Glyphosate Resistance of <em>Chloris virgata</em> Weed in Australia and Glyphosate Mobility Are Connected Problems

The purpose of this review paper is to address two major aspects of glyphosate application on farmers’ fields. The first aspect is the development of glyphosate resistance in weeds like Chloris virgata, and the second aspect is glyphosate mobility, which is directly controlled by soil sorption processes and indirectly by molecule degradation processes. This is a global problem, as excessive glyphosate residues in groundwater, drinking water, and urine of subsistence farmers from intensive agricultural localities have been reported, which can pose a risk to human health. Approaches like biochar as a possible strategy to control glyphosate leaching and crop competition as a cultural method to control glyphosate-resistant weed like Chloris virgata can be the potential solutions of the glyphosate resistance and glyphosate mobility

Procjena in vitro protoskolicidne učinkovitosti metanolnih biljnih ekstrakata na hidatidne ciste

The present study aimed at an evaluation of the protoscolicidal potential of methanolic extracts of three herbs; Ferula asafoetida (dried latex), Trachyspermum ammi (fruits) and Hippophae salicifolia (leaves) at three different concentrations (10, 20 and 30 mg/mL) for 20, 40 and 60 minute treatment intervals, with respect to standard allopathic drug albendazole. The in-vitro viability of the protoscolices was assessed by the Eosin exclusion method. The slope of mortality and lethal concentration for 50% (LC50) was determined from the regression graphs of the probit mortality of protoscolices plotted against log values of increasing concentrations of herbal extracts for 60 minute treatment intervals. The percentage of mortality caused by various extracts at concentrations ranging from 10-30 mg/mL varied from 29.54-97.76% with maximum mortality of 97.76, 97.30 and 81.91% recorded with methanolic extracts of F. asafoetida, T. ammi and H. salicifolia, respectively. Among all the extracts, the highest protoscolicidal activity was exhibited by F. asafoetida at 20 and 30 mg/mL concentrations in the 60 (97.16%) and 40/60 minutes (97.20% and 97.76%) treatments, respectively, and it showed a minimum LC50 value of 0.204, followed by T. ammi at 0.933. As compared to the standard allopathic drug, albendazole, the methanolic extracts of F. asafoetida and T. ammi exhibited better or comparable protoscolicidal activities.Cilj je istraživanja bila procjena protoskolicidnog potencijala metanolnih ekstrakata triju biljaka: Ferula asafoetida (sušena smola), Trachyspermum ammi (voće) i Hippophae salicifolia (lišće) u trima različitim koncentracijama (10, 20 i 30 mg/mL) u 20, 40 i 60-minutnim pokusnim intervalima u odnosu na standardni alopatski lijek albendazol. In vitro vitalnost protoskoleksa procijenjena je metodom isključivanja eozina. Krivulja pomora i smrtonosne koncentracije za 50 % (LC50) određena je iz regresijskih grafikona mortaliteta protoskoleksa u odnosu na log vrijednosti rastućih koncentracija biljnih ekstrakata tijekom 60-minutnog intervala. Pomor uzrokovan različitim ekstraktima u koncentracijama od 10 do 30 mg/mL varirao je od 29,54 do 97,76 % s najvišim postotkom od 97,76, 97,30 i 81,91 % u slučaju metanolnih ekstrakata F. asafoetida, T. ammi i H. salicifolia. Od svih primijenjenih ekstrakata najvišu protoskolicidnu aktivnost imala je F. asafoetida u koncentracijama od 20 i 30 mg/mL tijekom tretmana od 60 (97,16 %) i 40/60 minuta (97,20 i 97,76%), te je pokazala minimalnu vrijednost LC50 od 0,204, praćenu s T. ammi od 0,933. Usporedbom sa standardnim antiparazitikom albendazolom, metanolni ekstrakti biljaka F. asafoetida i T. ammi ostvarili su bolji ili slični protoskolicidni učinak

Dose optimization of ceftriaxone-vancomycin combination using fractional inhibitory concentration kinetics in resistant bacteria

