Alginate and cellulose nanofibrils (CNF) are attractive materials for tissue engineering and regenerative medicine. CNF gels are generally weaker and more brittle than alginate gels, while alginate gels are elastic and have high rupture strength. Alginate properties depend on their guluronan and mannuronan content and their sequence pattern and molecular weight. Likewise, CNF exists in various qualities with properties depending on, e.g., morphology and charge density. In this study combinations of three types of alginate with different composition and two types of CNF with different charge and degree of fibrillation have been studied. Assessments of the composite gels revealed that attractive properties like high rupture strength, high compressibility, high gel rigidity at small deformations (Young’s modulus), and low syneresis was obtained compared to the pure gels. The effects varied with relative amounts of CNF and alginate, alginate type, and CNF quality. The largest effects were obtained by combining oxidized CNF with the alginates. Hence, by combining the two biopolymers in composite gels, it is possible to tune the rupture strength, Young’s modulus, syneresis, as well as stability in physiological saline solution, which are all important properties for the use as scaffolds in tissue engineering.

Additive manufacturing (AM), or 3D printing, is a growing industry involving a wide range of different techniques and materials. The potential toxicological effects of emissions produced in the process, involving both ultrafine particles and volatile organic compounds (VOCs), are unclear, and there are concerns regarding possible health implications among AM operators. The objective of this study was to screen the presence of respiratory health effects among people working with liquid, powdered, or filament plastic materials in AM. Methods: In total, 18 subjects working with different additive manufacturing techniques and production of filament with polymer feedstock and 20 controls participated in the study. Study subjects filled out a questionnaire and underwent blood and urine sampling, spirometry, impulse oscillometry (IOS), exhaled NO test (FeNO), and collection of particles in exhaled air (PEx), and the exposure was assessed. Analysis of exhaled particles included lung surfactant components such as surfactant protein A (SP-A) and phosphatidylcholines. SP-A and albumin were determined using ELISA. Using reversed-phase liquid chromatography and targeted mass spectrometry, the relative abundance of 15 species of phosphatidylcholine (PC) was determined in exhaled particles. The results were evaluated by univariate and multivariate statistical analyses (principal component analysis). Results: Exposure and emission measurements in AM settings revealed a large variation in particle and VOC concentrations as well as the composition of VOCs, depending on the AM technique and feedstock. Levels of FeNO, IOS, and spirometry parameters were within clinical reference values for all AM operators. There was a difference in the relative abundance of saturated, notably dipalmitoylphosphatidylcholine (PC16:0_16:0), and unsaturated lung surfactant lipids in exhaled particles between controls and AM operators. Conclusion: There were no statistically significant differences between AM operators and controls for the different health examinations, which may be due to the low number of participants. However, the observed difference in the PC lipid profile in exhaled particles indicates a possible impact of the exposure and could be used as possible early biomarkers of adverse effects in the airways. 

Annually, an estimated seven million deaths are linked to exposure to airborne pollutants. Despite extensive epidemiological evidence supporting clear associations between poor air quality and a range of short- and long-term health effects, there are considerable gaps in our understanding of the specific mechanisms by which pollutant exposure induces adverse biological responses at the cellular and tissue levels. The development of more complex, predictive, in vitro respiratory models, including two- and three-dimensional cell cultures, spheroids, organoids and tissue cultures, along with more realistic aerosol exposure systems, offers new opportunities to investigate the cytotoxic effects of airborne particulates under controlled laboratory conditions. Parallel advances in high-resolution microscopy have resulted in a range of in vitro imaging tools capable of visualizing and analysing biological systems across unprecedented scales of length, time and complexity. This article considers state-of-the-art in vitro respiratory models and aerosol exposure systems and how they can be interrogated using high-resolution microscopy techniques to investigate cell-pollutant interactions, from the uptake and trafficking of particles to structural and functional modification of subcellular organelles and cells. These data can provide a mechanistic basis from which to advance our understanding of the health effects of airborne particulate pollution and develop improved mitigation measures. 

Den här texten presenterar resultat från tre aktiviteter för kunskapsinsamling om implementering av digitala verktyg inom vård- och omsorg: en litteratursammanställning, en workshopserie i två delar och en enkätundersökning. Den primära målgruppen har varit verksamhetsutvecklare och projektledare i regioner och kommuner. Antalet svarande i enkätstudien var för lågt för att kunna dra några statistiska slutsatser, men resultatet kan, tillsammans med workshopserien, ändå användas för att identifiera områden där det verkar finnas utmaningar. Både litteratursammanställningen och enkätundersökningen pekar på ett behov av att utveckla strukturerade utvärderingsmodeller för implementering. Även under workshoppen diskuterades den bristande förmågan att ”samla in evidens under projektens gång”, och det fanns en önskan om att ett sådant arbetssätt skulle utvecklas. Enkäten och workshoppen pekar även på flera återkommande problem under implementeringsprojekts olika faser. I den inledande fasen efterfrågas bättre analyser och förankringsarbete. Analyser med användarfokus missas speciellt ofta, så som användarresa, hållbarhetsanalys och intressent- och behovsanalys. Även i andra ändan av processen, då system och arbetssätt ska avvecklas, finns utmaningar och förbättringsförslag, t.ex. saknas ofta beslut om utfasning av gamla lösningar, och ett förslag är att man redan när man skriver kontakt med en leverantör ska säkerställa att leverantören hjälper till med migrering vid utfasning. En annan genomgående problematik är osäkerhet, och ibland avsaknad, av roller, ansvar och kommunikation. Detta handlar om att man inte riktigt vet varför man ska göra saker, eller att verksamheten och personerna som ska göra förändringen inte är tillräckligt inblandade. Det kan också handla om att support och förvaltning inte är tillräckligt väl utvecklat, och om att man inte vet hur man kan samarbeta med leverantörer. Här identifieras även förändringsledning som ett viktigt verktyg för att underlätta en god implementering.

Purpose: To investigate the sensitivity of Monte Carlo (MC) calculated lung dose distributions to lung tissue characterization in external beam radiotherapy of breast cancer under Deep Inspiration Breath Hold (DIBH). Methods: EGSnrc based MC software was employed. Mean lung densities for one hundred patients were analysed. CT number frequency and clinical dose distributions were calculated for 15 patients with mean lung density below 0.14 g/cm3. Lung volume with a pre-defined CT numbers was also considered. Lung tissue was characterized by applying different CT calibrations in the low-density region and air-lung tissue thresholds. Dose impact was estimated by Dose Volume Histogram (DVH) parameters. Results: Mean lung densities below 0.14 g/cm3 were found in 10% of the patients. CT numbers below −960 HU dominated the CT frequency distributions with a high rate of CT numbers at −990 HU. Mass density conversion approach influenced the DVH shape. V4Gy and V8Gy varied by 7% and 5% for the selected patients and by 9% and 3.5% for the pre-defined lung volume. V16Gy and V20Gy, were within 2.5%. Regions above 20 Gy were affected. Variations in air- lung tissue differentiation resulted in DVH parameters within 1%. Threshold at −990 HU was confirmed by the CT number frequency distributions. Conclusions: Lung dose distributions were more sensitive to variations in the CT calibration curve below lung (inhale) density than to air-lung tissue differentiation. Low dose regions were mostly affected. The dosimetry effects were found to be potentially important to 10% of the patients treated under DIBH.

