Digital hypertension management: clinical and cost outcomes of a pilot implementation of the OMRON hypertension management platform.

Importance: Home monitoring of blood pressure (BP) in hypertensive patients can improve outcomes, but challenges to both patient compliance and the effective transmission of home BP readings to physicians can limit the extent to which physicians can use this information to improve care. The OMRON Hypertension Management Platform (OMRON HMP) pairs a home BP cuff with a digital product that tracks data, provides reminders to improve patient compliance, and provides a streamlined source of information to physicians. Objective: The primary objective of the quality improvement (QI) project was to test the hypothesis that use of the OMRON HMP could reduce the number and cost of hypertension related claims, relative to a retrospectively matched cohort of insured members. A secondary objective was to demonstrate improvement in control of BP among patients. Design: Eligible members were recruited to the QI project between December 1, 2018 and December 30, 2020 and data collected for six months following recruitment. All members received the OMRON HMP intervention. Setting: Enrollment and data collection were coordinated on-site at selected PCP partner providers in Western Pennsylvania. Eligible members were identified from insurance claims data as those receiving care for primary hypertension from participating primary care physicians and/or cardiologists. Participants: Eligible members were between the ages of 35 and 85, with a diagnosis of primary hypertension. The retrospective cohort was selected from electronic medical records of Highmark-insured patients with hypertension who received care at Allegheny Health Network (AHN), a subsidiary of Highmark Health. Members were matched on baseline BP and lipid measures, age, smoking status, diabetes status, race and sex. Intervention: Daily home BP readings were recorded by the OMRON HMP app. Patient data was reviewed by clinical staff on a weekly basis and treatment plans could be adjusted in response to this data. Results: OMRON HMP users showed a significant increase in the number and cost of hypertension-related claims, contrary to the hypothesis, but did display improvements in control of BP. Conclusions and Relevance: The use of a digital platform to facilitate at-home BP monitoring appeared to improve BP control but led to increased hypertension-related costs in the short-term.

Quercetin@Gd3+ doped Prussian blue nanocubes induce the pyroptotic death of MDA-MB-231 cells: combinational targeted multimodal therapy, dual modal MRI, intuitive modelling of r1-r2 relaxivities.

Quercetin (Qu), a potential bioflavonoid has gained considerable interest as a promising chemotherapeutic drug which can inhibit the proliferation of triple-negative breast cancer (TNBC) cells due to its regulation of the expression of tumor-suppressor gene metastasis and antioxidant property. Notably, Qu exhibits a very negligible cytotoxic effect on normal cells, even with high-dose treatment, while it is shows high affinity to TNBC. However, the efficiency of Qu is limited clinically due to its poor bioavailability, caused by its low aqueous solubility (2.15 µg mL-1 at 25 °C), rapid gastrointestinal digestion and chemical instability in alkaline and neutral media. Herein, polydopamine (PDA)-coated, NH2-PEG-NH2 and hyaluronic acid (HA)-functionalized Gd3+-doped Prussian blue nanocubes (GPBNC) are reported as a multifunctional platform for the codelivery of Qu as a chemotherapeutic agent and GPBNC as a photodynamic (PDT) and photothermal (PTT) agent with improved therapeutic efficiency to overcome theses barriers. PDA, NH2-PEG-NH2 and HA stabilize GPBNC@Qu and facilitate bioavailability and active-targeting, while absorption of near infrared (NIR) (808 nm; 1 W cm-2) induces PDT and PTT activities and dual T1-T2-weighted magnetic resonance imaging (MRI) with high relaxometric parameters (r1 10.06 mM-1 s-1 and r2 24.96 mM-1 s-1 at a magnetic field of 3 T). The designed platform shows a pH-responsive Qu release profile and NIR-induced therapeutic efficiency of ∼79% in 20 minutes of irradiation, wherein N-terminal gardermin D (N-GSDMD) and a P2X7-receptor-mediated pyroptosis pathway induces cell death, corroborating the up-regulation of NLRP3, caspase-1, caspase-5, N-GSDMD, IL-1ß, cleaved Pannexin-1 and P2X7 proteins. More interestingly, the increasing relaxivity values of Prussian blue nanocubes with Gd3+ doping have been explained on the basis of Solomon-Bloembergen-Morgan theory, considering inner- and outer-sphere relaxivity, wherein crystal defects, coordinated water molecules, tumbling rate, metal to water proton distance, correlation time, magnetisation value etc. play a significant role. In summary, our study suggests that GPBNC could be a beneficial nanocarrier for theranostic purposes against TNBC, while our conceptual study clearly demonstrates the role of various factors in increasing relaxometric parameters.

