The Effect of Insecticide Synergists on the Response of Scabies Mites to Pyrethroid Acaricides

Synergists are commonly used in combination with pesticides to suppress metabolism-based resistance and increase the efficacy of the agents. They are also useful as tools for laboratory investigation of specific resistance mechanisms based on their ability to inhibit specific metabolic pathways. To determine the role of metabolic degradation as a mechanism for acaricide resistance in human scabies, PBO (piperonyl butoxide), DEF (S,S,S-tributyl phosphorotrithioate) and DEM (diethyl maleate) were used with permethrin as synergists in a bioassay of mite killing. A statistically significant difference in survival time of permethrin-resistant Sarcoptes scabiei variety canis was noted when any of the three synergists were used in combination with permethrin compared to survival time of mites exposed to permethrin alone (p<0.0001). These results indicate the potential utility of synergists in reversing tolerance to pyrethroid-based acaricides (i.e. the addition of synergists to permethrin-containing topical acaricide cream commonly used to treat scabies). To further verify specific metabolic pathways being inhibited by these synergists, enzyme assays were developed to measure esterase, glutathione S-transferase (GST) and cytochrome P450 monooxygenase activity in scabies mites. Results of in vitro enzyme inhibition experiments showed lower levels of esterase activity with DEF; lower levels of GST activity with DEM and lower levels of cytochrome monooxygenase activity with PBO. These findings indicate a metabolic mechanism as mediating pyrethroid resistance in scabies mites

Association of IGF1 and KDM5A polymorphisms with performance, fatness and carcass traits in chickens

Two functional and positional candidate genes were selected in a region of chicken chromosome 1 (GGA1), based on their biological roles, and also where several quantitative trait loci (QTL) have been mapped and associated with performance, fatness and carcass traits in chickens. The insulin-like growth factor 1 (IGF1) gene has been associated with several physiological functions related to growth. The lysine (K)-specific demethylase 5A (KDM5A) gene participates in the epigenetic regulation of genes involved with the cell cycle. Our objective was to find associations of selected single-nucleotide polymorphisms (SNPs) in these genes with performance, fatness and carcass traits in 165 F chickens from a resource population. In the IGF1 gene, 17 SNPs were detected, and in the KDM5A gene, nine SNPs were detected. IGF1 SNP c. 47673G > A was associated with body weight and haematocrit percentage, and also with feed intake and percentages of abdominal fat and gizzard genotype × sex interactions. KDM5A SNP c. 34208C > T genotype × sex interaction affected body weight, feed intake, percentages of abdominal fat (p = 0. 0001), carcass, gizzard and haematocrit. A strong association of the diplotype × sex interaction (p < 0. 0001) with abdominal fat was observed, and also associations with body weight, feed intake, percentages of carcass, drums and thighs, gizzard and haematocrit. Our findings suggest that the KDM5A gene might play an important role in the abdominal fat deposition in chickens. The IGF1 and KDM5A genes are strong candidates to explain the QTL mapped in this region of GGA1

Thermodynamics of SU(N) Yang-Mills theories in 2+1 dimensions II - The deconfined phase

We present a non-perturbative study of the equation of state in the deconfined phase of Yang-Mills theories in D=2+1 dimensions. We introduce a holographic model, based on the improved holographic QCD model, from which we derive a non-trivial relation between the order of the deconfinement phase transition and the behavior of the trace of the energy-momentum tensor as a function of the temperature T. We compare the theoretical predictions of this holographic model with a new set of high-precision numerical results from lattice simulations of SU(N) theories with N=2, 3, 4, 5 and 6 colors. The latter reveal that, similarly to the D=3+1 case, the bulk equilibrium thermodynamic quantities (pressure, trace of the energy-momentum tensor, energy density and entropy density) exhibit nearly perfect proportionality to the number of gluons, and can be successfully compared with the holographic predictions in a broad range of temperatures. Finally, we also show that, again similarly to the D=3+1 case, the trace of the energy-momentum tensor appears to be proportional to T^2 in a wide temperature range, starting from approximately 1.2 T_c, where T_c denotes the critical deconfinement temperature.Comment: 2+36 pages, 10 figures; v2: comments added, curves showing the holographic predictions included in the plots of the pressure and energy and entropy densities, typos corrected: version published in JHE