Purpose. To investigate the response of the CC13 ionization chamber under non-reference photon beam conditions, focusing on penumbra and build-up regions of static fields and on dynamic intensity-modulated beams. Methods. Measurements were performed in 6 MV 100 × 100, 20 × 100, and 20 × 20 mm2 static fields. Monte Carlo calculations were performed for the static fields and for 6 and 15 MV dynamic beam sequences using a Varian multi-leaf collimator. The chamber was modelled using EGSnrc egs_chamber software. Conversion factors were calculated by relating the absorbed dose to air in the chamber air cavity to the absorbed dose to water. Correction and point-dose correction factors were calculated to quantify the conversion factor variations. Results. The correction factors for positions on the beam central axis and at the penumbra centre were 0.98-1.02 for all static fields and depths investigated. The largest corrections were obtained for chamber positions beyond penumbra centre in the off-axis direction. Point-dose correction factors were 0.54-0.71 at 100 mm depth and their magnitude increased with decreasing field size and measurement depth. Factors of 0.99-1.03 were obtained inside and near the integrated penumbra of the dynamic field at 100 mm depth, and of 0.92-0.94 beyond the integrated penumbra centre. The variations in the ionization chamber response across the integrated dynamic penumbra qualitatively followed the behaviour across penumbra of static fields. Conclusions. Without corrections, the CC13 chamber was of limited usefulness for profile measurements in 20-mm-wide fields. However, measurements in dynamic small irregular beam openings resembling the conditions of pre-treatment patient quality assurance were feasible. Uncorrected ionization chamber response could be applied for dose verification at 100 mm depth inside and close to large gradients of dynamically accumulating high- and low-dose regions assuming 3% tolerance between measured and calculated doses. © 2023 The Author(s).

Objective: To determine to what extent accelerometer-based arm, leg and trunk activity is associated with sensorimotor impairments, walking capacity and other factors in subacute stroke. Design: Cross-sectional study. Patients: Twenty-six individuals with stroke (mean age 55.4 years, severe to mild motor impairment). Methods: Data on daytime activity were collected over a period of 4 days from accelerometers placed on the wrists, ankles and trunk. A forward stepwise linear regression was used to determine associations between free-living activity, clinical and demographic variables. Results: Arm motor impairment (Fugl-Meyer Assessment) and walking speed explained more than 60% of the variance in daytime activity of the more-affected arm, while walking speed alone explained 60% of the more-affected leg activity. Activity of the less-affected arm and leg was associated with arm motor impairment (R2=0.40) and independence in walking (R2=0.59). Arm activity ratio was associated with arm impairment (R2=0.63) and leg activity ratio with leg impairment (R2=0.38) and walking speed (R2=0.27). Walking-related variables explained approximately 30% of the variance in trunk activity. Conclusion: Accelerometer-based free-living activity is dependent on motor impairment and walking capacity. The most relevant activity data were obtained from more-affected limbs. Motor impairment and walking speed can provide some information about real-life daytime activity levels.

Bouillon cubes are a staple ingredient used in Sub-saharan African countries providing flavor enhancement to savory foods. Bouillon has been identified as a vehicle for fortification to overcome micronutrient deficiencies in Sub-saharan Africa. However, bouillon has a high sodium content (and in addition with other foods) contributes to dietary sodium intake above recommended guidelines. High dietary sodium intake is a key risk factor for hypertension and cardiovascular disease (CVD). Africa has the highest rates of hypertension and CVD globally with nearly half the adult population above 25 years affected. This review presents current state of research on sodium reduction strategies in bouillon. The key challenge is to reduce sodium levels while maintaining optimal flavor at the lowest possible production cost to ensure bouillon continues to be affordable in Sub-saharan Africa. To produce lower sodium bouillon with acceptable flavor at low cost will likely involve multiple sodium reduction strategies; direct reduction in sodium, sodium replacement and saltiness boosting flavor technologies. Efforts to reduce the sodium content of bouillon in Sub-saharan Africa is a worthwhile strategy to: (i) lower the overall sodium consumption across the population, and (ii) deliver population-wide health benefits in a region with high rates of hypertension and CVD. Copyright © 2022 Archer, Cochet-Broch, Mihnea, Garrido-Bañuelos, Lopez-Sanchez, Lundin and Frank.

Det pågår omfattande studier, framför allt i USA och Storbritannien, som undersöker möjligheterna att införa screening med hjälp av blodprover för tidig upptäckt av ett flertal cancerformer, så kallade MCED (Mulitple Cancer Early Detection). Ännu har inget faktiskt screeningsprogram med MCED-screening initierats i världen. I Sverige ställs idag höga krav på evidens från studier för att ett screeningprogram ska kunna införas. Det pågår studier som adresserar frågan om screening, men än så länge saknas mycket information. Med utgångspunkt i denna rapport kan därför inte en initiering av MCEDscreening i Sverige rekommenderas i dagsläget. För att vara i framkant bör Sverige dock följa området nogsamt. Grail är ett väletablerat företag som i augusti 2021 blev uppköpt av Illumina, ett företag som 2020 rapporterade en vinst på 2,34 miljarder USD. Företaget har stora ambitioner för framtida screeningprogram och kan bedömas ha de resurser som krävs att genomföra essentiella studier. De har säkrade medel och genomför projekt för att utveckla sin produkt för att fungera i en screeningsituation. Storbritanniens stora pågående studie ”NHS-Galleri Clinical Trial” beräknas publicera nya resultat under 2023. Om denna studie faller ut väl planeras en utvidgning av studien som ska omfatta en miljon personer. Denna större studie beräknas kunna avslutas 2030. Data att följa i nämnda ovanstående studie är bland annat: - Hur stor population ännu icke diagnostiserade utgör, i empiriska siffror - Utvecklingen av testmetoden gällande sensibilitet och sensitivitet - Patientnyttan, t.ex. ökar överlevnaden mot dagens siffror - Risken för överdiagnostik - Kostnader och logistik som kommer belasta sjukvården En problematik med MCED-screening är att testernas specificitet och sensitivitet behöver vara tillräckligt tillförlitliga för att det inte skall belasta snarare hjälpa samhället. Det är osannolikt att dessa värden kommer att vara 100-procentiga, men hur bra dessa värden bör vara innan man inför en screening är öppet för diskussion, däri ligger problematiken. I rapporten förklaras dessa begrepp i mer detalj. Det bör nämnas att Grail redan har kunnat presentera en ökad prestanda utifrån preliminära resultat ifrån pågående studier som presenterats i en så kallad sub-studie, där sensitivitet, sensibilitet och ”Tissue of Origin” (TOO) har förbättrats ytterligare gällande tolv olika cancerformer. Beräkningar i vår rapport har nyttjat dessa värden för att söka ge en bild över vad som kan förväntas vid ett införande av en Grail-MCED-screening i Sverige. För de tolv cancerformerna kan beräkningarna sammanfattas enligt; - Under förutsättning att det finns adekvat behandling att erbjuda vid tidigare diagnostik, kommer det ske en markant förskjutning av i vilket stadie som diagnostiserade individer detekteras och förhoppningsvis behandlas. Idag behandlas cirka 40 -45% av de cancerdiagnostiserade i stadie III/IV, att jämföras mot de beräknade 6% vid införande av årlig screening. - Ökningen av antalet individer som skulle överleva sin cancer uppskattas till mellan 3 - 5 000 individer, utöver de cirka 9 000 som överlever med hjälp av dagens diagnostik/behandling. - 25 – 35% kostnadsreducering både vad gäller direkta kostnader och samhällskostnader, extrapolerat från IHE rapport (1). Vi har dock inte tagit hänsyn till de kostnadsökningar ett införande av en MCED-screening skulle innebära. Det reella värdet av rapportens beräkningar bör vägas mot de empiriska data som kommer produceras av NHS studie av Grails metod. Starka avvikelser (”positiva/negativa”) från empiriska data kan då ligga till grund för om och i så fall hur pass snabbt man vill driva införande av MCED screening i Sverige. Rapportens sammantagna bedömning är att de av Socialstyrelsen uppsatta kriterier för införande av en screening, inte är uppfyllda i dagsläget. Men vi har även försökt visualisera vad som skulle komma att ske med dagens diagnostiserade cancerpatientgrupper om en MCED-screening införs i ålderspopulationen 40 – 80 år (96% av dagens diagnostiserade), på de tolv cancerformer som metoden visar bäst sensibilitet/sensitivitet mot. Dessa tolv cancerformer utgör 36% av dagens diagnostiserade patienter. Trots att ett införande av screening inte är att rekommendera i dagsläget, finns det alternativ att ta ställning till; - Endast avvakta utredningarna i Storbritannien (till 2023, eller till 2030). - Avvakta utredningarna men initiera samtal med beslutsfattare som styr över de ekonomiska medel som kan bistå med satsningar på större Grailtester i Sverige - Avvakta utredningarna, men initiera samtal med både NHS och Grail i syfte att behålla momentum i detta första initiativ till utredning. Författarnas uppfattning är att Grails teknik är signifikant och kommer med stor sannolikhet bedömas som tillämpbar för MCED-screening i framtiden.