The notorious Staphylococcus aureus resistant strains with ever changing resistance patterns have limited treatment options and have led to substantial number of deaths. Almost dried antibiotic pipeline has led us to look into combinations of already approved antibiotics for tackling rising incidence of antibacterial resistance. Recommended use of vancomycin and ceftriaxone together for treating severe infections involving resistant S. aureus is limited by dose adjustments and different dose frequencies. We have developed a pharmacodynamically synergistic fixed dose combination (FDC) of ceftriaxone and vancomycin (2:1), for eliminating individual component dose adjustments and frequencies. For identification of optimum exposure-response of FDC, one compartment in vitro system was used for dose escalation, fractionation and dose-response studies. The in-silico pharmacokinetic/pharmacodynamic (PK/PD) modeling, simulations and validations were done. The results suggested % T>MICcomb (percentage of time fractional inhibitory concentrations of the drugs combined remained above the MICcomb [minimum inhibitory concentration for FDC]) followed by AUCcomb/MICcomb (ratio of area under fractional inhibitory curves to MICcomb) can predict the exposure (dose of FDC)-response (reduction in bacterial load) relationships effectively (r2 >0.9). Total exposure of 6 g in two divided doses (3 g each) was identified to be optimum. Monte Carlo simulations were performed to evaluate the effect of increasing doses against different MICs. Clinical breakpoint of the FDC was identified to be 4 µg/mL, which was 2 fold higher than that of vancomycin suggesting better antibacterial coverage

Cardiovascular/Stroke Risk Stratification in Diabetic Foot Infection Patients Using Deep Learning-Based Artificial Intelligence: An Investigative Study

A diabetic foot infection (DFI) is among the most serious, incurable, and costly to treat conditions. The presence of a DFI renders machine learning (ML) systems extremely nonlinear, posing difficulties in CVD/stroke risk stratification. In addition, there is a limited number of well-explained ML paradigms due to comorbidity, sample size limits, and weak scientific and clinical validation methodologies. Deep neural networks (DNN) are potent machines for learning that generalize nonlinear situations. The objective of this article is to propose a novel investigation of deep learning (DL) solutions for predicting CVD/stroke risk in DFI patients. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) search strategy was used for the selection of 207 studies. We hypothesize that a DFI is responsible for increased morbidity and mortality due to the worsening of atherosclerotic disease and affecting coronary artery disease (CAD). Since surrogate biomarkers for CAD, such as carotid artery disease, can be used for monitoring CVD, we can thus use a DL-based model, namely, Long Short-Term Memory (LSTM) and Recurrent Neural Networks (RNN) for CVD/stroke risk prediction in DFI patients, which combines covariates such as office and laboratory-based biomarkers, carotid ultrasound image phenotype (CUSIP) lesions, along with the DFI severity. We confirmed the viability of CVD/stroke risk stratification in the DFI patients. Strong designs were found in the research of the DL architectures for CVD/stroke risk stratification. Finally, we analyzed the AI bias and proposed strategies for the early diagnosis of CVD/stroke in DFI patients. Since DFI patients have an aggressive atherosclerotic disease, leading to prominent CVD/stroke risk, we, therefore, conclude that the DL paradigm is very effective for predicting the risk of CVD/stroke in DFI patients

Community mobilisation and health management committee strengthening to increase birth attendance by trained health workers in rural Makwanpur, Nepal: study protocol for a cluster randomised controlled trial

Background: Birth attendance by trained health workers is low in rural Nepal. Local participation in improving health services and increased interaction between health systems and communities may stimulate demand for health services. Significant increases in birth attendance by trained health workers may be affected through community mobilisation by local women's groups and health management committee strengthening. We will test the effect of community mobilisation through women's groups, and health management committee strengthening, on institutional deliveries and home deliveries attended by trained health workers in Makwanpur District. Design: Cluster randomised controlled trial involving 43 village development committee clusters. 21 clusters will receive the intervention and 22 clusters will serve as control areas. In intervention areas, Female Community Health Volunteers are supported in convening monthly women's groups. The groups work through an action research cycle in which they consider barriers to institutional delivery, plan and implement strategies to address these barriers with their communities, and evaluate their progress. Health management committees participate in three-day workshops that use appreciative inquiry methods to explore and plan ways to improve maternal and newborn health services. Follow-up meetings are conducted every three months to review progress. Primary outcomes are institutional deliveries and home deliveries conducted by trained health workers. Secondary outcome measures include uptake of antenatal and postnatal care, neonatal mortality and stillbirth rates, and maternal morbidity

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

The regulation of IL-10 expression

Interleukin (IL)-10 is an important immunoregulatory cytokine and an understanding of how IL-10 expression is controlled is critical in the design of immune intervention strategies. IL-10 is produced by almost all cell types within the innate (including macrophages, monocytes, dendritic cells (DCs), mast cells, neutrophils, eosinophils and natural killer cells) and adaptive (including CD4(+) T cells, CD8(+) T cells and B cells) immune systems. The mechanisms of IL-10 regulation operate at several stages including chromatin remodelling at the Il10 locus, transcriptional regulation of Il10 expression and post-transcriptional regulation of Il10 mRNA. In addition, whereas some aspects of Il10 gene regulation are conserved between different immune cell types, several are cell type- or stimulus-specific. Here, we outline the complexity of IL-10 production by discussing what is known about its regulation in macrophages, monocytes, DCs and CD4(+) T helper cells

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe