Sex and stress modulate pupal defense response in tobacco hornworm

In insects, larval and adult defenses against predators have been well studied. However, pupal (also known as resting stage) defenses have been overlooked and not examined thoroughly. Although some pupa possess antipredator strategies such as hairs, spines, cryptic coloration, and exudation of chemicals, few studies have tested these responses and the factors affecting them. Here, we investigated the behavioral responses in tobacco hornworm Manduca sexta that pupates in soil by introducing an external stimulus using vibrations from an electric toothbrush to mimic predation. We observed that M. sexta made violent wriggling (twitching), followed by pulsating movements in response to the vibrational stimulus. Detailed examination showed that these twitches and pulsating events occurred more frequently and for longer periods of time in male pupa and were dependent on the magnitude of the stress (high and low frequency). However, when we estimated the angular force exerted by pupa using radian and angular momentum of twitches, it was found to be independent of pupal sex. A follow-up experiment on possible cascading effects of stress exposure on eclosion success revealed that low- and high-frequency stress exposure didn’t cause any of the common defects in eclosed adults. Our study clearly demonstrates that the so-called defenseless pupal stage uses a wide range of measurable defense behaviors that can actively defend against predators and should be examined further-linking observed behavior with underlying mechanisms

Redox-responsive nano-self assemblies for targeted cancer therapeutics

Background: Despite significant advances in cancer therapeutics, it remains one of the leading causes of deaths due to poor response to available treatment modalities and drug resistance. Combination therapy has shown the potential to provide a synergistic therapeutic effect and to overcome drug resistance. However, smart delivery systems that can improve the bioavailability and the delivery of multiple hydrophobic anti-cancer drugs simultaneously at the tumor site without normal organ toxicity could be an effective strategy for cancer treatment. Methods: Here, a PEGylated drug-drug conjugate (CUR-PEG-S-S-CPT) have been successfully synthesized by conjugating two hydrophobic anti-cancer molecules, curcumin and camptothecin through an ester and a redox-sensitive disulfide linkage (-S-S-), respectively, with the PEG chain, via in situ two-step reaction. This amphiphilic polymeric-dual drug conjugate was characterized in the presence and absence of the tannic acid (TA, a physical crosslinker) using various in vitro biophysical, analytical, and functional bioassays. Results: The newly synthesized amphiphilic CUR-PEG-S-S-CPT polymer was found to spontaneously self-assembled in presence of tannic acid into anionic comparatively smaller sized stable nano-assemblies in water in comparison to parent conjugate, where the drug forms hydrophobic core of the particle with negative chirality and left-handed helical arrangement. TA, in addition to help forming stable nano-assemblies in water, it was able produce FRET pair in water between these two anticancer drugs. These nano-assemblies exhibited enhanced cellular uptake and antiproliferative effect in cancer cells (AsPC1 and SW480) in comparison to the individual drugs. Interestingly, our nanoassemblies showed preferential cleavage, breakdown and release of drugs in tumor-relevant redox environment leading to disappearance of the FRET signal, thus can be highly effective for targeted cancer treatment. Conclusions: Our promising in vitro results with novel redox stimuli-responsive (CUR-PEG-S-S-CPT) conjugate system in presence of TA can be a highly useful advanced theranostic platform for effective cancer treatment/management

Comparación de columna total de ozono OMI-DOAS con mediciones terrestres en Argentina

