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The rising antimicrobial resistance crisis has diminished the effectiveness of traditional antibiotics against pathogenic bacteria. This study addresses this urgent challenge by exploring the antibacterial potential of novel quinolone derivatives (1–33). Using computational in silico modeling to simulate biological interactions, we aimed to identify candidates with potent antibacterial activity. A total of 33 quinolone derivatives were assessed for their physicochemical properties and effectiveness against a range of clinically relevant pathogens, including methicillin‐resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, Streptococcus pneumoniae, and Enterococcus faecalis. Molecular docking studies identified compounds 28, 29, 32, and 33 as having notable binding affinities, particularly against MRSA. Further molecular dynamics simulations of compound 29 confirmed its favorable stability and potential for disrupting MRSA, reinforcing the docking results and showing strong alignment with in vitro findings. These findings position compound 29 as a promising lead for developing alternative MRSA therapies and underscore the need for further in vivo studies to evaluate its therapeutic potential. [ABSTRACT FROM AUTHOR]

This review article aims to significantly advance the scientific community's efforts to develop effective nucleoside‐based drugs for treating severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and other emerging infectious diseases. This study concentrates on the main viral protease (Mpro) and explores nucleoside‐based compounds as potential therapeutic agents. This investigation investigated the impact of acylation‐induced modifications on the nucleoside hydroxyl group and subsequent properties. Nucleoside analogs, which are recognized for their diverse biochemical properties, were synthesized and rigorously screened to evaluate their antimicrobial efficacy. In the domain of pharmaceutical research, computational pharmacokinetics has emerged as a critical tool, especially in the pursuit of nucleoside analogs as potential therapeutics. In silico methods aid in predicting pharmacokinetic traits, interactions with crucial enzymes, and the stability of these analogs in biological environments, thereby streamlining drug design and reducing experimental costs. Concurrently, computational studies revealed the intricate interactions between the analogs and the active site of the main protease. The amalgamation of experimental screening and computational insights underscores the emergence of potent nucleoside candidates with inhibitory activity against SARS‐CoV‐2 Mpro. Additionally, this review integrates computational studies that provide valuable insights into the interactions between nucleoside analogs and the main protease of SARS‐CoV‐2. [ABSTRACT FROM AUTHOR]

We examined the changes in body weight (BW), back‐fat thickness (BFT) and blood metabolites in relation to postpartum (PP) ovarian activity status in twenty female yaks raised under semi‐intensive system. BFT and ovarian activities, like follicle development, ovulation (OV) and corpus luteum (CL) development, were monitored from 4 to 15 weeks (wk) PP using ultrasonography. Resumption of ovarian activity was confirmed with ovulation of dominant follicle (DF) and subsequent CL development, and >1 ng/ml progesterone concentration in blood plasma sample after 1week of ovulation. Yaks were further classified as cyclic (with CL), acyclic (without CL), and cystic (with >25 mm follicular cyst; FC). Within 20 weeks PP, 60% yaks resumed cyclic ovarian activity, while 25% failed to initiate cycling activity, and 15% developed follicular cysts. In all categories of yak, BW gradually decreased (p <.05) till nadir; however, nadir reached earlier (p <.05) in acyclic yaks. BFT differed (p <.05) among the yak groups, but it tended to be higher in cyclic yaks as compared to acyclic and cystic. No difference (p >.05) in non‐esterified fatty acids (NEFA) values was found among the different categories of yaks, whereas, beta‐hydroxy butyrate (BHB) levels were higher in cystic animals as compared to acyclic and cyclic. Blood glucose levels decreased in all yaks during initial 2 weeks after calving. Our findings suggest that yaks with low BW, BFT and glucose levels, and higher BHB values were at risk of delayed resumption of ovarian activity and concomitant development of follicular cysts. [ABSTRACT FROM AUTHOR]