Introduction: Individuals recovering from COVID-19 often experience a range of post-recovery symptoms. However, the literature on post-COVID-19 symptoms reveals conflicting results, necessitating a heightened focus on longitudinal studies to comprehend the trajectory of impairments over time. Our study aimed to investigate changes in long-term impairments among individuals infected with COVID-19 and explore potential predictors influencing these changes. Methods: We conducted a web-survey targeting individuals that had been infected with COVID-19 at four time-points: T0 (baseline), T1 (three months), T2 (six months), and T3 (twelve months). The survey included contextual factors, factors related to body functions and structures, and post-COVID impairments. The longitudinal sample included 213 individuals (with a mean age of 48.92 years). Linear mixed models were employed to analyze changes in post-COVID impairments over time and identify impacting factors. Results: Findings revealed a general decline in post-COVID impairments over time, with each symptom exhibiting a dynamic pattern of fluctuations. Factors such as initial infection severity, education level, and work status were significantly associated with the levels of impairments. Discussion: The study emphasizes that post-COVID impairments are not static but exhibit variations over time. Personalized care, especially for vulnerable populations, is crucial. The results underscore the need for long-term monitoring and multidisciplinary treatment approaches. Targeted support and interventions are highlighted for individuals with severe initial infections and those in socioeconomically disadvantaged groups. 

Background: The COVID-19 pandemic has triggered a global mental health crisis. Yet, we know little about the lasting effects of COVID-19 infection on mental health. This prospective longitudinal study aimed to investigate the trajectories of mental health changes in individuals infected with COVID-19 and to identify potential predictors that may influence these changes. Methods: A web-survey that targeted individuals that had been infected with COVID-19 was used at three time-points: T0 (baseline), T1 (six months), and T2 (twelve months). The survey included demographics, questions related to COVID-19 status, previous psychiatric diagnosis, post-COVID impairments, fatigue, and standardized measures of depression, anxiety, insomnia. Linear mixed models were used to examine changes in depression, anxiety, and insomnia over time and identify factors that impacted trajectories of mental health outcomes. Results: A total of 236 individuals completed assessments and was included in the longitudinal sample. The participants’ age ranged between 19 and 81 years old (M = 48.71, SD = 10.74). The results revealed notable changes in mental health outcomes over time. The trajectory of depression showed significant improvement over time while the trends in anxiety and insomnia did not exhibit significant changes over time. Younger participants and individuals who experienced severe COVID-19 infection in the acute phase were identified as high-risk groups with worst mental ill-health. The main predictors of the changes in the mental health outcomes were fatigue and post-COVID impairments. Conclusions: The findings of our study suggest that mental health outcomes following COVID-19 infection exhibit a dynamic pattern over time. The study provides valuable insights into the mental health trajectory following COVID-19 infection, emphasizing the need for ongoing assessment, support, and interventions tailored to the evolving mental health needs of this population. 

Calcium ion-crosslinked nanofibrillated cellulose (NFC) hydrogels were investigated as potential materials for wound healing dressings. The physicochemical properties of the hydrogels were examined by rheology and water retention tests. Skin cells and monocytes were selected for application-oriented biocompatibility studies. The NFC hydrogels presented entangled fibrous networks and solid-like behavior. Water retention tests showed the materialÂŽs potential to maintain a suitable moist environment for different type of wounds. The hydrogels did not affect dermal fibroblasts monolayer cultures upon direct contact, as cell monolayers remained intact after application, incubation and removal of the materials. Inflammatory response studies with blood-derived mononuclear cells revealed the inert nature of the hydrogels in terms of cytokine secretion and reactive oxygen species production. Results highlight the great potential of ion-crosslinked NFC hydrogels for the development of advanced wound dressings, where further functionalization of the material could lead to improved properties towards the healing of specific wound types.

Background: The clinical-stage drug candidate EBL-1003 (apramycin) represents a distinct new subclass of aminoglycoside antibiotics for the treatment of drug-resistant infections. It has demonstrated best-in-class coverage of resistant isolates, and preclinical efficacy in lung infection models. However, preclinical evidence for its utility in other disease indications has yet to be provided. Here we studied the therapeutic potential of EBL-1003 in the treatment of complicated urinary tract infection and acute pyelonephritis (cUTI/AP). Methods: A combination of data-base mining, antimicrobial susceptibility testing, time-kill experiments, and four murine infection models was used in a comprehensive assessment of the microbiological coverage and efficacy of EBL-1003 against Gram-negative uropathogens. The pharmacokinetics and renal toxicology of EBL-1003 in rats was studied to assess the therapeutic window of EBL-1003 in the treatment of cUTI/AP. Findings: EBL-1003 demonstrated broad-spectrum activity and rapid multi-log CFU reduction against a phenotypic variety of bacterial uropathogens including aminoglycoside-resistant clinical isolates. The basicity of amines in the apramycin molecule suggested a higher increase in positive charge at urinary pH when compared to gentamicin or amikacin, resulting in sustained drug uptake and bactericidal activity, and consequently in potent efficacy in mouse infection models. Renal pharmacokinetics, biomarkers for toxicity, and kidney histopathology in adult rats all indicated a significantly lower nephrotoxicity of EBL-1003 than of gentamicin. Interpretation: This study provides preclinical proof-of-concept for the efficacy of EBL-1003 in cUTI/AP. Similar efficacy but lower nephrotoxicity of EBL-1003 in comparison to gentamicin may thus translate into a higher safety margin and a wider therapeutic window in the treatment of cUTI/API. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section. © 2021 The Author(s)

Efficient, simple antibacterial materials to combat implant-associated infections are much in demand. Herein, the development of polyurethanes, both cross-linked thermoset and flexible and versatile thermoplastic, suitable for “click on demand” attachment of antibacterial compounds enabled via incorporation of an alkyne-containing diol monomer in the polymer backbone, is described. By employing different polyolic polytetrahydrofurans, isocyanates, and chain extenders, a robust and flexible material comparable to commercial thermoplastic polyurethane is prepared. A series of short synthetic antimicrobial peptides are designed, synthesized, and covalently attached in a single coupling step to generate a homogenous coating. The lead material is shown to be biocompatible and does not display any toxicity against either mouse fibroblasts or reconstructed human epidermis according to ISO and OECD guidelines. The repelling performance of the peptide-coated materials is illustrated against colonization and biofilm formation by Staphylococcus aureus and Staphylococcus epidermidis on coated plastic films and finally, on coated commercial central venous catheters employing LIVE/DEAD staining, confocal laser scanning microscopy, and bacterial counts. This study presents the successful development of a versatile and scalable polyurethane with the potential for use in the medical field to reduce the impact of bacterial biofilms. 

