Design, Synthesis and Bioactivity Evaluation of Ag(I)-, Au(I)- and Au(III)-Quinoxaline-Wingtip N-Heterocyclic Carbene Complexes Against Antibiotic Resistant Bacterial Pathogens.

Intending to homogenize the biological activities of both quinoxaline and imidazole moieties, the proligand, 1-methyl-3-quinoxaline-imidazolium hexaflurophosphate (1.HPF6), and [Ag(1)2][PF6], (2); [Au(1)2][PF6], (3); and [Au(1)Cl3], (4) NHC complexes were synthesized. All the synthesized compounds were characterized by elemental analysis, NMR, and UV-Vis spectroscopy. Finally, single crystal X-ray structures revealed a linear geometry for complex 2 whereas a square planar geometry for complex 4. The formation of complex 3 was confirmed and supported by its MS spectra. The antibacterial activities of all the synthesized complexes were investigated against gram-positive bacteria and gram-negative bacteria. The Au(III)-NHC complex, 4 showed the highest antibacterial activity with extremely low MIC values against both the bacterial strains (0.24 µg.mL-1).  Monitoring of zeta potential supports the higher activity of complex 4 compared to 2 and 3. ROS production by complex 4 has also been measured in vitro in the CT26 cancer cell lines, which is directly responsible for targetting and killing the bacterial pathogens. Cell cytotoxicity assay using 293T cell lines has been performed to investigate the biocompatibility nature of complex 4. Also, an excellent hemocompatibility was assigned to it from its hemolytic studies,   which provide valuable insights into the design of novel antibacterial agents.

Confirmation of the recognition of Culiseta (Culiseta) indica Edwards, 1920 as a distinct species based on integrated morphological and molecular data.

Theobaldia indica Edwards, 1920, classified as a subspecies of Culiseta (Culiseta) alaskaensis (Ludlow, 1906), was recently restored to its original species status, as Culiseta (Culiseta) indica (Edwards), based on comprehensive assessments of morphological, ecological and distributional data. Predating the recognition of indica as a separate species, we collected specimens of this nominal taxon in the Western Himalayan region of India during 20152017, and used morphological and molecular studies to assess its taxonomic status. Our detailed examination of adult morphology, male genitalia and larval characteristics revealed significant distinctions between putative Cs. alaskaensis alaskaensis and Cs. alaskaensis indica, and sequencing of the barcode region of the mitochondrial COI gene yielded a Kimura 2 parameter genetic distance of 5.9% between them, well above the standard 23% commonly accepted to indicate separate species. These results strongly support the formal recognition of Cs. indica as a separate species. Furthermore, the geographical distribution of Cs. indica provides additional evidence in support of its species status.

Impact of simulation on multidisciplinary NICU teamwork during delivery and transport of extremely preterm infants.

BACKGROUND AND OBJECTIVES: Multidisciplinary teamwork during delivery room (DR) resuscitation and timely transport to the neonatal intensive care unit (NICU) can reduce morbidity and mortality for infants born Extremely Preterm (EP). We aimed to assess the impact of a multidisciplinary high-fidelity simulation curriculum on teamwork during resuscitation and transport of EP infants. METHODS: In a prospective study conducted at a Level III academic center, seven teams (each consisting of one NICU fellow, two NICU nurses, and one respiratory therapist) performed three high-fidelity simulation scenarios. Videotaped scenarios were graded by three independent raters using the Clinical Teamwork Scale (CTS). Times of completion of key resuscitation and transport tasks were recorded. Pre- and post- intervention surveys were obtained. RESULTS: Overall, time of completion of key resuscitation and transport tasks decreased, with significant decreases in the time to attach the pulse oximeter, transfer of the infant to the transport isolette, and exit the DR. There was no significant difference in CTS scores from Scenario 1 to 3. Scenarios led by first-year fellows showed a trend towards improvement in all CTS categories. A comparison of teamwork scores pre- and post-simulation curriculum during direct observation of high-risk deliveries in real time revealed a significant increase in each CTS category. CONCLUSION: A high-fidelity teamwork-based simulation curriculum decreased time to complete key clinical tasks in the resuscitation and transport of EP infants, with a trend towards increased teamwork in scenarios led by junior fellows. There was improvement of teamwork scores during high-risk deliveries on pre-post curriculum assessment.

Mosquito Diversity in an Experimental Township in Tamil Nadu, India.

