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The present study aims to document the contamination levels and ecological risks of heavy metals in the sediments of Kavaratti lagoon, India. A total of 15 sediment samples were collected for the analysis of Al, Pb, Cd, Cu, Cr, Mn, Ni and Zn. The decreasing trend of heavy metals was observed in the lagoon sediment as Pb > Zn > Al > Mn > Ni > Cr > Cd > Cu. The Geo-accumulation index (Igeo) results indicate that Cu, Cr, Mn, Ni and Zn were uncontaminated, while Cd was strong to extremely contaminated and Al and Pb were moderately contaminated. The enrichment factors (EF) of Cd and Pb range from moderate to extremely high (EF > 1) indicating that they have anthropogenic origin on Kavaratti Island. The Contamination factor (Cf) indicated that Cd, Pb and Al belong to a high risk of contamination (Cf > 6). The pollution load index (PLI) value near one suggested that a moderate level of pollution occurs in the study area. The modified degree of contamination (mCd) shows that Al, Cd and Pb have an ultra- higher degree of contamination (mCd ≤ 32). The potential ecological risk (RI) index confirmed that Pb and Cd have considerable to the serious thread of ecological risk (RI > 600). Additionally, multivariate statistical analysis and pollution indexes showed that the Kavaratti lagoon is moderate to considerably polluted by heavy metals. Diesel-based power generation, activities related to shipping, untreated sewage, fishing and tourism activities are the main anthropogenic sources of heavy metal pollution on Kavaratti Island., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The present study aims to investigate the contamination of heavy metals in the sediments of a tropical ecosystem, India, and to evaluate the factors responsible for the dominance of specific macrobenthic communities, particularly in estuarine sediments. For the analysis of Cu, Cr, Ni, Zn, Pb and Cd in sediments, acid digestion and subsequent quantification by microwave plasma atomic emission spectroscopy was performed, whereas for Hg determination, cold vapour atomic absorption spectrophotometry was used. The general trend of the heavy metal concentration was observed as Cr > Cu > Zn > Ni > Pb > Cd > Hg, regardless of any seasonal alteration. The estuarine region was considerably contaminated by Cu and Cr (C.F. > 2) irrespective of any seasonal difference, and by Cd in 2017 non-monsoon (CF > 3). Heavy metal contamination was most pronounced during the monsoon (2018). Estuarine and marine zone together considered as deteriorated zone especially during monsoon seasons (PLI > 1, 2018 monsoon) while riverine zone remained poorly contaminated (PLI < 1). Clay Loam/Clay/Heavy Clay textures preferred polychaetes and bivalves in the estuarine and marine zone as compared to other macrobenthic communities (OMC). Among the hydrochemical parameters, total dissolved solids in general and euryhaline and slightly alkaline pH preferred domination of bivalves followed by polychaetes in non-monsoon seasons. The trace metal contamination in estuarine sediments increases the concern of bioaccumulation tendency of dominant bivalves of the estuarine and coastal sediments., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Parenteral nutrition (PN) is a therapy that delivers essential nutrients intravenously to patients who are unable to meet their nutrition requirements via standard enteral feeding. This methodology is often referred to as PN when accompanied by minimal or no enteral nutrition (EN). Although PN is lifesaving, significant complications can arise, such as intestinal failure-associated liver disease and gut-mucosal atrophy. The exact mechanism of injury remains ill defined. This review was designed to explore the available literature related to the drivers of injury mechanisms. The Farnesoid X receptor and fibroblast growth factor 19 signaling pathway seems to play an important role in gut-systemic signaling, and its alteration during PN provides insights into mechanistic links. Central line infections also play a key role in mediating PN-associated injury. Although lipid reduction strategies, as well as the use of multicomponent lipid emulsions and vitamin E, have shown promise, the cornerstone of preventing injury is the early establishment of EN., (© 2022 American Society for Parenteral and Enteral Nutrition.)

