Does coevolution in refugia drive mimicry in bumble bees? Insights from a South Asian mimicry group.

Müllerian mimicry was proposed to be an example of a coevolved mutualism promoted by population isolation in glacial refugia. This, however, has not been well supported in butterfly models. Here, we use genomic data to test this theory while examining the population genetics behind mimetic diversification in a pair of co-mimetic bumble bees, Bombus breviceps Smith and Bombus trifasciatus Smith. In both lineages, populations were structured by geography but not as much by color pattern, suggesting sharing of color alleles across regions of restricted gene flow and formation of mimicry complexes in the absence of genetic differentiation. Demographic analyses showed mismatches between historical effective population size changes and glacial cycles, and niche modeling revealed only mild habitat retraction during glaciation. Moreover, mimetic subpopulations of the same color form in the two lineages only in some cases exhibit similar population history and genetic divergence. Therefore, the current study supports a more complex history in this comimicry than a simple refugium-coevolution model.

Differentiation of Listeria monocytogenes serotypes using near infrared hyperspectral imaging.

Among the severe foodborne illnesses, listeriosis resulting from the pathogen Listeria monocytogenes exhibits one of the highest fatality rates. This study investigated the application of near infrared hyperspectral imaging (NIR-HSI) for the classification of three L. monocytogenes serotypes namely serotype 4b, 1/2a and 1/2c. The bacteria were cultured on Brain Heart Infusion agar, and NIR hyperspectral images were captured in the spectral range 900-2500 nm. Different pre-processing methods were applied to the raw spectra and principal component analysis was used for data exploration. Classification was achieved with partial least squares discriminant analysis (PLS-DA). The PLS-DA results revealed classification accuracies exceeding 80 % for all the bacterial serotypes for both training and test set data. Based on validation data, sensitivity values for L. monocytogenes serotype 4b, 1/2a and 1/2c were 0.69, 0.80 and 0.98, respectively when using full wavelength data. The reduced wavelength model had sensitivity values of 0.65, 0.85 and 0.98 for serotype 4b, 1/2a and 1/2c, respectively. The most relevant bands for serotype discrimination were identified to be around 1490 nm and 1580-1690 nm based on both principal component loadings and variable importance in projection scores. The outcomes of this study demonstrate the feasibility of utilizing NIR-HSI for detecting and classifying L. monocytogenes serotypes on growth media.

Disability Associated with Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation: Analysis of a Cross-Sectional US Patient Survey.

INTRODUCTION: Chronic graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation (HSCT) is associated with poor health-related quality of life (HRQoL) and functional status. However, few studies have evaluated chronic GVHD-related disability and specific activity limitations from a patient perspective. The objective of this analysis was to assess physical, cognitive, and work disability, and describe factors predictive of disability in patients with chronic GVHD in the potentially employable general workforce. METHODS: The cross-sectional, online, Living With Chronic GVHD Patient Survey was administered in 2020 to adult US patients who reported an active chronic GVHD diagnosis (i.e., within the previous 5 years) following HSCT. Data included demographics, diagnosis, work status, chronic GVHD symptoms per the Lee Symptom Scale (LSS), and effects on daily living activities. Descriptive and correlational analyses informed composite disability definitions: (1) severe cognitive disability, (2) severe physical disability, and (3) work disability. RESULTS: Of 137 respondents with GVHD included in this analysis, 47.0% reported severe cognitive disability, and approximately two-thirds each reported severe physical disability (67.4%) and work disability (62.8%). Chronic GVHD severity/duration, symptoms (Lee Symptom Scale), and number of transplant specialists consulted were associated with all types of disability (univariable analyses). Severe cognitive disability was associated with the number of transplant specialists consulted, severe physical disability with female sex, and work disability with nonwhite race. CONCLUSIONS: In this analysis, we found that the presence of specific symptoms and the number of transplant specialists consulted were associated with all types of severe disability; female sex was predictive of severe physical disability and nonwhite race of work disability. These findings add to the understanding of chronic GVHD-associated disability, suggest a need for improved social support for patients, and highlight potential indicators for those most in need.