A well-functioning systematic occupational safety and health management is beneficial for both individuals and organizations, and employee motivation seems to be crucial for positive outcomes. Occupational safety and health issues are a major concern for the Swedish equine sector since the work environment in horse stables is known to be characterized by low mechanization, high physical workloads, and high injury risks. The purpose of this study was to gain an increased understanding of how systematic occupational safety and health management is performed and which factors that influence motivation for occupational safety and health improvements in the Swedish equine sector. An explanatory sequential mixed-methods study, based on quantitative data from questionnaires and qualitative data from semi-structured interviews, was conducted. Various statistical analyses were performed to obtain quantitative data and an abductive applied thematic analysis was applied for the qualitative data. The results indicate that both intrinsic motivators, i.e. attitudes, values, and influence, as well as contextual factors such as motivational management, occupational culture, and workplace resources, influence compliance in systematic occupational safety and health management and participation in occupational safety and health improvements, which in turn affect workplace outcomes regarding safety and health. The positive relationship found between an implemented and functioning systematic occupational safety and health management and employee motivation for occupational safety and health improvements indicate the importance of employee involvement and participation. Understanding the motivational factors for occupational safety and health improvements from an employee perspective is an important step to creating healthy and sustainable workplaces.

The toxicity of particulate matter (PM) is dependent on particle physical and chemical properties and is commonly studied using in vivo and in vitro approaches. PM to be used for in vivo and in vitro studies is often collected on filters and then extracted from the filter surface using a solvent. During extraction and further PM sample handling, particle properties change, but this is often neglected in toxicology studies, with possible implications for health effect assessment. To address the current lack of knowledge and investigate changes in particle properties further, ambient PM with diameter less than 2.5 μm (PM2.5) was collected on filters at an urban site and extracted using a standard methanol protocol. After extraction, the PM was dried, dispersed in water and subsequently nebulized. The resulting aerosol properties were then compared to those of the ambient PM2.5. The number size distribution for the nebulized aerosol resembled the ambient in terms of the main mode diameter, and >90 % of particle mass in the nebulized size distribution was still in the PM2.5 range. Black carbon made up a similar fraction of PM mass in nebulized as in ambient aerosol. The sulfate content in the nebulized aerosol seemed depleted and the chemical composition of the organic fraction was altered, but it remains unclear to what extent other non-refractory components were affected by the extraction process. Trace elements were not distributed equally across size fractions, neither in ambient nor nebulized PM. Change in chemical form was studied for zinc, copper and iron. The form did not appear to be different between the ambient and nebulized PM for iron and copper, but seemed altered for zinc. Although many of the studied properties were reasonably well preserved, it is clear that the PM2.5 collection and re-aerosolization process affects particles, and thus potentially also their health effects. Because of this, the effect of the particle collection and extraction process must be considered when evaluating cellular and physiological outcomes upon PM2.5 exposure. © 2024 The Authors

In this paper some aspects of the stereotyping of China and Japan are explored by using a sample of articles from a Swedish business magazine. The main objective is to show how stereotypes are adapted to capture new developments in economy and technology. During the years of high hopes for the largest Asian economies, stereotypes proved to be far from timeless and unchanging. Also a large number of metaphors were used to express perceived similarities between East and West, further undermining tradi-tional Western understanding of Asia as inert and eternally different. The recent decline of Japan put an end to this, creating a return to a vocabulary of cultural characterisations and explanations.

Background: Persons on the autism spectrum exhibit poorer body awareness than neurotypical persons. Since movement quality may be regarded as an expression of body awareness, assessment of movement quality is important. Sound assessments of measurement properties are essential if reliable decisions about body awareness interventions for persons on the autism spectrum are to be made, but there is insufficient research. Objective: To assess measurement properties of the Body Awareness Scale Movement Quality (BAS MQ) in an autism and a neurotypical reference group. Methods: Persons on the autism spectrum (n=108) and neurotypical references (n=32) were included. All were assessed with BAS MQ. Data were analyzed according to the Rasch model. Results: BAS MQ was found to have acceptable unidimensionality, supported by the fit statistics. The hierarchical ordering showed that coordination ability was the most difficult, followed by stability and relating. Response category functioning worked as intended for 19 out of 23 items. There were few difficult items, which decreased targeting. Reliability measures were good. BAS MQ discriminated between the autism and the reference groups, with the autism group exhibiting poorer movement quality, reflecting clinical observations and previous research. Conclusions: BAS MQ was found to have acceptable measurement properties, though suffering from problems with targeting item difficulty to person ability for persons on the autism spectrum. The BAS MQ may, along with experienced movement quality, contribute to clinically relevant information of persons on the autism spectrum, although we encourage refinements and further analyses to improve its measurement properties. 

AIMS: To assess the measurement properties of the Ms. Olsen test for registered nurses and assistant nurses, respectively, and suggest cut-off points between competence levels. DESIGN: Cross-sectional study. The results were analysed by implementing the Rasch Measurement Theory. METHODS: Nursing staff working in various health care settings participated (n = 757). To measure the competence of nursing staff in clinical decision-making, a 19-item scale from the Nursing Older People-Competence Evaluation Tool-the 'Ms. Olsen test'-was used. Data were collected in October 2017, 2018 and 2019. RESULTS: The Ms. Olsen test showed reasonably good measurement properties for registered nurses and assistant nurses respectively. Results show slightly better measurement properties for registered nurses than for assistant nurses. The cut-off for registered nurses, 0.62, corresponds to managing approximately two-thirds of the items while, for assistant nurses, the cut-off of 0.01 corresponds to managing approximately half of the items. CONCLUSION: The Ms. Olsen test is a short (7- to 10-min) test measuring competence in clinical decision-making among nursing staff working in older people nursing. Despite reasonably good measurement properties, this should be considered an initial validation in the development of a short test for assessing clinical decision-making among nursing staff in various health care setting. IMPACT: Several scales aiming to measure nursing competence have been developed over the last decade, but measurement properties (beyond classical test theory) are seldom evaluated, few scales concern other staff groups than registered nurses and few scales have proposed or established cut-offs for safe practice. The Ms. Olsen test is a short test of clinical decision-making that demonstrates reasonably good measurement properties. Cut-off points for registered nurses and assistant nurses were established. The Ms. Olsen test may be used to measure and evaluate competence in clinical decision-making among nursing staff working in older people nursing and educational settings.

One application in the medical treatment at very small flow rates is the usage of an Insulin pump that delivers doses of insulin at constant cycle times for a specific basal rate as quasi-continuous insulin delivery, which is an important cornerstone in diabetes management. The calibration of these basal rates are performed by either gravimetric or optical methods, which have been developed within the European Metrology Program for Innovation and Research (EMPIR) Joint Research Project (JRP) 18HLT08 Metrology for drug delivery II (MeDDII). These measurement techniques are described in this paper, and an improved approach of the analytical procedure given in the standard IEC 60601-2-24:2012 for determining the discrete doses and the corresponding basal rates is discussed in detail. These improvements allow detailed follow up of dose cycle time and delivered doses as a function of time to identify some artefacts of the measurement method or malfunctioning of the insulin pump. Moreover, the calibration results of different basal rates and bolus deliveries for the gravimetric and the optical methods are also presented. Some analysis issues that should be addressed to prevent misinterpreting of the calibration results are discussed. One of the main issues is the average over a period of time which is an integer multiple of the cycle time to determine the basal rate with the analytical methods described in this paper. 

