Physical capacity and inactivity in obstructive airway diseases: a "can do, do do" analysis.

Introduction: Physical capacity is an important determinant of physical activity in people with obstructive airway disease (OAD). This study aimed to extend the "can do, do do" concept in people with OAD, to identify if people categorised into quadrants based on physical capacity and activity differ by clinical and movement behaviour characteristics. Methods: A total of 281 participants (bronchiectasis n=60, severe asthma n=93, COPD n=70 and control n=58) completed assessments to characterise physical capacity as "can do" versus "can't do" (6-min walk distance < or ≥70% pred) and physical activity as "do do" versus "don't do" (accelerometer-derived moderate to vigorous intensity physical activity (MVPA) < or ≥150 min·week-1). Results: The control group had a greater proportion of people in the "can do, do do" quadrant compared with the OAD groups (76% versus 10-33%). People with OAD in the "can't do, don't do" quadrant had worse clinical characteristics (airflow limitation, comorbidities, quality of life and functional dyspnoea) and spent less time doing light-intensity physical activity (LPA) and more time being sedentary compared with the "can do, do do" quadrant. Discussion: This study highlights that many people with OAD may be inactive because they do not have the physical capacity to participate in MVPA, which is further impacted by greater disease severity. It is important to consider the potential benefits of addressing LPA and sedentary behaviour due to suboptimal levels of these movement behaviours across different quadrants. Future research is needed to investigate if tailoring intervention approaches based on quadrant allocation is effective in people with OAD.

SARS-CoV-2 vaccination prevalence by mental health diagnosis: a population-based cross-sectional study in Ontario, Canada.

BACKGROUND: Since the onset of the COVID-19 pandemic, there has been concern about the impact of SARS-CoV-2 infection among individuals with mental illnesses. We analyzed the SARS-CoV-2 vaccination status of Ontarians with and without a history of mental illness. METHODS: We conducted a population-based cross-sectional study of all community-dwelling Ontario residents aged 19 years and older as of Sept. 17, 2021. We used health administrative data to categorize Ontario residents with a mental disorder (anxiety, mood, substance use, psychotic or other disorder) within the previous 5 years. Vaccine receipt as of Sept. 17, 2021, was compared between individuals with and without a history of mental illness. RESULTS: Our sample included 11 900 868 adult Ontario residents. The proportion of individuals not fully vaccinated (2 doses) was higher among those with substance use disorders (37.7%) or psychotic disorders (32.6%) than among those with no mental disorders (22.9%), whereas there were similar proportions among those with anxiety disorders (23.5%), mood disorders (21.5%) and other disorders (22.1%). After adjustment for age, sex, neighbourhood income and homelessness, individuals with psychotic disorders (adjusted prevalence ratio 1.19, 95% confidence interval [CI] 1.18-1.20) and substance use disorders (adjusted prevalence ratio 1.35, 95% CI 1.34-1.35) were more likely to be partially vaccinated or unvaccinated relative to individuals with no mental disorders. INTERPRETATION: Our study found that psychotic disorders and substance use disorders were associated with an increased prevalence of being less than fully vaccinated. Efforts to ensure such individuals have access to vaccinations, while challenging, are critical to ensuring the ongoing risks of death and other adverse consequences of SARS-CoV-2 infection are mitigated in this high-risk population.

New Evidence for the Role of Pituitary Adenylate Cyclase-Activating Polypeptide as an Antimicrobial Peptide in Teleost Fish.

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) is a multifunctional neuropeptide that is widely distributed and conserved across species. We have previously shown that in teleost fish, PACAP not only possesses direct antimicrobial properties but also immunomodulatory effects against the bacterial pathogens Flavobacterium psychrophilum and Pseudomonas aeruginosa using in vitro and in vivo experiments. These previous results suggest PACAP can be used as an alternative to antibiotics to prevent and/or treat bacterial infections in the aquaculture industry. To accomplish this goal, more studies are needed to better understand the effect of PACAP on pathogens affecting fish in live infections. In the present study, the transcripts PACAP, PRP/PACAP, and VPAC2 receptor were examined in rainbow trout (Oncorhynchus mykiss) naturally infected with Yersinia ruckeri, which exhibited an increase in their expression in the spleen when compared to healthy fish. Synthetic Clarias gariepinus PACAP-38 has direct antimicrobial activity on Y. ruckeri and inhibits up to 60% of the bacterial growth when the peptide is at concentrations between 50 and 100 µM in TSB. The growth inhibition increased up to 90% in the presence of 12.5 µM of PACAP-38 when salt-free LB broth was used instead of TSB. It was also found to inhibit Y. ruckeri growth in a dose-dependent manner when the rainbow trout monocyte/macrophage-like cell line (RTS11) was pre-treated with lower concentrations of the peptide (0.02 and 0.1 µM) before going through infection. Differential gene expression was analyzed in this in vitro model. Overall, the results revealed new evidence to support the role of PACAP as an antimicrobial and immunomodulatory peptide treatment in teleosts.