Chronic graft-versus-host disease (GVHD) is a possible serious complication that can occur after someone has received a bone marrow or stem cell transplant from another person. Symptoms of chronic GVHD can be severe and can affect quality of life. To better understand exactly how chronic GVHD affects quality of life, we asked adults in the USA with chronic GVHD to fill out a survey. The objective of this research was to find out how chronic GVHD affects daily activities and work. The survey asked about physical activities including personal hygiene, eating, shopping, and ability to use the restroom, and the survey asked about mental tasks including managing personal finances and interactions with other people. The survey also asked questions about work, such as the need to take disability leave or to leave a job due to chronic GVHD. Many people with chronic GVHD who completed the survey said they had severe difficulty with mental and/or physical tasks, and many had work-related disability. People with more severe chronic GVHD who had met with many transplant specialists were more likely to have difficulty with mental and physical tasks and also to have work disability. Women who completed the survey were more likely to report severe physical disability than men, and nonwhite participants were more likely to report work disability. The results of this survey highlight a need for improved social support for patients with chronic GVHD.

Transcatheter Aortic Valve Replacement With the Navitor System: Real-World United Kingdom Experience.

The Navitor transcatheter heart valve (THV) is the latest iteration of the Portico self-expanding valve system. Early prospective studies have shown promising outcomes, however, there is a lack of complementary 'real-world' data. This study aimed to assess early safety and efficacy outcomes of the Navitor THV using registry data from 6 high-volume United Kingdom transcatheter aortic valve replacement (TAVR) centers. Demographic, procedural, and in-hospital outcome data were retrieved from 6 United Kingdom centers. The primary safety end point was 30-day mortality. Primary efficacy end points were procedural success, mean aortic gradient, and ≥moderate paravalvular leak. Secondary end points included rates of new permanent pacemaker implantation, stroke, and vascular injury. A total of 574 patients (mean age 83.4 years; 54.5% female) underwent Navitor TAVR between January 2020 and May 2023. The 30-day mortality in this patient cohort was 1.6%. Procedural success was 98.1%, mean echo-derived gradient post-TAVR was 7.7 ± 4.8 mm Hg (95% confidence interval [CI] 7.2 to 8.3, p <0.001) and 5.1% of patients had ≥moderate paravalvular leak (sample proportion estimate [p̂] = 0.051, 95% CI [0.035, 0.073], p <0.001). New permanent pacemaker implantation to discharge was required in 11% (p̂ = 0.119, 95% CI 0.088 to 0.158, p <0.001), stroke occurred in 1.2% of patients (p̂ = 0.017, 95% CI 0.006 to 0.036, p <0.001) and significant vascular injury in 1.6% (p̂ = 0.014, 95% CI 0.005 to 0.032, p <0.001). In conclusion, early procedural outcomes with Navitor TAVR compare favorably to new-generation THVs. Procedural success was high with a low incidence of complications.

Psychometric analysis of the modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) in a prospective multicentre study.

BACKGROUND: Long COVID (LC) is a novel multisystem clinical syndrome affecting millions of individuals worldwide. The modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) is a condition-specific patient-reported outcome measure designed for assessment and monitoring of people with LC. OBJECTIVES: To evaluate the psychometric properties of the C19-YRSm in a prospective sample of people with LC. METHODS: 1314 patients attending 10 UK specialist LC clinics completed C19-YRSm and EuroQol 5D-5L (EQ-5D-5L) longitudinally. Scale characteristics were derived for C19-YRSm subscales (Symptom Severity (SS), Functional Disability (FD) and Overall Health (OH)) and internal consistency (Cronbach's alpha). Convergent validity was assessed using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale. Known groups validity was assessed for the Other Symptoms subscale as tertiles, as well as by hospitalisation and intensive care admission. Responsiveness and test-retest reliability was evaluated for C19-YRSm subscales and EQ-5D-5L. The minimal important difference (MID) and minimal clinically important difference (MCID) were estimated. Confirmatory factor analysis was applied to determine the instrument's two-factor structure. RESULTS: C19-YRSm demonstrated good scale characteristic properties. Item-total correlations were between 0.37 and 0.65 (for SS and FD), with good internal reliability (Cronbach's alphas>0.8). Item correlations between subscales ranged between 0.46 and 0.72. Convergent validity with FACIT was good (-0.46 to -0.62). The three subscales discriminated between different levels of symptom burden (p<0.001) and between patients admitted to hospital and intensive care. There was moderate responsiveness for the three subscales ranging from 0.22 (OH) to 0.50 (SS) which was greater than for the EQ-5D-5L. Test-retest reliability was good for both SS 0.86 and FD 0.78. MID was 2 for SS, 2 for FD and 1 for OH; MCID was 4 for both the SS and FD. The factor analysis supported the two-factor SS and FD structure. CONCLUSIONS: The C19-YRSm is a condition-specific, reliable, valid and responsive patient-reported outcome measure for LC.