In vitro Induction of Entamoeba histolytica Cyst-like Structures from Trophozoites

Inhibition of encystment can be conceived as a potentially useful mechanism to block the transmission of Entamoeba histolytica under natural conditions. Unfortunately, amoeba encystment has not been achieved in vitro and drugs inhibiting the formation of cysts are not available. Luminal conditions inducing encystment in vivo are also unknown, but cellular stress such as exposure to reactive oxygen species from immune cells or intestinal microbiota could be involved. A role for certain divalent cations as cofactors of enzymes involved in excystment has also been described. In this study, we show that trophozoite cultures, treated with hydrogen peroxide in the presence of trace amounts of several cations, transform into small-sized spherical and refringent structures that exhibit resistance to different detergents. Ultrastructural analysis under scanning and transmission electron microscopy revealed multinucleated structures (some with four nuclei) with smooth, thick membranes and multiple vacuoles. Staining with calcofluor white, as well as an ELISA binding assay using wheat germ agglutinin, demonstrated the presence of polymers of N-acetylglucosamine (chitin), which is the primary component of the natural cyst walls. Over-expression of glucosamine 6-phosphate isomerase, likely to be the rate-limiting enzyme in the chitin synthesis pathway, was also confirmed by RT-PCR. These results suggest that E. histolytica trophozoites activated encystment pathways when exposed to our treatment

Liver transplantation for patients with acute-on-chronic liver failure (ACLF) in Europe: Results of the ELITA/EF-CLIF collaborative study (ECLIS)

BACKGROUND AND AIMS: Liver transplantation (LT) has been proposed to be an effective salvage therapy even for the sickest patients with acute-on-chronic liver failure (ACLF). This large collaborative study was designed to address the current clinical practice and outcomes of ACLF patients wait listed (WL) for LT in Europe. METHODS: Retrospective study including 308 consecutive ACLF patients, listed in 20 centres across 8 European countries, from January 2018 to June 2019. RESULTS: 2677 patients received a LT, 1216 (45.4%) for decompensated cirrhosis (DC). Of these, 234 (19.2%) had ACLF at LT: ACLF-1, 58 (4.8%); ACLF-2, 78 (6.4%); and ACLF-3, 98 (8.1%). Wide variations were observed amongst countries: France and Germany had high rates of ACLF-2/3 (27-41%); Italy, Switzerland, Poland and Netherlands had medium rates (9-15%); and United Kingdom and Spain had low rates (3-5%) (p 4 mmol/L (HR 3.14, 95% CI 1.37-7.19), recent infection from multi-drug resistant organisms (HR 3.67, 95% CI 1.63-8.28), and renal replacement therapy (HR 2.74, 95% CI 1.37-5.51) were independent predictors of post-LT mortality. During the same period, 74 patients with ACLF died on the WL. In an intention-to-treat analysis, one-year survival of ACLF patients on the LT WL was 73% for ACLF-1 or -2 and 50% for ACLF-3. CONCLUSION: The results reveal wide variations in listing patients with ACLF in Europe despite favorable post-LT survival. Risk factors for mortality were identified, allowing a more precise prognostic assessment of ACLF patients for potential LT. LAY SUMMARY: Acute on chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation is an effective therapeutic option. This study has demonstrated that in Europe, referral and access to liver transplantation (LT) for patients with ACLF needs to be harmonized to avoid inequities. Post-LT survival for patients with ACLF was >80% after 1 year and some factors have been identified for selecting patients with favorable outcomes

Preoperative systemic inflammation and perioperative myocardial injury: prospective observational multicentre cohort study of patients undergoing non-cardiac surgery

Medical Research Council and British Journal of Anaesthesia clinical research training fellowship (grant reference MR/M017974/1) to T.E.F.A.; UK National Institute for Health Research Professorship to R.P.; British Journal ofAnaesthesia/Royal College of Anaesthetists basic science Career Development award, British Oxygen Company research chair grant in anaesthesia from the Royal College of Anaesthetists, and British Heart Foundation Programme Grant (RG/14/4/30736) to G.L.A