Factores sociodemográficos en la dinámica del comportamiento delictivo: análisis descriptivo de criminalidad en Colombia, año 2022 / Socio-demographic factors in the dynamics of criminal behaviour: descriptive analysis of criminality in Colombia, year 2022 / Fatores sociodemográficos na dinâmica do comportamento criminal: análise descritiva da criminalidade na Colômbia, ano de 2022

El presente estudio de carácter descriptivo y analítico tiene como objetivo principal presentar el comportamiento criminal en Colombia para el 2022, desde un enfoque cuantitativo empleado para la extracción, análisis e interpretación de los registros administrativos del Sistema de Información Estadístico, Delincuencial, Contravencional y Operativo (SIEDCO), constituyéndose como un insumo para aquellos interesados en el estudio de la dinámica criminal, así como para quienes se encargan de diseñar estrategias para la contención del delito y la generación de política pública en materia de seguridad. En este sentido y en el marco de las dinámicas sociodemográficas, en una primera parte se aborda de manera general el proceso de homogenización de los registros administrativos llevado a cabo por la Policía Nacional y la Fiscalía General de la Nación. Y en una segunda parte, con especial énfasis en el homicidio intencional, se presenta el análisis de la información que permitió identificar las principales variables que influyen en la comisión del delito, de acuerdo con las cifras contenidas en el SIEDCO, en el periodo comprendido entre el 1 de enero y el 31 de diciembre de 2022, comparado con la misma temporalidad del 2021, en el que se detallan los delitos que afectan la integridad personal y el patrimonio económico de quienes habitan el territorio colombiano; se hallaron incrementos considerables en estos y se resaltan los factores de oportunidad para su comisión, situación contraria a la que se evidenció sobre las afectaciones a la vida y la integridad, conjunto de conductas que, según lo registrado, decrecieron en el periodo analizado. Finalmente, se ofrece un aporte a la contención desde la actividad de policía y una serie de conclusiones que permitan ampliar la visión sobre los diversos fenómenos y enriquecer la generación de conocimiento en el campo de la criminología.

The main objective of this descriptive and analytical study is to present criminal behaviour in Colombia for 2022, from a quantitative approach used for the extraction, analysis and interpretation of the administrative records of the Statistical, Criminal, Contraventional and Operational Information System (SIEDCO), constituting an input for those interested in the study of criminal dynamics, as well as for those responsible for designing strategies for the containment of crime and the generation of public policy on security. In this sense, and within the framework of socio-demographic dynamics, the first part of the paper deals in a general way with the process of homogenisation of administrative records carried out by the National Police and the Attorney General's Office. The second part, with special emphasis on intentional homicide, presents the analysis of the information that made it possible to identify the main variables that influence the commission of the crime, according to the figures contained in SIEDCO, in the period between 1 January and 31 December 2022, compared with the same period in 2021, in which the crimes that affect the personal integrity and economic patrimony of those who live in Colombian territory are detailed; considerable increases were found in these and the factors of opportunity for their commission are highlighted, contrary to the situation that was evidenced in the affectations to life and integrity, a group of conducts that, according to what was recorded, decreased in the period analysed. Finally, we offer a contribution to containment from the police activity and a series of conclusions that allow us to broaden the vision of the diverse phenomena and enrich the generation of knowledge in the field of criminology.