SARS-CoV2 is a member of human coronaviruses and is the causative agent of the present pandemic COVID-19 virus. In order to control COVID-19, studies on viral structure and mechanism of infectivity and pathogenicity are sorely needed. The spike (S) protein is comprised of S1 & S2 subunits. These spike protein subunits enable viral attachment by binding to the host cell via ACE-2 (angiotensin converting enzyme-2) receptor, thus facilitating the infection. During viral entry, one of the key steps is the cleavage of the S1-S2 spike protein subunits via surface TMPRSS2 (transmembrane protease serine 2) and results in viral infection. Hence, the S-protein is critical for the viral attachment and penetration into the host. The rapid advancement of our knowledge on the structural and functional aspects of the spike protein could lead to development of numerous candidate vaccines against SARS-CoV2. Here the authors discuss about the structure of spike protein and explore its related functions. Our aim is to provide a better understanding that may aid in fighting against CoVID-19 and its treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Introduction: Many of the assessment tools used to study depression amongst older people in low- and middle- income countries (LMICs) are adaptations of instruments developed in other cultural settings. There is a need to validate those instruments in LMICs., Methods: 721 men and women aged 55-80 years from the Mysore Birth Records Cohort underwent standardised assessments for sociodemographic characteristics, cardiometabolic risk factors, cognitive function and mental health. Sensitivity, specificity and level of agreement of EURO-D diagnosis of depression with diagnosis of depression derived by the Geriatric Mental State (GMS) examination were calculated. To validate the EURO-D score against GMS depressive episode, we used maximum Youden's index as the criterion for each cut-off point. Concurrent validity was assessed by measuring correlations with the WHO Disability Assessment Schedule (WHO DAS II)., Results: Of the 721 (408 men and 313 women) who participated in this study, 138 (54 men and 84 women) were diagnosed with depression. Women had higher depression scores on the EURO-D scale and disability on the WHO DAS II scale. A maximum Youden's Index of 0.60 was observed at a EURO-D cut-off of 6, which corresponded to 95% sensitivity, 64% specificity, kappa value of 0.6 and area under the curve (AUC) of 80%. There was significant and positive correlation between EURO-D and WHO DAS II scores., Limitations: Future independent validation studies in other settings are required., Discussion: This study supports the use of the EURO-D scale for diagnosing depression amongst older adults in South India., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Begomoviruses are a major class of Geminiviruses that affects most dicotyledonous plants and causes heavy economic losses to farmers. Early detection of begomovirus is essential to control the spread of the disease and prevent loss. Many available detection methods like ELISA, immunosorbent electron microscopy, PCR or qPCR require expertise in handling sophisticated instruments, complex data interpretation and costlier chemicals, enzymes or antibodies. Hence there is a need for a simpler detection method, here we report the development of a visual detection method based on functionalized gold nanoparticles (AuNP assay). The assay was able to detect up to 500 ag/µl of begomoviral DNA (pTZCCPp3, a clone carrying partial coat protein gene) suspended in MilliQ water. Screening of chilli plants for begomoviral infection by PCR (Deng primers) and AuNP assay showed that AuNP assay (77.7%) was better than PCR (49.4%). The AuNP assay with clccpi1 probe was able to detect begomoviral infection in chilli, tomato, common bean, green gram and black gram plants which proved the utility and versatility of the AuNP assay. The specificity of the assay was demonstrated by testing with total DNA from different plants that are not affected by begomoviruses., (© 2021. The Author(s).)

Study Design: Randomized control trial., Objective: The purpose of the study is to evaluate the safety and efficacy of tranexamic acid in reducing blood loss when administered through various routes in instrumented spine surgeries., Methods: A total of 104 patients undergoing instrumented spine surgery were randomly assigned to 4 groups (n = 26 in each group). Groups included (1) ivTXA-intravenous administration of tranexamic acid (TXA) 1 hour prior to surgery, (2) loTXA-local infiltration of TXA bilaterally into the paraspinal musculature prior to incision, (3) tTXA-topical application of TXA just before wound closure, and (4) control group. Outcome measures included intraoperative blood loss, postoperative blood loss, need for blood transfusion, length of hospital stay, and hematological parameters., Results: All the 3 different modes of TXA administration were found to be effective in reducing blood loss in the treated groups compared with the control group. Intraoperative blood loss was significantly reduced in ivTXA (223.6 ± 40.1 mL, P < .0001) and loTXA (256.07 ± 119 mL, P = .0039) groups when compared with controls (344 ± 88.5 mL).The postoperative blood loss was least in tTXA followed by ivTXA, loTXA, and controls. There was 67% reduction in need for blood transfusion in tTXA group, 55.5% reduction in ivTXA group, and 33% reduction in loTXA group when compared with the control group., Conclusion: In instrumented spine surgery, ivTXA and loTXA were found to be equally effective in reducing the intraoperative blood loss. The tTXA has better postoperative blood conserving effects. This is the first study to detail about safety and efficacy on local infiltration of TXA in spine surgery, which is an effective and safe method for reducing intraoperative blood loss.

An acceptorless dehydrogenative strategy for the synthesis of polyfluoroalkylated bis-indoles is described by employing an earth-abundant nickel-based catalytic system under air. The notable feature of the present transformation is the use of bench stable and easily affordable polyfluorinated alcohols without any pre-functionalization for the introduction of precious polyfluoroalkyl groups. The developed straightforward protocol accomplished biologically relevant fluoroalkyl bis-indoles in a sustainable fashion. Extensive DFT study predicts the unique role of indole molecules which stabilizes the transition states during the dehydrogenation process of polyfluorinated alcohols, presumably through non-covalent π⋅⋅⋅π and H-bonding interactions., (© 2020 Wiley-VCH GmbH.)

