Use of the FebriDx® host-response point-of-care test may reduce antibiotic use for respiratory tract infections in primary care: a mixed-methods feasibility study.

INTRODUCTION: FebriDx® is a CE-marked, single-use point-of-care test with markers for bacterial [C-reactive protein (CRP)] and viral [myxovirus resistance protein A (MxA)] infection, using finger-prick blood samples. Results are available after 10-12 min. We explored the usability and potential impact of FebriDx® in reducing antibiotic prescriptions for lower respiratory tract infection (LRTI) in primary care, and the feasibility of conducting a randomized controlled trial (RCT). METHODS: Patients (aged ≥1 year) with LRTI deemed likely to receive antibiotic prescription were recruited at nine general practices and underwent FebriDx® testing. Data collection included FebriDx® results, antibiotic prescribing plan (before and after testing) and re-consultation rates. Staff completed System Usability Scale questionnaires. RESULTS: From 31 January 2023 to 9 June 2023, 162 participants participated (median age 57 years), with a median symptom duration of 7 days (IQR 5-14). A valid FebriDx® result was obtained in 97% (157/162). Of 155 patients with available results, 103 (66%) had no detectable CRP or MxA, 28 (18%) had CRP only, 5 (3%) had MxA only, and 19 (12%) had both CRP and MxA. The clinicians' stated management plan was to prescribe antibiotics for 86% (134/155) before testing and 45% (69/155) after testing, meaning a 41% (95% CI: 31%, 51%) difference after testing, without evidence of increased re-consultation rates. Ease-of-use questionnaires showed 'good' user-friendliness. CONCLUSIONS: Use of FebriDx® to guide antibiotic prescribing for LRTI in primary care was associated with a substantial reduction in prescribing intentions. These results support a fully powered RCT to confirm its impact and safety.

Riemerella anatipestifer UvrC is required for iron utilization, biofilm formation and virulence.

UvrC is a subunit of excinuclease ABC, which mediates nucleotide excision repair (NER) in bacteria. Our previous studies showed that transposon Tn4531 insertion in the UvrC encoding gene Riean_1413 results in reduced biofilm formation by Riemerella anatipestifer strain CH3 and attenuates virulence of strain YZb1. In this study, whether R. anatipestifer UvrC has some biological functions other than NER was investigated. Firstly, the uvrC of R. anatipestifer strain Yb2 was in-frame deleted by homologous recombination, generating deletion mutant ΔuvrC, and its complemented strain cΔuvrC was constructed based on Escherichia coli - R. anatipestifer shuttle plasmid pRES. Compared to the wild-type (WT) R. anatipestifer strain Yb2, uvrC deleted mutant ΔuvrC significantly reduced biofilm formation, tolerance to H2O2- and HOCl-induced oxidative stress, iron utilization, and adhesion to and invasion of duck embryonic hepatocytes, but not its growth curve and proteolytic activity. In addition, animal experiments showed that the LD50 value of ΔuvrC in ducklings was about 13-fold higher than that of the WT, and the bacterial loads in ΔuvrC infected ducklings were significantly lower than those in Yb2-infected ducklings, indicating uvrC deletion in R. anatipestifer attenuated virulence. Taken together, the results of this study indicate that R. anatipestifer UvrC is required for iron utilization, biofilm formation, oxidative stress tolerance and virulence of strain Yb2, demonstrating multiple functions of UvrC.RESEARCH HIGHLIGHTSDeletion of uvrC in R. anatipestfer Yb2 significantly reduced its biofilm formation.uvrC deletion led to reduced tolerance to H2O2- and HOCl-induced oxidative stress.The iron utilization of uvrC deleted mutant was significantly reduced.The uvrC deletion in R. anatipestifer Yb2 attenuated its virulence.

A comparison of excess deaths by UK country and region during the first year of the COVID-19 pandemic.