Assessing pollution and health risks from chromite mine tailings contaminated soils in India by employing synergistic statistical approaches.

Potentially toxic elements (PTEs) contamination in the agricultural soil can generate a detrimental effect on the ecosystem and poses a threat to human health. The present work evaluates the PTEs concentration, source identification, probabilistic assessment of health hazards, and dietary risk analysis due to PTEs pollution in the region of the chromite-asbestos mine, India. To evaluate the health risks associated with PTEs in soil, soil tailings and rice grains were collected and studied. The results revealed that the PTEs concentration (mainly Cr and Ni) of total, DTPA-bioavailable, and rice grain was significantly above the permissible limit in site 1 (tailings) and site 2 (contaminated) as compared with site 3 (uncontaminated). The Free ion activity model (FIAM) was applied to detect the solubility of PTEs in polluted soil and their probable transfer from soil to rice grain. The hazard quotient values were significantly higher than the safe (FIAM-HQ < 0.5) for Cr (1.50E+00), Ni (1.32E+00), and, Pb (5.55E+00) except for Cd (1.43E-03), Cu (5.82E-02). Severity adjustment margin of exposure (SAMOE) results denote that the PTEs contaminated raw rice grain has high health risk [CrSAMOE: 0.001; NiSAMOE: 0.002; CdSAMOE: 0.007; PbSAMOE: 0.008] for humans except for Cu. The Positive matrix factorization (PMF) along with correlation used to apportion the source. Self-organizing map (SOM) and PMF analysis identified the source of pollution mainly from mines in this region. Monte Carlo simulation (MCS) revealed that TCR (total carcinogenic risk) cannot be insignificant and children were the maximum sufferers relative to adults via ingestion-pathway. In the spatial distribution map, the region nearer to mine is highly prone to ecological risk with respect to PTEs pollution. Based on appropriate and reasonable evaluation methods, this work will help environmental scientists and policymakers' control PTEs pollution in agricultural soils near the vicinity of mines.

Pollution and health risk assessment of mine tailings contaminated soils in India from toxic elements with statistical approaches.

The rapid mining activities of mica mines in Giridih district, India, have led to toxic metal pollution of agricultural soil. This is a key concern for environmental risk and human health. 63 top soil samples were collected at a distance of 10 m (Zone 1), 50 m (Zone 2), and 100 m (Zone 3) from near 21 mica mines with agriculture fields. The mean concentration of total and bio-available toxic elements (TEs - Cr, Ni, Pb, Cu, Zn, and Cd) was higher in zone 1 across three zones. The Positive matrix factorization model (PMF) and Pearson Correlation analysis were used to identify waste mica soils with TEs. Based on PMF results, Ni, Cr, Cd, and Pb were the most promising pollutants and carried higher environmental risks than the other TEs. Using the self-organizing map (SOM), zone 1 was identified as a high-potential source of TEs. Soil quality indexes for TEs risk zone 1 were found to be higher across three zones. Based on the health risk index (HI), children are more adversely affected than adults. Monte Carlo simulations (MCS) model and sensitivity analysis of total carcinogenic risk (TCR), children were more affected by Cr and Ni than adults through ingestion exposure pathways. Finally, a geostatistical tool was developed to predict the spatial distribution patterns of TEs contributed by mica mines. In a probabilistic assessment of all populations, non-carcinogenic risks appeared to be negligible. The fact that there is a TCR can't be ignored, and children are more likely to develop it than adults. Mica mines with TEs contamination were found to be the most significant anthropogenic contributor to health risks based on source-oriented risk assessment.

Fundamental understanding of the size and surface modification effects on r 1, the relaxivity of Prussian blue nanocube@m-SiO2: a novel targeted chemo-photodynamic theranostic agent to treat colon cancer.

A targeted multimodal strategy on a single nanoplatform is attractive in the field of nanotheranostics for the complete ablation of cancer. Herein, we have designed mesoporous silica (m-SiO2)-coated Prussian blue nanocubes (PBNCs), functionalized with hyaluronic acid (HA) to construct a multifunctional PBNC@m-SiO2@HA nanoplatform that exhibited good biocompatibility, excellent photodynamic activity, and in vitro T 1-weighted magnetic resonance imaging ability (r 1 ∼ 3.91 mM-1 s-1). After loading doxorubicin into the as-prepared PBNC@m-SiO2@HA, the developed PBNC@m-SiO2@HA@DOX displayed excellent pH-responsive drug release characteristics. Upon irradiation with 808 nm (1.0 W cm-2) laser light, PBNC@m-SiO2@HA@DOX exhibited synergistic photodynamic and chemotherapeutic efficacy (∼78% in 20 minutes) for human colorectal carcinoma (HCT 116) cell line compared to solo photodynamic or chemotherapy. Herein, the chemo-photodynamic therapeutic process was found to follow the apoptotic pathway via ROS-mediated mitochondrion-dependent DNA damage with a very low cellular uptake of PBNC@m-SiO2@HA@DOX for the human embryonic kidney (HEK 293) cell line, illustrating its safety. Hence, it may be stated that the developed nanoplatform can be a potential theranostic agent for future applications. Most interestingly, we have noted variation in r 1 at each step of the functionalization along with size variation that has been the first time modelled on the basis of the Solomon-Bloembergen-Morgan theory considering changes in the defect crystal structure, correlation time, water diffusion rate, etc., due to varied interactions between PBNC and water molecules.

The Role of ECM Remodeling, EMT, and Adhesion Molecules in Cancerous Neural Invasion: Changing Perspectives.

Perineural invasion (PNI) refers to the cancerous invasion of nerves. It provides an alternative route for metastatic invasion and can exist independently in the absence of lymphatic or vascular invasion. It is a prominent characteristic of specific aggressive malignancies where it correlates with poor prognosis. The clinical significance of PNI is widely recognized despite a lack of understanding of the molecular mechanisms underlying its pathogenesis. The interaction between the nerve and the cancer cells is the most pivotal PNI step which is mediated by the activation or inhibition of multiple signaling pathways that include chemokines, interleukins, nerve growth factors, and matrix metalloproteinases, to name a few. The nerve-cancer cell interaction brings about specific changes in the perineural niche, which not only affects the regular nerve functions, but also enhances the migratory, invasive, and adherent properties of the tumor cells. This review aims to elucidate the vital role of adhesion molecules, extracellular matrix, and epithelial-mesenchymal proteins that promote PNI, which may serve as therapeutic targets in the future.

α-Actinin-4 drives invasiveness by regulating myosin IIB expression and myosin IIA localization.

The mechanisms by which the mechanoresponsive actin crosslinking protein α-actinin-4 (ACTN4) regulates cell motility and invasiveness remain incompletely understood. Here, we show that, in addition to regulating protrusion dynamics and focal adhesion formation, ACTN4 transcriptionally regulates expression of non-muscle myosin IIB (NMM IIB; heavy chain encoded by MYH10), which is essential for mediating nuclear translocation during 3D invasion. We further show that an indirect association between ACTN4 and NMM IIA (heavy chain encoded by MYH9) mediated by a functional F-actin cytoskeleton is essential for retention of NMM IIA at the cell periphery and modulation of focal adhesion dynamics. A protrusion-dependent model of confined migration recapitulating experimental observations predicts a dependence of protrusion forces on the degree of confinement and on the ratio of nucleus to matrix stiffness. Together, our results suggest that ACTN4 is a master regulator of cancer invasion that regulates invasiveness by controlling NMM IIB expression and NMM IIA localization. This article has an associated First Person interview with the first author of the paper.

Breast Cancer-Derived Microparticles Reduce Cancer Cell Adhesion, an Effect Augmented by Chemotherapy.

Tumor cell heterogeneity is primarily dictated by mutational changes, sometimes leading to clones that undergo a metastatic switch. However, little is known about tumor heterogeneity following chemotherapy perturbation. Here we studied the possible involvement of tumor-derived extracellular vesicles, often referred to as tumor-derived microparticles (TMPs), as mediators of the metastatic switch in the tumor microenvironment by hindering cell adhesion properties. Specifically, we show that highly metastatic or chemotherapy-treated breast cancer cells shed an increased number of TMPs compared to their respective controls. We found that these TMPs substantially reduce cell adhesion and disrupt actin filament structure, therefore increasing their biomechanical force pace, further implicating tumor cell dissemination as part of the metastatic cascade. Our results demonstrate that these pro-metastatic effects are mediated in part by CD44 which is highly expressed in TMPs obtained from highly metastatic cells or cells exposed to chemotherapy when compared to cells with low metastatic potential. Consequently, when we inhibited CD44 expression on TMPs by a pharmacological or a genetic approach, increased tumor cell adhesion and re-organized actin filament structure were observed. We also demonstrated that breast cancer patients treated with paclitaxel chemotherapy exhibited increased CD44-expressing TMPs. Overall, our study provides further insights into the role of TMPs in promoting metastasis, an effect which is augmented when tumor cells are exposed to chemotherapy.

Nuclear plasticity increases susceptibility to damage during confined migration.

Large nuclear deformations during migration through confined spaces have been associated with nuclear membrane rupture and DNA damage. However, the stresses associated with nuclear damage remain unclear. Here, using a quasi-static plane strain finite element model, we map evolution of nuclear shape and stresses during confined migration of a cell through a deformable matrix. Plastic deformation of the nucleus observed for a cell with stiff nucleus transiting through a stiffer matrix lowered nuclear stresses, but also led to kinking of the nuclear membrane. In line with model predictions, transwell migration experiments with fibrosarcoma cells showed that while nuclear softening increased invasiveness, nuclear stiffening led to plastic deformation and higher levels of DNA damage. In addition to highlighting the advantage of nuclear softening during confined migration, our results suggest that plastic deformations of the nucleus during transit through stiff tissues may lead to bending-induced nuclear membrane disruption and subsequent DNA damage.

Contemporary Multidisciplinary Management of Sinonasal Mucosal Melanoma.

Sinonasal mucosal melanoma (SNMM) is a rare tumor, comprising less than 10% of sinonasal malignancies. SNMM most frequently occurs in the nasal cavity (70%) and maxillary sinus (14%), typically as black patches. Overall, SNMM harbors a very poor prognosis; 5-year survival is less than 30%. Nasal cavity tumors confer a better prognosis than sinus melanoma. The primary management for SNMM is surgery, when feasible, followed by adjuvant radiotherapy. Recent studies suggest that immunotherapy may confer survival benefit to patients with advanced disease. The multidisciplinary team approach has been shown to optimize treatment, reduce costs, and minimize adverse events, while maximizing the chances for cure.

Dopamine promotes cathepsin B-mediated amyloid precursor protein degradation by reactive oxygen species-sensitive mechanism in neuronal cell.