Background and Aims: Associated with severe complications and morbidity, Diabetes Mellitus is a significant public health burden. The need for regular monitoring and adherence to treatment and lifestyle changes have a high impact on the quality of life of the patients. This study attempts to assess the effect of smartphone-based lifestyle modification intervention in the quality of life of patients with type 2 Diabetes through a randomized filed trial., Methods: A randomized field trial was performed among the patients attending the outpatient department of a tertiary care hospital in Mysuru city. A mobile application named DIAGURU, mainly focusing on the lifestyle modification and medication management was used for a period of 6 months from April 2019 to September 2019 by 150 patients in the intervention group while another 150 participants served as controls. The quality of life was assessed using the WHO QOL BREF questionnaire at the beginning of the study and after six months., Results: The change in the quality of life in a positive direction was significantly higher in the intervention group compared to the non-intervention group after six months. The differences in the change in scores of quality of life of participants recruited in intervention and non-intervention groups were statistically significant in all the four domains after the intervention with a p value < 0.001., Conclusion: The evidence generated in this study suggest that such technological approaches can be used as a public health measure to improve the quality of life of patients with type 2 Diabetes Mellitus., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Study Design: Prospective cohort study., Objective: To analyze the serum and drain concentrations of antibiotics administered by two different routes and compare the results., Summary of Background Data: Systemic antibiotics are expected to reach the surgical site and maintain adequate concentrations of the drug to prevent infection. However, it is unknown whether systemically administered antibiotics reach and maintain such adequate concentrations at the surgical wound or not., Methods: Forty patients undergoing elective spine surgery received intra-wound Vancomycin (1 GM) before the wound closure and single dose of intravenous Gentamycin (80MG) immediately after surgery. Blood and drain samples were collected postoperatively to estimate serum and drain concentrations of Gentamycin and Vancomycin. Drug Estimation Protocol: Drug concentrations were estimated by ADVIA Centaur CP immunoassay (direct chemiluminescence). Gentamycin and vancomycin in the test samples competes with their respective acridinium ester-labeled gentamicin and vancomycin derivatives for monoclonal mouse anti-gentamycin and anti-vancomycin antibodies which are covalently coupled to paramagnetic particles in the solid phase., Results: Gentamycin attained peak serum levels at 6 hours following administration with an average value of 9.90 ± 3.1 μg/mL which was decreased to 6.76 ± 2.6 μg/mL at 12 hours and steadily declining thereafter. Even though, the drug concentrations in the drain collection from the wound also attained peak levels at 6 hours, the drug concentrations were lower (3.75 ± 1.4 μg/mL) than that of serum concentrations and inadequately attained the recommended target peak of Gentamycin (4-12 μg/mL).Wound levels of local vancomycin were significantly higher at 6 hours (413.4 ± 217.3 μg/mL) and well maintained even at 72 hours. Serum vancomycin levels were observed to be highest at 6 hours in negligible concentrations of 6.06 ± 2.2 μg/mL., Conclusion: After prophylactic systemic administration of the antibiotics, the antibiotic drug concentrations in the wound are much lower than the serum concentrations at any given time. After local intra-wound application of antibiotics, the drug concentrations in the wound are well maintained even after 72 hours., Level of Evidence: 3.

Several reports of augmented hyperpolarisation-activated cyclic nucleotide-gated (HCN) currents in seizures have suggested a pro-convulsive identity for HCN channels. The mutations identified in one or more of the four HCN channel subunits are found to be contributing to different epileptic phenotypes. S126L, S632W, V246M and E515K are four different mutations affecting the HCN2 subunit and have been reported in febrile seizures and partial/generalised idiopathic epilepsies. From the visible outcomes in subjects with these mutations, it is evident that they must play important roles in altering dendritic excitability. Through this simulation study using NEURON, we created a three-compartmental, hippocampal CA1 pyramidal neuron synapse model expressing seven different ion channels (fast sodium (NaF), T-type calcium (CaT), R-type calcium (CaR), delayed rectifier potassium (KDR), A-type potassium (KA), small conductance potassium (SK), and HCN channels) and two glutamate receptors (AMPAR and NMDAR). We modelled an HCN2 channel and incorporated changes in it to obtain mutation kinetics. Their effects on excitability were studied by observing resting membrane potentials, input resistances and plasticity profiles for measuring the sliding modification threshold (SMT) of Bienenstock-Cooper-Munro (BCM) theory. Virtual knockouts of ion channels other than HCN were also performed to assess their role in altering excitability when they act alongside HCN2 mutations. Our results show that HCN2 mutations can potentially be a primary causative factor for excessive action potential firing through their effect on resting membrane potentials and input resistance., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

Study Design: Observational study., Purpose: The purpose of this study is to analyze the surgeon's neck postures while performing lumbar spinal surgeries., Overview of Literature: Lumbar spinal surgeries are on rising trend, and with increase in number of procedures, the average time spent by a spine surgeon performing surgical procedures is also increasing. The effect of operating posture on the surgeon's neck is largely unknown. From the studies conducted on usage of smartphones, abnormal neck postures, especially the forward head posture (FHP), were found to adversely affect the cervical spine of individuals. The present study analyzes the neck position of spine surgeons during lumbar spine surgeries., Methodology: Sixty video recordings (25 open transforaminal lumbar interbody fusions [TLIFs] and 35 lumbar decompression [LD] procedures - 15 with headlight and 20 with operating microscope) of surgeries performed by three spine surgeons of different heights were analyzed. Running videos of the surgeries were recorded concentrating on the surgeons with reflective markers taped to their surface landmarks corresponding to C7 spinous process, tragus of the ear, and outer canthus of the eye. Video recordings were standardized by a fixed video recorder in the same operating theater. Snapshots from the video were obtained whenever the surgeon changes the position. Head flexion angle (HFA), neck flexion angle (NFA), and cervical angle (CA) were measured and analyzed., Results: During TLIF, HFA and NFA were significantly higher during the phases of decompression and fusion ( P < 0.05). The average CA of all surgeons was lower, thereby adversely affecting the cervical spine (20.15° ± 5.05°). During LD, CA showed significant difference between usage of microscope and headlight ( P < 0.001)., Conclusion: Surgeon's FHP is frequently caused by a compromise between the need to perform surgery with hands, without elevating the arms, and simultaneous control of gaze at surgical field. The usage of microscope was found to reduce the stress on neck while performing surgery., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Indian Journal of Orthopaedics.)