We compare the impact of the first two waves of the COVID-19 pandemic on risk of age-standardized mortality by sex, UK country, and English region. Each wave is defined as lasting 26 weeks and are consecutive beginning in 2020 week 11. The expected rate is estimated from 2015 to 2019 mean and the projected mortality trend from the same period are used to estimate excess mortality. By both measures, excess mortality was highest and lowest in regions of England, London and the South-West, respectively. Excess mortality was consistently higher for males than females.

Estimating the Effectiveness of First Dose of COVID-19 Vaccine Against Mortality in England: A Quasi-Experimental Study.

Estimating real-world vaccine effectiveness is vital to assessing the coronavirus disease 2019 (COVID-19) vaccination program and informing the ongoing policy response. However, estimating vaccine effectiveness using observational data is inherently challenging because of the nonrandomized design and potential for unmeasured confounding. We used a regression discontinuity design to estimate vaccine effectiveness against COVID-19 mortality in England using the fact that people aged 80 years or older were prioritized for the vaccine rollout. The prioritization led to a large discrepancy in vaccination rates among people aged 80-84 years compared with those aged 75-79 at the beginning of the vaccination campaign. We found a corresponding difference in COVID-19 mortality but not in non-COVID-19 mortality, suggesting that our approach appropriately addressed the issue of unmeasured confounding factors. Our results suggest that the first vaccine dose reduced the risk of COVID-19 death by 52.6% (95% confidence limits: 15.7, 73.4) in those aged 80 years, supporting existing evidence that a first dose of a COVID-19 vaccine had a strong protective effect against COVID-19 mortality in older adults. The regression discontinuity model's estimate of vaccine effectiveness is only slightly lower than those of previously published studies using different methods, suggesting that these estimates are unlikely to be substantially affected by unmeasured confounding factors.

Ethnic differences in COVID-19 mortality in the second and third waves of the pandemic in England during the vaccine rollout: a retrospective, population-based cohort study.

BACKGROUND: Ethnic minority groups in England have been disproportionately affected by the COVID-19 pandemic and have lower vaccination rates than the White British population. We examined whether ethnic differences in COVID-19 mortality in England have continued since the vaccine rollout and to what extent differences in vaccination rates contributed to excess COVID-19 mortality after accounting for other risk factors. METHODS: We conducted a retrospective, population-based cohort study of 28.8 million adults aged 30-100 years in England. Self-reported ethnicity was obtained from the 2011 Census. The outcome was death involving COVID-19 during the second (8 December 2020 to 12 June 2021) and third wave (13 June 2021 to 1 December 2021). We calculated hazard ratios (HRs) for death involving COVID-19, sequentially adjusting for age, residence type, geographical factors, sociodemographic characteristics, pre-pandemic health, and vaccination status. RESULTS: Age-adjusted HRs of death involving COVID-19 were elevated for most ethnic minority groups during both waves, particularly for groups with lowest vaccination rates (Bangladeshi, Pakistani, Black African, and Black Caribbean). HRs were attenuated after adjusting for geographical factors, sociodemographic characteristics, and pre-pandemic health. Further adjusting for vaccination status substantially reduced residual HRs for Black African, Black Caribbean, and Pakistani groups in the third wave. Fully adjusted HRs only remained elevated for the Bangladeshi group (men: 2.19 [95% CI 1.72-2.78]; women: 2.12 [1.58-2.86]) and Pakistani men (1.24 [1.06-1.46]). CONCLUSIONS: Lower COVID-19 vaccination uptake in several ethnic minority groups may drive some of the differences in COVID-19 mortality compared to White British. Public health strategies to increase vaccination uptake in ethnic minority groups would help reduce inequalities in COVID-19 mortality, which have remained substantial since the start of the vaccination campaign.

Correlates of chronic hepatitis B virus infection in the general adult population of China: Systematic review and meta-analysis.