Inoculations with Arbuscular Mycorrhizal Fungi Increase Vegetable Yields and Decrease Phoxim Concentrations in Carrot and Green Onion and Their Soils

Background As one of the most widely used organophosphate insecticides in vegetable production, phoxim (C12H15N2O3PS) is often found as residues in crops and soils and thus poses a potential threat to public health and environment. Arbuscular mycorrhizal (AM) fungi may make a contribution to the decrease of organophosphate residues in crops and/or the degradation in soils, but such effects remain unknown. Methodology/Principal Findings A greenhouse pot experiment studied the influence of AM fungi and phoxim application on the growth of carrot and green onion, and phoxim concentrations in the two vegetables and their soil media. Treatments included three AM fungal inoculations with Glomus intraradices BEG 141, G. mosseae BEG 167, and a nonmycorrhizal control, and four phoxim application rates (0, 200, 400, 800 mg l−1, while 400 mg l−1 rate is the recommended dose in the vegetable production system). Carrot and green onion were grown in a greenhouse for 130 d and 150 d. Phoxim solution (100 ml) was poured into each pot around the roots 14d before plant harvest. Results showed that mycorrhizal colonization was higher than 70%, and phoxim application inhibited AM colonization on carrot but not on green onion. Compared with the nonmycorrhizal controls, both shoot and root fresh weights of these two vegetables were significantly increased by AM inoculations irrespective of phoxim application rates. Phoxim concentrations in shoots, roots and soils were increased with the increase of phoxim application rate, but significantly decreased by the AM inoculations. Soil phosphatase activity was enhanced by both AM inocula, but not affected by phoxim application rate. In general, G. intraradices BEG 141 had more pronounced effects than G. mosseae BEG 167 on the increase of fresh weight production in both carrot and green onion, and the decrease of phoxim concentrations in plants and soils. Conclusions/Significance Our results indicate a promising potential of AM fungi for enhancing vegetable production and reducing organophosphorus pesticide residues in plant tissues and their growth media, as well as for the phytoremediation of organophosphorus pesticide-contaminated soils

High-Throughput High-Resolution Class I HLA Genotyping in East Africa

HLA, the most genetically diverse loci in the human genome, play a crucial role in host-pathogen interaction by mediating innate and adaptive cellular immune responses. A vast number of infectious diseases affect East Africa, including HIV/AIDS, malaria, and tuberculosis, but the HLA genetic diversity in this region remains incompletely described. This is a major obstacle for the design and evaluation of preventive vaccines. Available HLA typing techniques, that provide the 4-digit level resolution needed to interpret immune responses, lack sufficient throughput for large immunoepidemiological studies. Here we present a novel HLA typing assay bridging the gap between high resolution and high throughput. The assay is based on real-time PCR using sequence-specific primers (SSP) and can genotype carriers of the 49 most common East African class I HLA-A, -B, and -C alleles, at the 4-digit level. Using a validation panel of 175 samples from Kampala, Uganda, previously defined by sequence-based typing, the new assay performed with 100% sensitivity and specificity. The assay was also implemented to define the HLA genetic complexity of a previously uncharacterized Tanzanian population, demonstrating its inclusion in the major East African genetic cluster. The availability of genotyping tools with this capacity will be extremely useful in the identification of correlates of immune protection and the evaluation of candidate vaccine efficacy

Proteomic Analysis of the Cyst Stage of Entamoeba histolytica

We used tandem mass spectrometry to identify E. histolytica cyst proteins in 5 cyst positive stool samples. We report the identification of 417 non-redundant E. histolytica proteins including 195 proteins that were not identified in existing trophozoite derived proteome or EST datasets, consistent with cyst specificity. Because the cysts were derived directly from patient samples with incomplete purification, a limited number of proteins were identified (N = 417) that probably represent only a partial proteome. Nevertheless, the study succeeded in identifying proteins that are likely to be abundant in the cyst stage of the parasite. Several of these proteins may play roles in E. histolytica stage conversion or cyst function. Proteins identified in this study may be useful markers for diagnostic detection of E. histolytica cysts. Overall, the data generated in this study promises to aid the understanding of the cyst stage of the parasite which is vital for disease transmission and pathogenesis in E. histolytica