Recent literature suggested an important function of native amyloid precursor protein (APP) as amine oxidase implicating in protection of brain cells from catecholamine-induced toxicity. However, any role of catecholamines on regulation of native APP has not been explored. Here we report that dopamine (DA), one of the most prominent catecholamine neurotransmitters in brain, down-modulates native APP protein in several neuronal cell types. Using SH-SY5Y cells as model, we detected no alteration of transcript expression and unaffected translation suggested that DA might induce APP degradation. We actually found that DA treatment decreased the stability of APP. Lysosomal blockers inhibited DA-induced APP degradation, but specific proteasomal blocker failed to do so. We detected the role of cathepsin B in DA-induced APP degradation by using pharmacological inhibitor and specific siRNA. We also revealed that DA could increase cathepsin B expression at both transcript and protein levels. Using antioxidant N-acetyl cysteine, we detected increased level of reactive oxygen species generation that was found responsible for induced cathepsin B expression by DA and resultant APP degradation. Our study reveals the existence of reciprocal regulation of a catecholamine and an amine oxidase implicating in brain catecholamine homeostasis.

Remarkable difference in Al3+ and Zn2+ sensing properties of quinoline based isomers.

Two positional isomers, 4-methyl-2-((quinolin-6-ylimino)methyl)phenol (6-QMP) and 4-methyl-2-((quinolin-2-ylimino)methyl)phenol (2-QMP), have been synthesized to compare their fluorescence sensing properties. 6-QMP and 2-QMP have been synthesized by Schiff-base condensation between 2-hydroxy-5-methylbenzaldehyde and the respective amine (6-aminoquinoline for 6-QMP and 2-aminoquinoline for 2-QMP) under mild conditions. These compounds have been characterized by standard methods. 6-QMP and 2-QMP have been found to be dual fluorescence chemosensors for Al3+ and Zn2+ ions but the increment of fluorescence intensity varies. 6-QMP can detect Al3+ (emission at 543 nm) and Zn2+ (emission at 525 nm) by the enhancement of emission intensity by 97 and 79 fold, respectively, with the same excitation wavelength at 415 nm. However, 2-QMP shows two different excitation and emission wavelengths for the detection of Al3+ (emission at 376 nm; λex = 330 nm) and Zn2+ (emission at 550 nm; λex = 435 nm). The increase in emission intensity is low (4.5 fold for Al3+ and 35 fold for Zn2+) compared to that with 6-QMP. The enhancement of intensity may be explained by the PET mechanism. Both the probes form a 1 : 1 complex with both the metal ions as indicated by the elemental and different spectral analysis. 6-QMP shows better sensitivity towards both the metal ions than 2-QMP. Both the probes are able to detect Al3+ and Zn2+ ions by producing distinct color changes that can be observed by the naked eye. Some theoretical calculations have been performed to investigate spectral transitions of the probes along with their aluminum and zinc compounds. These compounds have been used for living cell imaging studies. A comparison with the recently published studies has been made.

Functional characterization of two myo-inositol-1-phosphate synthase (MIPS) gene promoters from the halophytic wild rice (Porteresia coarctata).

MAIN CONCLUSION: The promoter deletion mutants from second isoform of INO1 (gene-encoding MIPS) from Porteresia coarctata of 932 bp (pPcINO1.2.932) and 793 bp (pPcINO1.2.793) prove to be very efficient as salt/drought stress-inducible promoters, while pPcINO1.2.932 is found to be responsive to cold stress as well. The promoters of the two identified myo-inositol-1-phosphate synthase (INO1) isoforms from salt-tolerant wild rice, Porteresia coarctata (PcINO1.1 and PcINO1.2) have been compared bioinformatically with their counterparts present in the salt-sensitive rice, Oryza sativa. PcINO1.2 promoter was found to be enriched with many abiotic stress-responsive elements, like abscisic acid-responsive elements, MYC-responsive elements, MYB-binding sites, low-temperature stress-responsive elements, and heat-shock elements similar to the ones found in the conserved motifs of the promoters of salt/drought stress-inducible INO1 promoters across Kingdom Planta. To have detailed analysis on the arrangement of cis-acting regulatory elements present in PcINO1 promoters, 5' deletion mutational studies were performed in dicot model plants. Both transient as well as stable transformation methods were used to check the influence of PcINO1 promoter deletion mutants under salt and physiologically drought conditions using ß-glucuronidase as the reporter gene. The deletion mutant from the promoter of PcINO1.2 of length 932 bp (pPcINO1.2.932) was found to be significantly upregulated under drought stress and also in cold stress, while another deletion mutant, pPcINO1.2.793 (of 793 bp), was significantly upregulated under salt stress. P. coarctata being a halophytic species, the high inducibility of pPcINO1.2.932 upon exposure to low-temperature stress was an unexpected result.