Chronic infection with hepatitis B virus (HBV) is a significant public health issue in China. Understanding factors associated with chronic HBV is important to enable targeted screening and education and to improve early diagnosis and prevention of disease progression. This systematic review and meta-analysis aimed to identify and describe correlates of chronic HBV among Chinese adults. Searches were conducted in MEDLINE, EMBASE and grey literature up to 25 June 2020. Eligible papers included observational studies in adults of the general population in China that reported factors associated with chronic HBV, measured by Hepatitis B surface antigen (HBsAg). Meta-analysis was performed using fixed-effect models of HBsAg prevalence among factors, and of adjusted odds ratios (ORs) for chronic HBV associated with each factor. Overall 39 articles were included, covering 22 factors, including a range of sociodemographic, behavioural and medical factors. In meta-analysis of eligible studies, a range of factors were significantly associated with higher HBsAg prevalence, including middle age, male sex, being married, rural residence, lower education, smoking, having a HBsAg positive household contact, family history of HBV, history of surgery or blood transfusion. The adjusted ORs varied, from 1.11 (95% CI 1.05-1.18) for smoking to 5.13 (95% CI 4.99-5.26) for having a HBsAg positive household contact. In Chinese adults, a range of factors are associated with chronic HBV infection, which may help inform targeted screening in the general population.

A comprehensive analysis of all-cause and cause-specific excess deaths in 30 countries during 2020.

The impact of COVID-19 on mortality from specific causes of death remains poorly understood. This study analysed cause-of-death data provided by the World Health Organization from 2011 to 2019 to estimate excess deaths in 2020 in 30 countries. Over-dispersed Poisson regression models were used to estimate the number of deaths that would have been expected if the pandemic had not occurred, separately for men and women. The models included year and age categories to account for temporal trends and changes in size and age structure of the populations. Excess deaths were calculated by subtracting observed deaths from expected ones. Our analysis revealed significant excess deaths from ischemic heart diseases (IHD) (in 10 countries), cerebrovascular diseases (CVD) (in 10 countries), and diabetes (in 19 countries). The majority of countries experienced excess mortality greater than 10%, including Mexico (+ 38·8% for IHD, + 34·9% for diabetes), Guatemala (+ 30·0% for IHD, + 10·2% for CVD, + 39·7% for diabetes), Cuba (+ 18·8% for diabetes), Brazil (+ 12·9% for diabetes), the USA (+ 15·1% for diabetes), Slovenia (+ 33·8% for diabetes), Poland (+ 30·2% for IHD, + 19·5% for CVD, + 26 1% for diabetes), Estonia (+ 26·9% for CVD, + 34·7% for diabetes), Bulgaria (+ 22·8% for IHD, + 11·4% for diabetes), Spain (+ 19·7% for diabetes), Italy (+ 18·0% for diabetes), Lithuania (+ 17·6% for diabetes), Finland (+ 13·2% for diabetes) and Georgia (+ 10·7% for IHD, + 19·0% for diabetes). In 2020, 22 out of 30 countries had a significant increase in total mortality. Some of this excess was attributed to COVID-19, but a substantial increase was also observed in deaths attributed to cardiovascular diseases and diabetes.

Associations of circulating fatty acids with incident coronary heart disease: a prospective study of 89,242 individuals in UK Biobank.

BACKGROUND: The role of fatty acids in coronary heart disease (CHD) remains uncertain. There is little evidence from large-scale epidemiological studies on the relevance of circulating fatty acids levels to CHD risk. This study aims to examine the independent associations of the major circulating types of fatty acids with CHD risk. METHODS: UK Biobank is a prospective study of adults aged 40-69 in 2006-2010; in 2012-2013, a subset of the participants were resurveyed. Analyses were restricted to 89,242 participants with baseline plasma fatty acids (measured using nuclear magnetic resonance spectroscopy) and without prior CHD. Cox proportional hazards models were used to estimate hazard ratios (HRs) for the associations with incidence CHD, defined as the first-ever myocardial infarction, unstable angina pectoris, coronary-related death, or relevant procedure. And the major types of fatty acids were mutually adjusted to examine the independent associations. Hazard ratios were corrected for regression dilution using the correlation of baseline and resurvey fatty acids measures. RESULTS: During a median follow-up of 11.8 years, 3,815 incident cases of CHD occurred. Independently of other fatty acids, CHD risk was positively associated with saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA), inversely associated with omega-3 polyunsaturated fatty acids (PUFA), but there was no strong evidence of an association with omega-6 PUFA: HR per standard deviation higher were 1.14 (95% CI, 1.09-1.20), 1.15 (1.10-1.21), 0.91 (0.87-0.94), and 1.04 (0.99-1.09) respectively. Independently of triglycerides and cholesterol, the inverse association with omega-3 PUFA was not materially changed, but the positive associations with SFA and MUFA attenuated to null after adjusting for triglycerides levels. CONCLUSIONS: This large-scale study has quantitated the independent associations of circulating fatty acids with CHD risk. Omega-3 PUFA was inversely related to CHD risk, independently of other fatty acids and major lipid fractions. By contrast, independently of other fatty acids, the positive associations of circulating SFA and MUFA with CHD risk were mostly attributed to their relationship with triglycerides.