A 15‐kDa lectin, termed SeviL, was isolated from Mytilisepta virgata (purplish bifurcate mussel). SeviL forms a noncovalent dimer that binds strongly to ganglio‐series GM1b oligosaccharide (Neu5Acɑ2‐3Galβ1‐3GalNAcβ1‐4Galβ1‐4Glc) and its precursor, asialo‐GM1 (Galβ1‐3GalNAcβ1‐4Galβ1‐4Glc). SeviL also interacts weakly with the glycan moiety of SSEA‐4 hexaose (Neu5Acα2‐3Galβ1‐3GalNAcβ1‐3Galα1‐4Galβ1‐4Glc). A partial protein sequence of the lectin was determined by mass spectrometry, and the complete sequence was identified from transcriptomic analysis. SeviL, consisting of 129 amino acids, was classified as an R(icin B)‐type lectin, based on the presence of the QxW motif characteristic of this fold. SeviL mRNA is highly expressed in gills and, in particular, mantle rim tissues. Orthologue sequences were identified in other species of the family Mytilidae, including Mytilus galloprovincialis, from which lectin MytiLec‐1 was isolated and characterized in our previous studies. Thus, mytilid species contain lectins belonging to at least two distinct families (R‐type lectins and mytilectins) that have a common β‐trefoil fold structure but differing glycan‐binding specificities. SeviL displayed notable cytotoxic (apoptotic) effects against various cultured cell lines (human breast, ovarian, and colonic cancer; dog kidney) that possess asialo‐GM1 oligosaccharide at the cell surface. This cytotoxic effect was inhibited by the presence of anti‐asialo‐GM1 oligosaccharide antibodies. With HeLa ovarian cancer cells, SeviL showed dose‐ and time‐dependent activation of kinase MKK3/6, p38 MAPK, and caspase‐3/9. The transduction pathways activated by SeviL via the glycosphingolipid oligosaccharide were triggered apoptosis. Database: Nucleotide sequence data have been deposited in the GenBank database under accession numbers MK434191, MK434192, MK434193, MK434194, MK434195, MK434196, MK434197, MK434198, MK434199, MK434200, and MK434201. [ABSTRACT FROM AUTHOR]

To foster ‘creative destruction,’ entrants must survive the turbulent conditions they face in their first crucial years in the industry. We investigate how the external knowledge milieu of an entrant, conceptualized as its innovative environment, causes systematic variation in survival patterns. We test our model from 3,431 firms in 33 industries over 80 years. We depict the innovative environment along two knowledge-related dimensions, namely technology regime and technology intensity. While the aligned state of the innovative environment, where product innovation exists in tandem with abundant innovation opportunities, promotes entrant survival, we find that this beneficial effect is more pronounced for small entrants due to a possible mitigation of scale disadvantages. [ABSTRACT FROM AUTHOR]

This paper extends entrepreneurship into the domain of alliances, and investigates the effect of alliance proactiveness on market-based firm performance (defined in terms of sales growth, market share, market development and product development). Alliance proactiveness is defined as the extent to which an organization engages in identifying and responding to partnering opportunities. The effect of alliance proactiveness on performance is tested within a contingency framework, with size and perceived environmental uncertainly as moderators, and using data from 182 firms. We estimated the model using partial least squares. Results indicate that alliance proactiveness leads to superior market-based performance, and that this effect is stronger for small firms and in unstable market environments. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The genetic testing to confirm or rule out an acute promyelocytic leukemia (APL) typically takes a minimum of 24‐72 hours. Flow cytometric immunophenotyping (FCI) on the other hand provides rapid and objective information to differentiate APL from non‐APL. Methods: FCI features, with single‐tube 8‐color combination using CD45, CD34, HAL‐DR, CD11b, CD13, CD33, and CD117 and CD64, were compared for the 30 consecutive APL and 30 non‐APL acute myeloid leukemia (AML) cases which morphologically mimicked an APL. The diagnosis was confirmed by cytogenetic or molecular genetic testing in the form of t (15:17) (q22; q21)/variant translocations or PML‐RARA fusion transcript analysis. Results: The APL cells lacked CD34, HLA‐DR, and CD11b in 90%, 90%, and 93.3% cases, respectively. Myeloid antigens such as CD33, CD13, CD117, and CD64 were expressed in 96.7%, 96.7%, 76.7%, and 70% cases, respectively. The dual negative profiles, CD34‐/HLA‐DR‐ or HLA‐DR‐/CD11b‐, were noted in 90% and 93.3% cases. The triple‐negative (CD34‐/HLA‐DR‐/CD11b‐) profile was noted in 90% of the cases. The sensitivity, specificity, and positive predictive value (PPV) of CD34‐/HLA‐DR‐ and HLA‐DR‐/CD11b‐ profiles for the diagnosis of APL were found to be 90%, 80% & 81.1% and 93.3%, 86.7%& 87.5%, respectively. Combining the above two profiles resulted in a triple‐negative profile (CD34‐, HLA‐DR‐ and CD11b‐), which had a better specificity (93.3%) and positive predictive value (93.1%), with similar sensitivity. Conclusion: FCI is a rapid and reliable modality for the diagnosis of an APL. The triple‐negative profile (CD34‐/HLA‐DR‐/CD11b‐) rapidly and specifically identifies an APL case. [ABSTRACT FROM AUTHOR]

Capturing of the best-focused image using focus measure function (FMF) from a stack of images acquired at different focus distances is a crucial step in automatic microscopy development. Detection of bacilli present in Ziehl-Neelsen (ZN) stained sputum smears conventional microscope (CM) images is critical to disease diagnosis. Studies have revealed that the performances of FMFs are sensitive to image contents and background noise. In this article, 24 diverse FMFs were implemented on 31 stacks of CM's field of view images acquired from three different microscopes to determine the best-focused one. Seven FMFs achieved the accuracies of greater than 90%. Accuracy, focus error, and false maxima were calculated for each FMF, and overall score and ranking were also calculated for better interpretation. Preprocessing techniques such as filtering and image distortions (noise, contrast, saturation, illumination, etc.) were performed to evaluate the robustness of every FMF. Gaussian derivative, steerable filters, Tenengrad, and Hemli and Scherer's mean FMFs were identified as the most robust and accurate functions with the accuracy >90%. These FMFs have a relatively less focus error and false maxima rate. Full widths at half maximum of these four FMFs were also computed to determine their efficacy for the optimization process. These four FMFs can be implemented for automated capturing of the image from ZN-stained sputum smear slide. Gaussian derivative FMF can also be used effectively for both CM and fluorescence microscope's field of view image stacks to determine the best-focused one from each stack. © 2017 International Society for Advancement of Cytometry [ABSTRACT FROM AUTHOR]

Contents The objective of this study was to document the expression and localization of angiopoietin ( ANGPT) family members comprising of angiopoietin ( ANGPT1 and ANGPT2), and their receptors (Tie1 and Tie2) in buffalo corpus luteum ( CL) obtained from different stages of the oestrous cycle, and the modulatory role of ANGPT1 and ANGPT2 alone or in combinations on progesterone (P4) secretion and mRNA expression of phosphotidylinositide-3kinase-protein kinase B ( PI3K- AKT), phosphoinositide-dependent kinase ( PDK), protein kinase B ( AKT), Bcl2 associated death promoter ( BAD), caspase 3 and von willebrand factor ( vWF) in luteal cells obtained from midluteal phase ( MLP) of oestrous cycle in buffalo. Real-time RT- PCR ( qPCR), Western blot and immunohistochemistry were applied to investigate mRNA expression, protein expression and localization of examined factors whereas, the P4 secretion was assessed by RIA. The mRNA and protein expression of ANGPT1 and Tie2 was maximum ( p < .05) in mid luteal phase ( MLP) of oestrous cycle. The ANGPT2 mRNA and protein expression was maximum ( p < .05) in early luteal phase, decreased in MLP and again increased in late luteal phase of oestrous cycle. ANGPT family members were localized in luteal cells and endothelial cells with a stage specific immunoreactivity. P4 secretion was highest ( p < .05) with 100 ng/ml at 72 hr when luteal cells were treated with either protein alone. The mRNA expression of PDK, AKT and vWF was highest ( p < .05) and BAD along with caspase 3 were lowest ( p < .05) at 100 ng/ml at 72 hr of incubation period, when cultured luteal cells were treated with either protein alone or in combination. To conclude, our study explores the steroidogenic potential of angiopoietins to promote P4 secretion, luteal cell survival and angiogenesis through an autocrine and paracrine actions in buffalo CL. [ABSTRACT FROM AUTHOR]