Therapeutic applications of arsenic trioxide (ATO) are limited due to their severe adverse effects. However, nanoparticles of ATO might possess inimitable biologic effects based on their structure and size which differ from their parent molecules. Based on this conception, AsNPs were synthesized from ATO and comparatively analysed for their interaction mechanism with DNA using spectroscopic & electrochemical techniques. Finally, anti-proliferative activity was assessed against different breast cancer cells (MDA-MB-231 & MCF-7) and normal non-cancerous cells (HEK-293). The DNA interaction study revealed that AsNPs and ATO exhibit binding constant values in the order of 10 6 which indicates strong binding interaction. Binding of AsNPs did not disturb the structural integrity of DNA, on the other hand an opposing effect was observed with ATO through biophysical techniques. Further, in vitro study, confirms cytotoxicity of ATO and AsNPs against different cells, however at particular concentration ATO exhibits more cytotoxicity than that of AsNPs. Furthermore, cytotoxicity was confirmed through acridine orange and comet assay. In conclusion, AsNPs are safer than ATO with comparable efficacy and might be a suitable candidate for the development of novel therapeutic agent against breast cancer and other solid tumours., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Copper-catalysed N-arylation of fused triazoles using diaryliodonium salts as an aryl source is described. This scalable protocol displayed good compatibility towards diverse sensitive functional groups like ester, alkyl and nitro groups and halogens (F, Cl, Br). The synthetic usefulness of the prepared triazolium salts was proved by preparing α-hydroxyketone through benzoin condensation. Photophysical studies of these compounds showed promising Stokes-shifted fluorescence emission in aqueous medium, so this molecular framework could be a proficient probe for biological applications.

A simple and rapid microwave-assisted synthesis of heteroaromatic appended porphyrins using the Pd/Cu-catalyzed C-C coupling of meso-bromoporphyrins with various five- and six-membered heteroaromatic azoles has been successfully developed. The prepared heteroaromatic porphyrins 7a-lNi were found to exhibit slightly red-shifted (∼5-10 nm) Soret and Q bands. The developed reaction conditions are useful for the preparation of diversely substituted heteroaromatic porphyrins (A 3 B- and A 2 B 2 -types).

A novel series of ketohydrazide-hydrazones as analogues of naturally occurring coscinamides has been synthesized and evaluated for their anticancer activity against five cancer cell lines. Of the twenty-synthesized ketohydrazide-hydrazones, compounds, 21c, 21f, 21g, 21k and 21o showed cytotoxic effects (less than 50% cell survival) against multiple cancer cell lines when tested at a final concentration of 10 μM. IC 50 of three compounds 21f, 21k and 21o was determined to be less than 5 μM for all tested cancer cell lines. Compound 21k exhibited significant anticancer activity against MCF-7, MDA-MB-231, HCT-116 and JURKAT cancer cell lines with IC 50 values of 0.8 μM, 0.50 μM, 0.15 μM, and 0.22 μM, respectively. Also, 21k was found to be more selectively cytotoxic against tumor cells when compared to normal cells. Preliminary mechanism of action studies indicated that the most active compound 21k induced caspase-dependent apoptosis in cells. 21k arrests cell cycle in G2/M phase by inhibiting of tubulin polymerization (IC 50  = 0.6 μM)., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Banana bunchy top virus (BBTV) affects all varieties of banana plants and causes heavy economic loss in most of the banana cultivating areas. The BBTV genome comprises of six DNA components; in this study, we have cloned the six BBTV-DNA components from one of the BBTV-infected plants (Tri-8) and were submitted to GenBank. Analysis of the BBTV DNA-R component showed that it belonged to south Pacific group. Resistance against BBTV has not been observed so far in banana plants and removal and killing of the infected plants has been routinely practiced. Hence, early detection of BBTV infection would be desirable and various detection methods routinely employed include enzyme linked immunosorbent assay (antigen-antibody based) and molecular-based methods such as polymerase chain reaction (PCR), qPCR, or LAMP PCR. Most of these methods require enzymes or antibodies for detection and hence are expensive. Here, we report a visual detection method (AuNP probe assay) using gold nanoparticles (AuNPs) functionalized with an ssDNA-thiolated probe (CR1). This method is based on the hybridization of the functionalized AuNPs with the target DNA (BBTV). In the AuNP probe assay, the functionalized AuNPs retains red colour when BBTV DNA is present, and in the absence of BBTV DNA, the colour of the functionalized AuNPs changes to purple when salt is added. The AuNP probe assay was compared with PCR for the detection of banana plants and it was found that AuNP probe assay was better than PCR in detecting BBTV infection (86.5% for AuNP probe assay and 65% for PCR). The AuNP probe assay was found to be highly specific to BBTV and was found to detect up to 1 pg/μl of the plasmid (pTZBBTri 4, BBTV DNA) mixed with healthy banana DNA.

Regioselective construction of crucial C-N and C-O bonds leading to N-arylquinolones and aryloxyquinolines has been accomplished by employing easily accessible diaryliodonium salts and quinolones in water under metal- and ligand-free conditions. This operationally simple strategy is significant due to mild reaction conditions, high product yields, recyclability of released iodoarenes and scalability to the gram level. The practical utility of the developed protocol was proved by the arylation of medicinally important heterocycles like acridin-9(10H)-one, 3-methylquinoxalin-2(1H)-one and 1H-benzo[d]imidazol-2(3H)-one.

Easily accessible heteroaromatic carboxylic acids and diaryliodonium salts were successfully employed to construct valuable 2-arylindoles and heteroaryl carboxylates in a regioselective fashion. C2-arylated indoles were produced using a Pd-catalyzed decarboxylative strategy in water without any base, oxidant, or ligand. Heteroaryl carboxylates were prepared under metal and base-free conditions. This protocol was successfully utilized to synthesize Paullone, a cyclin-dependent kinase (CDK) inhibitor., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Transplantation of hematopoietic stem and progenitor cells (HSCs) i.e., self-renewing cells that retain multipotentiality, is now a widely performed therapy for many hematopoietic diseases. However, these cells are present in low number and are subject to replicative senescence after extraction; thus, the acquisition of sufficient numbers of cells for transplantation requires donors able to provide repetitive blood samples and/or methods of expanding cell numbers without disturbing cell multipotentiality. Previous studies have shown that HSCs maintain their multipotentiality and self-renewal activity if TCF3 transcription function is blocked under B cell differentiating conditions. Taking advantage of this finding to devise a new approach to HSC expansion in vitro, we constructed an episomal expression vector that specifically targets and transiently represses the TCF3 gene. This consisted of a vector encoding a transcription activator-like effector (TALE) fused to a Krüppel-associated box (KRAB) repressor. We showed that this TALE-KRAB vector repressed expression of an exogenous reporter gene in HEK293 and COS-7 cell lines and, more importantly, efficiently repressed endogenous TCF3 in a human B lymphoma cell line. These findings suggest that this vector can be used to maintain multipotentiality in HSC being subjected to a long-term expansion regimen prior to transplantation.