Life expectancy following a cardiovascular event in individuals with and without type 2 diabetes: A UK multi-ethnic population-based observational study.

BACKGROUND AND AIMS: We aimed to evaluate the life expectancy following the first cardiovascular disease (CVD) event by type 2 diabetes (T2D) status and ethnicity. METHODS AND RESULTS: We used the Clinical Practice Research Datalink database in England (UK), linked to the Hospital Episode Statistics information, to identify individuals with and without T2D who survived a first CVD event between 1st Jan 2007 and 31st Dec 2017; subsequent death events were extracted from the Office for National Statistics database. Ethnicity was categorised as White, South Asian (SA), Black, or other. Flexible parametric survival models were used to estimate survival and predict life expectancy. 59,939 individuals with first CVD event were included: 7596 (12.7%) with T2D (60.9% men; mean age at event: 69.7 years [63.2 years in SA, 65.9 in Black, 70.2 in White]) and 52,343 without T2D (56.7% men; 65.9 years [54.7 in Black, 58.2 in SA, 66.3 in White]). Accounting for potential confounders (sex, deprivation, lipid-lowering medication, current smoking, and pre-existing hypertension), comparing individuals with vs without T2D the mortality rate was 53% higher in White (hazard ratio [HR]: 1.53 [95% CI: 1.44, 1.62]), corresponding to a potential loss of 3.87 (3.30, 4.44) life years at the age of 50 years in individuals with T2D. No evidence of a difference in life expectancy was observed in individuals of SA (HR: 0.82 [0.52, 1.29]; -1.36 [-4.58, 1.86] life years), Black (HR: 1.26 [0.59, 2.70]; 1.21 [-2.99, 5.41] life years); and other (HR: 1.64 [0.80, 3.39]; 3.89 [-2.28, 9.99] life years) ethnic group. CONCLUSION: Following a CVD event, T2D is associated with a different prognosis and life years lost among ethnic groups.

Reporting of Factorial Randomized Trials: Extension of the CONSORT 2010 Statement.

Importance: Transparent reporting of randomized trials is essential to facilitate critical appraisal and interpretation of results. Factorial trials, in which 2 or more interventions are assessed in the same set of participants, have unique methodological considerations. However, reporting of factorial trials is suboptimal. Objective: To develop a consensus-based extension to the Consolidated Standards of Reporting Trials (CONSORT) 2010 Statement for factorial trials. Design: Using the Enhancing the Quality and Transparency of Health Research (EQUATOR) methodological framework, the CONSORT extension for factorial trials was developed by (1) generating a list of reporting recommendations for factorial trials using a scoping review of methodological articles identified using a MEDLINE search (from inception to May 2019) and supplemented with relevant articles from the personal collections of the authors; (2) a 3-round Delphi survey between January and June 2022 to identify additional items and assess the importance of each item, completed by 104 panelists from 14 countries; and (3) a hybrid consensus meeting attended by 15 panelists to finalize the selection and wording of items for the checklist. Findings: This CONSORT extension for factorial trials modifies 16 of the 37 items in the CONSORT 2010 checklist and adds 1 new item. The rationale for the importance of each item is provided. Key recommendations are (1) the reason for using a factorial design should be reported, including whether an interaction is hypothesized, (2) the treatment groups that form the main comparisons should be clearly identified, and (3) for each main comparison, the estimated interaction effect and its precision should be reported. Conclusions and Relevance: This extension of the CONSORT 2010 Statement provides guidance on the reporting of factorial randomized trials and should facilitate greater understanding of and transparency in their reporting.