Translocations of large carnivores like tiger to restore extirpated populations are increasingly becoming important conservation tools in the face of persistent anthropogenic pressures and relentless habitat loss. Reintroduction success in Panna Tiger Reserve, India was variously attributed to high genetic diversity, less anthropogenic disturbance and stress, efficient execution and technological integrations. Here, we establish parentage relationships and explore the potential of mate choice and appropriate adult sex ratio to explain the successful reintroduction in Panna. We used a combination of radio-telemetry and genetic analyses to understand mating interactions of translocated tigers and their outcomes. Surprisingly, relatedness and parentage analyses of nine cubs born in 2010-2012 suggested that five cubs (55.5%) were not sired by the single translocated male tiger, emphasizing the difficulty of assessing the persistence of tiger presence over a large geographic area. Genotype data of tigers originally from Panna prior to the present reintroduced population revealed that four cubs were sired by an original Panna tiger which possibly ranged transiently within the released tigers' home ranges. Presence of additional male for mate choice can be a strong factor for successful reintroduction of tigers in Panna. Although number of females released is a good indicator of reintroduction success, the number of males released is also a very important factor for success. We hypothesize that while tigers live in female-dominated population structure within male territories, mate selection strategies operate strongly between sexes. Translocation programs should therefore deliberate on this aspect of mate selection and accordingly consider founder compositions to achieve desirable results. This also reinforces the need for post-release monitoring and thorough investigations into intraspecific interactions and behavior which will facilitate proper management and revival of tiger populations. [ABSTRACT FROM AUTHOR]

African Americans coinfected with HIV and hepatitis C virus ( HCV) have lower liver-related mortality than Caucasians and Hispanics. While genetic polymorphisms near the IFNL3 and IFNL4 genes explain a significant fraction of racial differences in several HCV-related outcomes, the impact of these variants on liver-related mortality has not been investigated. We conducted a cohort study of HIV/ HCV-coinfected women followed in the multicentre, NIH-funded Women's Interagency HIV Study ( WIHS) to investigate whether 10 polymorphisms spanning the IFN-λ region were associated with liver-related mortality by dominant, recessive or additive genetic models. We also considered whether these polymorphisms contributed to previously reported differences in liver-related death by race/ethnicity (ascertained by self-report and ancestry informative markers). Among 794 coinfected women, there were 471 deaths including 55 liver-related deaths during up to 18 years of follow-up. On adjusted analysis, rs12980275 GG genotype compared to AG+ AA hazards ratios [( HR) 0.36, 95% CI 0.14-0.90, P = 0.029] and rs8109886 AA genotype compared to CC+ AC ( HR 0.67, 95% CI 0.45-0.99, P = 0.047) were most strongly associated with liver-related death although these associations were no longer significant after adjusting for race/ethnicity ( HR 0.41, 95% CI 0.16-1.04, P = 0.060 and HR 0.78, 95% CI 0.51-1.19, P = 0.25, respectively). African American women had persistently lower liver-related death independent of IFN-λ variants ( HRs ≤ 0.44, P values ≤ 0.04). The lower risk of death among African American HIV/ HCV-coinfected women is not explained by genetic variation in the IFN-λ region suggesting, that other genetic, behavioural and/or environmental factors may contribute to racial/ethnic differences in liver-related mortality. [ABSTRACT FROM AUTHOR]

Contents The aim of this study was to document the expression and localization of VEGF system comprising of VEGF isoforms ( VEGF 120, VEGF 164 and VEGF 188) and their receptors ( VEGFR1 and VEGFR2) in buffalo corpus luteum (CL) obtained from different stages of the oestrous cycle. Real-time RT-PCR ( qPCR), Western blot and immunohistochemistry were applied to investigate mRNA expression, protein expression and localization of examined factors. In general, all the components of VEGF system (the VEGF isoforms and their receptors) were found in the water buffalo CL during the oestrous cycle. The mRNA as well as protein expression of VEGF system was highest during the early and mid-luteal phase, which later steadily decreased (p < 0.05) after day 10 to reach the lowest level in regressed CL. As demonstrated by immunohistochemistry, VEGF protein was localized predominantly in luteal cells; however, VEGFR1 and VEGFR2 were localized in luteal cells as well as in endothelial cells. In conclusion, the dynamics of expression and localization of VEGF system in buffalo corpora lutea during the luteal phase were demonstrated in this study, indicating the possible role of VEGF system in the regulation of luteal angiogenesis and proliferation of luteal as well as endothelial cells through their non-angiogenic function. [ABSTRACT FROM AUTHOR]

