, compared with combination therapy (61.53% vs. 95.23%, P = 0.01, 38.46 vs. 85.71%, P = 0.004, respectively). The OR for cyst clearance and response was also significantly lower with nitazoxanide alone, in comparison with combination therapy ( OR: 0.65, 95% CI: 0.34-0.92, P = 0.01, OR: 0.45, 95% CI: 0.21-0.81, respectively). Four (16%) of 24 patients with response had relapse. Conclusion Patients with Tac and mycophenolate mofetil combination therapy had a significantly high risk of Cryptosporidium infection. Cryptosporidial infection may require prolonged nitazoxanide therapy, either alone or in combination, with or without reduction in immunosuppression. [ABSTRACT FROM AUTHOR]

Due to selenium (Se) deficiency, Se fortification of food and feed is applied in many countries. Therefore, potential use of Se-enriched kenaf was investigated based on its Se accumulation, its potential to transform accumulated Se to other Se species, and effect of Se accumulation on its growth. Kenaf was grown with different levels of two Se fertilizers (selenite and selenate) at concentrations ranging from 0 to 4 mg Se (kg soil)-1. Total Se concentrations in the plants grown on selenate-treated soil amounted to (1019 ± 136) mg Se (kg dry weight)-1 and were much higher compared to plants grown on selenite-treated soil. Identified Se species were selenite, selenate, Se-methionine, and Se-cystine. Biomass yield, net photosynthesis, and chlorophyll index of the plants decreased when plants were grown on soils treated with high doses of selenate. [ABSTRACT FROM AUTHOR]

J. Neurochem. (2010) 113, 454–464. Abnormal iron accumulation is linked to a variety of neurological disorders and may contribute to the progressive damage seen in these diseases. The biochemical processes responsible for iron accumulation are not known but are likely to entail alteration in transport into injured brain areas. The major transport protein responsible for uptake of iron is divalent metal transporter 1 (DMT1) and recent studies demonstrate that the 1B species is regulated post-translationally by degradation via the proteasomal pathway. As reported in this paper, the E3 ligase, parkin, when over-expressed in SH-SY5Y cells, results in a decrease in 1B-DMT1 isoforms and also a significant reduction in manganese transport and toxicity. Incubating cells over-expressing parkin with the proteasomal inhibitor, MG-132, restores 1B-DMT1 levels emphasizing that the observed changes are caused by degradation via the proteasomal pathway. Expression of the 1B species of DMT1 was also shown to be elevated in human lymphocytes containing a homozygous deletion of exon 4 of parkin and in brains of parkin knockout animals. Immunoprecipitation and immunofluorescent studies confirm that parkin co-localizes with DMT1 in SH-SY5Y cells transfected with wild-type parkin. These results demonstrate that parkin is the E3 ligase responsible for ubiquitination of the 1B species of DMT1. [ABSTRACT FROM AUTHOR]

A 52-year-old male underwent living-related renal transplantation. He received prednisolone, azathioprine, and cyclosporine as immunosuppression protocol. Eleven years after transplantation, he developed pyrexia with multiple nodular lesions on his limbs, trunk, and face. Skin biopsy and smears showed the presence of numerous acid-fast bacilli with 5% sulfuric acid indicative of Mycobacterium leprae. He was initiated on multidrug therapy (MDT) including dapsone, clofazimine, and rifampicin. After 2 years of MDT, he developed new multiple erythematous, tender subcutaneous nodules in crops over his face and upper limbs. Skin biopsies and histopathological examination confirmed the diagnosis of type 2 lepra reaction or erythema nodosa leprosum. He was managed with an increase in the dose of prednisolone and thalidomide. He was continued on MDT. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis C virus (HCV) infection is a common cause of liver disease in post-renal transplant period and causes poor patient and graft survival. We analyzed the effects of antiviral therapy using ribavirin monotherapy or ribavirin in combination with interferon (IFN)-alpha in our kidney transplant recipients with chronic hepatitis C. Methods: Total of 14 patients received antiviral therapy, all of whom had stable graft function, raised aminotransferases and positive HCV viremia at the start of treatment. Eight patients received ribavirin alone for a period of six months to two yr, in doses of 400–800 mg daily. Five patients received IFN-alpha therapy for a period of two months to 1.5 yr, in doses of 1.5 million units daily or three million units thrice weekly with ribavirin. One patient received pegylated IFN 50 μg once weekly in combination with ribavirin. The response was seen in terms of biochemical and virological improvement at the end of study period. Results: In patients treated with ribavirin alone (n = 8), mean alanine aminotransferase (ALT) levels before and after treatment were significantly different (198.4 ± 147.6 and 104.8 ± 66.5 IU/L respectively; p < 0.05). ALT levels normalized completely in three patients at the end of treatment, improved in three patients and deteriorated in two. Only in one of eight patients on ribavirin alone, HCV-RNA became negative after six months of treatment while in the rest (n = 7) HCV-RNA continued to be positive. In subjects on IFN plus ribavirin (n = 6), the mean ALT levels decreased significantly (from 280.2 ± 114.9 IU/L at baseline to 71 ± 49 IU/L at end of therapy; p < 0.05). Two patients had sustained remission (33.3%) on IFN plus ribavirin (persistently negative HCV-RNA), two patients relapsed after initial remission and in two patients treatment was stopped after two months because of graft dysfunction. Totally four patients developed graft dysfunction at some time during the course of IFN therapy (66.6%), but it was discontinued in only two (33.3%). All patients regained normal creatinine levels after discontinuation of IFN, although one patient developed chronic allograft nephropathy as shown by kidney biopsy. Four patients in IFN group developed leucopenia. Two patients developed severe anemia one of whom required blood transfusion and one developed severe flu-like syndrome requiring stoppage of therapy. Conclusion: Ribavirin monotherapy in renal transplant recipients with chronic hepatitis C infection results in good biochemical response but is not associated with virological clearance. IFN in combination with ribavirin is effective in two-thirds of patients after a minimum therapy of six months, but it is poorly tolerated, results in graft dysfunction in significant number of patients, and relapse can occur after stopping treatment. [ABSTRACT FROM AUTHOR]

Summary Background Many asthmatics report worsening of symptoms following exposure to odours and sensory irritants commonly found in household and cosmetic products. Despite this, little evidence exists to confirm the degree to which such subjective reports are correlated with localized, objective changes in the upper or lower airways following a fragranced product exposure. Objective Subjective symptom reports were compared to objective measures in mild asthmatics, moderate asthmatics and non-asthmatics following exposure to one of two fragranced household aerosol mixtures and a clean air control condition to determine if asthmatics reported greater subjective symptoms of nasal congestion or exhibited objective measures of elevated ocular irritation and nasal congestion following exposure than did healthy controls. Methods Measures of nasal mucosal swelling, using acoustic rhinometry, and photographic assessments of ocular hyperemia, using macro-photography, were taken before exposure, immediately after an initial 5-min exposure and again following a 30-min exposure to either of two, fragranced aerosol products and a clean air control. Self-reports of nasal patency at each time-point were also obtained. Results Although moderate asthmatics tended to report more nasal congestion following fragranced product exposure than did non-asthmatics, no exposure-related changes in ocular redness or nasal mucosal swelling were observed among the three groups. Spirometry readings also failed to show evidence of any exposure-related changes in pulmonary function. Conclusion Despite claims that exposure to fragranced products may trigger ocular and respiratory symptoms among asthmatics, we found no evidence that 30 min of exposure to one of two fragranced aerosols elicited objective adverse effects in the ocular or nasal mucosa of mild and moderate asthmatics. While physiological mechanisms of fragrance impact may yet be responsible for some of the adverse reports among asthmatics following fragrance exposure, such reports may also reflect a non-physiological locus of symptom perception triggered by other sensory cues. [ABSTRACT FROM AUTHOR]

Aims: Focal nodular hyperplasia-like lesions have rarely been described in cirrhotic livers. We describe five cases of such lesions. Methods and results: Between 1998 and 2001, 146 liver transplants were performed at the Royal Free Hospital for cirrhosis of the liver. Nodular lesions identified in the livers removed at transplantation were defined histologically according to the International Working Party classification (Hepatology 1995; 22; 983). They were present in 63 of these livers, as follows: 36 dysplastic nodules, 121 macroregenerative nodules, and 71 hepatocellular carcinomas. In five patients, an additional 12 nodules (size range 4–23 mm, median 10.5 mm) showed histological features suggestive of focal nodular hyperplasia including mildly inflamed vascular fibrous septa, and ductular proliferation. Pre-transplantation imaging showed features suspicious for hepatocellular carcinoma, in three of these lesions (12, 23 and 23 mm diameter) from two different patients. These lesions were histologically indistinguishable from focal nodular hyperplasia occurring in non-cirrhotic livers, with fibrous scars and septa which contained vascular and ductular structures. Conclusions: It is important to recognize that these lesions may occur in the context of cirrhosis and that they should be considered in the differential diagnosis with hepatocellular carcinoma, dysplastic nodules and macroregenerative nodules. [ABSTRACT FROM AUTHOR]

Cardiac lipomas are one of the rare primary benign neoplasms composed of mature fat cells. The tumor originates mostly in the subendocardium and subepicardium but very rarely within the myocardium. Clinically, this tumor is asymptomatic and found incidentally in the vast majority of cases. We report a 26-year-old female presenting with atypical chest pain. Transthoracic echocardiogram showed a mass in relation to interatrial septum suggestive of atrial myxoma, but was confirmed to be cardiac lipoma on magnetic resonance imaging. Owing to the asymptomatic character and the benign nature of the tumor, a decision for conservative management was made. [ABSTRACT FROM AUTHOR]

Abstract: Aim: This study evaluates the safety and efficacy of direct‐acting antivirals (DAAs) including sofosbuvir, ledipasvir and daclatasvir in patients with hepatitis C viraemia who were on maintenance haemodialysis. Methods: Data on patients who received sofosbuvir and ribavirin were analysed. Patients who experienced treatment failure with the above regimen received sofosbuvir and ledipasvir for infection with hepatitis C virus (HCV) genotype 1. Those having HCV genotype 3 infection received sofosbuvir and daclatasvir. All treatment regimens were of 12 weeks duration. Side‐effects were investigated. The HCV viral load was determined by RT‐PCR at 4,16 and 24 weeks after the initiation of therapy; haemoglobin levels and liver function tests were monitored at regular intervals during therapy. Results: Of the 22 subjects initially treated with sofosbuvir and ribavirin, 72.72% attained sustained virologic response at 12 weeks (SVR12). Four patients experienced treatment failure and received genotype specific therapy. Patients with HCV genotype one received sofosbuvir with ledipasvir. One patient with HCV genotype 3 infection received sofosbuvir and daclatasvir. All of them attained SVR12. A statistically significant reduction in the median serum glutamic‐oxaloacetic transaminase (SGOT) and Serum glutamic pyruvic transaminase (SGPT) were observed from the baseline until the end of treatment. Anaemia was observed in 45% of patients receiving ribavirin. Conclusions: Our study demonstrates that sofosbuvir‐based therapy is efficacious for HCV viraemia in patients on maintenance haemodialysis. The therapy was found to be reasonably safe with no major adverse effects noted with the use of sofosbuvir, ledipasvir or daclatasvir. However, larger studies are needed to validate our results. [ABSTRACT FROM AUTHOR]