Cytotoxic and Bactericidal Effects of Inhalable Ciprofloxacin-Loaded Poly(2-ethyl-2-oxazoline) Nanoparticles with Traces of Zinc Oxide.

The bactericidal effects of inhalable ciprofloxacin (CIP) loaded-poly(2-ethyl-2-oxazoline) (PEtOx) nanoparticles (NPs) with traces of zinc oxide (ZnO) were investigated against clinical strains of the respiratory pathogens Staphylococcus aureus and Pseudomonas aeruginosa. CIP-loaded PEtOx NPs retained their bactericidal activity within the formulations compared to free CIP drugs against these two pathogens, and bactericidal effects were enhanced with the inclusion of ZnO. PEtOx polymer and ZnO NPs did not show bactericidal activity alone or in combination against these pathogens. The formulations were tested to determine the cytotoxic and proinflammatory effects on airway epithelial cells derived from healthy donors (NHBE), donors with chronic obstructive pulmonary disease (COPD, DHBE), and a cell line derived from adults with cystic fibrosis (CFBE41o-) and macrophages from healthy adult controls (HCs), and those with either COPD or CF. NHBE cells demonstrated maximum cell viability (66%) against CIP-loaded PEtOx NPs with the half maximal inhibitory concentration (IC50) value of 50.7 mg/mL. CIP-loaded PEtOx NPs were more toxic to epithelial cells from donors with respiratory diseases than NHBEs, with respective IC50 values of 0.103 mg/mL for DHBEs and 0.514 mg/mL for CFBE41o- cells. However, high concentrations of CIP-loaded PEtOx NPs were toxic to macrophages, with respective IC50 values of 0.002 mg/mL for HC macrophages and 0.021 mg/mL for CF-like macrophages. PEtOx NPs, ZnO NPs, and ZnO-PEtOx NPs with no drug were not cytotoxic to any cells investigated. The in vitro digestibility of PEtOx and its NPs was investigated in simulated lung fluid (SLF) (pH 7.4). The analysed samples were characterized using Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), and UV-Vis spectroscopy. Digestion of PEtOx NPs commenced one week following incubation and was completely digested after four weeks; however, the original PEtOx was not digested after six weeks of incubation. The outcome of this study revealed that PEtOx polymer could be considered an efficient drug delivery carrier in respiratory linings, and CIP-loaded PEtOx NPs with traces of ZnO could be a promising addition to inhalable treatments against resistant bacteria with reduced toxicity.

One Pot Synthesis, Biological Efficacy of AuNPs and Au-Amoxicillin Conjugates Functionalized with Crude Flavonoids Extract of Micromeria biflora.

