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Abstract The antibody response to vaccination and infection is a key component of the immune response to pathogens. Sequencing of peripheral B cells may not represent the complete B cell receptor repertoire. Here we present a method for sequencing human plasma-derived polyclonal IgG using a combination of mass spectrometry and B-cell sequencing. We investigate the IgG response to the Moderna Spikevax COVID-19 vaccine. From the sequencing data of the natural polyclonal response to vaccination, we generate 12 recombinant antibodies. Six derived recombinant antibodies, including four generated with de novo protein sequencing, exhibit similar or higher binding affinities than the original natural polyclonal antibody. Neutralization tests reveal that the six antibodies possess neutralizing capabilities against the target antigen. This research provides insights into sequencing polyclonal IgG antibodies and the potential of our approach in generating recombinant antibodies with robust binding affinity and neutralization capabilities. Directly examining the circulating IgG pool is crucial due to potential misrepresentations by B-cell analysis alone.

Abstract Recent studies have identified inequality in the distribution of air pollution attributable health impacts, but to our knowledge this has not been examined in Canadian cities. We evaluated the extent and sources of inequality in air pollution attributable mortality at the census tract (CT) level in seven of Canada's largest cities. We first regressed fine particulate matter (PM2.5) and nitrogen dioxide (NO2) attributable mortality against the neighborhood (CT) level prevalence of age 65 and older, low income, low educational attainment, and identification as an Indigenous (First Nations, Métis, Inuit) or Black person, accounting for spatial autocorrelation. We next examined the distribution of baseline mortality rates, PM2.5 and NO2 concentrations, and attributable mortality by neighborhood (CT) level prevalence of these characteristics, calculating the concentration index, Atkinson index, and Gini coefficient. Finally, we conducted a counterfactual analysis of the impact of reducing baseline mortality rates and air pollution concentrations on inequality in air pollution attributable mortality. Regression results indicated that CTs with a higher prevalence of low income and Indigenous identity had significantly higher air pollution attributable mortality. Concentration index, Atkinson index, and Gini coefficient values revealed different degrees of inequality among the cities. Counterfactual analysis indicated that inequality in air pollution attributable mortality tended to be driven more by baseline mortality inequalities than exposure inequalities. Reducing inequality in air pollution attributable mortality requires reducing disparities in both baseline mortality and air pollution exposure.

ABSTRACTBackground Standard methods assessing pain in rodents are often observer dependent, potentially resulting in biased outcomes. Advanced dynamic weight bearing (ADWB) offers an observer-independent approach that can provide objective, reliable data in preclinical pain research.Aims The aim of this study was to characterize the use of ADWB in assessing murine responses to allyl isothiocyanate (AITC)-induced hyperacute hypersensitivity and identify best practices for use of the device.Methods Male C57BL/6J mice received intraplantar injections of saline or 0.1% AITC solution and were assessed using the ADWB system; simultaneous observer-dependent durations of paw licking and biting were measured. ADWB data were analyzed using the proprietary software from Bioseb and correlated to observer-dependent results, with parameters assessed to optimize data collected.Results ADWB detected pain-directed changes in weight and surface area distribution in AITC-treated mice, with paw weight and surface area placement correlating to paw licking and biting. Optimization of adjustable threshold parameters allowed for reduced coefficients of variability and increased duration of validated data.Conclusions The ADWB assay provides an efficient and unbiased measure of chemical-induced hyperacute hypersensitivity in mice. ADWB detection parameters influence amount of validated data and variability, a consideration for data analysis in future studies.

The antibody response to vaccination and infection is a key component of the immune response to pathogens. Sequencing of peripheral B cells may not represent the complete B cell receptor repertoire. Here we present a method for sequencing human plasma-derived polyclonal IgG using a combination of mass spectrometry and B-cell sequencing. We investigate the IgG response to the Moderna Spikevax COVID-19 vaccine. From the sequencing data of the natural polyclonal response to vaccination, we generate 12 recombinant antibodies. Six derived recombinant antibodies, including four generated with de novo protein sequencing, exhibit similar or higher binding affinities than the original natural polyclonal antibody. Neutralization tests reveal that the six antibodies possess neutralizing capabilities against the target antigen. This research provides insights into sequencing polyclonal IgG antibodies and the potential of our approach in generating recombinant antibodies with robust binding affinity and neutralization capabilities. Directly examining the circulating IgG pool is crucial due to potential misrepresentations by B-cell analysis alone. The antibody response to infection and vaccination is an essential component of the anti-infective immune response. Here the authors present a de novo protein sequencing method for antibody discovery from polyclonal IgG from human plasma and characterise the antibody response to the Moderna Spikevax COVID-19 vaccine. [ABSTRACT FROM AUTHOR]