Background: The primary aim of this study was to compare the incidence of accidental arterial puncture during right internal jugular vein (RIJV) cannulation with and without ultrasound guidance (USG). The secondary end points were to assess if USG improves the chances of successful first pass cannulation and if BMI has an impact on incidence of arterial puncture and the number of attempts that are to be made for successful cannulation., Settings and Design: Prospective observational study performed at a single tertiary cardiac care center., Material and Methods: 255 consecutive adult and pediatric cardiac surgical patients were included. In Group I (n = 124) USG was used for the right internal jugular vein cannulation and in Group II (n = 81) it was not used. There were 135 adult patients and 70 pediatric patients., Statistical Analysis: Demographic and categorical data were analyzed using Student 't' test and chi- square test was used for qualitative variables., Results: The overall incidence of accidental arterial puncture in the entire study population was significantly higher when ultrasound guidance was not used (P< 0.001). In subgroup analysis, incidence of arterial puncture was significant in both adult (P = 0.03) and pediatric patients (P< 0.001) without USG. First attempt cannulation was more often possible in pediatric patients under USG (P = 0.03). In adult patients USG did not improve first attempt cannulation except in underweight patients., Conclusions: USG helped in the avoidance of inadvertent arterial puncture during RIJV cannulation and simultaneously improved the chances of first attempt cannulation in pediatric and in underweight adult cardiac surgical patients.

A series of bis(indolyl)glyoxylamides 10a-n has been designed and synthesized. In situ generated indole-3-glyoxalylchloride from the reaction of readily available indole 9 with oxalyl chloride was treated with tryptamine to produce bis(indolyl)glyoxylamides 10a-n in 82-93% yields. All the synthesized bis(indolyl)glyoxylamides were well characterized and tested for their antibacterial activity against Gram-positive and Gram-negative bacterial strains. Compounds 10d, 10g and 10i were found to display potent antibacterial activity against Gram-negative strain. Further, the cytotoxicity of bis(indolyl)glyoxylamides 10a-n were evaluated against a panel of human cancer cell lines. Of the screened analogues, compound 10f (IC50=22.34μM; HeLa, 24.05μM; PC-3, 21.13μM; MDA-MB-231 and 29.94μM; BxPC-3) was identified as the most potent analogue of the series. Exposure of PC-3 cells to either 10a or 10f resulted in increased levels of cleaved PARP1, indicating that bis(indolyl)glyoxylamides induce apoptosis in PC-3 cells. Most importantly, compounds 10d, 10g and 10i were completely ineffective in mammalian cells, suggesting that they target bacterial-specific targets and thus will not display any toxicity in host cells., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Mercury is a toxic heavy metal and occurs in organic and inorganic forms. Inorganic mercury includes elemental mercury and mercury salts. Mercury salts are usually white powder or crystals, and widely used in indigenous medicines and folk remedies in Asia. Inorganic mercury poisoning causes acute kidney injury (AKI) and gastrointestinal manifestations and can be life-threatening. We describe a case with unknown substance poisoning who developed AKI and disseminated intravascular coagulation (DIC). Renal biopsy showed acute tubular necrosis. Later, the consumed substance was proven to be mercuric chloride. His renal failure improved over time, and his creatinine normalized after 2 months.

We report a 40-year-old male who self-administered sildenafil for 10 years, in progressively increasing doses from 100 mg per occasion in the 1(st) year to 1300 mg per occasion in the 9(th)-10(th) years of (ab)use. The frequency of abuse was 2-3/week. The only adverse effect of concern that was reported was transient (up to about 12 h), self-limited blurring of vision in the last 2 years, especially in the last 2 months at the highest dose. The patient was otherwise normal. This report is unique because it describes what may be the highest dose of sildenafil reported in literature, abused across a protracted period of time. We discuss issues related to dose and safety of and tolerance to the drug.

Purpose: The aim of the study was to evaluate salivary flow rate, pH, buffering capacity, calcium, total protein content and total antioxidant capacity in relation to dental caries, age and gender., Materials and Methods: The study population consisted of 120 healthy children aged 7-15 years that was further divided into two groups: 7-10 years and 11-15 years. In this 60 children with DMFS/dfs = 0 and 60 children with DMFS/dfs ≥5 were included. The subjects were divided into two groups; Group A: Children with DMFS/dfs = 0 (caries-free) Group B: Children with DMFS/dfs ≥5 (caries active). Unstimulated saliva samples were collected from all groups. Flow rates were determined, and samples analyzed for pH, buffer capacity, calcium, total protein and total antioxidant status. Salivary antioxidant activity is measured with spectrophotometer by an adaptation of 2,2'-azino-di-(3-ethylbenzthiazoline-6-sulphonate) assays., Results: The mean difference of the two groups; caries-free and caries active were proved to be statistically significant (P < 0.05) for salivary calcium, total protein and total antioxidant level for both the sexes in the age group 7-10 years and for the age 11-15 years the mean difference of the two groups were proved to be statistically significant (P < 0.05) for salivary calcium level for both the sexes. Salivary total protein and total antioxidant level were proved to be statistically significant for male children only., Conclusions: In general, total protein and total antioxidants in saliva were increased with caries activity. Calcium content of saliva was found to be more in caries-free group and increased with age.