Amoxicillin is the most widely used antibiotic in human medicine for treating bacterial infections. However, in the present research, Micromeria biflora's flavonoids extract mediated gold nanoparticles (AuNPs) were conjugated with amoxicillin (Au-amoxi) to study their efficacy against the inflammation and pain caused by bacterial infections. The formation of AuNPs and Au-amoxi conjugates were confirmed by UV-visible surface plasmon peaks at 535 nm and 545 nm, respectively. The scanning electron microscopy (SEM), zeta potential (ZP), and X-ray diffraction (XRD) studies reveal that the size of AuNPs and Au-amoxi are found to be 42 nm and 45 nm, respectively. Fourier-transform infrared spectroscopy (FT-IR) absorption bands at 3200 cm-1, 1000 cm-1, 1500 cm-1, and 1650 cm-1 reveal the possible involvement of different moieties for the formation of AuNPs and Au-amoxi. The pH studies show that AuNPs and Au-amoxi conjugates are stable at lower pH. The carrageenan-induced paw edema test, writhing test, and hot plate test were used to conduct in vivo anti-inflammatory and antinociceptive studies, respectively. According to in vivo anti-inflammatory activity, Au-amoxi compounds have higher efficiency (70%) after 3 h at a dose of 10 mg/kg body weight as compared to standard diclofenac (60%) at 20 mg/kg, amoxicillin (30%) at 100 mg/kg, and flavonoids extract (35%) at 100 mg/kg. Similarly, for antinociceptive activities, writhing test results show that Au-amoxi conjugates produced the same number of writhes (15) but at a lower dose (10 mg/kg) compared to standard diclofenac (20 mg/kg). The hot plate test results demonstrate that the Au-amoxi has a better latency time of 25 s at 10 mg/kg dose when compared to standard Tramadol of 22 s at 30 mg/ kg, amoxicillin of 14 s at 100 mg/kg, and extract of 14 s at 100 mg/kg after placing the mice on the hot plate for 30, 60, and 90 min with a significance of (p ≤ 0.001). These findings show that the conjugation of AuNPs with amoxicillin to form Au-amoxi can boost its anti-inflammatory and antinociceptive potential caused by bacterial infections.

Quantitative proteomic analyses reveal the dynamics of protein and amino acid accumulation during soybean seed development.

Using high throughput tandem mass tag (TMT) based tagging technique, we identified 4172 proteins in three developmental stages: early, mid, and late seed filling. We mapped the identified proteins to metabolic pathways associated with seed filling. The elevated abundance of several kinases was observed from the early to mid-stages of seed filling, indicating that protein phosphorylation was a significant event during this period. The early to late seed filling stages were characterized by an increased abundance of proteins associated with the cell wall, oil, and vacuolar-related processes. Among the seed storage proteins, 7S (ß-subunit) and 11S (Gy3, Gy4, Gy5) steadily increased in abundance during early to late stages of seed filling, whereas 2S albumin exhibited a decrease in abundance during the same period. An increased abundance of proteases, senescence-associated proteins, and oil synthesis proteins was observed from the mid to late seed filling stages. The mid to late stages of seed filling was also characterized by a lower abundance of transferases, transporters, Kunitz family trypsin, and protease inhibitors. Two enzymes associated with methionine synthesis exhibited lower abundance from early to late stages. This study unveiled several essential enzymes/proteins related to amino acid and protein synthesis and their accumulation during seed development. All data can be accessed through this link: https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=38784ecbd0854bb3801afc0d89056f84. (Accession MSV000087577).

Variabilities of δ13C and carbonaceous components in ambient PM2.5 in Northeast India: Insights into sources and atmospheric processes.

A year-long sampling campaign of ambient PM2.5 (particulate matter with aerodynamic diameter ≤2.5 mm) at a regional station in the North-Eastern Region (NER) of India was performed to understand the sources and formation of carbonaceous aerosols. Mass concentration, carbon fractions (organic and elemental carbon), and stable carbon isotope ratio (δ13C) of PM2.5 were measured and studied along with cluster analysis and Potential Source Contribution Function (PSCF) modelling. PM2.5 mass concentration was observed to be highest during winter and post-monsoon seasons when the meteorological conditions were relatively stable compared to other seasons. Organic carbon (OC) concentration was more than two times higher in the post-monsoon and winter seasons than in the pre-monsoon and monsoon seasons. Air mass back trajectory cluster analysis showed the dominance of local and regional air masses during winter and post-monsoon periods. In contrast, long-range transported air masses influenced the background site in pre-monsoon and monsoon. Air mass data and PSCF analysis indicated that aerosols during winter and post-monsoon are dominated by freshly generated emissions from local sources along with the influence from regional transport of polluted aerosols. On the contrary, the long-range transported air masses containing aged aerosols were dominant during pre-monsoon. No significant variability was observed in the range of δ13C values (-28.2‰ to -26.4‰) during the sampled seasons. The δ13C of aerosols indicates major sources to be combustion of biomass/biofuels (C3 plant origin), biogenic aerosols, and secondary aerosols. The δ13C variability and cluster/PSCF modelling suggest that aged aerosols (along with enhanced photo-oxidation derived secondary aerosols) influenced the final δ13C during the pre-monsoon. On the other hand, lower δ13C in winter and post-monsoon is attributed to the freshly emitted aerosols from biomass/biofuels.