Total ozone column (TOC) measurements through the Ozone Monitoring Instrument (OMI/NASA EOSAura) are compared with ground-based observations made using Dobson and SAOZ instruments for the period 2004–2019 and 2008–02/2020, respectively. The OMI data were inverted using the Differential Optical Absorption Spectroscopy algorithm (overpass OMI-DOAS). The four ground-based sites used for the analysis are located in subpolar and subtropical latitudes spanning from 34°S to 54°S in the Southern Hemisphere, in the Argentine cities of Buenos Aires (34.58°S, 58.36°W; 25 m a.s.l.), Comodoro Rivadavia (45.86°S, 67.50°W; 46 m a.s.l.), Río Gallegos (51.60°S, 69.30°W; 72 m a.s.l.) and Ushuaia (54.80°S, 68.30°W; 14 m a.s.l.). The linear regression analyzes showed correlation values greater than 0.90 for all sites. The OMI measurements revealed an overestimation of less than 4 % with respect to the Dobson instruments, while the comparison with the SAOZ instrument presented a very low underestimation of less than 1 %.En este trabajo se comparan mediciones de columna total de ozono (CTO) del Ozone Monitoring Instrument (OMI/NASA EOS-Aura), con observaciones terrestres de instrumentos Dobson y SAOZ para el periodo 2004–2019 y 2008–02/2020, respectivamente. Los datos del OMI analizados fueron los invertidos mediante el algoritmo Differential Optical Absorption Spectroscopy (overpass OMI-DOAS). Las 4 estaciones terrestres están ubicadas en latitudes subpolares y subtropicales del Hemisferio Sur, en las ciudades argentinas de Buenos Aires (34,58°S, 58,36°O; 25 m s.n.m.), Comodoro Rivadavia (45,86°S, 67,50°O; 46 m s.n.m.), Río Gallegos (51,60°S, 69,30°O; 72 m s.n.m.) y Ushuaia (54,80°S, 68,30°O; 14 m s.n.m.) cubriendo un rango latitudinal desde los 34°S hasta los 54°S. Los análisis de regresión lineal presentan valores de correlación superior a 0,90. Las mediciones OMI– DOAS muestran una sobrestimación menor al 4 % respecto de los instrumentos Dobson, mientras que la comparación respecto al instrumento SAOZ presenta una muy baja subestimación, menor al 1 %.Fil: Orte, Pablo Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; Argentina. Ministerio de Defensa. Instituto de Investigaciones Científicas y Técnicas para la Defensa; ArgentinaFil: Luccini, Eduardo Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Química e Ingeniería-Rosario; ArgentinaFil: Wolfram, Elian Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Ministerio de Defensa. Secretaria de Planeamiento. Servicio Meteorológico Nacional; Argentina. Universidad Tecnológica Nacional. Facultad Regional Buenos Aires; ArgentinaFil: Nollas, Fernando Martin. Ministerio de Defensa. Secretaria de Planeamiento. Servicio Meteorológico Nacional. Servicio Metereológico Nacional (sede Dorrego).; ArgentinaFil: Pallotta, Juan Vicente. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; ArgentinaFil: D'elia, Raul Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; ArgentinaFil: Carbajal, G.. Ministerio de Defensa. Secretaria de Planeamiento. Servicio Meteorológico Nacional. Servicio Metereológico Nacional (sede Dorrego).; ArgentinaFil: Mbatha, N.. University of Zululand; SudáfricaFil: Hlongwana, N.. University of Zululand; Sudáfric

A new formulation of oxalic acid for Varroa destructor control applied in Apis mellifera colonies in the presence of brood

International audienceAbstractAn organic product based on oxalic acid was evaluated for use in Varroa control under spring/summer climatic conditions in Argentina. The formulation consists of four strips made of cellulose impregnated with a solution based on oxalid acid. Forty-eight beehives were used to assess the product efficacy. Residues of the product were also tested in honey, bees, and wax. Each trial had respective control groups without oxalic treatment. At the beginning of the experiment, four strips of the formulation were applied to the colonies belonging to the treated group. Falling mites were counted after 7, 14, 21, 28, 35, and 42 days. After the last count, the strips were removed and colonies received two flumethrin strips for 45 days. Falling mites were counted throughout this period. Average efficacy of the organic product was 93.1 % with low variability. This product is an organic treatment designed for Varroa control during brood presence and represents a good alternative to the synthetic treatments

Internal health locus of control as a predictor of pain reduction in multidisciplinary inpatient treatment for chronic pain: a retrospective study.

Purpose Chronic pain is a major health concern and its treatment requires physiological as well as psychological interventions. This study investigates the predictive value of health locus of control (HLOC) in pain intensity in chronic pain patients in an inpatient treatment setting. Patients and methods Data of 225 patients with a chronic pain condition were collected in a psychosomatic university clinic in Switzerland. Self-report assessment tools were used to measure pain intensity pre- and posttreatment and with a questionnaire dimensions of the HLOC were captured. Using hierarchic linear regression analysis, the predictive value of HLOC was investigated. Results A higher internal HLOC at pre-treatment was associated with a greater reduction in pain intensity from pre- to posttreatment (β = -0.151, p<0.05). For social-external and fatalistic-external HLOC no significant effects were observed. Conclusion Internal HLOC showed predictive value regarding the reduction in pain intensity in a multidisciplinary inpatient treatment for chronic pain, whereas social-external and fatalistic-external HLOC did not. Early interventions to strengthen internal beliefs of health control may be a promising component in multidisciplinary inpatient treatment for patients with chronic pain

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the healthcare environment: a bacterial genome-wide association study

Staphylococcus aureus is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in S. aureus remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in S. aureus disease. To investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic S. aureus nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage. All major global lineages were represented in both bacteraemia and carriage, with no evidence for different infection rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in dfrB were significantly associated with bacteraemia-vs-carriage (P=10-8.9-10-9.3). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of mecA (HMP=10-5.3) as well as the presence of SCCmec (HMP=10-4.4). Among S. aureus carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein prsA, where kmers representing conserved sequence allele were associated with CA carriage (P=10-7.1-10-19.4), while in gyrA, a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (P=10-7.2). In an extensive study of S. aureus bacteraemia and nasal carriage in the UK, we found strong evidence that all S. aureus lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment. Genomic variation in the foldase protein prsA is a novel genomic marker of healthcare origin in S. aureus but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and healthcare-associated carriage, suggesting that AMR increases the propensity not only to survive in healthcare environments, but also to cause invasive disease

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication