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Abstract Rationale While tobacco industry data suggests that switching from combustible cigarettes to heated tobacco products (HTPs), like IQOS, may reduce the users’ exposure to respiratory toxicants, it is not known if using HTPs impacts the outcomes of acute respiratory infections. Objectives Does switching from cigarettes to HTPs improve responses to pulmonary infection. Methods We conducted experiments in which 3 groups of mice were pre-exposed to cigarette smoke for 8 weeks, followed by 8-week exposure to (1) HTPs (tobacco product switching), (2) air (smoking cessation), or (3) continued exposure to cigarette smoke. Pulmonary bacterial clearance and surrogate markers of lung damage were assessed as study outcomes. Main results Significantly compromised clearance of bacteria from the lungs post-acute challenge occurred in both the switching group and in mice continuously exposed to cigarette smoke. Bacterial clearance, inflammatory T-cell infiltration into the lungs, and albumin leak improved at 12 h post-acute challenge in the switching group compared to mice continuously exposed to cigarette smoke. Bacterial clearance, total lung immune-cell infiltration, inflammatory T-cell infiltration into the lungs, the content of total proteins in the BAL, and albumin leak measured post-acute challenge were compromised in the switching group compared to mice in the cessation group. Switching from cigarettes to HTPs did not improve lung myeloperoxidase and neutrophil elastase levels (markers for lung inflammation and damage), which, however, were significantly reduced in the cessation group. Conclusions This study reveals only a modest improvement in respiratory infection outcomes after switching exposure from cigarettes to HTPs and significantly compromised outcomes compared to a complete cessation of exposure to all tobacco products.

AI-based simulations for educational and assessment purposes are gaining global recognition. Informed by cultural comparison research, this study investigates cross-country variations in users' utilization and perceptions of a simulation-based assessment. Specifically, we conducted a comparative analysis between a sample of South African and Canadian students to uncover potential differences in assessment scores, communication patterns, and reactions vis-a-vis a simulation assessment for evaluating teamwork skills. Data were collected from over 500 undergraduate students in South Africa and Canada who completed a simulation assessment and reported their reactions and perceptions. The findings yielded several noteworthy observations. First, South African students attained higher assessment scores than Canadian students; although, the difference did not quite reach statistical significance at p < 0.05. Second, significant variations were observed in the quantity and style of communication. South African students used fewer words and more polite language, while Canadian students tended to use more decisive language and provided more explanations and help to their virtual teammates. Third, South African students were more likely to perceive their virtual teammates as "human" and were less concerned whether they were real people or virtual. Lastly, compared with their Canadian counterparts, South African students reported more positive reactions and perceived the assessment to be more accurate. These findings warrant further investigation.

Out-of-equilibrium electrochemical reaction mechanisms are notoriously difficult to characterize. However, such reactions are critical for a range of technological applications. For instance, in metal-ion batteries, spontaneous electrolyte degradation controls electrode passivation and battery cycle life. Here, to improve our ability to elucidate electrochemical reactivity, we for the first time combine computational chemical reaction network (CRN) analysis based on density functional theory (DFT) and differential electrochemical mass spectroscopy (DEMS) to study gas evolution from a model Mg-ion battery electrolyte─magnesium bistriflimide (Mg(TFSI)2) dissolved in diglyme (G2). Automated CRN analysis allows for the facile interpretation of DEMS data, revealing H2O, C2H4, and CH3OH as major products of G2 decomposition. These findings are further explained by identifying elementary mechanisms using DFT. While TFSI- is reactive at Mg electrodes, we find that it does not meaningfully contribute to gas evolution. The combined theoretical-experimental approach developed here provides a means to effectively predict electrolyte decomposition products and pathways when initially unknown.

The rational design of electrolytes has been a long-standing challenge in chemistry and materials science. In this work, we demonstrate a computational rationale for improving the performance of weakly coordinating electrolytes in currently challenging multivalent-ion battery applications, based on enhanced thermodynamic and kinetic stability against reductive decomposition. A series of fluorinated alkoxyborate and alkoxyaluminate salts are systematically examined based on their reduction and oxidation potentials and, motivated by NMR spectroscopy, detailed reductive decomposition pathways involving the breaking of Al/B-O, C-O, or C-F bonds are obtained. Based on the decomposition kinetics, the hexafluoro-tert-isopropoxy (hfip) ligand for borates and the trifluoro-tert-butoxy (tftb) ligand for aluminates are identified as promising ligands for constructing the salt anions. This borate prediction corroborates previous experimental work on Mg[B(hfip)4]2and Ca[B(hfip)4]2, in which excellent electrochemical properties were reported. We find that steric factors govern the B-O bond-breaking decomposition kinetics while electronic factors are more important for aluminate salts. There is more charge transfer character in the aluminate transition states compared with borates for Al/B-O bond-breaking decomposition and thus electron-withdrawing ligands tend to stabilize the aluminate transition states. Such molecular-level understandings allow for better design principles for developing new electrolytes with improved stability and performance.

Modelling a dataset of 5230 globally listed firms through two statistical approaches reflecting the primary principles of Natural-Resource-Based Theory and Institutional Theory, respectively, this study provides evidence that sustainability initiatives developed by firms are being rewarded in the form of improved Corporate Financial Performance (CFP). Culture has a significant influence on both firm sustainability performance, captured in ESG ratings, and CFP and also interacts with other variables, including industry sector and socio-economic development of a firm’s markets. This study is unique in hypothesising and statistically proving that sustainability is a mechanism that activates the potential of culture to produce CFP. Natural-Resource-Based Theory (NRBT) and Institutional Theory (DiMaggio & Powell, 1983) provide complementary explanations for the relationship between the culture of a firm and its CFP being mediated by sustainability, effectively determining firms’ approach to the use of their resources in a sustainable or unsustainable way. Certain relationships between culture, sustainability performance, and CFP, however, are better explained by Institutional Theory than NRBT.

ABSTRACTGonorrhea, caused by the bacterium Neisseria gonorrhoeae (Gc), is characterized by neutrophilic influx to infection sites. Gc has developed mechanisms to resist killing by neutrophils that include modifications to its surface lipooligosaccharide (LOS). One such LOS modification is sialylation: Gc sialylates its terminal LOS sugars with cytidine-5′-monophosphate-N-acetylneuraminic acid, which is scavenged from the host using LOS sialyltransferase (Lst) since Gc cannot make its sialic acid. Sialylation enables sensitive strains of Gc to resist complement-mediated killing in a serum-dependent manner. However, little is known about the contribution of sialylation to complement-independent, direct Gc-neutrophil interactions. In the absence of complement, we found sialylated Gc expressing opacity-associated (Opa) proteins decreased the oxidative burst and granule exocytosis from primary human neutrophils. In addition, sialylated Opa+ Gc survived better than vehicle treated or Δlst Gc when challenged with neutrophils. However, Gc sialylation did not significantly affect Opa-dependent association with or internalization of Gc by neutrophils. Previous studies have implicated sialic acid-binding immunoglobulin-type lectins (Siglecs) in modulating neutrophil interactions with sialylated Gc. Blocking neutrophil Siglecs with antibodies that bind to their extracellular domains eliminated the ability of sialylated Opa+ Gc to suppress the oxidative burst and resist neutrophil killing. These findings highlight a new role for sialylation in Gc evasion of human innate immunity, with implications for the development of vaccines and therapeutics for gonorrhea.IMPORTANCENeisseria gonorrhoeae, the bacterium that causes gonorrhea, is an urgent global health concern due to increasing infection rates, widespread antibiotic resistance, and its ability to thwart protective immune responses. The mechanisms by which Gc subverts protective immune responses remain poorly characterized. One way N. gonorrhoeae evades human immunity is by adding sialic acid that is scavenged from the host onto its lipooligosaccharide, using the sialyltransferase Lst. Here, we found that sialylation enhances N. gonorrhoeae survival from neutrophil assault and inhibits neutrophil activation, independently of the complement system. Our results implicate bacterial binding of sialic acid-binding lectins (Siglecs) on the neutrophil surface, which dampens neutrophil antimicrobial responses. This work identifies a new role for sialylation in protecting N. gonorrhoeae from cellular innate immunity, which can be targeted to enhance the human immune response in gonorrhea.

