Activity of telithromycin and comparators against bacterial pathogens isolated from 1,336 patients with clinically diagnosed acute sinusitis

BACKGROUND: Increasing antimicrobial resistance among the key pathogens responsible for community-acquired respiratory tract infections has the potential to limit the effectiveness of antibiotics available to treat these infections. Since there are regional differences in the susceptibility patterns observed and treatment is frequently empirical, the selection of antibiotic therapy may be challenging. PROTEKT, a global, longitudinal multicentre surveillance study, tracks the activity of telithromycin and comparator antibacterial agents against key respiratory tract pathogens. METHODS: In this analysis, we examine the prevalence of antibacterial resistance in 1,336 bacterial pathogens, isolated from adult and paediatric patients clinically diagnosed with acute bacterial sinusitis (ABS). RESULTS AND DISCUSSION: In total, 58.0%, 66.1%, and 55.8% of S. pneumoniae isolates were susceptible to penicillin, cefuroxime, and clarithromycin respectively. Combined macrolide resistance and reduced susceptibility to penicillin was present in 200/640 (31.3 %) of S. pneumoniae isolates (128 isolates were resistant to penicillin [MIC >= 2 mg/L], 72 intermediate [MIC 0.12–1 mg/L]) while 99.5% and 95.5% of isolates were susceptible to telithromycin and amoxicillin-clavulanate, respectively. In total, 88.2%, 87.5%, 99.4%, 100%, and 100% of H. influenzae isolates were susceptible to ampicillin, clarithromycin, cefuroxime, telithromycin, and amoxicillin-clavulanate, respectively. In vitro, telithromycin demonstrated the highest activity against M. catarrhalis (MIC(50 )= 0.06 mg/L, MIC(90 )= 0.12 mg/L). CONCLUSION: The high in vitro activity of against pathogens commonly isolated in ABS, together with a once daily dosing regimen and clinical efficacy with 5-day course of therapy, suggest that telithromycin may play a role in the empiric treatment of ABS

Gender Differences in Inhaled Pharmacotherapy Utilization in Patients with Obstructive Airway Diseases (OADs): A Population-Based Study

Purpose: Gender differences in the incidence, susceptibility and severity of many obstructive airway diseases (OADs) have been well recognized. However, gender differences in the inhaled pharmacotherapy profile are not well characterized. Methods: We conducted a retrospective cohort study to investigate gender differences in new-users of inhaled corticosteroids (ICS), short-or long-acting beta2-agonist (SABA or LABA), ICS/LABA, short-or long-acting muscarinic antagonist (SAMA or LAMA) among patients with asthma, COPD or asthma-COPD overlap (ACO). We used Clinical Practice Research Datalink to identify OAD patients, 18 years and older, who were new-users (1-year washout period) from 01-January-1998 to 31-July-2018. Multivariable logistic regression was used to examine gender differences in each of the inhaled pharmacotherapies after controlling for potential confounders. Results: A total of 242,079 new-users (asthma: 84.93%; COPD: 10.19%; ACO: 4.88%) of inhaled pharmacotherapies were identified. The multivariable analyses showed that males with COPD were more likely to be a new user of a LABA (odds ratio [OR] 1.29; 95% confidence interval [CI], 1.12– 1.49), LAMA (OR 1.21; 95% CI 1.10– 1.33), SAMA (OR 1.11; 95% CI 1.01– 1.21) and less likely to be a new user of a SABA (OR 0.84; 95% CI, 0.80– 0.89) compared to females. Similar patterns were also observed for patients with ACO; males were more likely to be prescribed with LABA (OR 1.26; 95% CI 1.03– 1.55), LAMA (OR 1.28; 95% CI 1.11– 1.48), SAMA (OR 1.28; 95% CI 1.11– 1.48), and less likely to be a new user of a SABA (OR 0.89; 95% CI, 0.82– 0.96). Also, males with asthma were more likely to be a new-user of ICS/LABA (OR 1.15; 95% CI, 1.08– 1.23) and less likely to start an ICS (OR 0.97; 95% CI, 0.95– 0.99) in comparison with females. Conclusion: Our study showed significant gender differences in new-users of inhaled pharmacotherapies among OAD patients. Adjusting for proxies of disease severity, calendar year, smoking and socioeconomic status did not change the association by gender

Author Correction: A consensus-based transparency checklist.