To glean more information on mosquito diversity and distribution in Auroville, a cross-sectional study was carried out by mapping the distribution of water bodies and habitats supporting immature stages on the one hand and the distribution of water bodies/habitats supporting mosquito immature stages on the other. A satellite image covering an area of 8.08 km2 was overlaid with a grid of 500 × 500 m. Fifteen modules were selected and the area of each module served as the sampling site for the entomological survey. Adult and larval stages were sampled. Diversity indices were analyzed to compare mosquito diversity. Rarefaction estimations were used to compare abundance and richness of the mosquito species between different zones. In total, 750 mosquito larvae and 84 resting adults were sampled. Eighteen species of mosquitoes belonging to 11 subgenera and 7 genera were documented. Genera included Aedes (Johann Wilhelm Meigen 1818, Diptera, Culicidae), Anopheles (Johann Wilhelm Meigen 1818, Diptera, Culicidae), Armigeres (Theobald 1901, Diptera, Culicidae), Culex (Carl Linnaeus 1758, Diptera, Culicidae), Lutzia (Theobald 1903, Diptera, Culicidae), and Mimomyia (Theobald 1903, Diptera, Culicidae). Of the 18 mosquito species identified, 8 species are new records for Auroville. The Alpha (α) biodiversity indices show that the mosquito fauna is diverse (S = 18; DMg = 2.732 [95% CI: 2.732-2.732]). The Shannon-Weiner (H' = 2.199 [95% CI: 2.133-2.276]) and Simpson indices (λ = 0.8619 [95% CI: 0.8496-0.8723]) measured species richness, evenness, and dominance. The values of these indices suggest high species richness, evenness, and dominance. Prevailing conditions can provide suitable environment for establishment of different mosquito species in this ecosystem. Given the sociodemographic characteristics of this area, research on mosquito diversity and risk of vector-borne diseases will be of great use.

A new species of the genus Downsiomyia Vargas (Diptera: Culicidae) from Himachal Pradesh, India.

The adult, larval and pupal stages of Downsiomyia rajaveli, a new species (Diptera: Culicidae) from India, are described and illustrated, and the mitochondrial COI barcode is provided for the species. The morphological relationship of the new species to other members of the genus Downsiomyia is discussed.

Heizmannia rajagopalani n. sp. (Diptera: Culicidae) in Kerala, India, a species previously misidentified as Hz. metallica (Leicester).

The original description of Heizmannia (Heizmannia) metallica (Leicester) from Malaysia, and specimens collected in India that were provisionally identified as Hz. metallica, were re-examined for their taxonomic status. Heizmannia metallica from Malaysia was found by Mattingly (1970) to be a junior synonym of Hz. indica (Theobald), whereas we found the specimens identified as Hz. metallica from India to differ distinctly from the holotype of Hz. metallica. We collected adults near Malabar Coast, Western Ghats which corresponded with Indian Hz. metallica sensu auctorum and here describe the previously misidentified species as Hz. (Hez.) rajagopalani n. sp. The adult male and female of the new species, and their genitalia, are described and illustrated.

Description of a new species of the genus Paraedes (Diptera: Culicidae) in Assam, India.

A new species, Paraedes jambulingami, is described from Assam, northeastern India. The adult male and female are described in detail and an illustration of the male is provided. This species is easily distinguished from all known species of the genus Paraedes by the presence of broad silvery or golden scales on the paratergite and the outer arm of the basal mesal lobe of the male genitalia bearing a long, flattened blade-like seta. Dichotomous keys are provided for the identification of the adult females and males of the five species of the genus that are known to occur in India.

Description of the adult male, larva and pupa of Topomyia (Topomyia) aureoventer (Diptera: Culicidae) in India.

The original description of Topomyia aureoventer by Theobald (1910) included only the adult female. Description of the adult male, pupa and larva, with figures of the male genitalia, pupa and larva, are provided. The larva is predacious with well-developed mandibles and inhabits leaf axils of Colocasia plants.

Uranotaenia pseudostricklandi, a new species in subgenus Pseudoficalbia (Diptera: Culicidae) from Kerala, India.

The female and male adults, male genitalia, pupa and larva of Uranotaenia (Pseudoficalbia) pseudostricklandi sp. nov. (Diptera: Culicidae) are described from specimens collected in India.

The effect of adjunctive telmisartan treatment on psychopathology and cognition in patients with schizophrenia.