School children may be exposed to secondhand smoke (SHS) either at home, in transit or in social gatherings permitting smoking in their presence. Questionnaires about SHS often underestimate prevalence and extent of exposure. A more accurate tool is the use of biomarkers such as cotinine (COT) and trans-3'-hydrocycotinine (3HC) as biomarkers of SHS exposure, alongside 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a reduction product in the body of the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), both potent carcinogens. We measured urinary COT, 3HC and total NNAL using sensitive and specific high-performance LC-MS/MS methods. The limit of quantification (LOQ) for each assay were 0.05 ng/mL, 0.1 ng/mL and 0.25 pg/mL respectively. The aim of this study was to evaluate the exposure to SHS of school children (9-11 years), from five public schools in the island of Malta, from questionnaire information about smoking at home and verify it by urinary biomarker data of COT, 3HC and NNAL. These biomarkers were measurable in 99.4%, 95.4% and 98.3% of the participating children respectively. From the children reporting smoking at home, 11% had a history of asthma and had COT, 3HC and NNAL geometric mean concentrations double compared to the non-asthmatic group. In has been confirmed that non-smokers exposed to SHS and THS have a higher NNAL/COT ratio than the group identified as smokers according to specific and defined COT threshold levels (despite the fact that a priori, the entire study group was composed of non-smokers). The implication of high measured levels of urinary NNAL in children should be of concern given its potency. A main effects multifactor ANOVA model was developed and the children's house and school locations and the smoking frequency were statistically significant to predict the levels of the three metabolites. For 3HC only, the status of the employment of the mother was also an important predictor.

AimMost of the carcinogenic pollutants coming from tobacco smoking or other combustion processes tend to accumulate in settled house dust (SHD) over time. This study evaluated the load of these pollutants in smokers and non-smokers' houses from relatively fresh SHD collected in five different districts on the island of Malta.MethodsAn improved, efficient extraction method to obtain three fractions from a 200 mg of SHD was developed. It was validated for the analysis of nicotine and polycyclic aromatic hydrocarbons (PAH) by GC-MS/MS and nicotelline and TSNA by LC-MS/MS. Kruskal-Wallis H tests were used to evaluate differences across districts, while a Mann-Whitney U test was used to check differences between smokers and non-smokers' houses. Diagnostic ratios were used to evaluate the carcinogenicity of PAH in SHD in Malta.ResultsFor all analytes, no statistical difference was observed across different districts, but, in smokers' houses, 97.9% of the total concentration of all target analytes found in SHD is nicotine, 0.1% is TSNA, and 2.0% is PAH. In non-smokers' houses, nicotine represents 16.8% of the load, while 0.4% and 82.8% are TSNA and PAH, respectively. The carcinogenicity of the PAH mixture in Maltese SHD, expressed as the mean benzo(a)pyrene equivalent (BaPeq) is 371 ng/g.ConclusionIndoor activities, ventilation practices, and infiltration of outdoor pollutants contribute to a complex SHD composition. Although the BaPeq is on the lower end of carcinogenicity, the effects of a mixture including tobacco-related potent carcinogens in SHD are largely unknown. In view of indoor, continuous exposure to SHD through several pathways, further research is warranted.