O principal objetivo deste estudo descritivo e analítico é apresentar o comportamento criminal na Colômbia para 2022, a partir de uma abordagem quantitativa utilizada para a extração, análise e interpretação dos registros administrativos do Sistema de Informação Estatística, Criminal, Contravencional e Operacional (SIEDCO), constituindo um insumo para os interessados no estudo da dinâmica criminal, bem como para os responsáveis pela elaboração de estratégias para a contenção do crime e a geração de políticas públicas de segurança. Nesse sentido, e dentro da estrutura da dinâmica sociodemográfica, a primeira parte do artigo trata de forma geral do processo de homogeneização dos registros administrativos realizado pela Polícia Nacional e pela Procuradoria Geral da República. A segunda parte, com ênfase especial no homicídio doloso, apresenta a análise das informações que permitiram identificar as principais variáveis que influenciam o cometimento do crime, de acordo com os números contidos no SIEDCO, no período entre 1º de janeiro e 31 de dezembro de 2022, em comparação com o mesmo período de 2021, no qual são detalhados os crimes que afetam a integridade pessoal e o patrimônio econômico daqueles que vivem em território colombiano; Neles foram encontrados aumentos consideráveis e são destacados os fatores de oportunidade para seu cometimento, ao contrário da situação que se evidenciou nas afetações à vida e à integridade, grupo de condutas que, segundo o que foi registrado, diminuiu no período analisado. Finalmente, oferecemos uma contribuição para a contenção da atividade policial e uma série de conclusões que nos permitem ampliar a visão dos diversos fenômenos e enriquecer a geração de conhecimento no campo da criminologia.

Poor Air Quality Is Linked to Stress in Honeybees and Can Be Compounded by the Presence of Disease.

Climate change-related extreme weather events have manifested in the western United States as warmer and drier conditions with an increased risk of wildfires. Honeybees, essential for crop pollination in California, are at the center of these extreme weather events. We associated the maximum daily temperature and air quality index values with the performance of colonies placed in wildfire-prone areas and determined the impact of these abiotic stressors on gene expression and histopathology. Our results indicate that poor air quality was associated with higher maximum daily temperatures and a lower gene expression level of Prophenoloxidase (ProPO), which is tied to immune system strength; however, a higher gene expression level of Vitellogenin (Vg) is tied to oxidative stress. There was a positive relationship between Varroa mites and N. ceranae pathogen loads, and a negative correlation between Varroa mites and Heat Shock Protein 70 (HSP70) gene expression, suggesting the limited ability of mite-infested colonies to buffer against extreme temperatures. Histological analyses did not reveal overt signs of interaction between pathology and abiotic stressors, but N. ceranae infections were evident. Our study provides insights into interactions between abiotic stressors, their relation to common biotic stressors, and the expression of genes related to immunity and oxidative stress in bees.

The prevalence of sarcopenia in Parkinson's disease and related disorders- a systematic review.

BACKGROUND: The prevalence of sarcopenia (reduced skeletal muscle strength and mass), Parkinson's disease (PD) and Parkinson's related disorders (PRD) all increase with age. They also share risk factors and pathogenetic features. An increased prevalence of sarcopenia in PD and PRD than the general population was thus postulated. METHODS: Four databases were searched using predefined literature search strategies. Studies conducted in participants with PD or PRD reporting the prevalence of sarcopenia and those providing data to compute the prevalence were included. Pre-sarcopenia, probable/possible sarcopenia and confirmed sarcopenia were defined according to the main sarcopenia working groups. Risk of bias was assessed using the AXIS tool. RESULTS: 1978 studies were identified; 97 assessed in full; 14 met inclusion criteria. The median study quality score was 15/20. The range of probable sarcopenia was 23.9 to 66.7%, and it did not change after excluding PRD participants. The prevalence of confirmed sarcopenia in participants with any parkinsonian disorder ranged from 2 to 31.4%. Including just PD participants, the range was 10.9 to 31.4%. In studies with controls, sarcopenia was more prevalent in PD and PRD. There was a positive non-significant trend between severity of motor symptoms and prevalence of sarcopenia or components of sarcopenia. High heterogeneity precluded meta-analysis, therefore there was insufficient evidence to conclude whether sarcopenia is more prevalent in PD or PRD. CONCLUSIONS: Probable and confirmed sarcopenia are common in PD and PRD and they may be associated with disease severity. This co-occurrence supports the value of screening for sarcopenia in parkinsonian populations.

