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Background Prostate cancer patients with locoregional lymph node disease at diagnosis (N1M0) still have a limited prognosis despite the improvements provided by aggressive curative intent multimodal locoregional external beam radiation therapy (EBRT) with systemic androgen deprivation therapy (ADT). Although some patients can be cured and the majority of patients have a long survival, the 5-year biochemical failure rate is currently 29–47%. [177Lu]Lu-PSMA-617 has shown impressive clinical and biochemical responses with low toxicity in salvage setting in metastatic castration-resistant prostate cancer. This study aims to explore the combination of standard EBRT and ADT complemented with a single administration of [177Lu]Lu-PSMA-617 in curative intent treatment for N1M0 prostate cancer. Hypothetically, this combined approach will enhance EBRT to better control macroscopic tumour localizations, and treat undetected microscopic disease locations inside and outside EBRT fields. Methods The PROQURE-I study is a multicenter prospective phase I study investigating standard of care treatment (7 weeks EBRT and 3 years ADT) complemented with one concurrent cycle (three, six, or nine GBq) of systemic [177Lu]Lu-PSMA-617 administered in week two of EBRT. A maximum of 18 patients with PSMA-positive N1M0 prostate cancer will be included. The tolerability of adding [177Lu]Lu-PSMA-617 will be evaluated using a Bayesian Optimal Interval (BOIN) dose-escalation design. The primary objective is to determine the maximum tolerated dose (MTD) of a single cycle [177Lu]Lu-PSMA-617 when given concurrent with EBRT + ADT, defined as the occurrence of Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 grade three or higher acute toxicity. Secondary objectives include: late toxicity at 6 months, dosimetric assessment, preliminary biochemical efficacy at 6 months, quality of life questionnaires, and pharmacokinetic modelling of [177Lu]Lu-PSMA-617. Discussion This is the first prospective study to combine EBRT and ADT with [177Lu]Lu-PSMA-617 in treatment naïve men with N1M0 prostate cancer, and thereby explores the novel application of [177Lu]Lu-PSMA-617 in curative intent treatment. It is considered likely that this study will confirm tolerability as the combined toxicity of these treatments is expected to be limited. Increased efficacy is considered likely since both individual treatments have proven high anti-tumour effect as mono-treatments. Trial registration ClinicalTrials, NCT05162573. Registered 7 October 2021.

Implant-based reconstruction is currently the most common postmastectomy breast reconstruction modality. The one-stage subpectoral approach is widely performed but entails many complications. Prepectoral direct-to-implant (DTI) reconstruction resolves many of these issues. Currently, only a relatively small number of studies have compared the outcomes of these two approaches. The aim of this study is to evaluate and compare the outcomes of prepectoral and subpectoral direct-to-implant immediate breast reconstruction. Data was obtained from all patients between November 2017 and January 2020 from accrual patient records. They were organized into one of two cohorts, prepectoral and subpectoral reconstruction, according to surgeon’s assessment of the postmastectomy flap viability. A total of 113 women (150 breasts) underwent direct-to-implant reconstruction by a single plastic surgeon (Y.G), with 82 patients (72.6%) in the prepectoral cohort. In the prepectoral group, the mean postoperative day of drain removal was 13.59 (SD=5.43) days, while in the subpectoral group, it was a mean of 16.13 (SD=5.75) (p=0.016). The total mean number of days when postoperative narcotics were administered was 2.61 (SD=2.93) in the prepectoral cohort and 5.16 (SD=4.57) in the subpectoral cohort (p=0.003). There were no statistically significant differences regarding major or minor complications between the groups. A wrapping technique analysis in the prepectoral cohort shows no complications in the oblique subgroup. This study demonstrates that prepectoral direct-to-implant reconstruction is a safe modality with a lower usage of postoperative narcotics and a shorter period until drainage removal.

Gaseous fuels are increasingly used to power internal combustion engines. Spark-ignition engines are fuelled with liquefied petroleum gas. Engines powered by gaseous fuels are characterized by good ecological properties due to the emission of pollutants. The paper presents the results of empirical tests of two passenger cars with spark-ignition engines powered alternatively: with gasoline and LPG fuel. The engines were equipped with fifth generation LPG fuelling systems. The tests were performed on a chassis dynamometer in tests used in approval procedures in Europe (NEDC test) and in the United States of America (FTP-75 test). These tests were the basis for determining the average specific distance emission of pollutants (carbon monoxide, hydrocarbons, nitrogen oxides and carbon dioxide) during the tests. The engines were also tested in the conditions of the external speed characteristics while accelerating the car in third gear. It was found that the type of fuelling the engines with both fuels has little influence on the dynamic properties of the engine due to the effective power. The tests clearly showed a decrease in specific distance emission of carbon monoxide and carbon dioxide. The relative reduction in specific distance emission of carbon monoxide was in the order of (45–65)%, and carbon dioxide—about 10%. For hydrocarbons, there was an increase in specific distance emission of hydrocarbons for the fuelling of engines with LPG, while for hydrocarbons, there was a large difference in the value of the relative specific distance emission difference for both tests. (The relative difference was from 25 to 175%.) Specific distance emission of nitrogen oxides turned out to be significantly higher when running engines with LPG. The reason for this is leaning of the fuel mixture at high rotational speed during acceleration of the car, which may result from insufficient conversion efficiency of engine control algorithms in the LPG fuel mode.