Background: Healthcare workers are at high risk of developing occupational hand dermatitis (HD) due to their frequent exposure to wet‐work and use of gloves. Complaints of HD may interfere with work and cause loss of work productivity, or sick leave, and may have impact on job pleasure and performing daily activities. The prevalence of HD among intensive care unit (ICU) nurses is unknown. Objectives: To investigate the point prevalence and the 1‐year prevalence of HD among ICU nurses, and to determine the impact of HD on work and daily activities. Method: A questionnaire‐based cross‐sectional study was performed among ICU nurses. Participants were recruited in the Amsterdam University Medical Centre. A symptom‐based questionnaire was used to determine HD and atopic predisposition, and an additional questionnaire was used concerning the influence of HD. ICU nurses with an atopic predisposition or symptoms suiting HD were invited for the hand dermatitis consultation hour (HDCH). Data were analysed with logistic regression. Results: A total of 184 ICU nurses were included. The point prevalence of HD was 9.8% (95% CI: 5.9–15.0) and the 1‐year prevalence was 26.6% (95% CI: 20.4–33.6). Sick leave was reported by 0.5%. HD seemed to have more impact on job pleasure than on work productivity. Conclusion: The high prevalence rate of HD resulting from our study highlights the need for the prevention of occupational HD among healthcare workers. [ABSTRACT FROM AUTHOR]

BackgroundUltra-marathon running participation has become increasingly more popular in recent years; however, there is inconclusive evidence concerning the effects of participation on cognition and cardiovascular function. The purpose of this study was to examine alterations in cardiovascular function and cognitive performance and their association in ultra-marathon runners prior to and following an ultra-endurance event.MethodsIn total, 24 runners (19 males and 5 females) participated in an ultra-marathon race (FatDog120) held in British Columbia, Canada. Participants competed in varying races distances [48 km (n = 2), 80 km (n = 7), 113 km (n = 3), and 193 km (n = 12)]. Cognition was assessed prior to and upon race completion using simple reaction time, choice reaction time, discrimination reaction time, and recognition memory (% correct). Cardiovascular function was assessed prior to and upon race completion using radial applanation tonometry for diastolic pulse contour examination.ResultsCognitive performance displayed significantly (p < 0.001) slower reaction times post-race for simple (30.2%), discrimination (22.7%), and choice reaction time (30.5%), as well as a significant (p < 0.05) reduction in memory test performance (−8.2%). A significant association between systemic vascular resistance and choice reaction time was observed post-race (r = 0.41, p < 0.05). Significant changes in post-race cardiovascular function were observed in resting heart rate (31.5%), cardiac output (27.5%), mean arterial blood pressure (−5.6%), total systemic resistance (−17.6%), systolic blood pressure (−7.0%), pulse pressure (−11.2%), and rate pressure product (22.4%). There was evidence of enhanced cardiovascular function being associated with improved cognitive performance before and after the ultra-endurance event.ConclusionUltra endurance running is associated with marked impairments in cognitive performance that are associated (at least in part) with changes in cardiovascular function in healthy adults.

Community-based and Indigenous-led health and wellness approaches have been widely advocated for Indigenous peoples. However, remarkably few Indigenous designed and led interventions exist within the field. The purpose of this study was to evaluate an Indigenous-led and community-based health and wellness intervention in a remote and rural Indigenous community. This protocol was designed by and for Indigenous peoples based on the aspirations of the community (established through sharing circles). A total of 15 participants completed a 13-week walking and healthy lifestyle counselling program (incorporating motivational interviewing) to enhance cardiometabolic health. Measures of moderate-to-vigorous physical activity (MVPA; 7-day accelerometry and self-report), predicted maximal aerobic power (VO2max; 6-min walk test), resting heart rate and blood pressure, and other health-related physical fitness measures (musculoskeletal fitness and body composition) were taken before and after the intervention. The intervention led to significant (p < 0.05) improvements in VO2max (7.1 ± 6.3 % change), with the greatest improvements observed among individuals with lower baseline VO2max (p < 0.05, r = -0.76). Resting heart rate, resting systolic blood pressure, and resting diastolic blood pressure decreased significantly (p < 0.05) after the intervention. Self-reported and accelerometry-measured frequency of MVPA increased significantly (p < 0.05), and the total MVPA minutes (~275 min/week) were above international recommendations. Change in VO2max was significantly correlated with change in self-reported (r = 0.42) and accelerometry-measured (r = 0.24) MVPA minutes. No significant changes were observed in weight, body mass index, waist circumference, body fat (via bioelectrical impedance), grip strength, and flexibility. These findings demonstrate that a culturally relevant and safe, community-based, Indigenous-led, health and wellness intervention can lead to significant and clinically relevant improvements in cardiometabolic health and physical activity behaviour, with the greatest changes being observed in the least active/fit individuals. [ABSTRACT FROM AUTHOR]

The pyrochlore iridates, A 2 Ir 2 O 7 , show a wide variety of structural, electronic, and magnetic properties controlled by the interplay of different exchange interactions, which can be tuned by external pressure. In this work, we report pressure-induced iso-structural phase transitions at ambient temperature using synchrotron-based x-ray diffraction (up to ∼20 GPa) and Raman-scattering measurements (up to ∼25 GPa) of the pyrochlore series (Sm&#95;{1-x}Bi x ) 2 Ir 2 O 7 ( x = 0, 0.02, and 0.10). Our Raman and x-ray data suggest an iso-structural transition in Sm 2 Ir 2 O 7 atPc∼ 11.2 GPa, associated with the rearrangement of IrO 6 octahedra in the pyrochlore lattice. The transition pressure decreases to ∼10.2 and 9 GPa for x = 0.02 and 0.10, respectively. For all the samples, the linewidth of three phonons associated with Ir-O-Ir (A1gand E g ) and Ir-O (T2g4) vibrations show anomalous decrease up toPc, due to decrease in electron-phonon interaction., (© 2024 IOP Publishing Ltd.)