Background: Chronic obstructive pulmonary disease (COPD) is a common disease causing significant socioeconomic burden. COPD patients, commonly smokers develop resistance to inhaled steroids attributed to deficiency of histone deacetylase 2 (HDAC2). The study of relationship between systemic inflammation and functional performance demonstrated that increased CRP level is inversely related to six minute walk distance (SMWD) and Forced Expired Volume in one second (FEV1). Theophylline restores HDAC2 activity thereby unlocking steroid resistance and potentiating inhaled corticosteroids (ICS) action culminating in reduced airway inflammation and mortality., Aim: To study the effects of addition of Theophylline to the combination of Formoterol plus Budesonide on various objective and subjective parameters in moderate to severe COPD patients and to assess the safety profile of the combination. Setting and Study design: A single blinded, prospective, randomized, placebo controlled study at a tertiary care hospital in Jaipur, India., Materials and Methods: Fifty eight patients diagnosed with moderate to severe COPD were randomized into two groups. Group A patients received Formoterol 24μg plus budesonide 800μg daily in divided doses along with Theophylline while group B patients received Formoterol 24μg plus budesonide 800μg daily in divided doses along with placebo tablets. Both groups were followed up on 15th, 30th &60th day. During every visit all patients were assessed subjectively (symptom scoring) and objectively (spirometry, CRP, SMWT) and adverse effects if any were recorded. The obtained data subject to statistical analysis using"Graph pad Instat3" software., Results: Statistically significant improvement with a decline in total symptom score (p < 0.0001) was found with respect to "Night symptoms"&"SOB on rising" in group A. Theophylline group showed significant improvement in SMWD and FEV1.Mean fall in CRP was greater in Group A (not statistically significant). No side effects requiring withdrawal of drug were noted with Theophylline., Conclusion: Addition of Theophylline to Formoterol plus Budesonide reduces dyspnea, improves exercise performance and pulmonary functions in moderate to severe COPD. Further studies are required to explore if reduced dosage would have equal efficacy with better safety and tolerability profile.

Purpose: To evaluate the diagnostic performances of risk of malignancy index (RMI), CA-125 and ultrasound score in differentiating between benign and borderline or malignant ovarian tumors and find the best diagnostic test for referral of suspected malignant ovarian cases to gynaecologic oncologists., Materials and Methods: This prospective study covered 467 women with pelvic tumors scheduled for surgery at our hospital between July 2011 and July 2013. The RMI was obtained from ultrasound score, CA125 and menopausal status. The diagnostic values of each parameter and the RMI were determined and compared using Statistical Packages for Social Sciences Version 14.0.1., Results: In our study, 61% of ovarian tumors were malignant in the post-menopausal age group. RMI with a cut-off 150 had sensitivity of 84% and specificity of 97% in detecting ovarian cancer. CA-125>30 had a sensitivity of 84% and a specificity of 83%. An ultrasound score more than 2 had a sensitivity of 96% and specificity of 81%. RMI had the least false malignant cases thus avoiding unnecessary laparotomies. Ultrasound when used individually had the best sensitivity but poor specificity., Conclusions: Our study has demonstrated the RMI to be an easy, simple and applicable method in the primary evaluation of patients with pelvic masses. It can be used to refer suspected malignant patients to be operated by a gynaecologic oncologist. Other models of preoperative evaluation should be developed to improve the detection of early stage invasive, borderline and non-epithelial ovarian cancers.

Neurofibromin (NF1) is encoded by the NF1 tumour suppressor gene. Mutations result in a disorder known as Neurofibromatosis Type 1 (NF-1), and patients are often diagnosed due to the presence of unusual pigmentary patterns that include Café au lait macules (CALMs). Little is known about how loss of NF1 results in pigmentary defects in melanocytes. We sought to identify novel NF1 interacting proteins and elucidate the molecular mechanisms underlying the pigmentary defects. The cytoplasmic Dynein Heavy Chain 1 (DHC) was found to interact with NF1 along microtubules in vesicular structures identified to be melanosomes. Our studies suggest that NF1 is involved in melanosomal localization, and that disruptions in NF1-DHC interactions may contribute to the abnormal pigmentary features commonly associated with this debilitating syndrome., (Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Purpose: The aim of this study is to report the short-term efficacy of aflibercept in the treatment of neovascular age-related macular degeneration (AMD) with associated retinal pigment epithelial detachment (PED) which is refractory or develops tachyphylaxis to bevacizumab and ranibizumab., Methods: The method comprised a retrospective review of the medical records of patients with neovascular AMD and associated PEDs recently treated with aflibercept and previously treated with bevacizumab and ranibizumab., Results: Three eyes of three female patients of ages 49, 55, and 65 years old with large serous PEDs and subretinal fluid (SRF) associated with occult choroidal neovascularization and neovascular AMD were treated with aflibercept after intravitreal bevacizumab and/or ranibizumab failed to resolve the lesions. All had complete resolution of SRF and complete or near-complete resolution of the PEDs after aflibercept injections over a 3-month period. Visual acuity improved in all three eyes., Conclusion: Intravitreal aflibercept may be an effective treatment option for serous PED in neovascular AMD patients after bevacizumab and ranibizumab have previously failed. Larger studies with longer follow-up are required to determine the role of aflibercept in treatment of PED in neovascular AMD.