An Endophytic Bacterial Consortium modulates multiple strategies to improve Arsenic Phytoremediation Efficacy in Solanum nigrum.

Endophytic microbes isolated from plants growing in contaminated habitats possess specialized properties that help their host detoxify the contaminant/s. The possibility of using microbe-assisted phytoremediation for the clean-up of Arsenic (As) contaminated soils of the Ganga-Brahmaputra delta of India, was explored using As-tolerant endophytic microbes from an As-tolerant plant Lantana camara collected from the contaminated site and an intermediate As-accumulator plant Solanum nigrum. Endophytes from L. camara established within S. nigrum as a surrogate host. The microbes most effectively improved plant growth besides increasing bioaccumulation and root-to-shoot transport of As when applied as a consortium. Better phosphate nutrition, photosynthetic performance, and elevated glutathione levels were observed in consortium-treated plants particularly under As-stress. The consortium maintained heightened ROS levels in the plant without any deleterious effect and concomitantly boosted distinct antioxidant defense mechanisms in the shoot and root of As-treated plants. Increased consortium-mediated As(V) to As(III) conversion appeared to be a crucial step in As-detoxification/translocation. Four aquaporins were differentially regulated by the endophytes and/or As. The most interesting finding was the strong upregulation of an MRP transporter in the root by the As + endophytes, which suggested a major alteration of As-detoxification/accumulation pattern upon endophyte treatment that improved As-phytoremediation.

Lignin-graft-Polyoxazoline Conjugated Triazole a Novel Anti-Infective Ointment to Control Persistent Inflammation.

Lignin, one of the most abundant renewable feedstock, is used to develop a biocompatible hydrogel as anti-infective ointment. A hydrophilic polyoxazoline chain is grafted through ring opening polymerization, possess homogeneous spherical nanoparticles of 10-15 nm. The copolymer was covalently modified with triazole moiety to fortify the antimicrobial and antibiofilm activities. The hydrogel was capable of down regulating the expression level of IL-1ß in LPS induced macrophage cells, and to cause significant reduction of iNOS production. It supported cellular anti-inflammatory activity which was confirmed with luciferase assay, western blot, and NF-κB analysis. This novel lignin-based hydrogel tested in-vivo has shown the abilities to prevent infection of burn wound, aid healing, and an anti-inflammatory dressing material. The hydrogel reported here provides a new material platform to introduce a cost-effective and efficient ointment option after undertaking further work to look at its use in the area of clinical practice.

Different dehydrins perform separate functions in Physcomitrella patens.

MAIN CONCLUSION: Dehydrins, PpDHNA and PpDHNB from Physcomitrella patens provide drought and cold tolerance while PpDHNC shows antimicrobial property suggesting different dehydrins perform separate functions in P. patens. The moss Physcomitrella patens can withstand extremes of environmental condition including abiotic stress such as dehydration, salinity, low temperature and biotic stress such as pathogen attack. Osmotic stress is inflicted under both cold and drought stress conditions where dehydrins have been found to play a significant protective role. In this study, a comparative analysis was drawn for the three dehydrins PpDHNA, PpDHNB and PpDHNC from P. patens. Our data shows that PpDHNA and PpDHNB play a major role in cellular protection during osmotic stress. PpDHNB showed several fold upregulation of the gene when P. patens was subjected to cold and osmotic stress in combination. PpDHNA and PpDHNB provide protection to enzyme lactate dehydrogenase under osmotic as well as freezing conditions. PpDHNC possesses antibacterial activity and thus may have a role in biotic stress response. Overexpression of PpDHNA, PpDHNB and PpDHNC in transgenic tobacco showed a better performance for PpDHNB with respect to cold and osmotic stress. These results suggest that specific dehydrins contribute to tolerance of mosses under different stress conditions.