Contents The effect of uterine infection on size and follicular fluid composition of the largest follicle was studied in buffalo. Reproductive tracts were collected from 102 graded Murrah buffaloes at an abattoir. Uterine infection was diagnosed by physical examination of uterine mucus, white side test and uterine cytology. Samples with pus-containing mucus, positive reaction on white side test and/or >5% neutrophils were considered to be positive for uterine infection. Diameter of the largest follicle was measured, and follicular fluid was aspirated and assayed for nitric oxide (NO), ascorbic acid (AA), cholesterol, oestradiol (E2) and progesterone (P4). Infected buffaloes had smaller-sized (p < 0.0001) largest follicles than non-infected buffaloes. Follicular fluid collected from the largest follicle in infected buffaloes had greater (p < 0.0001) NO and P4 concentrations coincident with lesser AA (p < 0.001), cholesterol (p < 0.0001) and E2 (p < 0.0001) concentrations. Results indicated that uterine infection has an inhibitory effect on growth of the largest follicle in buffalo. The changes in follicular fluid composition in infected buffaloes suggest that the direct effect of uterine infection on ovarian function may be mediated through an alteration in the follicular microenvironment. Greater NO and lesser AA concentrations in the follicular fluid of infected animals are novel findings. [ABSTRACT FROM AUTHOR]

. Asians Americans have a high burden of hepatitis B virus (HBV) associated hepatocellular carcinoma (HCC). HCC screening practices in this population are unknown. We aimed to investigate predictors and patterns of HCC screening and its impact on survival in HBV-infected Asian Americans. Clinical data were obtained from a retrospective cohort of 1870 HBsAg-positive Asians in San Francisco's safety net clinics. In 824 patients at-risk for HCC, screening (≥1 imaging and/or AFP per year) decreased from 67% to 47% to 24% from the 1st to 2nd to 10th year after HBV diagnosis, respectively. AFP, imaging, and imaging plus AFP were used in 37%, 14%, and 49% during the first year after diagnosis, and imaging plus AFP increased to 64% by the 10th year. Among 1431 patients followed in 2007, age 40-64 years, female gender, cirrhosis, hepatologist evaluation, HBV diagnosis after 2003, and testing for HBeAg were associated with HCC screening. Of the 51 patients with HCC, more cirrhotics received screening and were diagnosed with early stage disease. Median survival following HCC diagnosis was higher in screened patients (1624 days vs. 111 days, P = 0.02). MELD score at HCC diagnosis (HR 1.2, 95% CI 1.1-1.3) and receipt of curative therapy (HR 0.3, 95% CI 0.08-0.94) were associated with survival. Screening rates in at-risk Asian Americans, particularly among noncirrhotics, were suboptimal and decreased over time. Among patients with HCC, receipt of prior screening improved survival, and this survival benefit was related to better liver function at HCC diagnosis and receipt of curative therapy. [ABSTRACT FROM AUTHOR]

Contents Thrombopoietin (TPO) is known to be involved in megakaryocytopoiesis, but its role in the control of ovarian function is unknown in cattle. The aims of this study were to demonstrate the expression of TPO and its receptor (c-MPL) in detail in bovine corpus luteum (CL) obtained from different stages of the oestrous cycle and during pregnancy - and to demonstrate that TPO/c-MPL system is expressed clearly in bovine follicles. Real-time RT-PCR (qPCR) and ELISA were applied to investigate mRNA expression of examined factors and TPO protein, respectively. In this investigation, increases in the concentrations of TPO protein and the mRNA expression of TPO and c-MPL were noticed during both early luteal stage and late luteal stage of the oestrous cycle. Furthermore, the expression of TPO/c-MPL system does not show any significant regulation in the CL throughout pregnancy. Highest co-expression of TPO/c-MPL system in both theca interna (TI) and granulosa cells (GC) in small follicles (<10 mm in diameter) was observed in this study that may suggest the possible role of TPO/c-MPL system in proliferation of TI and GC cells. To conclude, the results demonstrate the possible involvement of locally produced TPO/c-MPL system as a 'physiological filter' in bovine ovary where they may promote cell selection by inducing proliferation of viable cells and scavenging non-viable cells and thereby may play an important role in modulation of ovarian function. [ABSTRACT FROM AUTHOR]