A practical approach to the sampling, fixation, softening, and sectioning of whole honey bees for histologic evaluation.

The Western honey bee (Apis mellifera) is economically important as the primary managed pollinator of many agricultural crops and for the production of various hive-related commodities. Honey bees are not classically or thoroughly covered in veterinary pathology training programs. Given their unique anatomic and biological differences from the other species more traditionally evaluated by veterinary pathologists, establishing routine and consistent methods for processing samples for histology ensures accurate diagnostic and research conclusions. We developed and tested several field protocols for the sampling of honey bees. We compared the tissue-quality outcomes for worker bees fixed, collected, and/or softened under the following protocols: 1) routine formalin fixation; 2) softening chitin via exposure to Nair for 2 d or 3) 5 d; 4) shortened times between formalin submersion and trimming of body segments to enhance penetration of formalin into internal tissues; 5) ethanol submersion of specimen prior to formalin fixation; 6) indirect dry ice exposure; and 7) prolonged -80°C storage. Routine formalin fixation, exposure to Nair for 2 d, indirect dry ice exposure, and trimming body segments within 2 h of formalin submersion resulted in the highest quality histologic tissue sections. The poorest quality sections resulted from softening of chitin by exposure to Nair for 5 d, submersion in ethanol for 3 d before formalin fixation, and prolonged storage at -80°C. Our results indicate that routine formalin fixation is adequate, and that immobilizing bees with indirect dry ice exposure aids in sample collection without negatively impacting the quality of histologic sections.

Subjective well-being, happiness, and environmental health factors related to women planning a pregnancy or pregnant, using mobile health intervention.

Objectives: To compare the environmental health results in women trying to get pregnant or pregnant using a mobile health application (Green Page) through healthcare professionals or self-completed by women, and to explore the relationship between the subjective well-being of these women with their lifestyles and environmental factors. Methods: A descriptive study with mixed methods was conducted in 2018. A mobile health survey was used in two phases. Phase 1 was a cross-sectional study through professionals (n = 1100) followed by phase 2, a convenience sampling through women's self-reporting (n = 3425). A personalized report was downloadable with health recommendations for the well-being of the mother and child. Results: Of the 3205 participants (mean age = 33 years, SD = 0.2 years), 1840 were planning a pregnancy and 1365 were pregnant. One in five pregnant women had a low level of happiness. Globally, subjective well-being and happiness were found to be negatively associated with lack of contact with nature, sedentary lifestyle, excess weight, environmental exposure, and older age in pregnancy. Precisely 45%, 60%, and 14% of women were exposed to tobacco, alcohol, and illegal drugs, respectively. The women self-reported levels of risk factors higher than when the tool was used by or through professionals. Conclusions: The use of mobile health interventions focused on environmental health during planning or pregnancy periods could help improve the quality of healthcare and foster greater involvement of women in their self-care process, thus promoting empowerment, healthier environments, and lifestyles. Ensuring equity of access and data protection are global challenges to be addressed.

Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism.

Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement Factor H Related 5 protein (CFHR5), a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.

Identification of a Noxo1 inhibitor by addition of a polyethylene glycol chain.

Reactive oxygen species (ROS) are a heterogeneous group of highly reactive ions and molecules derived from molecular oxygen (O2) which can cause DNA damage and lead to skin cancer. NADPH oxidase 1 (Nox1) is a major producer of ROS in the skin upon exposure to ultraviolet light. Functionally, Nox1 forms a holoenzyme complex that generates two superoxide molecules and reduces NADPH. The signaling activation occurs when the organizer subunit Noxo1 translocates to the plasma membrane bringing a cytochrome p450, through interaction with Cyba. We propose to design inhibitors that prevent Cyba-Noxo1 binding as a topical application to reduce UV-generated ROS in human skin cells. Design started from an apocynin backbone structure to generate a small molecule to serve as an anchor point. The initial compound was then modified by addition of a polyethylene glycol linked biotin. Both inhibitors were found to be non-toxic in human keratinocyte cells. Further in vitro experiments using isothermal calorimetric binding quantification showed the modified biotinylated compound bound Noxo1 peptide with a KD of 2 nM. Both using isothermal calorimetric binding and MALDI (TOF) MS showed that binding of a Cyba peptide to Noxo1 was blocked. In vivo experiments were performed using donated skin explants with topical application of the two inhibitors. Experiments show that ultraviolet light exposure of with the lead compound was able to reduce the amount of cyclobutene pyrimidine dimers in DNA, a molecule known to lead to carcinogenesis. Further synthesis showed that the polyethylene glycol but not the biotin was essential for inhibition.