Comparing Stop Signal Reaction Times in Alzheimer's and Parkinson's Disease.

BACKGROUND: To investigate the relative contributions of cerebral cortex and basal ganglia to movement stopping, we tested the optimum combination Stop Signal Reaction Time (ocSSRT) and median visual reaction time (RT) in patients with Alzheimer's disease (AD) and Parkinson's disease (PD) and compared values with data from healthy controls. METHODS: Thirty-five PD patients, 22 AD patients, and 29 healthy controls were recruited to this study. RT and ocSSRT were measured using a hand-held battery-operated electronic box through a stop signal paradigm. RESULT: The mean ocSSRT was found to be 309 ms, 368 ms, and 265 ms in AD, PD, and healthy controls, respectively, and significantly prolonged in PD compared to healthy controls (p = 0.001). The ocSSRT but not RT could separate AD from PD patients (p = 0.022). CONCLUSION: Our data suggest that subcortical networks encompassing dopaminergic pathways in the basal ganglia play a more important role than cortical networks in movement-stopping. Combining ocSSRT with other putative indices or biomarkers of AD (and other dementias) could increase the accuracy of early diagnosis.

Using health economic modelling to inform the design and development of an intervention: estimating the justifiable cost of weight loss maintenance in the UK.

BACKGROUND: There is a need to develop cost-effective weight loss maintenance interventions to prolong the positive impact of weight loss on health outcomes. Conducting pre-trial health economic modelling is recommended to inform the design and development of behavioural interventions. We aimed to use health economic modelling to estimate the maximum cost per-person (justifiable cost) of a cost-effective behavioural weight loss maintenance intervention, given an estimated intervention effect for individuals with: i) a Body Mass Index (BMI) of 28 kg/m2 or above without diabetes and ii) a diagnosis of type 2 diabetes prescribed a single non-insulin diabetes medication. METHODS: The School for Public Health Research Diabetes prevention model was used to estimate the lifetime Quality-adjusted life year (QALY) gains, healthcare costs, and maximum justifiable cost associated with a weight loss maintenance intervention. Based on a meta-analysis, the estimated effect of a weight loss maintenance intervention following a 9 kg weight loss, was a regain of 1.33 kg and 4.38 kg in years one and two respectively compared to greater regain of 2.84 kg and 5.6 kg in the control group. Sensitivity analysis was conducted around the rate of regain, duration of effect and initial weight loss. RESULTS: The justifiable cost for a weight loss maintenance intervention at an ICER of £20,000 per QALY was £104.64 for an individual with a BMI of 28 or over and £88.14 for an individual with type 2 diabetes. Within sensitivity analysis, this varied from £36.42 to £203.77 for the former, and between £29.98 and £173.05 for the latter. CONCLUSIONS: Researchers developing a weight loss maintenance intervention should consider these maximum justifiable cost estimates and the potential impact of the duration of effect and initial weight loss when designing intervention content and deciding target populations. Future research should consider using the methods demonstrated in this study to use health economic modelling to inform the design and budgetary decisions in the development of a behavioural interventions.

Robust Wet Milling Technique for Producing Micronized Ibuprofen Particles with Improved Solubility and Dissolution.