Contents An attempt was undertaken to investigate the efficacy of Ovsynch protocol for timed artificial insemination (TAI) with or without Norprolac (antiprolactin) treatment during non-breeding season (winter months) in yaks (n = 25). During non-breeding season, plasma prolactin profile has been reported high due to cold and nutritional stress. The Norprolac dose of i.m. administration was standardized for prolactin suppression. Three different doses viz. 2.5, 5.0 and 7.5 mg were attempted and the dose of 7.5 mg Norprolac i.m. per animal was found to be suitable for suppression of prolactin levels up to 30 h. Ovsynch treatment with Norprolac induced more number of oestrous symptoms per animal (4.8 vs 2.1), higher LH peak concentration (24.01 vs 16.16 ng/ml), longer duration of LH surge (6.8 vs 5.2 h) and higher conception rate (70 vs 30%) in Ovsynch plus Norprolac treated animals compared with animals treated with Ovsynch alone. Therefore, this study clearly indicates the opportunity for practical application of the Ovsynch plus Norprolac protocol for TAI in yaks during non-breeding seasons. [ABSTRACT FROM AUTHOR]

Contents An attempt was made to determine plasma concentrations of, 13, 14-dihydro-15-keto-prostaglandin F2α (PGFM), cortisol and progesterone during periparturient period in yak. Plasma PGFM level showed an increasing trend beginning day 5 prior to parturition (0.48 ± 0.14 ng/ml) and increased steeply thereafter to reach a peak level (17.16 ± 1.31 ng/ml) on the day of parturition. The levels, then, declined sharply on day 1 postpartum to reach 1.20 ± 0.40 ng/ml and thereafter declined gradually over the days to reach 0.28 ± 0.09 ng/ml on day 20 postpartum and this level was maintained with fluctuation within narrow limits thereafter till conclusion of the blood sampling on day 90 post-calving. The plasma progesterone concentration on days 7 and 6 before parturition was high (2.10 ± 0.10 and 2.12 ± 0.10 ng/ml, respectively). The level then decreased gradually and abrupt fall was observed 1–2 days before parturition and became basal on day of parturition (0.24 ± 0.04 ng/ml). This basal level was maintained till the end of the blood sampling on day 90 postpartum. Plasma cortisol level showed an increasing trend beginning day 2 prior to parturition (2.36 ± 0.65 ng/ml) and increased steeply thereafter to reach a peak level (26.65 ± 5.28 ng/ml) on the day of parturition. The levels, then, declined gradually over the days and touched 2.36 ± 0.25 ng/ml on day 3 postpartum and this level was maintained with fluctuation within narrow limits thereafter till day 7 post-calving. [ABSTRACT FROM AUTHOR]

The insecticide resistance status of Culex quinquefasciatus Say (Diptera: Culicidae) to DDT and deltamethrin across army cantonments and neighbouring villages in northeastern India was investigated. In India, DDT is still the insecticide of choice for public health programmes. In military stations, pyrethroids, especially deltamethrins, are used for insecticide-treated nets (ITNs). Recent information on the levels of resistance to DDT and deltamethrin in mosquito populations of northeastern India is scare. Continued monitoring of insecticide resistance status, identification of the underlying mechanisms of resistance in local mosquito populations and the establishment of a baseline data bank of this information are of prime importance. Insecticide susceptibility assays were performed on wild-caught adult female Cx. quinquefasciatus mosquitoes to the discriminating doses recommended by the World Health Organisation (WHO) to DDT (4%) and deltamethrin (0.05%). Across all study sites, mortality as a result of DDT varied from 11.9 to 50.0%, as compared with 91.2% in the susceptible laboratory strain (S-Lab), indicating that Cx. quinquefasciatus is resistant to DDT. The species was found to be 100% susceptible to deltamethrin in all study sites except Benganajuli and Rikamari. Knock-down times (KDT) in response to deltamethrin varied significantly between study sites ( P < 0.01) from 8.3 to 17.8 min for KDT50 and 37.4 to 69.5 min for KDT90. All populations exceeded the threshold level of alpha-esterase, beta-esterase and glutathion S-transferase (GST) established for the S-Lab susceptible strain, and all populations had 100% elevated esterase and GST activity, except Missamari and Solmara. Beta-esterase activity in Field Unit II (96.9%) was less than in any of the other populations. Benganajuli had the highest activity level for all the enzymes tested. There was a significant correlation between all enzyme activity levels and insecticide resistance phenotype by populations ( P < 0.05). The results presented here provide the first report and baseline information of the insecticide resistance status of Cx. quinquefasciatus in northeastern India, and associated information about biochemical mechanisms that are essential for monitoring the development of insecticide resistance in the area. [ABSTRACT FROM AUTHOR]