Peptidomic Characterization and Amino Acid Availability after Intake of Casein vs. a Casein Hydrolysate in a Pig Model.

It is known that casein hydrolysis accelerates gastrointestinal transit in comparison to intact casein, although the effect of the protein hydrolysis on the composition of the digests is not fully understood. The aim of this work is to characterize, at the peptidome level, duodenal digests from pigs, as a model of human digestion, fed with micellar casein and a previously described casein hydrolysate. In addition, in parallel experiments, plasma amino acid levels were quantified. A slower transit of nitrogen to the duodenum was found when the animals received micellar casein. Duodenal digests from casein contained a wider range of peptide sizes and a higher number of peptides above five amino acids long in comparison with the digests from the hydrolysate. The peptide profile was markedly different, and although ß-casomorphin-7 precursors were also found in hydrolysate samples, other opioid sequences were more abundant in the casein digests. Within the same substrate, the evolution of the peptide pattern at different time points showed minimal changes, suggesting that the protein degradation rate relies more on the gastrointestinal location than on digestion time. Higher plasma concentrations of methionine, valine, lysine and amino acid metabolites were found in animals fed with the hydrolysate at short times (<200 min). The duodenal peptide profiles were evaluated with discriminant analysis tools specific for peptidomics to identify sequence differences between both substrates that can be used for future human physiological and metabolic studies.

Systematic Review: Neurodevelopmental Benefits of Active/Passive School Exposure to Green and/or Blue Spaces in Children and Adolescents.

Today more than half of the world's population lives in urban areas. Children spend about 40 h a week in the school environment. Knowing the influence of school exposure to green/blue spaces could improve the children's health, creating healthier environments and preventing exposure to legal/illegal drugs. This systematic review summarized the main results of published studies on active or passive exposure to green or blue spaces in different domains of child neurodevelopment. In August 2022, five databases were searched and twenty-eight eligible studies were included in the analysis. Cognitive and/or academic performance was the most frequently studied (15/28). Most studies evaluate passive exposure to green/blue spaces (19/28) versus active exposure (9/28). Only three studies addressed the relationship between blue space and neurodevelopment. The main results point toward mixed evidence of a protective relationship between green/blue space exposure and neurodevelopment, especially in improving cognitive/academic performance, attention restoration, behavior, and impulsivity. Renaturalizing school spaces and promoting "greener" capacities for school environmental health could improve children's neurodevelopment. There was great heterogeneity in methodologies and adjustment for confounding factors across studies. Future research should seek a standardized approach to delivering school environmental health interventions beneficial to children's development.

Keratinocyte Response to Infection with Sporothrix schenckii.

Sporotrichosis is a subacute, or chronic mycosis caused by traumatic inoculation of material contaminated with the fungus Sporothrix schenckii which is part of the Sporothrix spp. complex. The infection is limited to the skin, although its progression to more severe systemic or disseminated forms remains possible. Skin is the tissue that comes into contact with Sporothrix first, and the role of various cell lines has been described with regard to infection control. However, there is little information on the response of keratinocytes. In this study, we used the human keratinocyte cell line (HaCaT) and evaluated different aspects of infection from modifications in the cytoskeleton to the expression of molecules of the innate response during infection with conidia and yeast cells of Sporothrix schenckii. We found that during infection with both phases of the fungus, alterations of the actin cytoskeleton, formation of membrane protuberances, and loss of stress fibers were induced. We also observed an overexpression of the surface receptors MR, TLR6, CR3 and TLR2. Cytokine analysis showed that both phases of the fungus induced the production of elevated levels of the chemokines MCP-1 and IL-8, and proinflammatory cytokines IFN-α, IFN-γ and IL-6. In contrast, TNF-α production was significant only with conidial infection. In late post-infection, cytokine production was observed with immunoregulatory activity, IL-10, and growth factors, G-CSF and GM-CSF. In conclusion, infection of keratinocytes with conidia and yeast cells of Sporothrix schenckii induces an inflammatory response and rearrangements of the cytoskeleton.