The rapid emergence of antibiotic-resistant microbes worldwide and the urgent need of new antimicrobial agents have stimulated interest in antimicrobial peptides (AMPs) as new therapeutics for treatment of infectious diseases. AMPs are present in all living species and constitute an important part of the innate immune system in multicellular organisms, including humans. AMPs display a remarkably broad spectrum of antimicrobial activity covering both Gram-positive and Gram-negative bacteria, including many antibiotic-resistant strains, as well as fungi, viruses, and protozoa. Further, in contrast to many conventional antibiotics, AMPs rapidly kill bacteria instead of just inhibiting bacterial growth. In addition, AMPs act as modulators of the innate immune system and, importantly, bacteria seem less efficient in developing resistance towards AMPs than towards conventional antibiotics. Together these properties make AMPs highly attractive as a new class of antimicrobials, with clinical potential also extending to diseases where inflammation is part of the pathology. The aim of this thesis was to study novel AMPs with respect to their mechanism of action (MOA), antimicrobial spectrum, propensity to select for resistance, and in vivo efficacy and safety. To achieve this, we used a number of in vitro and in vivo assays, together generating a comprehensive preclinical evaluation of the peptides. The hypothesis was that the AMPs in this thesis have potential to be developed as therapeutic agents for several infectious and inflammatory conditions, including treatment of skin and soft tissue infections and prevention of postsurgical adhesion formation. The results showed that all AMPs tested (i.e. PXL03, PXL150, HLR1r, and five variants of CEN1 HC-Br) had broad antimicrobial spectra in vitro with varying sensitivity to salt and serum. Furthermore, PXL150 caused a rapid permeabilization of bacterial membrane in vitro, indicating that this is at least one part of the MOA of this peptide. Under selection pressure in vitro, bacteria did not develop resistance to the peptides tested, i.e. PXL150 and CEN1 HC. Interestingly, all peptides showed anti-inflammatory activity by inhibiting the secretion of proinflammatory mediators from stimulated human cell lines. In addition, PXL01, PXL150, and HLR1r demonstrated fibrinolytic ability in vitro by suppressing the release of plasminogen activator inhibitor-1 (PAI-1). In ex vivo and in vivo skin/wound infection models, the peptides reduced the number of viable bacteria and yeast cells. Further, PXL01 decreased postsurgical adhesion formation in vivo. Notably, nonclinical safety studies showed that PXL150 was safe and well tolerated. In conclusion, several of the peptides evaluated in this thesis demonstrated a promising preclinical efficacy and safety profile motivating further development as drug candidates for local treatment of infectious and inflammatory conditions.

Antimicrobial peptides (AMPs) have emerged as a new class of drug candidates for the treatment of infectious diseases. Here we describe a novel AMP, HLR1r, which is structurally derived from the human milk protein lactoferrin and demonstrates a broad spectrum microbicidal action in vitro. The minimum concentration of HLR1r needed for killing ≥99% of microorganisms in vitro, was in the range of 3-50 μg/ml for common Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and for the yeast Candida albicans, when assessed in diluted brain-heart infusion medium. We found that HLR1r also possesses anti-inflammatory properties as evidenced by inhibition of tumor necrosis factor alpha (TNF-α) secretion from human monocyte-derived macrophages and by repression of interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) secretion from human mesothelial cells, without any cytotoxic effect observed at the concentration range tested (up to 400 μg/ml). HLR1r demonstrated pronounced anti-infectious effect in in vivo experimental models of cutaneous candidiasis in mice and of excision wounds infected with MRSA in rats as well as in an ex vivo model of pig skin infected with S. aureus. In conclusion, HLR1r may constitute a new therapeutic alternative for local treatment of skin infections.

About 15% of the population suffer from migraines and it is estimated that about 40% of all people with migraines would benefit from preventive treatment, but only 3-13% use it. Migraine is a huge burden for society and individuals. Migraines can be intensified by light, and some patients need to stay in a dark room until the attack is over. People with this type of photosensitivity show a clear preference for light color, specifically green, which has been shown to be more comfortable and even pain relieving in some cases. We will present a feasibility study with the aim of preparing a series of experiments to investigate if regular short-term green-light-exposure can prevent migraines. We will present findings from the literature, developed light equipment, and plans for future testing of migraine friendly light solutions.

Mikroorganismer kan växa på alla material om förutsättningarna är de rätta. Fukt är alltid den begränsande faktorn men andra faktorer, till exempel temperatur, kan påverka kritisk fuktnivå med avseende på start och etablering av mikrobiologisk påväxt. Mikrobiologisk påväxt på byggnadsmaterial är därför inte materialfråga utan snarare en hanterings- eller byggnadsteknisk fråga. 2009 konstaterar WHO i sin rapport Guidlines for indoor air quality att negativa hälsoeffekter motverkas effektivast genom att fukt och mikrobiella skador på och i byggnader förhindras. Nya studier har adderats sedan 2009 och ett antal vetenskapligt granskade artiklar i ämnet har publicerats. I arbetet med denna sammanställning har ingen artikel påträffats som motstrider den idag, på empiri, grundade uppfattningen att fukt och mögelskador i byggnader kan påverka innemiljön. En påverkan som i sin tur kan leda till negativa hälsoeffekter för människor. I nordiska länder så är det vanligast att fukt- och mögelskador finns inuti konstruktioner. För trähus som ofta är konstruerade av flera olika byggnadsmaterial finns en problematik som dels uppstår genom att mikroorganismer kan växa på dessa material dels genom att det finns risk att emissioner från påväxten sprids till innemiljön. För att bättre förstå när och hur människor exponeras för dessa ämnen behövs mer kunskap inhämtas om: - Hur och när emissioner från skador inuti konstruktioner når innemiljön. - Emissionernas sammansättning. - Skador på trä och hälsa specifikt - Kunskap om mögelarter och deras förekomst på olika byggnadsmaterial inklusive trä. - Vilka åtgärder behöver sättas in för att förhindra att påväxt uppstår vid fukt- och vattenskador (tid, temperatur, material mm)?

Dust collected in New Orleans homes mold-contaminated because of the flooding after hurricane Katrina was analyzed for molds and mycotoxins. The mycoflora was studied by cultivation and quantitative PCR for selected molds. The most commonly found mold taxa were Aspergillus, Cladosporium, and Penicillium. Verrucarol, a hydrolysis product of macrocyclic trichothecenes predominately produced by Stachybotrys spp. was identified in three dust samples by gas chromatography-tandem mass spectrometry, and sterigmatocystin (produced by various Aspergillus spp.) was found in two samples by high pressure liquid chromatography-tandem mass spectrometry. This is the first demonstration of mycotoxins in Katrina-associated dust samples. The analytical methods used represent valuable tools in further studies on bioaerosol exposure and health risks.

Mycotoxins are toxic secondary metabolites frequently produced by molds in waterdamaged indoor environments. The objectives of this work were to characterize the mycoflora (by microscopy and culture) and to study the prevalence of selected mycotoxins and levels of fungal biomass (by gas chromatography- and high pressure liquid chromatography tandem mass spectrometry) in samples collected by building inspectors from water-damaged indoor environments in Sweden during a one-year period. Sixty-six percent of the analyzed building materials (n=100), 11% of the settled dust samples (n=18), and 51% of the cultured dust samples (n=37) were positive for at least one of the studied mycotoxins. Except in the case of gliotoxin, mycotoxin-positive building material samples contained 2-6 times more ergosterol than mycotoxin-negative samples. The study result shows that the majority of molds contaminating indoor materials in Swedish water-damaged buildings produce mycotoxins, and that mycotoxin-containing particles settle on surfaces above floor level in these environments.