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Evidence for local and international spread of Mycobacterium avium subspecies paratuberculosis through whole genome sequencing of isolates from the island of Ireland

Publication history: Accepted - 1 April 2022; Published online - 5 April 2022We describe application of whole genome sequencing (WGS) to a collection of 197 Mycobacterium avium subsp paratuberculosis (MAP) isolates gathered from 122 cattle herds across 27 counties of the island of Ireland. We compare WGS to MAP diversity quantified using mycobacterial interspersed random unit – variable number tandem repeats (MIRU-VNTR). While MIRU-VNTR showed only two major types, WGS could split the 197 isolates into eight major groups. We also found six isolates corresponding to INMV 13, a novel MIRU-VNTR type for Ireland. Evidence for dispersal of MAP across Ireland via cattle movement could be discerned from the data, with mixed infections present in several herds. Furthermore, comparisons of MAP WGS data from Ireland to data from Great Britain and continental Europe revealed many instances of close genetic similarity and hence evidence for international transmission of infection. BEAST MASCOT structured coalescent analyses, with relaxed and strict molecular clocks, estimated the substitution rate to be 0.10–0.13 SNPs/site/year and disclosed greater transitions per lineage per year from Europe to Ireland, indicating transmission into Ireland. Our work therefore reveals new insight into the seeding of MAP infection across Ireland, highlighting how WGS can inform policy formulation to ultimately control MAP transmission at local, national and international scales.We acknowledge funding from the Department of Agriculture, Food and Marine awards 15/S/651 (‘NexusMAP’) and 2019R404 (’BTBGe- nIE’)

The Beetle Tree of Life Reveals that Coleoptera Survived End-Permium Mass Extinction to Diversify During the Cretaceous Terrestrial Revolution

Here we present a phylogeny of beetles (Insecta: Coleoptera) based on DNA sequence data from eight nuclear genes, including six single-copy nuclear protein-coding genes, for 367 species representing 172 of 183 extant families. Our results refine existing knowledge of relationships among major groups of beetles. Strepsiptera was confirmed as sister to Coleoptera and each of the suborders of Coleoptera was recovered as monophyletic. Interrelationships among the suborders, namely Polyphaga (Adephaga (Archostemata, Myxophaga)), in our study differ from previous studies. Adephaga comprised two clades corresponding to Hydradephaga and Geadephaga. The series and superfamilies of Polyphaga were mostly monophyletic. The traditional Cucujoidea were recovered in three distantly related clades. Lymexyloidea was recovered within Tenebrionoidea. Several of the series and superfamilies of Polyphaga received moderate to maximal clade support in most analyses, for example Buprestoidea, Chrysomeloidea, Coccinelloidea, Cucujiformia, Curculionoidea, Dascilloidea, Elateroidea, Histeroidea and Hydrophiloidea. However, many of the relationships within Polyphaga lacked compatible resolution under maximum-likelihood and Bayesian inference, and/or lacked consistently strong nodal support. Overall, we recovered slightly younger estimated divergence times than previous studies for most groups of beetles. The ordinal split between Coleoptera and Strepsiptera was estimated to have occurred in the Early Permian. Crown Coleoptera appeared in the Late Permian, and only one or two lineages survived the end-Permian mass extinction, with stem group representatives of all four suborders appearing by the end of the Triassic. The basal split in Polyphaga was estimated to have occurred in the Triassic, with the stem groups of most series and superfamilies originating during the Triassic or Jurassic. Most extant families of beetles were estimated to have Cretaceous origins. Overall, Coleoptera experienced an increase in diversification rate compared to the rest of Neuropteroidea. Furthermore, 10 family-level clades, all in suborder Polyphaga, were identified as having experienced significant increases in diversification rate. These include most beetle species with phytophagous habits, but also several groups not typically or primarily associated with plants. Most of these groups originated in the Cretaceous, which is also when a majority of the most species-rich beetle families first appeared. An additional 12 clades showed evidence for significant decreases in diversification rate. These clades are species-poor in the Modern fauna, but collectively exhibit diverse trophic habits. The apparent success of beetles, as measured by species numbers, may result from their associations with widespread and diverse substrates – especially plants, but also including fungi, wood and leaf litter – but what facilitated these associations in the first place or has allowed these associations to flourish likely varies within and between lineages. Our results provide a uniquely well-resolved temporal and phylogenetic framework for studying patterns of innovation and diversification in Coleoptera, and a foundation for further sampling and resolution of the beetle tree of life

The Beetle Tree of Life Reveals the Order Coleoptera Survived End Permain Mass Extinction to Diversify During the Cretaceous Terrestrial Revolution