A novel CD34-specific T-cell engager efficiently depletes acute myeloid leukemia and leukemic stem cells in vitro and in vivo.

Less than a third of patients with acute myeloid leukemia (AML) are cured by chemotherapy and/or hematopoietic stem cell transplantation, highlighting the need to develop more efficient drugs. The low efficacy of standard treatments is associated with inadequate depletion of CD34+ blasts and leukemic stem cells, the latter a drug-resistant subpopulation of leukemia cells characterized by the CD34+CD38- phenotype. To target these drug-resistant primitive leukemic cells better, we have designed a CD34/CD3 bi-specific T-cell engager (BTE) and characterized its anti-leukemia potential in vitro, ex vivo and in vivo. Our results show that this CD34-specific BTE induces CD34-dependent T-cell activation and subsequent leukemia cell killing in a dose-dependent manner, further corroborated by enhanced T-cell-mediated killing at the singlecell level. Additionally, the BTE triggered efficient T-cell-mediated depletion of CD34+ hematopoietic stem cells from peripheral blood stem cell grafts and CD34+ blasts from AML patients. Using a humanized AML xenograft model, we confirmed that the CD34-specific BTE had in vivo efficacy by depleting CD34+ blasts and leukemic stem cells without side effects. Taken together, these data demonstrate that the CD34-specific BTE has robust antitumor effects, supporting development of a novel treatment modality with the aim of improving outcomes of patients with AML and myelodysplastic syndromes.

Looking Towards 2030: Strengthening the Environmental Health in Childhood-Adolescent Cancer Survivor Programs.

Childhood and adolescent cancer survivors (CACS) are a high-risk population for non-communicable diseases and secondary carcinogenesis. The Environmental and Community Health Program for Longitudinal Follow-up of CACS in the region of Murcia, Spain, is an ongoing pioneering program that constitutes a model for social innovation. This study aims to present the program tools and protocol as a whole, as well as a profile of the incidence, survival, and spatiotemporal distribution of childhood cancer in the region of Murcia, Spain, using 822 sample cases of cancer diagnosed in children under 15 years of age (1998-2020). While the crude incidence rate across that entire period was 149.6 per 1 million, there was an increase over that time in the incidence. The areas with a higher standardized incidence ratio have shifted from the northwest (1998-2003) to the southeast (2016-2020) region. Overall, the ten-year survival rate for all tumor types was 80.1% over the entire period, increasing the five-year survival rate from 76.1 (1998-2003) to 85.5 (2014-2018). CACS living in areas with very poor outdoor air quality had lower survival rates. Furthermore, integrating environmental health into clinical practice could improve knowledge of the etiology and prognosis, as well as the outcomes of CACS. Finally, monitoring individual carbon footprints and creating healthier lifestyles, alongside healthier environments for CACS, could promote wellbeing, environmental awareness, and empowerment in order to attain Sustainable Development Goals for non-communicable diseases in this population.

Bacillus licheniformis and Bacillus subtilis, Probiotics That Induce the Formation of Macrophage Extracellular Traps.

Probiotics are considered living microorganisms that help preserve the health of the host who uses them. Bacillus are a genus of Gram-positive bacteria used as probiotics for animal and human consumption. They are currently distributed in various commercial forms. Two of the species used as probiotics are B. licheniformis and B. subtilis. Macrophages are central cells in the immune response, being fundamental in the elimination of microbial pathogens, for which they use various mechanisms, including the formation of extracellular traps (METs). There have been very few studies carried out on the participation of macrophages in response to the interaction of probiotics of the genus Bacillus with the host. In this work, we used macrophages from the J774A mouse cell line.1, and we found that they are susceptible to infection by the two Bacillus species. However, both species were eliminated as the infection progressed. Using confocal microscopy, we identified the formation of METs from the first hours of infection, which were characterized by the presence of myeloperoxidase (MPO) and citrullinated histone (Hit3Cit). Quantitative data on extracellular DNA release were also obtained; release was observed starting in the first hour of infection. The induction of METs by B. licheniformis caused a significant decrease in the colony-forming units (CFU) of Staphylococcus aureus. The induction of METS by bacteria of the Bacillus genus is a mechanism that participates in controlling the probiotic and potentially pathogenic bacteria such as S. aureus. The induction of METs to control pathogens may be a novel mechanism that could explain the beneficial effects of probiotics of the genus Bacillus.