OBJECTIVE: This study examined the effect of adjunctive telmisartan on psychopathology and cognition in olanzapine- or clozapine-treated patients with schizophrenia. METHOD: In a 12-week randomized, double-blind, placebo-controlled study, patients diagnosed with schizophrenia or schizoaffective disorder received either telmisartan (80 mg once per day) or placebo. Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Scale for Assessment of Negative Symptoms (SANS), and a neuropsychological battery was used to assess cognitive performance. Assessments for psychopathology and cognition were conducted at baseline and week 12. RESULTS: Fifty-four subjects were randomized, and 43 completed the study (22 in the telmisartan group, 21 in the placebo group). After 12-weeks of treatment, the telmisartan group had a significant decrease in PANSS total score compared withthe placebo group (mean ± SD: - 4.1 ± 8.1 vs. 0.4 ± 7.5, P = 0.038, SCohen's d = 0.57). There were no significant differences between the two groups in change from baseline to week 12 in PANSS subscale scores, SANS total score, or any cognitive measures (P > 0.100). CONCLUSION: The present study suggests that adjunctive treatment with telmisartan may improve schizophrenia symptoms. Future trials with larger sample sizes and longer treatment durations are warranted.

Bilateral arthrodesis of the distal tibiofibular joint for deforming osteochondromatas.

The first case of bilateral distal tibiofibular joint fusions for osteochondromas is reported with excellent long-term outcomes.

Descriptions of three new species of Uranotaenia (Pseudoficalbia) Diptera: Culicidae) from India.

Female and male adults, male genitalia, pupa and larva of Uranotaenia (Pseudoficalbia) maikalensis, Ur. (Pfc.) dandakaranyensis and Ur. (Pfc.) satpuraensis, three new mosquito species, are described from India.

Description of a new species of the genus Hulecoeteomyia (Diptera: Culicidae) from Meghalaya, India.

Female and male adults, female and male genitalia, pupa and larva of Hulecoeteomyia cherrapunjiensis, a new mosquito species, are described from Meghalaya, India. Keys to separate larvae and adults are provided.

Morphological and molecular characterization of the ecological, biological and behavioural variants of the JE vector Culex tritaeniorhynchus: an assessment of its taxonomic status.

BACKGROUND & OBJECTIVES: Culex tritaeniorhynchus (Diptera: Culicidae), an important vector of Japanese encephalitis belongs to the Culex vishnui subgroup which includes two other vector species namely, Cx. Vishnui and Cx. pseudovishnui. Many varieties and types of Cx. tritaeniorhynchus have been reported, besides populations that exhibit behavioural and biological differences. This study was undertaken to find out whether Cx. tritaeniorhynchus populations exhibiting behavioural and biological variations, and those from different geographical areas, are comprised of more than one taxon or belong to a single taxon. METHODS: Morphological characterization was done by examining 153 morphological and morphometric characters in the larval (75), pupal (60) and adult stages (18) of five geographical populations of Cx. tritaeniorhynchus. Molecular characterization was done by PCR amplification of mitochondrial cytochrome c oxidase (COI) gene sequences (DNA barcodes) and another hypervariable genetic marker, the ribosomal DNA (16S). One-way ANOVA, principal component analysis (PCA) and discriminant factor analysis (DFA) were done for statistical analyses using the statistical package SPSS IBM version 19.0. RESULTS: Morphological characterization showed that no intraspecific differentiation can be made among the five geographical populations of Cx. tritaeniorhynchus. Molecular characterization done by DNA barcoding also showed that the COI sequences of all the five populations of Cx. tritaeniorhynchus grouped into a single taxonomic clade plus the genetic differentiation among these was non-significant and the overall gene flow among the populations was very high. Analysis of the ribosomal DNA also confirmed that the Cx. tritaeniorhynchus populations belonged to a single taxon. INTERPRETATION & CONCLUSION: Culex tritaeniorhynchus is a taxon that does not involve cryptic species.

Fractalkine and its receptor mediate extracellular matrix accumulation in diabetic nephropathy in mice.

AIMS/HYPOTHESIS: Fractalkine (FKN) is a unique chemokine that works as a chemoattractant and an adhesion molecule. Previous studies have demonstrated that FKN plays a role in ischaemic and protein-overload renal injury via its cognate receptor chemokine (C-X3-C motif) receptor 1 (CX3CR1). However, involvement of the FKN/CX3CR1 system in diabetic nephropathy remains unclear. We examined the role of FKN/CX3CR1 in diabetic mice and mouse mesangial cells (MMCs). METHODS: Streptozotocin (50 mg kg(-1) day(-1)) was intraperitoneally administered for 5 days to male Cx3cr1-knockout (KO) mice and wild-type (WT) mice. MMCs transfected with Fkn (also known as Cx3cl1) or Cx3cr1 siRNA, respectively, were used to elucidate the role of FKN/CX3CR1 in extracellular matrix (ECM) synthesis. RESULTS: At 12 weeks, diabetic Cx3cr1 KO mice showed no significant changes in plasma glucose, but markers of renal inflammation, fibrosis and ECM, such as the fractional mesangial area, fibronectin and collagen, were significantly lower in diabetic Cx3cr1 KO mice compared with diabetic WT mice. High glucose, oleic acid and TGF-ß1 stimulated FKN and CX3CR1 expression, together with the expression of ECM proteins in MMCs, but the effects were significantly attenuated by Fkn or Cx3cr1 siRNA. More importantly, FKN itself increased mesangial ECM through CX3CR1 and subsequent activation of reactive oxygen species and mitogen-activated protein kinases. A neutralising TGF-ß antibody inhibited FKN/CX3CR1 in MMCs treated with diabetic stimuli and decreased FKN-induced ECM accumulation. CONCLUSIONS/INTERPRETATION: These results demonstrate that FKN/CX3CR1 may play an important role in diabetic renal injury through upregulation of ECM synthesis and could therefore be a therapeutic target for preventing diabetic nephropathy.

