The role of gamma globulin, complement component 1q, factor B, properdin, body temperature, C-reactive protein and serum amyloid alpha to the activity and the function of the human complement system and its pathways.

The complement system plays a crucial role in orchestrating the activation and regulation of inflammation within the human immune system. Three distinct activation pathways-classical, lectin, and alternative-converge to form the common lytic pathway, culminating in the formation of the membrane-attacking complex that disrupts the structure of pathogens. Dysregulated complement system activity can lead to tissue damage, autoimmune diseases, or immune deficiencies. In this study, the antimicrobial activity of human serum was investigated by using a bioluminescent microbe probe, Escherichia coli (pEGFPluxABCDEamp). This probe has previously been used to determine the antimicrobial activity of complement system and the polymorphonuclear neutrophils. In this study, blocking antibodies against key serum activators and components, including IgG, complement component 1q, factor B, and properdin, were utilized. The influence of body temperature and acute phase proteins, such as C reactive protein (CRP) and serum amyloid alpha (SAA), on the complement system was also examined. The study reveals the critical factors influencing complement system activity and pathway function. Alongside crucial factors like C1q and IgG, alternative pathway components factor B and properdin played pivotal roles. Results indicated that the alternative pathway accounted for approximately one third of the overall serum antimicrobial activity, and blocking this pathway disrupted the entire complement system. Contrary to expectations, elevated body temperature during inflammation did not enhance the antimicrobial activity of human serum. CRP demonstrated complement activation properties, but at higher physiological concentrations, it exhibited antagonistic tendencies, dampening the response. On the other hand, SAA enhanced the serum's activity. Overall, this study sheds a light on the critical factors affecting both complement system activity and pathway functionality, emphasizing the importance of a balanced immune response.

Indoor microbial exposure increases complement component C3a and C-reactive protein concentrations in serum.

Indoor exposure to microbial growth, caused by moisture damage, has been an established health risk for several decades. It is likely that a damp indoor environment contains biological pollutants that trigger both the innate and adaptive branches of the immune system. In this study, we investigated the association between moisture damage related microbial exposure and serum C3a, C5a and CRP concentrations in Finnish adults. Serum C3a and CRP concentrations were elevated in individuals exposed to moisture damage and microbial growth in an indoor air environment. The elevated concentrations may be due to environmental factors present in moisture-damaged buildings. Complement activation and the resulting proinflammatory cleavage products may be a driving factor in inflammatory responses following exposure to indoor moisture damage and related microbial growth.

Creating Designer Engineered Extracellular Vesicles for Diverse Ligand Display, Target Recognition, and Controlled Protein Loading and Delivery.

Efficient and targeted delivery of therapeutic agents remains a bottleneck in modern medicine. Here, biochemical engineering approaches to advance the repurposing of extracellular vesicles (EVs) as drug delivery vehicles are explored. Targeting ligands such as the sugar GalNAc are displayed on the surface of EVs using a HaloTag-fused to a protein anchor that is enriched on engineered EVs. These EVs are successfully targeted to human primary hepatocytes. In addition, the authors are able to decorate EVs with an antibody that recognizes a GLP1 cell surface receptor by using an Fc and Fab region binding moiety fused to an anchor protein, and they show that this improves EV targeting to cells that overexpress the receptor. The authors also use two different protein-engineering approaches to improve the loading of Cre recombinase into the EV lumen and demonstrate that functional Cre protein is delivered into cells in the presence of chloroquine, an endosomal escape enhancer. Lastly, engineered EVs are well tolerated upon intravenous injection into mice without detectable signs of liver toxicity. Collectively, the data show that EVs can be engineered to improve cargo loading and specific cell targeting, which will aid their transformation into tailored drug delivery vehicles.

Occupational Risk Factors for Hoarseness Among Police Officers in Finland.

PURPOSE: Police officers have many work-related risks. In Finland, hoarseness and other respiratory symptoms and related risk factors have not been investigated on a national level. In many of the work tasks carried out by the police, an excellent physical and mental condition is essential. METHOD: Our aim was to determine the prevalence of hoarseness and related respiratory symptoms and to investigate eventual occupational risk factors associated with hoarseness. We also compared different work tasks and remediation procedures in three police stations with indoor air problems. MATERIAL: In all, 767 persons completed a nation-wide e-mail survey. The study population is approximately 11% of the total police force in Finland. Half of the study population were men. In three cities, we evaluated the outcome of different type of remediation methods after the moisture damaged buildings were renovated. The prevalence of hoarseness was compared in different work tasks and the risk associated with indoor air, work-related stress, and background factors were estimated. Information on the remediation was obtained from the employer. RESULTS: Altogether, 30.5% of the respondents had hoarseness and 15.5% had work-related stress. Almost 9% were smokers and 43% had pets at home. Of all the respondents, 13% had asthma. Hoarseness was not related to work-related stress. The strongest risk factors for hoarseness were asthma and exposure to mold odor, dusts and cold temperatures after adjusting for age, gender, smoking and pet-owning. When three renovation techniques were compared, the best results were found in the building with a thorough remediation and the removal of mold from the building. CONCLUSIONS: We conclude that the exposure to irritant gases, fumes, and bioaerosols should be minimized whenever possible in order to avoid incident asthma and voice problems.