Mycotoxins are toxic, secondary metabolites frequently produced by molds in water-damaged indoor environments. We studied the prevalence of selected, potent mycotoxins and levels of fungal biomass in samples collected from water-damaged indoor environments in Sweden during a 1- year period. One hundred samples of building materials, 18 samples of settled dust, and 37 samples of cultured dust were analyzed for: (a) mycoflora by microscopy and culture; (b) fungal chemical marker ergosterol and hydrolysis products of macrocyclic trichothecenes and trichodermin (verrucarol and trichodermol) by gas chromatography-tandem mass spectrometry; and (c) sterigmatocystin, gliotoxin, aflatoxin B1, and satratoxin G and H by high performance liquid chromatography-tandem mass spectrometry. Sixty-six percent of the analyzed building materials samples, 11% of the settled dust samples, and 51% of the cultured dust samples were positive for at least one of the studied mycotoxins. In addition, except in the case of gliotoxin, mycotoxin-positive building material samples contained 2,6 times more ergosterol than mycotoxin-negative samples. We show that (a) molds growing on a range of different materials indoors in water-damaged buildings generally produce mycotoxins, and (b) mycotoxincontaining particles in mold-contaminated environments may settle on surfaces above floor level. The mass spectrometry methods used in this study are valuable tools in further research to survey mycotoxin exposure and investigate potential links with health effects. © 2009 JOEH, LLC.

The number of antibiotic-resistant bacteria is increasing worldwide, and the demand for novel antimicrobials is constantly growing. Antimicrobial peptides (AMPs) could be an important part of future treatment strategies of various bacterial infection diseases. However, AMPs have relatively low stability, because of proteolytic and chemical degradation. As a consequence, carrier systems protecting the AMPs are greatly needed, to achieve efficient treatments. In addition, the carrier system also must administrate the peptide in a controlled manner to match the therapeutic dose window. In this work, lyotropic liquid crystalline (LC) structures consisting of cubic glycerol monooleate/water and hexagonal glycerol monooleate/oleic acid/water have been examined as carriers for AMPs. These LC structures have the capability of solubilizing both hydrophilic and hydrophobic substances, as well as being biocompatible and biodegradable. Both bulk gels and discrete dispersed structures (i.e., cubosomes and hexosomes) have been studied. Three AMPs have been investigated with respect to phase stability of the LC structures and antimicrobial effect: AP114, DPK-060, and LL-37. Characterization of the LC structures was performed using small-angle X-ray scattering (SAXS), dynamic light scattering, ζ-potential, and cryogenic transmission electron microscopy (Cryo-TEM) and peptide loading efficacy by ultra performance liquid chromatography. The antimicrobial effect of the LCNPs was investigated in vitro using minimum inhibitory concentration (MIC) and time-kill assay. The most hydrophobic peptide (AP114) was shown to induce an increase in negative curvature of the cubic LC system. The most polar peptide (DPK-060) induced a decrease in negative curvature while LL-37 did not change the LC phase at all. The hexagonal LC phase was not affected by any of the AMPs. Moreover, cubosomes loaded with peptides AP114 and DPK-060 showed preserved antimicrobial activity, whereas particles loaded with peptide LL-37 displayed a loss in its broad-spectrum bactericidal properties. AMP-loaded hexosomes showed a reduction in antimicrobial activity.

Nutritional quality of 142 plant-based meat analogues (PBMAs) on the Swedish market were assessed by nutritional contribution (NC) to recommended nutrient intake, three labelling systems (Keyhole, Nutri-Score, nutrition claims) and comparisons to meat references. Based on median (min-max) NC for macronutrients, PBMAs in general appeared as healthy options to meat due to higher NC per 100 g for fibre [PBMAs: 15% (1-33%) vs meat: 0% (0-2%)] and lower NC for saturated fat [PBMAs: 4% (0-59%) vs meat: 15% (1-51%)]. The NC per 100 g for salt was substantial for both PBMAs [25% (5-52%)] and meat [24% (2-55%)]. Limited data for micronutrients indicated that PBMAs are higher in iron compared to meat. Nutrition quality varied both between and within product categories. Mince, bite/fillet and nugget analogues were the main healthier categories, according to labelling systems. Bioavailability of iron, protein quality and effects of processing are important future aspects to consider. © 2022 The Author(s).

A novel ceria-stabilized zirconia-alumina-aluminate composite (Ce-TZP-comp) that is not prone to aging presents a potential alternative to yttrium-stabilized zirconia for ceramic oral implants. The objective of this study was to evaluate the long-term stability of a one-piece narrow-diameter implant made of Ce-TZP-comp. Implant prototypes with a narrow (3.4 mm) and regular (4.0 mm) diameter were embedded according to ISO 14801, and subgroups (n = 8) were subsequently exposed to dynamic loading (107 cycles, 98N) and/or hydrothermal treatment (aging, 85◦C). Loading/aging was only applied as a combined protocol for the 4.0 mm diameter implants. One subgroup of each diameter remained untreated. One sample was cross-sectioned from each subgroup and evaluated with a scanning electron microscope for phase-transformation of the lattice. Finally, the remaining samples were loaded to fracture. A multivariate linear regression model was applied for statistical analyses (significance at p < 0.05). All samples withstood the different loading/aging protocols and no transformation propagation was observed. The narrow diameter implants showed the lowest fracture load after combined loading/aging (628 ± 56 N; p < 0.01), whereas all other subgroups exhibited no significantly reduced fracture resistance (between 762 ± 62 and 806 ± 73 N; p < 0.05). Therefore, fracture load values of Ce-TZP-comp implants suggest a reliable intraoral clinical application in the anterior jaw regions. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Objective: To evaluate the influence of artificial aging on the transformation propagation and fracture resistance of zirconia implants. Methods: One-piece (with integrated implant abutment, 1P; regular diameter [4.1mm]; n = 16) and two-piece (with separate implant abutment, 2P; wide diameter [5 mm]; n = 16) zirconia implants were embedded according to ISO 14801. A two-piece titanium–zirconium implant (Ti-Zr; 4.1 mm diameter) served as a control (n = 16). One subgroup (n = 8) of each system was simultaneously dynamically loaded (107 cycles; 98N) and hydrothermally aged (85°C, 58 days), while the other subgroup (n = 8) remained untreated. Finally, specimens were statically loaded to fracture. Potential crystal phase transformation was examined at cross sections using scanning electron microscopy (SEM). A multivariate linear regression model was applied for statistical analyses. Results: The fracture resistance of 1P (1,117 [SD = 38] N; loaded/aged: 1,009 [60] N), 2P (850 [36] N; loaded/aged: 799 [84] N), and Ti-Zr implants (1,338 [205] N; loaded/aged: 1,319 [247] N) was not affected significantly by loading/aging (p =.171). However, when comparing the systems, they revealed significant differences independent of loading/aging (p ≤.001). Regarding the crystal structure, a transformation zone was observed in SEM images of 1P only after aging, while 2P showed a transformation zone even before aging. After hydrothermal treatment, an increase of this monoclinic layer was observed in both systems. Conclusions: The Ti-Zr control implant showed higher fracture resistance compared to both zirconia implants. Loading/aging had no significant impact on the fracture resistance of both zirconia implants. The wide-body 2P zirconia implant was weaker than the regular body 1P implant. © 2021 The Authors. 