Systematic list of the species added to the mosquito museum at the Vector Control Research Centre, Pondicherry, India.

Mosquito species housed in the mosquito museum at the Vector Control Research Centre, Pondicherry, India, were increased from 181 to 266 species belonging to 22 genera. The systematic list of the 85 species added to the collection is provided. The collection consists of a total of 31,874 adult specimens, of which 23,696 are individually mounted on minuten pins, while the rest are held in stock vials. It also includes 2,456 male genitalia and 470 female genitalia preparations, 3,523 larvae, 4,745 larval exuviae, and 3,057 pupal exuviae on microscope slides. Representative specimens of different species are available from 16 states and 3 union territories of India.

First record of genus Ayurakitia in India: occurrence of Ayurakitia peytoni in Meghalaya state.

Larvae of Ayurakitia peytoni were collected in July 2008 from Pandanus axils during a survey of mosquito fauna in Meghalaya. This is the 1st record of the genus Ayurakitia in India, extending the known distribution of this genus farther west.

New topological indices with very high discriminatory power.

Several molecular descriptors are used in developing quantitative structure-activity relationships (QSARs). A large number of them are already in use and new descriptors are added every year. Two new topological indices with very high discriminatory power are reported in this paper. The two indices ranked all planar graphs of alkanes C(4) to C(6) uniquely and were found to have non-degenerate values for all the 7668 constitutional isomers (alkane trees) from C(4) to C(15). Low intercorrelation with several of the commonly used topological indices was studied using a diverse data set of 820 chemicals and the new indices proposed in the study were found to cluster in different nodes. This further confirmed their low intercorrelation with other molecular descriptors used in the study. The new descriptors were found to be useful in QSAR modelling.

Extension of molecular similarity analysis approach to classification of DNA sequences using DNA descriptors.

Several alignment-free sequence comparison methods are available which use similarity, based on a particular numerical descriptor of biological sequences. Any loss of information incurred in the transformation of a sequence into a numerical descriptor affects the results. A pool of descriptors that use different algorithms in their computation is expected to suffer minimum loss of information and an attempt is made in this direction to study the similarity of DNA sequences. A number of descriptors based on information theory and connectivity were computed for DNA sequences. Principal component analysis (PCA) was used to extract minimum number (N) of orthogonal descriptors, principal components (PCs). Similarity/dissimilarity clustering of DNA sequences were carried out in the N-dimensional similarity space constructed using the PCs extracted from the DNA descriptors. The paper explains the extension of quantitative molecular similarity analysis (QMSA) from the prediction of physicochemical properties and toxicity of chemicals to bioinformatics for the classification of DNA sequences.

Hypoxia inducible factor-1α in human emphysema lung tissue.

The pathobiology of chronic obstructive pulmonary disease (COPD) is not completely understood. The aim of this study was to assess the expression of hypoxia inducible factor (HIF)-1α in lung tissue from patients with COPD/emphysema. Lung tissue samples from 26 patients were included in this study. Seven samples were obtained from patients with normal lung function, the remainder of the samples were taken from patients with moderate COPD (n = 6; stage I and II Global Initiative for Chronic Obstructive Lung Disease classification) and severe COPD (n = 13; stage III and IV). We analysed mRNA and protein expression in the lung tissue samples and found that: 1) HIF-1α and histone deacetylase 2 proteins were significantly decreased and were correlated; 2) HIF-1α and vascular endothelial growth factor (VEGF) proteins, and forced expiratory volume in 1 s % predicted were correlated in all patients; 3) the changes in VEGF and HIF-1α protein levels in all patients were not age-related and not related to the pack-yr smoking history; and 4) the reduced HIF-1α protein expression was seen in lung endothelial cells and alveolar septal cells by immunohistochemistry. In conclusion, reduced expression of HIF-1α protein in severe COPD is consistent with the concept of a lung structure maintenance programme which is impaired on a molecular level.