Hoarseness among nurses.

While many occupations are at risk for vocal health issues much of the current research has focused on teachers. The prevalence of hoarseness among nurses has not received much attention. The aim of this study was to determine the current prevalence of hoarseness among nurses and also to identify potential environmental risk factors from their working environment. The health data was collected from Finnish healthcare workers. Our findings are based on 13,560 health questionnaires which were statistically analyzed. Our results suggest that the one-year period prevalence of hoarseness was 30% and all the environmental problems which we evaluated (draft, room temperature too high, variable room temperature, room temperature too low, dry air, stuffy indoor air, moist air/ high humidity, inadequate ventilation, smell of mold or cellar, sewer odor, other unpleasant odors, tobacco smoke, noise and detectable dust or dirt) had an increasing effect on hoarseness. In conclusion, clear associations were found between environmental problems and hoarseness in nurses. Furthermore, efforts should be made to repair defective ventilation systems, remediate indoor air problems due to moisture damage and improve overall maintenance to protect the vocal health of nurses.

The prevalence of hoarseness among health care professionals: time trends and effect of remediation in working conditions in 2007-2018.

PURPOSE: The purpose of this study was to investigate time trends in the prevalence of hoarseness among health care professionals in primary health care units (PHC) and in hospitals from 2007 to 2018. Moreover, purpose was to discover potential indoor environmental quality (IEQ) risk factors as well as to determine the effect of the remediation of the indoor air problems on the prevalence of hoarseness. METHODS: The health status was collected from all employees in these units/hospitals (N = 1564/1199) with questionnaires and the follow-ups were carried out as an open cohort. Based on building condition inspections, buildings were classified to be an "exposed" or "reference" buildings by third-party experts. The before and after remediation results were compared to reference buildings. RESULTS: During follow-up, hoarseness has not increased in those PHC units with good IEQ. In the pilot study, the prevalence of hoarseness in non-exposed reference building was 5.9%, and it stayed approximately at the same level throughout the follow-up. Whereas in buildings with an IEQ problem the prevalence of hoarseness varied between 16.2 and 36.1% and it decreased to 11.4% after the remediations. In a large hospital with severe IEQ problems, the prevalence of hoarseness was 39.1%, and in hospital buildings with a milder exposure 23.3%. The most important risk factors for hoarseness were asthma, allergic rhinitis and IEQ problems. CONCLUSION: A good indoor environment and the remediation of damaged buildings seem to promote a better condition of the voice in health care workers.

Integrated experimental-computational analysis of a HepaRG liver-islet microphysiological system for human-centric diabetes research.

Microphysiological systems (MPS) are powerful tools for emulating human physiology and replicating disease progression in vitro. MPS could be better predictors of human outcome than current animal models, but mechanistic interpretation and in vivo extrapolation of the experimental results remain significant challenges. Here, we address these challenges using an integrated experimental-computational approach. This approach allows for in silico representation and predictions of glucose metabolism in a previously reported MPS with two organ compartments (liver and pancreas) connected in a closed loop with circulating medium. We developed a computational model describing glucose metabolism over 15 days of culture in the MPS. The model was calibrated on an experiment-specific basis using data from seven experiments, where HepaRG single-liver or liver-islet cultures were exposed to both normal and hyperglycemic conditions resembling high blood glucose levels in diabetes. The calibrated models reproduced the fast (i.e. hourly) variations in glucose and insulin observed in the MPS experiments, as well as the long-term (i.e. over weeks) decline in both glucose tolerance and insulin secretion. We also investigated the behaviour of the system under hypoglycemia by simulating this condition in silico, and the model could correctly predict the glucose and insulin responses measured in new MPS experiments. Last, we used the computational model to translate the experimental results to humans, showing good agreement with published data of the glucose response to a meal in healthy subjects. The integrated experimental-computational framework opens new avenues for future investigations toward disease mechanisms and the development of new therapies for metabolic disorders.

Transferring from moisture damaged school building to clean facilities - The avoidance of mold exposure induces a decline in symptoms and improvement in lung function among personnel.