In the past 15 years, close to 1000 of new psychoactive substances (NPS) have been reported in Europe and globally. At the time of identification, data on safety, toxicity and carcinogenic potential of many NPS are not available or very limited. To work more efficiently, a strategy and collaboration between the Public Health Agency of Sweden (PHAS) and the National Board of Forensic Medicine was established involving in vitro receptor activity assays to demonstrate neurological activity of NPS. This report summarizes the first results on the synthetic cannabinoid receptor agonists (SCRAs), and subsequent actions taken by PHAS. A total of 18 potential SCRAs were selected by PHAS for in vitro pharmacological characterization. 17 compounds could be acquired and investigated for their activity on the human cannabinoid-1 (CB1) receptors expressed together with the AequoScreen system in CHO-K1 cells. Dose-response curves were established using eight different concentrations in triplicates at three occasions with JWH-018 as reference. For the MDMB-4en-PINACA, MMB-022, ACHMINACA, ADB-BUTINACA, 5F-CUMYL-PeGACLONE, 5C-AKB48, NM-2201, 5F-CUMYL-PINACA, JWH-022, 5Cl-AB-PINACA, MPhP-2201, 5F-AKB57 the half maximal effective concentration values ranged from 2.2 nM (5F-CUMYL-PINACA) to 171 nM (MMB-022). EG-018 and 3,5-AB-CHMFUPPYCA were none-active. The results contributed to 14 of these compounds being scheduled as narcotics in Sweden. In conclusion, many of the emerging SCRAs are potent activators of the CB1 receptor in vitro, although some lack activity or are partial agonists. The new strategy proved useful when data on psychoactive effects of the SCRAs under investigation were not available or limited. © 2023 The Authors

While there is a large variation of prevalence of asthma symptoms worldwide, what we do know is that it is on the rise in developing countries. However, there are few studies on allergens, moulds and mycotoxin exposure in schools in tropical countries. The aims were to measure selected fungal DNA, furry pet allergens and mycotoxins in dust samples from schools in Malaysia and to study associations with pupils’ respiratory health effects. Eight secondary schools and 32 classrooms in Johor Bahru, Malaysia were randomly selected. A questionnaire with standardized questions was used for health assessment in 15 randomly selected pupils from each class. The school buildings were inspected and both indoor and outdoor climate were measured. Dust samples were collected by cotton swabs and Petri dishes for fungal DNA, mycotoxins and allergens analysis. The participation rate was 96% (462/480 invited pupils), with a mean age of 14yr (range 14-16). The pupils mostly reported daytime breathlessness (41%), parental asthma or allergy (22%), pollen or pet allergy (21%) and doctor-diagnosed asthma (13%) but rarely reported night-time breathlessness (7%), asthma in the last 12months (3%), medication for asthma (4%) or smoking (5%). The inspection showed that no school had any mechanical ventilation system, but all classrooms had openable windows that were kept open during lectures. The mean building age was 16yr (range 3-40) and the mean indoor and outdoor CO2 levels were 492ppm and 408ppm, respectively. The mean values of indoor and outdoor temperature and relative humidity were the same, 29°C and 70% respectively. In cotton swab dust samples, the Geometric Mean (GM) value for total fungal DNA and Aspergillus/Penicillium (Asp/Pen) DNA in swab samples (Cell Equivalents (CE)/m2) was 5.7*108 and 0.5*108, respectively. The arithmetic mean (CE/m2) for Aspergillus versicolor DNA was 8780, Stachybotrys chartarum DNA was 26 and Streptomyces DNA was 893. The arithmetic means (pg/m2) for the mycotoxins sterigmatocystin and verrucarol were 2547 and 17, respectively. In Petri dish dust samples, the GM value for total fungal DNA and Asp/Pen DNA (CE/m2 per day) was 9.2*106 and 1.6*106, respectively. The arithmetic mean (CE/m2 per day) for A. versicolor DNA was 1478, S. chartarum DNA was 105 and Streptomyces DNA was 1271, respectively. The GM value for cat(Fel d1) allergen was 5.9ng/m2 per day. There were positive associations between A. versicolor DNA, wheeze and daytime breathlessness and between Streptomyces DNA and doctor-diagnosed asthma. However, the associations were inverse between S. chartarum DNA and daytime breathlessness and between verrucarol and daytime breathlessness. In conclusion, fungal DNA and cat allergen contamination were common in schools from Malaysia and there was a high prevalence of respiratory symptoms among pupils. Moreover, there were associations between levels of some fungal DNA and reported respiratory health in the pupils. 

Valid and precise quantification of clinical variables is essential for appropriate interpretation to inform healthcare decision making. The outcomes produced from different measurement procedures and instruments, purporting to quantify the same measurand, should be directly comparable. This ensures the appropriate application and widespread adoption of clinical research findings. Metrology provides a framework for the development of a common language of reference measurement systems, which have the potential to improve the accuracy and comparability of patients’ results. However, the practices, procedures and instruments used in social measurement are currently excluded from any formal metrological framework. In this paper, we build on previous arguments, and propose a new international body to bring together metrology, psychometrics, philosophy, and clinical management to support the global comparability and equivalence of measurement results in patient centred outcome measurement to improve healthcare.

Patient centered outcomes pertain to a patient's beliefs, opinions and needs in conjunction with a clinician's medical expertise and assessment. The rise of patient-centered outcome (PCO) measurement parallels increased interest in patient-centered care. PCO measures offer the opportunity for more meaningful measurement of health outcomes informative enough to guide treatment decisions. However, it has been suggested that, for practical and scientific reasons, existing PCO measures are currently not capable of delivering the kind of quality assured measurement required for high-stakes decision making. Potential solutions include: addressing the lack of units in PCO measurement through recourse to mathematical models devised to define meaningful, invariant, and additive units of measurement with known uncertainties; establishing coordinated international networks of key stakeholders guided by five principles (i.e., collaboration, alignment, integration, innovation and communication); better use of technology leveraging measurement through item banks linking PCO reports via common items, common patients, or specification equations based in strong explanatory theory. And finally ensuring PCO measurement always is associated with: (1) a clear definition of the measurand in regards to the intended clinical use; (2) a clear definition of the clinically allowable error of measurement; (3) international cooperation and consensus to navigate the complexities of the development of metrologically sound reference measurement systems; and (4) continued clinical validation of newly calibrated measures. In this article, we illustrate the principles to improve PCO measures with examples from breast cancer, vision-related patient-reported outcome measures, and dementia clinician-reported and performance outcome measures.

This article evaluates the current gaps around the impact of post-manufacturing processes on the product qualities of protein-based biologics, with a focus on user centricity. It includes the evaluation of the regulatory guidance available, describes a collection of scientific literature and case studies to showcase the impact of post-manufacturing stresses on product and dosing solution quality. It also outlines the complexity of clinical handling and the need for communication, and alignment between drug providers, healthcare professionals, users, and patients. Regulatory agencies provide clear expectations for drug manufacturing processes, however, guidance supporting post-product manufacturing handling is less defined and often misaligned. This is problematic as the pharmaceutical products experience numerous stresses and processes which can potentially impact drug quality, safety and efficacy. This article aims to stimulate discussion amongst pharmaceutical developers, health care providers, device manufacturers, and public researchers to improve these processes. Patients and caregivers’ awareness can be achieved by providing relevant educational material on pharmaceutical product handling. 