Here we present a phylogeny of beetles (Insecta: Coleoptera) based on DNA sequence data from eight nuclear genes, including six single-copy nuclear protein-coding genes, for 367 species representing 172 of 183 extant families. Our results refine existing knowledge of relationships among major groups of beetles. Strepsiptera was confirmed as sister to Coleoptera and each of the suborders of Coleoptera was recovered as monophyletic. Interrelationships among the suborders, namely Polyphaga (Adephaga (Archostemata, Myxophaga)), in our study differ from previous studies. Adephaga comprised two clades corresponding to Hydradephaga and Geadephaga. The series and superfamilies of Polyphaga were mostly monophyletic. The traditional Cucujoidea were recovered in three distantly related clades. Lymexyloidea was recovered within Tenebrionoidea. Several of the series and superfamilies of Polyphaga received moderate to maximal clade support in most analyses, for example Buprestoidea, Chrysomeloidea, Coccinelloidea, Cucujiformia, Curculionoidea, Dascilloidea, Elateroidea, Histeroidea and Hydrophiloidea. However, many of the relationships within Polyphaga lacked compatible resolution under maximum-likelihood and Bayesian inference, and/or lacked consistently strong nodal support. Overall, we recovered slightly younger estimated divergence times than previous studies for most groups of beetles. The ordinal split between Coleoptera and Strepsiptera was estimated to have occurred in the Early Permian. Crown Coleoptera appeared in the Late Permian, and only one or two lineages survived the end-Permian mass extinction, with stem group representatives of all four suborders appearing by the end of the Triassic. The basal split in Polyphaga was estimated to have occurred in the Triassic, with the stem groups of most series and superfamilies originating during the Triassic or Jurassic. Most extant families of beetles were estimated to have Cretaceous origins. Overall, Coleoptera experienced an increase in diversification rate compared to the rest of Neuropteroidea. Furthermore, 10 family-level clades, all in suborder Polyphaga, were identified as having experienced significant increases in diversification rate. These include most beetle species with phytophagous habits, but also several groups not typically or primarily associated with plants. Most of these groups originated in the Cretaceous, which is also when a majority of the most species-rich beetle families first appeared. An additional 12 clades showed evidence for significant decreases in diversification rate. These clades are species-poor in the Modern fauna, but collectively exhibit diverse trophic habits. The apparent success of beetles, as measured by species numbers, may result from their associations with widespread and diverse substrates - especially plants, but also including fungi, wood and leaf litter - but what facilitated these associations in the first place or has allowed these associations to flourish likely varies within and between lineages. Our results provide a uniquely well-resolved temporal and phylogenetic framework for studying patterns of innovation and diversification in Coleoptera, and a foundation for further sampling and resolution of the beetle tree of life.Facultad de Ciencias Naturales y Muse

In Vitro and In Vivo Characterization of the Alkaloid Nuciferine

RationaleThe sacred lotus (Nelumbo nucifera) contains many phytochemicals and has a history of human use. To determine which compounds may be responsible for reported psychotropic effects, we used in silico predictions of the identified phytochemicals. Nuciferine, an alkaloid component of Nelumbo nucifera and Nymphaea caerulea, had a predicted molecular profile similar to antipsychotic compounds. Our study characterizes nuciferine using in vitro and in vivo pharmacological assays.MethodsNuciferine was first characterized in silico using the similarity ensemble approach, and was followed by further characterization and validation using the Psychoactive Drug Screening Program of the National Institute of Mental Health. Nuciferine was then tested in vivo in the head-twitch response, pre-pulse inhibition, hyperlocomotor activity, and drug discrimination paradigms.ResultsNuciferine shares a receptor profile similar to aripiprazole-like antipsychotic drugs. Nuciferine was an antagonist at 5-HT2A, 5-HT2C, and 5-HT2B, an inverse agonist at 5-HT7, a partial agonist at D2, D5 and 5-HT6, an agonist at 5-HT1A and D4 receptors, and inhibited the dopamine transporter. In rodent models relevant to antipsychotic drug action, nuciferine blocked head-twitch responses and discriminative stimulus effects of a 5-HT2A agonist, substituted for clozapine discriminative stimulus, enhanced amphetamine induced locomotor activity, inhibited phencyclidine (PCP)-induced locomotor activity, and rescued PCP-induced disruption of prepulse inhibition without induction of catalepsy.ConclusionsThe molecular profile of nuciferine was similar but not identical to that shared with several approved antipsychotic drugs suggesting that nuciferine has atypical antipsychotic-like actions

A simple spreadsheet-based, MIAME-supportive format for microarray data: MAGE-TAB

BACKGROUND: Sharing of microarray data within the research community has been greatly facilitated by the development of the disclosure and communication standards MIAME and MAGE-ML by the MGED Society. However, the complexity of the MAGE-ML format has made its use impractical for laboratories lacking dedicated bioinformatics support. RESULTS: We propose a simple tab-delimited, spreadsheet-based format, MAGE-TAB, which will become a part of the MAGE microarray data standard and can be used for annotating and communicating microarray data in a MIAME compliant fashion. CONCLUSION: MAGE-TAB will enable laboratories without bioinformatics experience or support to manage, exchange and submit well-annotated microarray data in a standard format using a spreadsheet. The MAGE-TAB format is self-contained, and does not require an understanding of MAGE-ML or XML