Quantum dot as probe for disease diagnosis and monitoring.

Semiconductor quantum dots (QD) possess unique optical and electric properties like size-tunable light emission, narrow emission range, high brightness and photostability. Recent research advances have minimized the toxicity of QDs and they are successfully used in in vitro and in vivo imaging. Encapsulation of QDs into polymeric nanoparticles and linking them with targeting ligands enabled the detection of tumors and cancer cells in vivo. QD-antibody conjugates were successfully used in monitoring and diagnosis of HIV and myocardial infarction. Application of near infrared (NIR) QDs was found to minimize the absorption and scattering of light by native tissues thus rendering them suitable in deep tissue analysis. Aggregation and endosomal sequestration of QDs pose major challenges for the effective delivery of QDs to the cell cytosol. Toxicity minimization and effective delivery strategies may further increase their suitability for utilization in disease diagnosis. New synthesis of QDs may provide new types of bioconjugates of QDs to biomolecules, which leads to a variety of applications to many challenged research areas. QDs with narrow emission wavelength ranges are very suitable for monitoring multiple cellular targets simultaneously, and still remain the best known probes for imaging as an alternative to traditional fluorophores in disease diagnosis.

Cadmium-induced oxidative stress tolerance in cadmium resistant Aspergillus foetidus: its possible role in cadmium bioremediation.

Toxic effects of cadmium (Cd) were examined on a cadmium-resistant strain of Aspergillus foetidus isolated from wastewater. The Cd removal potential was analyzed. The results indicated that the strain could tolerate up to 25 mM and 63 mM Cd in liquid and solid Czapek-Dox media, respectively. It efficiently removed Cd from liquid growth media and industrial wastewater by mycelial biosorption. The strain produced oxalic acid for the purpose of Cd bioleaching as confirmed by the presence of cadmium oxalate crystals on the mycelial surface. Intracellular proline contents and the antioxidative enzyme activities increased up to a certain level to detoxify the overproduced free radicals. These data indicate that the strain has inherent mechanisms to grow in Cd contaminated environment, tolerate high Cd doses and high Cd uptake potential which are pre-requisite for acting as a suitable candidate for Cd bioremediation.

Primary biliary cirrhosis presenting with gastritis, hyperlipidemia and marked weight loss.

We report an unusual presentation of primary biliary cirrhosis. We present the case of a 31-year-old Indian woman who presented to the hospital with non specific complaints of gastritis, reduced appetite and marked weight loss and no complaints of pruritus. Serum liver enzymes were elevated. Cytoplasmic pattern of antinuclear antibodies was found on immunofluorescence microscopy accompanied by positive anti smooth muscle antibody. Endoscopy revealed esophageal varices. Following a liver biopsy, the diagnosis of primary biliary cirrhosis was made. It is important to consider the diagnosis of hepatic cirrhosis when patient presents with gastritis, reduced appetite and marked weight loss in both the presence and absence of ascites.

Purification and characterization of a thiol amylase over produced by a non-cereal non-leguminous plant, Tinospora cordifolia.

A 43kDa α-amylase was purified from Tinospora cordifolia by glycogen precipitation, ammonium sulfate precipitation, gel filtration chromatography, and HPGPLC. The enzyme was optimally active in pH 6.0 at 60°C and had specific activity of 546.2U/mg of protein. Activity was stable in the pH range of 4-7 and at temperatures up to 60°C. PCMB, iodoacetic acid, iodoacetamide, DTNB, and heavy metal ions Hg(2+)>Ag(+)>Cd(2+) inhibited enzyme activity while Ca(2+) improved both activity and thermostability. The enzyme was a thiol amylase (3 SH group/mole) and DTNB inhibition of activity was released by cysteine. N-terminal sequence of the enzyme had poor similarity (12-24%) with those of plant and microbial amylases. The enzyme was equally active on soluble starch and amylopectin and released maltose as the major end product.