Working in a moisture-damaged building can cause different symptoms and effects on lung functions. Moving to a clean environment, it is believed to reduce symptoms and alleviate potential adverse health effects. This case study monitors the health effects of personnel in one school building before and after all school activities were transferred from a moisture-damaged school building to clean premises. The whole school staff was invited to attend this follow-up study. All participants (N = 45) were interviewed, and pulmonary functions were measured by spirometry and exhaled nitric oxide testing (FENO) before transferring the school activities to a new building and the control measurements were performed twice; three months and six months after the transfer. After transferring to temporary facilities, 82% of participants felt that their symptoms were improved or resolved and the pulmonary functions were improved; 50% of those who had decreased pulmonary functions at the beginning, their pulmonary function values returned to normal after three months. Over the next six months, the perceived symptoms continued to reduce so that 93% of the respondents felt fully asymptomatic with respect to indoor air, and the spirometry results improved further. Transferring workers from the damaged building to healthy environment provided beneficial health effects on pulmonary functions and to perceived symptoms even in a relatively short time period. Based on this study, and from the perspective of promoting and protecting the health and well-being of personnel, transferring school activities from a moisture damaged building to clean facilities brought considerable advantages, despite the possible cost and difficulties of finding replacement facilities.

Prevalence of Hoarseness in Primary Health Care and Hospitals-Associations With Different Work Tasks and Environmental Factors Among Nurses.

OBJECTIVES: The voice is one of the most essential tools necessary for nurses achieve high care satisfaction and safety. Research on hoarseness has mainly focused on professional speakers, like teachers. The aim of this study was to determine the current prevalence of hoarseness among six subgroups of nurses (registered nurses, primary care nurses, pediatric nurses, laboratory nurses, dental nurses, and midwives) and also to identify potential environmental risk factors in their working environment. METHODS: The health data was collected in collaboration with two health care professional trade unions. The findings are based on 15,553 returned health questionnaires which were statistically analyzed. RESULTS: The 1-year prevalence of hoarseness among all participating nurses was 30.2 % in this data, but the variation between different occupational subgroups was significant; ranging from 25 % for laboratory nurses to 38 % for midwives. These findings were in line with perceived environmental problems and the differences between the sub-groups were not explained by the participants suffering from asthma, sinusitis, rhinitis, or common respiratory infections; there were no explanatory differences in the prevalence's of the above-mentioned diseases. CONCLUSIONS: The variation in prevalence of hoarseness between the different occupational subgroups was significant and the prevalence was found to be in line with perceived environmental problems. The most common problems were stuffiness, dry air, and inadequate ventilation. In addition, both a perceived "sewer odor" and "smell of mold or cellar" in one's own working environment were also found to be significant risk factors for hoarseness. Based on this study, the current indoor air problems in Finnish health care facilities can be verified and are a source of risk to nurses' voices.

The Association Between Work-Related Stress, Indoor Air Quality, and Voice Problems Among Teachers is There a Trend?

INTRODUCTION: Hoarseness and other voice problems are common in occupations where the person has to speak, sing or shout in a work environment containing dust, noise, gaseous or particulate irritants. In recent years, stress has often been associated with voice problems. OBJECTIVE: The aim of this study was to examine trends over a period of time of the prevalence of voice problems and reported stress in Finnish school buildings. STUDY DESIGN: School buildings from different parts of the country were studied for ten years using a similar questionnaire (N = 1721). Five schools participated before and after the remediation of an indoor air problem in the school buildings (n = 315). RESULTS: In the pilot study (2007-2008), the reported work-related stress was on a very low level (3%) and the prevalence of hoarseness was 10%. After the economic crisis in 2008, the stress was observed to have increased. During the follow-up (2008-2017), the reported stress had continued to increase and in the latest surveys it was 21% and the prevalence of hoarseness 34%. Indoor air factors correlated significantly with hoarseness even when controlling for age, gender, owning pets and job satisfaction in a logistic regression model. In the school buildings where the remediation of the building was completed, the prevalence of hoarseness decreased but the level of stress increased. In general, the proportion of respondents reporting stress was lower than the proportion of respondents with hoarseness. Additionally, the reported stress also correlated with factors other than health in the education branch, especially economic resources and major changes in the core curriculum. CONCLUSION: Hoarseness and work-related stress have, to a large extent, different risk factors. Over time, the proportion of individuals with stress has been at a lower level than the proportion of respondents with voice problems; hence, we conclude that it is quite unlikely that stress would be a causative risk factor for hoarseness. We recommend that irritant dust and gases should be reduced from the work environment of teachers to enable recovery from hoarseness and other voice problems. Coping with work-related stress should be alleviated with other measures.

Indoor-related microbe damage induces complement system activation in building users.