The most important tobacco-specific nitrosamine found in cigarette smoke and formed in ageing smoke after cigarettes are extinguished is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). It is formed from nitrosation of nicotine, under particular conditions both in indoor and outdoor environments. NNK has been classified as a potent lung carcinogen which is expected to be found primarily in the particle-phase and to be stable in particulate matter. In this study tests have been carried out to show that a bisulfate-treated filter is more efficient than an untreated filter to collect both nicotine and NNK, and that the latter is stable in outdoor particulate matter. To characterize NNK in the outdoor environment, airborne samples were collected from 11 cities in USA, UK, Hong Kong and Malta with characteristics varying from low to high population densities and from urban to suburban to rural, and with desert characteristics and distinct climates. It has been shown that airborne particle + gas phase nicotine and particle-phase NNK behave in a linearly correlated manner. A seasonal analysis was carried out on a subset of data available from five sites in California, where the load of NNK in PM10 is driven by long range transport of the air masses passing over densely populated cities. In the winter season, the load of NNK in PM is higher than in summer in a statistically significant manner. The contamination of PM with NNK shows variability, but is observed at all sites. This paper highlights the potential risk of chronic exposure to NNK in particulate matter by the inhalation pathway.

Objective Urinary tract infections (UTIs) stand as a prominent global health concern. This study entails a 5-year retrospective analysis, using a cross-sectional study design to examine microbiology laboratory data of individuals clinically diagnosed with UTIs at Bugando Medical Centre to gain insights into the prevalence and factors linked to candiduria.Methodology Data extracted were meticulously cleaned and coded in an MS Excel sheet, subsequently transferred to STATA V.15 for analysis. Binary logistic regression analysis was used to identify factors associated with candiduria. A probability value below 0.05 at a 95% CI was considered statistically significant.Results Urine samples for culture and sensitivity comprised 33.4% (20755) of the total biological samples (62335). The median age of the patients stood at 19 years. A slight majority were female, accounting for 52.8% (10051), and two-thirds sought treatment at outpatient departments (67.5%, 12843). Among patients with significant pathogenic growth, the prevalence of candiduria was 4.6% (221 out of 4772). Notably, inpatients exhibited a higher incidence of candiduria compared with outpatients, with rates of 9.4% (1882) versus 1.6% (2890), p value of 0.000. Non-albicans Candida spp. (NAC) remained the most prevalent pathogen. Factors significantly associated with candiduria included being female (OR=1.7, 95% CI 1.3 to 2.3) and hospital admission (OR=6.6, 95% CI 4.7 to 9.2). In conclusion, candiduria affect 5 out of every 100 UTI-diagnosed patients, predominantly among females and those admitted to the hospital. Clinicians at tertiary hospitals should consider urinary candidiasis as a potential diagnosis for patients at risk who present with UTI-like symptoms.

Second Hand Smoke (SHS) has always been primarily linked with indoor pollution. To date nicotine was the favoured marker for SHS alongside measurements of particulate matter (PM) levels. As nicotine is mainly found in the gas-phase and reactive in the outdoor environment it is not ideal as a marker for the SHS-driven particulate component in PM. Nicotelline, a minor tobacco alkaloid that is stable, found almost exclusively in the particle phase and easy to quantify even at low concentrations, is being proposed as a better marker. It is the first study using bisulfate-treated quartz fiber filters to show that airborne nicotine (gas+particle phase) is directly proportional to airborne nicotelline in countries that have different climates. The analytical method developed has been validated to show that the use of untreated filters is suitable for the quantification of nicotelline even at low concentrations. Although nicotelline exhibits a seasonal and geographical variation, this is the first comprehensive study which demonstrates the ubiquitous presence of nicotelline in PM from outdoor air samples collected in the USA (0.1-285.6 pgm-3), UK (2.3-9.1 pgm-3), Hong Kong (3.8-109.3 pgm-3) and Malta (4.2-280.8 pgm-3). From the nicotelline apportionment factor of 1589 ng/mg of tobacco smoke PM we estimate the fraction of outdoor airborne PM derived from SHS to be in the range of 0.03-0.08%. While it is unlikely for tobacco smoke-related toxics in outdoor PM to be considered a major health hazard, in heavily polluted microenvironments this marker would be useful in tracing the presence of SHS and emerging Third Hand Smoke components that form or are found in airborne and settled PM that could induce serious health effects.