This study investigated a systematic approach for producing ibuprofen (IBF) particles with leucine by wet milling. Using a high shear homogenizer, the particles size of the IBF was reduced. Prepared IBF microparticles were freeze-dried and characterized by using Mastersizer, SEM, DSC, XRD, ATR-FTIR, and TGA. The drug saturation solubility and in-vitro dissolution performance were carried out in phosphate buffer solution (PBS, pH 7.4) at 37°C temperature and IBF were determined using a validated HPLC method. The wet-milled method reduced the particle size from 71.3 to 1.7 µm. The minimum particle size of IBF was obtained in 0.05% Tween 80 solution homogenized at 17,000 rpm for 15 min. The saturated solubility (168.7 µg/mL) of the micronized IBF particles with leucine showed higher compared to that of the original IBF (147.4 µg/mL) in PBS solution. The prepared IBF particles containing 2.5-6.25% leucine showed significantly higher IBF release (100%) compared to that of original drug particles (55.9%) in 120 min. The excipient leucine played a major role in enhancing the solubility and dissolution profile of the prepared IBF particles probably by the formation of hydrogen bonding. The developed wet milling was an efficient and robust technique for reducing the particle size of IBF and could be a useful method for manufacturing drug particles with enhanced solubility and dissolution.

Personality and travel intentions during and after the COVID-19 pandemic: An artificial neural network (ANN) approach.

The tourism sector has been deeply ravaged by the COVID-19 pandemic as many individuals abstained entirely from travel. Thus, before contemplating the trajectory of the sector's recovery, it is essential to understand individuals' travel intentions both during and after the pandemic. The present study contributes in this regard by examining the impact of individuals' personality traits categorised by the five-factor model, or the Big Five, on their leisure travel intentions during and after the pandemic. To this end, we utilised an artificial neural network (ANN) approach to analyse 500 responses from individuals residing in Japan. The results reveal that extraversion has the strongest relative influence on intentions to travel during the pandemic, whereas openness to experience has the strongest influence on travel intentions after the pandemic. This study is the first of its kind to examine the influence of the Big Five personality traits on travel intentions in the context of a pandemic.

Developing a mental health index using a machine learning approach: Assessing the impact of mobility and lockdown during the COVID-19 pandemic.

Governments worldwide have implemented stringent restrictions to curtail the spread of the COVID-19 pandemic. Although beneficial to physical health, these preventive measures could have a profound detrimental effect on the mental health of the population. This study focuses on the impact of lockdowns and mobility restrictions on mental health during the COVID-19 pandemic. We first develop a novel mental health index based on the analysis of data from over three million global tweets using the Microsoft Azure machine learning approach. The computed mental health index scores are then regressed with the lockdown strictness index and Google mobility index using fixed-effects ordinary least squares (OLS) regression. The results reveal that the reduction in workplace mobility, reduction in retail and recreational mobility, and increase in residential mobility (confinement to the residence) have harmed mental health. However, restrictions on mobility to parks, grocery stores, and pharmacy outlets were found to have no significant impact. The proposed mental health index provides a path for theoretical and empirical mental health studies using social media.

Identification of genetic determinants of hemolytic activity of Riemerella anatipestifer using random transposon mutagenesis.

Riemerella anatipestifer causes epizootic infectious disease in poultry resulting in serious economic losses especially to the duck industry. In our previous study, R. anatipestifer was found to lyse duck erythrocytes in vitro. In the present study, a random Tn4351 mutagenesis library of hemolytic R. anatipestifer strain SX containing 4000 mutants was constructed to investigate the genetic basis of hemolytic activity. Thirty mutants with reduced hemolytic activity and one with increased hemolytic activity were screened and insertions in 24 genes were identified. Of these genes, four were predicted to encode outer membrane proteins, one encoded a cytoplasmic membrane protein, 11 encoded cytoplasmic proteins, and eight encoded proteins with unknown locations. Based on current annotations of the R. anatipestifer genomes, of the 24 genes, 7 (29.17%) were involved in iron utilization. The hemolytic activities of the complemented strains M2 (pRES-Riean_0790) and M18 (pRES-Riean_0653) were restored, indicating that both Riean_0653 and Riean_0790 are involved in the hemolytic activity of strain SX. However, the recombinant proteins rRiean_0317, rRiean_0790, rRiean_0653, rRiean_1027, rRiean_1143, and rRiean_1561 had no hemolytic activity, suggesting that none were hemolysins.