Contents Yak and mithun are two domesticated herbivores of high economic importance to the farming community living in highlands. Improved yak and mithun production could significantly enhance the living standards of these highlanders. Over the years, their dwindling numbers have been a cause of serious concern. In view of the lack of knowledge on the reproductive physiology of these ruminants, studies have been undertaken to investigate their reproductive endocrinology in recent years. This paper attempts to present the latest information on the endocrine changes associated with their various reproductive processes viz. growth and puberty, oestrous cyclicity and oestrous behaviour, ovulation, and, pregnancy and parturition. The paper also provides the recent developments on research done towards the enhancement of yak and mithun reproductive efficiencies through endocrine and embryo biotechniques. [ABSTRACT FROM AUTHOR]

Questioning the underlying assumptions of the process of creative destruction, we conceptualize an alternative process of creative construction that may characterize the dynamics between entrants and incumbents. We discuss the underlying mechanism of knowledge spillover strategic entrepreneurship whereby knowledge investments by existing organizations, when coupled with entrepreneurial action by individuals embedded in their context, results in new venture creation, heterogeneity in performance, and subsequent growth in industries, regions, and economies. The framework has implications for future research in entrepreneurship, strategy, and economic growth. Copyright © 2008 Strategic Management Society. [ABSTRACT FROM AUTHOR]

Summary objective Zinc may be a limiting factor in restricting catch-up growth in severely malnourished children. This study had two aims: (i) to examine the effect of different zinc supplementation regimens on IGF-I, its binding proteins and on markers of bone and collagen turnover in severely malnourished children and (ii) to investigate mechanisms underlying catch-up growth by examining changes in these markers during nutritional rehabilitation, their inter-relationships and their relationships with ponderal and linear growth. design Double-blind randomized intervention study of three regimens of oral zinc supplementation. patients One hundred and forty-one children, aged 6–36 months, mean (SD) age 15·4 (8·7) months, with day 1 weight-for-height SD score (whz) -2·6 (0·93) and height-for-age SD score (haz) -3·79 (1·29). measurements Weight, height, lower leg length (by knemometry) at 15-day intervals from day 1 to day 90 of nutritional rehabilitation. Blood collection on days 1, 15 and 30 for IGF-I, IGFBP3, IGFBP2, bone alkaline phosphatase (BAP, osteoblast marker), procollagen type I C -terminal propeptide (PICP, marker of type I collagen synthesis), procollagen type III N -terminal propeptide (P3NP, marker of soft tissue type III collagen synthesis) and type I collagen telopeptide (ICTP, marker of type I collagen breakdown). results There was early rapid weight gain during refeeding, whereas height gain occurred later in the trial. IGF-I, IGFBP3, BAP, PICP and P3NP were low or very low on day 1 compared to well-nourished age-matched European children, and all increased within 15 days (P < 0·001), with PICP and P3NP reaching levels higher than European norms. IGFBP2 and ICTP were high on day 1 and decreased over the same period ( P < 0·001). There were no differences in anthropometric outcome or marker responses among zinc regimens. Day 1 whz was correlated with BAP, PICP and P3NP ( P < 0·001). Changes in... [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about difficult airway management published in the previous issue.