Olaparib for childhood tumors harboring defects in DNA damage repair genes: arm H of the NCI-COG Pediatric MATCH trial.

BACKGROUND: The National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice (MATCH) precision oncology platform trial enrolled children aged 1-21 years with treatment-refractory solid tumors and predefined actionable genetic alterations. Patients with tumors harboring alterations in DNA damage repair (DDR) genes were assigned to receive olaparib. METHODS: Tumor and blood samples were submitted for centralized molecular testing. Tumor and germline sequencing were conducted in parallel. Olaparib was given twice daily for 28-day cycles starting at a dose 30% lower than the adult recommended phase 2 dose (RP2D). The primary endpoint was the objective response. RESULTS: Eighteen patients matched (1.5% of those screened) based on the presence of a deleterious gene alteration in BRCA1/2, RAD51C/D, or ATM detected by tumor sequencing without germline subtraction or analysis of loss of heterozygosity (LOH). Eleven (61%) harbored a germline mutation, with only one exhibiting LOH. Six patients enrolled and received the olaparib starting dose of 135 mg/m2/dose. Two participants were fully evaluable; 4 were inevaluable because <85% of the prescribed dose was administered during cycle 1. There were no dose-limiting toxicities or responses. Minimal hematologic toxicity was observed. CONCLUSION: Most DDR gene alterations detected in Pediatric MATCH were germline, monoallelic, and unlikely to confer homologous recombination deficiency predicting sensitivity to olaparib monotherapy. The study closed due to poor accrual. CLINICALTRIALS.GOV IDENTIFIER: NCT03233204. IRB approved: initial July 24, 2017.

Effect of support structure of Pt/silicaite-1 catalyst on non-thermal plasma (NTP) assisted chlorobenzene degradation and PCDD/Fs formation.

Development of efficient catalysts for non-thermal plasma (NTP) assisted catalysis to mitigate the formation of harmful by-products is a significant challenge in the degradation of chlorinated volatile organic compounds (Cl-VOCs). In this study, catalytically active Pt nanoparticles supported on non-porous SiO2 and silicalite-1 zeolites (S1) with different pore structure were comparatively investigated for catalytic chlorobenzene degradation under NTP condition. It was shown that the pore structure could significantly impact the metal size and metal dispersion rate. Pt supported on modified S1 hierarchical meso-micro-porous silicalite-1 (Pt/D-S1) exhibited the smallest particle size (∼6.19 nm) and the highest dispersion rate (∼1.87). Additionally, Pt/D-S1 demonstrated superior catalytic performance compared to the other catalysts, achieving the highest chlorobenzene conversion and COx selectivity at about 80% and 75%, respectively. Furthermore, the pore structure also affected the formation of by-products according to the findings from GC-MS analysis. Pt/SiO2 generated a total of 18 different species of organic compounds, whereas only 12 species of organic by-products were identified in the Pt/D-S1 system (e.g. polychlorinated compounds like 3,4 dichlorophenol were exclusively identified in Pt/SiO2). Moreover, dioxin-like polychlorinated biphenyl and other chlorinated organic compounds, which have potential to form highly toxic dioxins, were detected in the catalysts. HRGC-HRMS confirmed and quantified the 17 different dioxin/furans formed on Pt/SiO2 (25,100 ng TEQ kg-1), Pt/S1 (515 ng TEQ kg-1) and Pt/D-S1 (367 ng TEQ kg-1). The correlation between synthesis-structure-performance in this study provides insights into the design of catalysts for deep oxidation of Cl-VOCs in NTP system.

Antimicrobial therapeutic drug monitoring in critically ill adult patients - An international perspective on access, utilisation, and barriers.