Loss-of-function mutations and deletions in the neurofibromin tumor suppressor gene (NF1) cause neurofibromatosis type 1 (NF-1), the most common inherited syndrome of the nervous system in humans, with a birth incidence of 1:3,000. The most visible features of NF-1 are the neoplastic manifestations caused by the loss of Ras-GTPase-activating protein (Ras-GAP) activity mediated through the GAP-related domain (GRD) of neurofibromin (NF1), the protein encoded by NF1. However, the syndrome is also characterized by cognitive dysfunction and a number of developmental abnormalities. The molecular etiology of many of these nonneoplastic phenotypes remains unknown. Here we show that the tubulin-binding domain (TBD) of NF1 is a binding partner of the leucine-rich pentatricopeptide repeat motif-containing (LRPPRC) protein. These two proteins complex with Kinesin 5B, hnRNP A2, Staufen1, and Myelin Basic Protein (MBP) mRNA, likely in RNA granules. This interaction is of interest in that it links NF-1 with Leigh's syndrome, French Canadian variant (LSFC), an autosomal recessive neurodegenerative disorder that arises from mutations in the LRPPRC gene. Our findings provide clues to how loss or mutation of NF1 and LRPPRC may contribute to the manifestations of NF-1 and LSFC., (Copyright © 2013 Wiley Periodicals, Inc.)

Objective: To assess the reliability and accuracy of smartphones in diagnosing transmitted fundus images in comparison with a laptop., Materials and Methods: Fundus images captured with a Topcon NW 200 camera were transferred onto a conventional laptop and a smartphone and given to ophthalmologists for diagnosis. The smartphone and the laptop diagnosis were compared with the actual face to face diagnosis statistically to assess their diagnostic accuracy., Results: Fundus images of 228 eyes of 114 patients (mean age 47 years,73.6% males) were included in the study. 92.5% eyes were correctly diagnosed by both smartphones and laptop. Smartphone analysis revealed 98% sensitivity,57% specificity and kappa value of 0.62 in comparison to laptop, suggessting substantial interrater agreement., Conclusions: Smartphones are as effective as the laptop in diagnosing fundus pathologies and hold promise for teleophthalmology in future.

A study was carried out in Coimbatore district of Tamil Nadu (India) to assess the distribution pattern of heavy metals in the soils and plants irrigated with sewage effluent/sludge. About 69 soil samples (surface and subsurface), 65 plant samples as well as 34-sewage sludge samples were collected from various tehsils of Coimbatore. Six tehsils in Coimbatore have been identified and categorized into two groups--Class I City (densely populated tehsils) and Class II city (thinly populated tehsils). The available micronutrients like Fe, Mn, Zn and Cu; heavy metals: Cr, Cd, Ni, and Pb were within the safe limits. However, the total Cr and Cd concentrations were relatively higher in the sludge samples collected from Coimbatore and Tiruppur tehsils compared to other tehsils, while for Ni, the sequence was in the order Coimbatore > Tiruppur > Palladam > Pollachi > Avinashi > Mettupalayam and for Pb, Coimbatore > Mettupalayam > Palladam > Tiruppur > Avinashi > Pollachi. Soil analysis results indicated that heavy metal concentration recorded higher level in soils of Class I city (densely populated tehsils) compared to Class II city (thinly populated tehsils). The plant samples analyzed had also registered higher concentration of total Cd, Ni and Pb, which were classified under toxic, excessive and below excessive level, respectively. Correlation analysis revealed that iron (Fe), zinc (Zn), copper (Cu), cadmium (Cd) and lead (Pb) were significantly negatively correlated with pH of soil. EC had a significant positive correlation with available iron (Fe), zinc (Zn), cadmium (Cd) and lead (Pb). A significant positive correlation of Fe, Mn, Zn, Cu, Cd and Pb was also registered with OC. Among the plant samples collected, it was evident that heavy metal concentrations were recorded higher in grass spp followed by Amaranthus spp. It was inferred from the study that soils samples had higher levels of heavy metals even though the values recorded were below the critical value/toxic limit. However, long-term and indiscriminate application of untreated (raw) sewage sludge and/or letting of sewage effluent directly to agricultural field without prior treatment may result in accumulation of toxic metals in surface and subsurface soils and subsequent biotransfer (bioaccumlation) into the food chain, it may further lead to toxicity not only to plants and animals but also to consumers of the harvested crops.

T-urf13, a well-documented cms-associated gene from maize, has been shown to render methomyl sensitivity to heterologous systems like rice, yeast and bacteria when expressed constitutively. Since these transgenic plants were fertile, it was hypothesized that T-urf13 gene if expressed in anthers may result in male sterility that could be used for hybrid seed production. Hence, this work was aimed at analysing whether T-urf13 gene when expressed in anthers can result in male sterile plants or requires methomyl treatment to cause male sterility (controllable). This is the first report of transformation of tobacco with T-urf13 gene under anther-specific promoter (TA29) with or without mitochondrial targeting sequence. Most of the transgenic plants obtained were fertile; this was surprising as many male sterile plants were expected as T-urf13 gene is a cms associated gene. Our results suggest that it may not be possible to obtain male sterility by expressing URF13 in the anther by itself or by methomyl application.