Background Mosquitoes are responsible for disease transmission worldwide. They possess the ability to discriminate between different ecological resources, including nectar sources, animal hosts and oviposition sites, a feature mediated by their olfactory system. Insect repellents, such as N,N-diethyl-meta-toluamide (also called DEET), have been shown to activate and inhibit mosquito odorant receptors, resulting in behavioral modulation. This and other repellents currently available for personal protection against mosquitoes are topically applied to the skin and operate at a short range. In our search for potential long-range inhibitors of attractants to human hosts, we have hypothesized that the shared chemical similarities between indole and DEET may confer the former with the ability to block odorant receptor function and inhibit human host attraction in a similar way as DEET. Methods We used the two-electrode voltage clamp system to assay Xenopus laevis oocytes as a platform to compare the pharmacological effect of commercially available insect repellents and indole on the Aedes aegypti (R)-1-octen-3-ol receptor, OR8, a receptor involved in the decision-making of female mosquitoes to identify human hosts. We also conducted arm-in-a-cage and wind-tunnel bioassays to explore the effect of indole on human host-seeking female Aedes aegypti mosquitoes. Results Our results demonstrate that indole inhibited the Aedes aegypti (R)-1-octen-3-ol receptor OR8. In our arm-in-a-cage assay, 1 M of DEET reduced mosquito visits on average by 69.3% while the same indole concentration achieved 97.8% inhibition. This effect of indole on flight visits was dose-dependent and disappeared at 1 μM. In the flight tunnel, indole elicited on average 27.5% lower speed, 42.3% lower upwind velocity and 30.4% higher tortuosity compared to the control. Conclusions Indole significantly inhibits OR8 activation by (R)-1-octen-3-ol, mosquito visits to a human hand and long-range human host-seeking. The volatility of indole may be leveraged to develop a novel insect repellent in the context of personal mosquito protection. Graphical abstract

Microbial community analysis of crude oil containing sludge collected from Duliajan oil field, Assam, India, showed the predominance of hydrocarbon-degrading bacteria such as Pseudomonas (20.1%), Pseudoxanthomonas (15.8%), Brevundimonas (1.6%), and Bacillus (0.8%) alongwith anaerobic, fermentative, nitrogen-fixing, nitrate-, sulfate-, and metal-reducing, syntrophic bacteria, and methanogenic archaea. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis indicated gene collection for potential hydrocarbon degradation, lipid, nitrogen, sulfur, and methane metabolism. The culturable microbial community was predominated by Pseudomonas and Bacillus with the metabolic potential for utilizing diverse hydrocarbons, crude oil, and actual petroleum sludge as sole carbon source during growth and tolerating various environmental stresses prevailing in such contaminated sites. More than 90% of the isolated strains could produce biosurfactant and exhibit catechol 2,3-dioxygenase activity. Nearly 30% of the isolates showed alkane hydroxylase activity with the maximum specific activity of 0.54 μmol min-1 mg-1. The study provided better insights into the microbial diversity and functional potential within the crude oil containing sludge which could be exploited for in situ bioremediation of contaminated sites.

The influence of fluctuating water temperature and dietary oxytetracycline (OTC) at 0 (0X), 80 (1X), 240 (3X), 400 (5X) and 800 mg (10X)/kg biomass/day for 30 consecutive days on the safety of monosex (all male) Nile tilapia Oreochromis niloticus fries in terms of feeding, growth, survival and histopathology of vital organs were assessed. A dose-dependent decline in feed intake and biomass was recorded. The OTC-dosed groups recorded higher mortalities than the control. The therapeutic OTC-dosing (1X) in conjunction with low temperature caused 75.56 ± 8.01% mortality and 25.75% reduced feed intake in 30 days. The mortalities increased with increasing OTC-doses from 85.19 ± 3.39% (1X) to 95.56 ± 2.22% (10X) and fluctuating temperature (12.00-21.50°C) even after the withdrawal of OTC. Relatively mild to moderate histopathological lesions were observed in the kidney, liver and intestine of OTC-dosed fries. These results suggested that dietary OTC and low water temperature may cause adverse effects on monosex O. niloticus fries.

Endoglucanase, particularly those, which can withstand extreme conditions are in demand in different industrial settings. In this direction, a halophilic cellulolytic bacterial strain EN1 was isolated from decomposed wood particles of India’s largest inland hypersaline Sambhar Lake in Rajasthan. Based on 16S rRNA gene sequence homology, the bacterium was identified as Salisediminibacterium halotolerans. It constitutively secretes extracellular endoglucanase in heterotrophic culture supernatant supplemented with or without carboxy-methyl cellulose. EN1 endoglucanase is active at pH 8.0–11.0, and 10–30% NaCl with optimum values of pH 11.0, and 25% NaCl. Under these optimum conditions, the enzyme retained up to 90% activity for 8 h. Activity was enhanced by some metal ions (5 mM) in order of Cu2+ (273%), Ni2+ (139%) and Fe2+ (125%); and decreased by Mg2+ (72%) and EDTA (56%). The enzyme was stable in different organic solvents (30% v/v), namely ethanol (108%), hexane (95%), methanol (93%), and iso-propanol (92%). The endoglucanase was effectively used for in situ saccharification of alkali-pretreated rice straw with 50 µg mL−1 reducing ends released after 120 h. These unique features of the extracellular endoglucanase reported for the first time from the genera Salisediminibacterium indicate its prospects in different industrial settings particularly for bioethanol production.