BACKGROUND: Therapeutic drug monitoring (TDM) is an effective method for individualising antimicrobial therapy in critically ill patients. The 2021 ADMIN-intensive care unit survey studied a wide range of intensive care unit clinicians worldwide to gain their perspectives on antimicrobial TDM. This article reports the responses from this survey relating to TDM access, utilisation, and barriers. METHODS: An online survey consisted of multiple-choice questions and 5-point Likert scales. The survey examined respondent's access to minimum inhibitory concentration (MIC) results, drug assays, and dosing software, as well as barriers to TDM. RESULTS: The survey included 538 clinicians from 409 hospitals in 45 countries, with 71% physicians and 29% pharmacists. Despite most respondents having access to assays, 21% and 26% of respondents lacked access to vancomycin and aminoglycosides, respectively. In lower-income countries, almost 40% reported no access. Delayed drug assay turnaround time was the most significant barrier to TDM, particularly in lower-income countries. Routine access to MIC results was unavailable for 41% of respondents, with 25% of lower-income country respondents having no access to MIC or susceptibility reports. CONCLUSIONS: This global survey indicated that consistent TDM usage is hindered by assay access in some sites and the timeliness of assay results in others. Addressing barriers to TDM, particularly in low-income countries, should be a priority to ensure equitable access to affordable TDM.

The nematode (Ascaris suum) intestine is a location of synergistic anthelmintic effects of Cry5B and levamisole.

A novel group of biocidal compounds are the Crystal 3D (Cry) and Cytolytic (Cyt) proteins produced by Bacillus thuringiensis (Bt). Some Bt Cry proteins have a selective nematocidal activity, with Cry5B being the most studied. Cry5B kills nematode parasites by binding selectively to membrane glycosphingolipids, then forming pores in the cell membranes of the intestine leading to damage. Cry5B selectively targets multiple species of nematodes from different clades and has no effect against mammalian hosts. Levamisole is a cholinergic anthelmintic that acts by selectively opening L-subtype nicotinic acetylcholine receptor ion-channels (L-AChRs) that have been found on muscles of nematodes. A synergistic nematocidal interaction between levamisole and Cry5B at the whole-worm level has been described previously, but the location, mechanism and time-course of this synergism is not known. In this study we follow the timeline of the effects of levamisole and Cry5B on the Ca2+ levels in enterocyte cells in the intestine of Ascaris suum using fluorescence imaging. The peak Ca2+ responses to levamisole were observed after approximately 10 minutes while the peak responses to activated Cry5B were observed after approximately 80 minutes. When levamisole and Cry5B were applied simultaneously, we observed that the responses to Cry5B were bigger and occurred sooner than when it was applied by itself. It is proposed that the synergism is due to the cytoplasmic Ca2+ overload that is induced by the combination of levamisole opening Ca2+ permeable L-subtype nAChRs and the Ca2+ permeable Cry5B toxin pores produced in the enterocyte plasma membranes. The effect of levamisole potentiates and speeds the actions of Cry5B that gives rise to bigger Ca2+ overloads that accelerates cell-death of the enterocytes.

Exploring the potential of hyperspectral imaging for microbial assessment of meat: A review.

Food safety is always of paramount importance globally due to the devasting social and economic effects of foodborne disease outbreaks. There is a high consumption rate of meat worldwide, making it an essential protein source in the human diet, hence its microbial safety is of great importance. The food industry stakeholders are always in search of methods that ensure safe food whilst maintaining food quality and excellent sensory attributes. Currently, there are several methods used in microbial food analysis, however, these methods are often time-consuming and do not allow real-time analysis. Considering the recent technological breakthroughs in artificial intelligence and machine learning, it raises the question of whether these advancements could be leveraged within the meat industry to improve turnaround time for microbial assessments. Hyperspectral imaging (HSI) is a highly prospective technology worth exploring for microbial analysis. The rapid, non-destructive method has the potential to be integrated into food production systems and allows foodborne pathogen detection in food samples, thus saving time. Although there has been a substantial increase in research on the utilisation of HSI in food applications over the past years, its use in the microbial assessment of meat is not yet optimal. This review aims to provide a basic understanding of the visible-near infrared HSI system, recent applications in the microbial assessment of meat products, challenges, and possible future applications.

Long COVID Clinical Severity Types Based on Symptoms and Functional Disability: A Longitudinal Evaluation.

Background: Long COVID (LC) is a multisystem clinical syndrome with functional disability and compromised overall health. Information on LC clinical severity types is emerging in cross-sectional studies. This study explored the pattern and consistency of long COVID (LC) clinical severity types over time in a prospective sample. Methods: Participants with LC completed the condition-specific outcome measure C19-YRSm (Yorkshire Rehabilitation Scale modified version) at two assessment time points. A cluster analysis for clinical severity types was undertaken at both time points using the k-means partition method. Results: The study included cross-sectional data for 759 patients with a mean age of 46.8 years (SD = 12.7), 69.4% females, and a duration of symptoms of 360 days (IQR 217 to 703 days). The cluster analysis at first assessment revealed three distinct clinical severity type clusters: mild (n = 96), moderate (n = 422), and severe (n = 241). Longitudinal data on 356 patients revealed that the pattern of three clinical severity types remained consistent over time between the two assessments, with 51% of patients switching clinical severity types between the assessments. Conclusions: This study is the first of its kind to demonstrate that the pattern of three clinical severity types is consistent over time, with patients also switching between severity types, indicating the fluctuating nature of LC.

Maternal Aggression Driven by the Transient Mobilisation of a Dormant Hormone-Sensitive Circuit.

Aggression, a sexually dimorphic behaviour, is prevalent in males and typically absent in virgin females. Following parturition, however, the transient expression of aggression in adult female mice protects pups from predators and infanticide by male conspecifics. While maternal hormones are known to elicit nursing, their potential role in maternal aggression remains elusive. Here, we show in mice that a molecularly defined subset of ventral premammillary (PMvDAT) neurons, instrumental for intermale aggression, switch from quiescence to a hyperexcitable state during lactation. We identify that the maternal hormones prolactin and oxytocin excite these cells through actions that include T-type Ca2+ channels. Optogenetic manipulation or genetic ablation of PMvDAT neurons profoundly affects maternal aggression, while activation of these neurons impairs the expression of non-aggression-related maternal behaviours. This work identifies a monomorphic neural substrate that can incorporate hormonal cues to enable the transient expression of a dormant behavioural program in lactating females.

Comparison of Contemporary Risk Scores in All Groups of Pulmonary Hypertension: A Pulmonary Vascular Research Institute GoDeep Meta-Registry Analysis.

BACKGROUND: Pulmonary hypertension (PH) is a heterogeneous disease with a poor prognosis. Accurate risk stratification is essential for guiding treatment decisions in pulmonary arterial hypertension (PAH). Although various risk models have been developed for PAH, their comparative prognostic potential requires further exploration. Additionally, the applicability of risk scores in PH groups beyond group 1 remains to be investigated. RESEARCH QUESTION: Are risk scores originally developed for PAH predictive in PH groups 1 through 4? STUDY DESIGN AND METHODS: We conducted a comprehensive analysis of outcomes among patients with incident PH enrolled in the multicenter worldwide Pulmonary Vascular Research Institute GoDeep meta-registry. Analyses were performed across PH groups 1 through 4 and further subgroups to evaluate the predictive value of PAH risk scores, including REVEAL Lite 2, REVEAL 2.0, ESC/ERS 2022, COMPERA 3-strata, and COMPERA 4-strata. RESULTS: Eight thousand five hundred sixty-five patients were included in the study, of whom 3,537 patients were assigned to group 1 PH, whereas 1,807 patients, 1,635 patients, and 1,586 patients were assigned to group 2 PH, group 3 PH, and group 4 PH, respectively. Pulmonary hemodynamics were impaired with median mean pulmonary arterial pressure of 42 mm Hg (33-52 mm Hg) and pulmonary vascular resistance of 7 WU (4-11 WU). All risk scores were prognostic in the entire PH population and in each of the PH groups 1 through 4. The REVEAL scores, when used as continuous prediction models, demonstrated the highest statistical prognostic power and granularity; the COMPERA 4-strata risk score provided subdifferentiation of the intermediate-risk group. Similar results were obtained when separately analyzing various subgroups (PH subgroups 1.1, 1.4.1, and 1.4.4; PH subgroups 3.1 and 3.2; group 2 with isolated postcapillary PH vs combined precapillary and postcapillary PH; patients of all groups with concomitant cardiac comorbidities; and severe [> 5 WU] vs nonsevere PH). INTERPRETATION: This comprehensive study with real-world data from 15 PH centers showed that PAH-designed risk scores possess predictive power in a large PH cohort, whether considered as common to the group or calculated separately for each PH group (1-4) and various subgroups.