Background/aims: Carbon monoxide exposure can be monitored in adult smokers (SM) by determining carboxyhemoglobin (COHb) levels. The purpose of this research was to develop a population based pharmacokinetic model for COHb in SMs.Methods: Data from three open-labeled randomized controlled studies in SM of 10-30 conventional cigarettes (CC) per day were used. COHb levels were determined in SM at baseline while smoking CC1 (FTC Tar 11 mg) or CC2 (FTC Tar 6 mg), on Days 3 and 8 when randomized to continue smoking CC1 or CC2, switched to another CC3 (FTC Tar 1 mg), or stop smoking. COHb levels were measured at 7am, 11am, 3pm, 7pm and 11pm. Data were analyzed using NONMEM (version V, Level 1.1). Model building and goodness of fit were evaluated using standard methods. The data were best described by a two-compartment model with zero order input and an endogenous COHb level. The model was parameterized for clearance (CL), central (Vc) and peripheral (Vp) volumes of distribution, inter-compartmental clearance (Q), baseline COHb (c0), and relative COHb bioavailability (F1). Each cigarette was treated as a unit dose, assuming a linear relationship between cigarettes smoked and measured COHb.Results: The half-lives were estimated at 1.94±0.58 hrs and 15.4±5.38 hrs (alpha and beta phases, respectively). The model suggested COHb F1 increased with increasing FTC Tar, and COHb CL decreased as BW increased.Conclusions: A robust model was developed to (a) predict COHb levels in SM and (b) to determine optimum COHb sampling times.Clinical Pharmacology & Therapeutics (2005) 79, P47–P47; doi: 10.1016/j.clpt.2005.12.166 [ABSTRACT FROM AUTHOR]

Background: This research was conducted to develop models for estimating the amount excreted over a 24-hour period (AE24H) from spot urine (SU) for biomarkers of exposure to smoke constituents.Methods: Thirty-seven adult smokers (females and males) were enrolled into the study and confined for three days. They smoked at the level of their normal daily consumption from 7 AM to 11 PM. AE24H and three SU (7 AM, 1 PM and 6 PM) samples were collected for three days. Concentrations of nicotine (nicotine and five metabolites) and metabolites of nitrosamines (NNAL), pyrene (1-OHP), benzene (S-PMA), acrolein (HPMA) and butadiene (MHBMA) were determined in the urine samples by validated LC/MS/MS methods. Multiple regression models were developed based on the pooled data of Day 1 and 2 and were tested with the Day 3 data for model robustness.Results: Moderate linear relationships (R-square = 0.40 to 0.55) were found for nicotine, NNAL, S-PMA and MHBMA. The relationships were weaker in 1-OHP and HPMA. The incorporation of gender and cigarette consumption as regressors substantially improved the relationships for all biomarkers (R-square = 0.55 to 0.69).Conclusions: AE24H values can be estimated relatively well using a model including creatinine-adjusted SU values, gender and number of cigarettes smoked as the regressors.Clinical Pharmacology & Therapeutics (2005) 79, P48–P48; doi: 10.1016/j.clpt.2005.12.172 [ABSTRACT FROM AUTHOR]

Background: Exposure to cigarettes in adult smokers (SM) is often determined by measuring urinary excretion of selected smoke constituents or metabolites. Complete 24-hour urine (24H) collections are difficult and inconvenient in ambulatory studies, therefore spot urine is often considered as an alternative. The purpose of this study was to determine the optimum time for a spot urine (SU) collection that best reflects a 24H collection.Methods: SU samples were collected at three time points (early morning, post-lunch and evening) along with 24H collections in 37 healthy SM . Samples were collected for nicotine and its five metabolites, Nicotine equivalents (NE), metabolites of butadiene (MHBMA), Nitrosamine (NNAL), acrolein (HPMA), benzene (S-PMA) and pyrene (1-OHP). Correlation and agreement between creatinine adjusted SU and 24H were determined from the Pearson product-moment correlation, Bland and Altman and Lin's concordance correlation analyses.Results: There were no significant differences (p>0.05) between the three SU collections for all the biomarkers of exposure except for HPMA. The pearson correlation values were (0.66- 0.97) for NE, NNAL, S-PMA and MHBMA, and ranged (0.45- 0.82) for 1-OHP and HPMA.Conclusions: Spot urine can be used as an alternative to 24 hour urine collections for most of the selected biomarkers. The early morning creatinine adjusted SU appears to be the most feasible and practical option as an alternative to 24H collections.Clinical Pharmacology & Therapeutics (2005) 79, P22–P22; doi: 10.1016/j.clpt.2005.12.078 [ABSTRACT FROM AUTHOR]