In this comparative study, serum complement system antimicrobial activity was measured from 159 serum samples, taken from individuals from microbe-damaged (70 samples) and from reference buildings (89 samples). Antimicrobial activity was assessed using a probe-based bacterial Escherichia coli-lux bioluminescence system and comparison was made at a group level between the experimental and reference group. The complement activity was higher in users of microbe-damaged buildings compared with the reference group and the significant (P < 0.001) increase in activity was found in the classical reaction pathway. This study strengthens our notion that exposure to indoor-related microbe damage increases the risk for systemic subclinical inflammation and creates a health risk for building users.

Primary Human Hepatocyte Spheroid Model as a 3D In Vitro Platform for Metabolism Studies.

3D cultures of primary human hepatocytes (PHH) are emerging as a more in vivo-like culture system than previously available hepatic models. This work describes the characterisation of drug metabolism in 3D PHH spheroids. Spheroids were formed from three different donors of PHH and the expression and activities of important cytochrome P450 enzymes (CYP1A2, 2B6, 2C9, 2D6, and 3A4) were maintained for up to 21 days after seeding. The activity of CYP2B6 and 3A4 decreased, while the activity of CYP2C9 and 2D6 increased over time (P < 0.05). For six test compounds, that are metabolised by multiple enzymes, intrinsic clearance (CLint) values were comparable to standard in vitro hepatic models and successfully predicted in vivo CLint within 3-fold from observed values for low clearance compounds. Remarkably, the metabolic turnover of these low clearance compounds was reproducibly measured using only 1-3 spheroids, each composed of 2000 cells. Importantly, metabolites identified in the spheroid cultures reproduced the major metabolites observed in vivo, both primary and secondary metabolites were captured. In summary, the 3D PHH spheroid model shows promise to be used in drug discovery projects to study drug metabolism, including unknown mechanisms, over an extended period of time.

Indoor exposure to Streptomyces albus and Aspergillus versicolor elevates the levels of spore-specific IgG, IgG1 and IgG3 serum antibodies in building users - A new ELISA-based assay for exposure assessment.

Moisture-indicative microbes in buildings are associated with a variety of symptoms, ranging from mild irritation to severe clinical illnesses. These symptoms are caused principally by dried, dormant and dead microbe material like spores, mycelium and microbe metabolites, leading to the activation of the immune system and formation of the antigen-specific immunoglobulins. This activation presumably takes place through the respiratory track and is a normal immune reaction against pathogenic invaders. During continuous exposure, a prolonged state of inflammation will follow, and this forms a considerable health risk for a building's occupant. A new ELISA system utilizing spores from two species Streptomyces albus and Aspergillus versicolor as an antigen was developed to reveal the related immunological processes. In 159 persons, microbial exposure was observed to increase the levels of spore-specific IgG, IgG1 and IgG3 serum antibody levels of individuals residing in microbe-dense buildings compared with the control reference buildings. No differences were detected in the levels of S. albus- and A. versicolor-specific serum IgA or IgM levels.

The Response of Phagocytes to Indoor Air Toxicity.

This perspective presents a viewpoint on potential methods assessing toxicity of indoor air. Until recently, the major techniques to document moldy environment have been microbial isolation using conventional culture techniques for fungi and bacteria as well as in some instances polymerase chain reaction to detect microbial genetic components. However, it has become increasingly evident that bacterial and fungal toxins, their metabolic products, and volatile organic substances emitted from corrupted constructions are the major health risks. Here, we illustrate how phagocytes, especially neutrophils can be used as a toxicological probe. Neutrophils can be used either in vitro as probe cells, directly exposed to the toxic agent studied, or they can act as in vivo indicators of the whole biological system exposed to the agent. There are two convenient methods assessing the responses, one is to measure chemiluminescence emission from activated phagocytes and the other is to measure quantitatively by flow cytometry the expression of complement and immunoglobulin receptors on the phagocyte surface.

Nurse teacher candidates learned to use social media during the international teacher training course.

The purpose of this study was to describe the nurse teacher candidates' learning outcomes and experiences in social media during the international nurse teacher training course, Empowering learning environments in nursing education, Intensive Program (EleneIP). The pre-post research design was used. The data was collected before and after the course, with the questionnaire consisting of structured and open questions. Altogether, 24 nurse teacher candidates from four different European countries participated in the course and this study. The results showed that the knowledge of using social media applications increased during the course from 5.2 (range 1-9) to 8.1 (range 4-10), and their skills increased from 4.5 (range 1-8) to 7.6 (range 4-10).The main topics learnt during the course were divided in two categories: subjects of the course and teaching and learning methods. The students' experiences concerning the EleneIP course were positive in both categories. The international group created during EleneIP course also allowed the students to achieve another important aim, learning from a collaborative group the importance and possibilities of different learning environments, considering the cultural and social characteristics of each country participating in it.