Prevalence of orthostatic intolerance in long covid clinic patients and healthy volunteers: A multicenter study.

Orthostatic intolerance (OI), including postural orthostatic tachycardia syndrome (PoTS) and orthostatic hypotension (OH), are often reported in long covid, but published studies are small with inconsistent results. We sought to estimate the prevalence of objective OI in patients attending long covid clinics and healthy volunteers and associations with OI symptoms and comorbidities. Participants with a diagnosis of long covid were recruited from eight UK long covid clinics, and healthy volunteers from general population. All undertook standardized National Aeronautics and Space Administration Lean Test (NLT). Participants' history of typical OI symptoms (e.g., dizziness, palpitations) before and during the NLT were recorded. Two hundred seventy-seven long covid patients and 50 frequency-matched healthy volunteers were tested. Healthy volunteers had no history of OI symptoms or symptoms during NLT or PoTS, 10% had asymptomatic OH. One hundred thirty (47%) long covid patients had previous history of OI symptoms and 144 (52%) developed symptoms during the NLT. Forty-one (15%) had an abnormal NLT, 20 (7%) met criteria for PoTS, and 21 (8%) had OH. Of patients with an abnormal NLT, 45% had no prior symptoms of OI. Relaxing the diagnostic thresholds for PoTS from two consecutive abnormal readings to one abnormal reading during the NLT, resulted in 11% of long covid participants (an additional 4%) meeting criteria for PoTS, but not in healthy volunteers. More than half of long covid patients experienced OI symptoms during NLT and more than one in 10 patients met the criteria for either PoTS or OH, half of whom did not report previous typical OI symptoms. We therefore recommend all patients attending long covid clinics are offered an NLT and appropriate management commenced.

Getting around the roundworms: Identifying knowledge gaps and research priorities for the ascarids.

The ascarids are a large group of parasitic nematodes that infect a wide range of animal species. In humans, they cause neglected diseases of poverty; many animal parasites also cause zoonotic infections in people. Control measures include hygiene and anthelmintic treatments, but they are not always appropriate or effective and this creates a continuing need to search for better ways to reduce the human, welfare and economic costs of these infections. To this end, Le Studium Institute of Advanced Studies organized a two-day conference to identify major gaps in our understanding of ascarid parasites with a view to setting research priorities that would allow for improved control. The participants identified several key areas for future focus, comprising of advances in genomic analysis and the use of model organisms, especially Caenorhabditis elegans, a more thorough appreciation of the complexity of host-parasite (and parasite-parasite) communications, a search for novel anthelmintic drugs and the development of effective vaccines. The participants agreed to try and maintain informal links in the future that could form the basis for collaborative projects, and to co-operate to organize future meetings and workshops to promote ascarid research.

Balloon aortic valvuloplasty with or without percutaneous coronary intervention in the TAVR era.

Introduction The role of balloon aortic valvuloplasty (BAV) amid the era of transcatheter aortic valve replacement (TAVR) remains a topic of debate. We sought to study the safety and feasibility of combined balloon aortic valvuloplasty and percutaneous coronary intervention (BAV-PCI). Methods Between November 2009 and July 2020, all patients undergoing BAV were identified and divided into three groups: combined BAV-PCI (group A), BAV with significant unrevascularised CAD (group B) and BAV without significant CAD (group C). Procedural outcomes, 30-day and one-year mortality were compared. Results A total of 264 patients were studied (n = 84, 93 and 87 patients in group A, B and C, respectively). The STS score was 10.2 ±8, 13.3 ±19 and 8.1 ±7, p = 0.026, in group A, B and C, respectively. VARC-3 adjudicated complications were similar among groups (11%, 13% and 5%, respectively, p = 0.168, respectively). Thirty-day and one-year mortality were 9.8% (n =26) and 32% (n = 86) of the entire cohort. The differences among groups did not reach statistical significance. Using univariate Cox regression analysis, group B were at higher risk of dying compared to group A patients (HR 1.58, 95% CI 1.11 - 2.25, p = 0.010). With multivariate Cox regression analysis, the predictors of mortality were STS score, cardiogenic shock, and mode of presentation and lack of subsequent definitive valve intervention. Conclusion In high-risk patients with aortic valve stenosis, combined BAV-PCI is safe and feasible with comparable outcomes to BAV with and without significant CAD.