Identification of Endothelial Proteins in Plasma Associated With Cardiovascular Risk Factors.

OBJECTIVE: Endothelial cell (EC) dysfunction is a well-established response to cardiovascular disease risk factors, such as smoking and obesity. Risk factor exposure can modify EC signaling and behavior, leading to arterial and venous disease development. Here, we aimed to identify biomarker panels for the assessment of EC dysfunction, which could be useful for risk stratification or to monitor treatment response. Approach and Results: We used affinity proteomics to identify EC proteins circulating in plasma that were associated with cardiovascular disease risk factor exposure. Two hundred sixteen proteins, which we previously predicted to be EC-enriched across vascular beds, were measured in plasma samples (N=1005) from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study) pilot. Thirty-eight of these proteins were associated with body mass index, total cholesterol, low-density lipoprotein, smoking, hypertension, or diabetes. Sex-specific analysis revealed that associations predominantly observed in female- or male-only samples were most frequently with the risk factors body mass index, or total cholesterol and smoking, respectively. We show a relationship between individual cardiovascular disease risk, calculated with the Framingham risk score, and the corresponding biomarker profiles. CONCLUSIONS: EC proteins in plasma could reflect vascular health status.

Sedentary time in people with obstructive airway diseases.

Sedentary time (ST) and light-intensity physical activity (LIPA) are movement behaviours associated with important health outcomes, but are not widely explored in respiratory diseases. We aimed to describe their volume and/or accumulation patterns in moderate-severe COPD, bronchiectasis and severe asthma using the accurate postural-based accelerometer activPAL, contrasting these values with a non-respiratory population. We also sought to test the cross-sectional associations of these behaviours with disease characteristics by diagnostic group, and as a combined label-free disease group. RESULTS: Adults with COPD (n = 64), bronchiectasis (n = 61), severe asthma (n = 27), and controls (n = 61) underwent cross-sectional measurements of volume and/or accumulation patterns of ST and LIPA. The prevalence and characteristics, and associations with exercise capacity, health-status, airflow-limitation, dyspnoea, systemic inflammation and exacerbations were analysed. ST volumes in COPD were higher than that of bronchiectasis and severe asthma. Values in bronchiectasis and severe asthma were similar to each other and controls (≈8.9 h/day). Their accumulation patterns were also significantly better than in COPD, but similar if not worse compared to controls. LIPA volumes in bronchiectasis and severe asthma were also higher than those of COPD (p < 0.05) and controls. In bronchiectasis and COPD, lower levels/better patterns of ST accumulation, as well as higher LIPA volume were associated with better clinical characteristics. These associations may be mediated by airflow limitation. CONCLUSIONS: The discordance between engagement in ST volume versus ST patterns highlights the importance of accounting for both these different yet complementary metrics. ST and LIPA are low-intensity activities associated with important clinical characteristics in people with chronic respiratory diseases. TRIAL REGISTRATION: Not applicable.

Bacitracin is a non-competitive inhibitor of porcine M1 family neutral and glutamyl aminopeptidases.

Membrane alanyl and glutamyl aminopeptidases (APN and APA, respectively) are established targets for the development of biomedical tools in human pathologies. APN overexpression correlates with the progression of tumours, including melanoma. Bacitracin, widely used as a topical antibiotic, inhibits subtilisin-like serine peptidases and disulphide isomerases. In the present contribution, we demonstrate that bacitracin is a non-competitive α = 1 and α < 1 inhibitor of porcine kidney APN and APA, respectively, with Ki values in the micromolar range. To test a potential application of this result, we assayed the effect of bacitracin on murine melanoma MB16F10 cell line viability. We demonstrated the cell line expresses an APN-like activity inhibited by bacitracin and bestatin. Additionally, we identified a cytotoxic effect of bacitracin. Further experiments are required to understand in depth the mechanisms of action of bacitracin on melanoma cells. They will clarify the therapeutic potential of bacitracin for melanoma treatment.