Neurofibromatosis type 1 (NF1) patients are prone to the development of malignant tumors, the most common being Malignant Peripheral Nerve Sheath Tumor (MPNST). NF1-MPNST patients have an overall poor survival due to systemic metastasis. Currently, the management of MPNSTs includes surgery and radiation; however, conventional chemotherapy is not very effective, underscoring the need for effective biologically-targeted therapies. Recently, the NF1 gene product, neurofibromin, was shown to negatively regulate the phosphoinositide-3-kinase (PI3K)/Protein Kinase-B (Akt)/mammalian Target Of Rapamycin (mTOR) pathway, with loss of neurofibromin expression in established human MPNST cell lines associated with high levels of mTOR activity. We developed and characterized a human NF1-MPNST explant grown subcutaneously in NOD-SCID mice, to evaluate the effect of the mTOR inhibitor rapamycin. We demonstrate that rapamycin significantly inhibited human NF1-MPNST mTOR pathway activation and explant growth in vivo at doses as low as 1.0 mg/kg/day, without systemic toxicities. While rapamycin was effective at reducing NF1-MPNST proliferation and angiogenesis, with decreased CyclinD1 and VEGF respectively, there was no increase in tumor apoptosis. Rapamycin effectively decreased activation of S6 downstream of mTOR, but there was accompanied increased Akt activation. This study demonstrates the therapeutic potential and limitations of rapamycin in NF1-associated, and likely sporadic, MPNSTs.

The Schiff base compounds N,N'-bis[(E)-quinoxalin-2-ylmethylidene]propane-1,3-diamine, C(21)H(18)N(6), (I), and N,N'-bis[(E)-quinoxalin-2-ylmethylidene]butane-1,4-diamine, C(22)H(20)N(6), (II), crystallize in the monoclinic crystal system. These molecules have crystallographically imposed symmetry. Compound (I) is located on a crystallographic twofold axis and (II) is located on an inversion centre. The molecular conformations of these crystal structures are stabilized by aromatic pi-pi stacking interactions.

Inter-specific hybrids were produced between the threatened catfish species Mystus gulio x Mystus montanus. The differences in percentage of fertilization and hatching between control and interspecies were significant. The survival of hybrid was significantly lower (24.80 +/- 4.3%) when compared to control (95.1 +/- 3.5%). Time difference in yolk absorption by hybrid (73.30 h) was higher than that of control (72 h). When compared to interspecific fertilized egg the hatching time (24-25 h) and viability of larvae of the control were significantly better. In hybrids more deformed hatchlings (52.7 +/- 4.2 %) were noticed than the control (24.80 +/- 4.3%).

The asymmetric unit of the title compound, C(11)H(8)N(4), contains two independent mol-ecules. In the crystal structure, inter-molecular N-H⋯N hydrogen bonds link mol-ecules into ribbons extended in the [100] direction.

We report the first Australian use of the Impella LP 5.0, a minimally invasive, high-output left ventricular assist device. The device was inserted intra-operatively for cardiac failure following coronary artery grafting. Although it facilitated a temporary post-operative recovery, the patient ultimately succumbed due to left ventricular failure more than 30 days after the original procedure. This device has several advantages over existing forms of left ventricular support, and has the potential for widespread use in Australian centres.

Purpose: To determine the incidence and natural history of cataracts in children with congenital toxoplasmosis., Methods: Children referred to the National Collaborative Chicago-based Congenital Toxoplasmosis Study (NCCCTS) between 1981 and 2005 were examined by ophthalmologists at predetermined times according to a specific protocol. The clinical course and treatment of patients who developed cataracts were reviewed., Results: In the first year of life, 134 of 173 children examined were treated with pyrimethamine, sulfadiazine, and leukovorin, while the remaining 39 were not treated. Cataracts occurred in 27 eyes of 20 patients (11.6%, 95% confidence interval [7.2%, 17.3%]). Fourteen cataracts were present at birth and 13 developed postnatally. Locations of the cataracts included anterior polar (three eyes), anterior subcapsular (six eyes), nuclear (five eyes), posterior subcapsular (seven eyes), and unknown (six eyes). Thirteen cataracts were partial, nine total, and five with unknown complexity. Twelve cataracts remained stable, 12 progressed, and progression was not known for 3. Five of 27 eyes had cataract surgery, with 2 of these developing glaucoma. Sixteen eyes of 11 patients had retinal detachment and cataract. All eyes with cataracts had additional ocular lesions., Conclusions: In the NCCCTS cohort, 11.6% of patients were diagnosed with cataracts. There was considerable variability in the presentation, morphology, and progression of the cataracts. Associated intraocular pathology was an important cause of morbidity.

Objective: To determine if type II statistical errors (also known as beta errors) are a common problem in published clinical research., Methods: Type II statistical errors occur when sample sizes are too small to show an effect of treatment, even when an effect truly exists. Searching the Medline data base, we identified ten meta-analyses published during 1986-1994 in the American Journal of Obstetrics and Gynecology, Obstetrics and Gynecology, and The Journal of Reproductive Medicine. Meta-analyses were used as sources of component or individual studies for the following reason: When small component studies have negative findings that differ from the overall conclusions of the meta-analysis, the component studies may have type II statistical errors., Results: We found that only 6.5% (15 of 231) of component studies provided any documentation that power calculations to determine sample sizes had been done a priori (before) the research began. Thus, many of these component studies with findings of no treatment effect may have had type II errors because of too-small sample sizes. When stratifying the component studies by year of publication, we found that 7.9% (14 of 178) of studies published in the 1980s and 1990s had any documented evidence of a priori power calculations. In the 1960s and 1970s, only one of 53 component studies had documented evidence of power calculations., Conclusion: To ensure that truly effective treatments are introduced into clinical practice as quickly as possible, we believe that a priori power calculations should always be done in quantitative clinical research.