Design, Synthesis, and Evaluation of New 1H-Benzo[d]imidazole Based PqsR Inhibitors as Adjuvant Therapy for Pseudomonas aeruginosa Infections.

Pseudomonas aeruginosa is one of the top priority pathogens that requires immediate attention according to the World Health Organisation (WHO). Due to the alarming shortage of novel antimicrobials, targeting quorum sensing (QS), a bacterial cell to cell signaling system controlling virulence, has emerged as a promising approach as an antibiotic adjuvant therapy. Interference with the pqs system, one of three QS systems in P. aeruginosa, results in reduction of bacterial virulence gene expression and biofilm maturation. Herein, we report a hit to lead process to fine-tune the potency of our previously reported inhibitor 1 (IC50 3.2 µM in P. aeruginosa PAO1-L), which led to the discovery of 2-(4-(3-((6-chloro-1-isopropyl-1H-benzo[d]imidazol-2-yl)amino)-2-hydroxypropoxy)phenyl)acetonitrile (6f) as a potent PqsR antagonist. Compound 6f inhibited the PqsR-controlled PpqsA-lux transcriptional reporter fusion in P. aeruginosa at low submicromolar concentrations. Moreover, 6f showed improved efficacy against P. aeruginosa CF isolates with significant inhibition of pyocyanin, 2-alkyl-4(1H)-quinolones production.

Improving the Quality of Bio-oil Using the Interaction of Plastics and Biomass through Copyrolysis Coupled with Nonthermal Plasma Processing.

Bio-oil produced from the pyrolysis of biomass is chemically complex, viscous, highly acidic, and highly oxygenated. Copyrolysis of biomass and plastics can enhance oil quality by raising the H/C ratio, leading to improved biofuel properties. In this work, copyrolysis of polystyrene and biomass was passed to a second-stage dielectric barrier discharge nonthermal plasma reactor with the aim to further improve the product bio-oil. Pyrolysis of the polystyrene and biomass produces volatiles that pass to the second stage to undergo cracking and autohydrogenation reactions under nonthermal plasma conditions. There was a synergistic interaction between biomass and polystyrene in terms of overall oil and gas yield and composition even in the absence of the nonthermal plasma. However, the introduction of the nonthermal plasma produced a marked increase in monocyclic aromatic hydrocarbons (e.g., ethylbenzene), whereas polycyclic aromatic compounds decreased in concentration. Most notably, the influence of the plasma markedly reduced the quantity of oxygenated compounds in the product oil. It is suggested that the unique reactive environment produced by the plasma involving high-energy electrons, excited radicals, ions, and intermediates increases the interaction of the polystyrene and biomass pyrolysis volatiles. Increasing input plasma power from 50 to 70 W further enhanced the effects of the nonthermal plasma.

Predicting Egg Storage Time with a Portable Near-Infrared Instrument: Effects of Temperature and Production System.

Determining egg freshness is critical for ensuring food safety and security and as such, different methods have been evaluated and implemented to accurately measure and predict it. In this study, a portable near-infrared (NIR) instrument combined with chemometrics was used to monitor and predict the storage time of eggs under two storage conditions-room temperature (RT) and cold (CT) storage-from two production systems: cage and free-range. A total of 700 egg samples were analyzed, using principal component analysis (PCA) and partial least squares (PLS) regression to analyze the NIR spectra. The PCA score plot did not show any clear separation between egg samples from the two production systems; however, some egg samples were grouped according to storage conditions. The cross-validation statistics for predicting storage time were as follows: for cage and RT eggs, the coefficient of determination in cross validation (R2CV) was 0.67, with a standard error in cross-validation (SECV) of 7.64 days and residual predictive deviation (RPD) of 1.8; for CT cage eggs, R2CV of 0.84, SECV of 5.38 days and RPD of 3.2; for CT free-range eggs, R2CV of 0.83, SECV of 5.52 days and RPD of 3.2; and for RT free-range eggs, R2CV of 0.82, SECV of 5.61 days, and RPD of 3.0. This study demonstrated that NIR spectroscopy can predict storage time non-destructively in intact egg samples. Even though the results of the present study are promising, further research is still needed to further extend these results to other production systems, as well as to explore the potential of this technique to predict other egg quality parameters associated with freshness.