The pathological mechanisms underlying Alzheimer's disease (AD) are still not understood. The disease pathology is characterized by the accumulation and aggregation of amyloid-β (Aβ) peptides into extracellular plaques, however the factors that promote neurotoxic Aβ aggregation remain elusive. Imaging mass spectrometry (IMS) is a powerful technique to comprehensively elucidate the spatial distribution patterns of lipids, peptides and proteins in biological tissues. In the present study, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS)-based imaging was used to study Aβ deposition in transgenic mouse brain tissue and to elucidate the plaque-associated chemical microenvironment. The imaging experiments were performed in brain sections of transgenic Alzheimer's disease mice carrying the Arctic and Swedish mutation of amyloid-beta precursor protein (tgArcSwe). Multivariate image analysis was used to interrogate the IMS data for identifying pathologically relevant, anatomical features based on their chemical identity. This include cortical and hippocampal Aβ deposits, whose amyloid peptide content was further verified using immunohistochemistry and laser microdissection followed by MALDI MS analysis. Subsequent statistical analysis on spectral data of regions of interest revealed brain region-specific differences in Aβ peptide aggregation. Moreover, other plaque-associated protein species were identified including macrophage migration inhibitory factor suggesting neuroinflammatory processes and glial cell reactivity to be involved in AD pathology. The presented data further highlight the potential of IMS as a powerful approach in neuropathology. Hanrieder et al. described an imaging mass spectrometry based study on comprehensive spatial profiling of C-terminally truncated Aβ species within individual plaques in tgArcSwe mice. Here, brain region-dependent differences in Aβ truncation and other plaque-associated proteins, such as macrophage migration inhibitory factor, were observed. The data shed further light on plaque-associated molecular mechanisms implicated in Alzheimer's pathogenesis.

The objective of the present study was to investigate some commonly detected halogenated textile pollutants for their bioavailability and hazardous properties. Release into artificial sweat and skin absorption in vitro were examined as well as mutagenic effects by Ames test, and skin-sensitizing properties from a peptide reactivity assay combined with a cell test. All investigated compounds were shown to migrate from the textile into sweat and be absorbed by the skin, although to a different extent. The experimental values for migration were found to be up to 390 times higher compared to literature values. Two of the studied compounds, 2,5-dinitrochlorobenzene and 3,5-dinitrobromobenzene, both exhibited mutagenic effects in the Ames test, while both 2,5-dinitrochlorobenzene and 2,6-dichlorobenzene-1,4-diamine were classified as skin sensitizers. The allergenic reactivity of the latter was found to be due to an oxidized transformation product. Risks for the induction of skin allergy and other non-carcinogenic effects from dermal exposure to the individual compounds were found low, even when considering clothing with the highest reported levels. However, the complex mixtures of chemicals often present in garments may still constitute a health risk, especially when considering the many hours of daily exposure. It is important to further study the toxicity of other frequently occurring chemicals as well as the synergistic effects of chemicals that co-occur in clothing.

Nanofibrillated cellulose (NFC) offers a wide range of interesting opportunities and advantages, being biodegradable, renewable and thus environmentally sound. Extensive research has been performed on the effective production and application of NFC. The proposed applications extend from being a component in paper, coatings and composite materials to being applied in bio-medicine as part of wound dressings or in drug delivery systems. Some of the major advantages of NFC are the dimensions and the structural and chemical composition of nanofibrils, which lead to the formation of dense networks with optimized optical and mechanical properties. In this respect, the concept of nanopaper has been introduced. Nanopapers are strong structures, with high light transmittance and smooth surfaces. These characteristics open for novel applications, including the formation of smooth substrates for printing functionality. A recently explored example is the printing of bioactive biomacromolecules and conductive structures on tailor-made nanopapers, which could form the basis for novel biosensors. Additionally, nanobarriers are most promising in novel packaging applications where the self-assembly properties of the material facilitate the formation of dense structures with high barrier against oxygen. However, NFC alone does not seem to be sufficient for the formation of adequate nanobarriers due to the brittle and hygroscopic characteristics of the material. Novel biocomposite concepts need thus closer attention, where the strong and high barrier properties of NFC could be complemented with adequate bioplastics and additives for the formation of ductile films, suitable for conversion processes. From the biomedical point of view, NFC offers several advantages. Depending on the structural and chemical composition of the material and the cross-linking with adequate polymers and particles, micro-porous and elastic gels can be formed. Such gels can hold a considerable amount of water, thus being an excellent material for keeping a moist environment during wound healing and for facilitating the regeneration process of human tissue. Additionally, NFC gels based on oxidized nanofibrils can have pH-sensitive characteristics, a property with potential in drug delivery. With the intention of giving an extensive description of NFC and its modern applications, this presentation will be divided into three main sections; i) production and definition, ii) characterization including structural, chemical and biological aspects and iii) novel applications of NFC from nanopapers to biomedical devices.

Wood nanocellulose is a novel biomaterial for wound dressing applications. Wood nanocellulose was produced from never-dried P. radiata pulp fibres. The applied pre-treatment was 2,2,6,6-tetramethylpiperidinyl-1-oxyl  (TEMPO) mediated oxidation. To characterise bacterial growth, P. aeruginosa PAO1 biofilms were grown in Mueller Hinton broth on air-dried films. Various microscopy techniques, including atomic force microscopy (AFM), confocal laser scanning microscopy (CLSM) and field-emission scanning electron microscopy (FESEM), were applied to characterise the nanocellulose material and the bacterial-nanocellulose interactions.   Multiscale assessments, including FESEM and AFM, revealed the effective fibrillation of the fibre wall structure, yielding nanofibrils with diameters less than 20 nm and lengths in the micrometre-scale. Importantly, we have demonstrated that the growth of PAO1 was inhibited in the presence of the nanocellulose suspensions when compared to the control. Additionally, SEM imaging revealed distinct clusters of PAO1 cells growing on the surfaces of nanocellulose films. This work highlights the potential usefulness of novel nanocellulose materials in wound dressings with optimized characteristics.

During the last decades major efforts have been made to produce nanocellulose from wood, where the cellulose fibres are disintegrated into individualized nanofibrils with diameters < 20 nm and lengths in the micrometre scale. Production procedures include various pre-treatments, which yield nanocelluloses with varying chemical and structural properties. One important area of research is nanocellulose as a biomaterial with potential applications within the health sector. As an example, the superior mechanical properties, good moisture retention capability and the ability to form elastic macro-porous structures are advantageous properties for utilizing nanocellulose substrates for wound dressings. However, the utilization of nanocellulose as a substrate for wound dressings requires a thorough assessment of the biocompatibility of the material.  In this respect, it has been demonstrated in-vitro that nanocellulose does not exert acute toxic phenomena on fibroblast cells. However, in addition to in-vitro cytotoxicity testing, in-vivo testing of nanocellulose and the ability of nanocellulose to resist bacterial colonization need a closer attention. This presentation will give an overview of the current research on nanocellulose as a biomaterial for wound dressing applications, considering the morphology of nanocellulose structures, mechanical properties, moisture absorption, cytotoxicity tests and nanocellulose-bacteria interactions.

Background Risk of indoor exposure to volatile organic compounds of purported microbial origin on childhood symptoms of wheezing, rhinitis, and/or eczema, and doctor-diagnosed asthma, rhinitis, and eczema, respectively, remain unclear. Objective To test hypotheses that total sum of 28 microbial volatile organic compounds (Σ26 MVOCs): 1) poses independent risk on doctor-diagnosed asthma, rhinitis, and eczema, respectively, as well as multiple symptom presentation with a minimum of the two of the above conditions (i.e. case); 2) is associated with significant interaction with absolute humidity (AH) on additive scale. Methods In a case-control investigation, 198 cases and 202 controls were examined during November 2001 – March 2002 period through home indoor air sampling, air quality inspection, and health outcome ascertainment. Results Not only the Σ28 MVOCs but also the global MVOC index were significantly higher within the homes of the cases with a high AH, compared to the controls with a low AH (all Ps < 0.001). Only the cases, but not the controls, were associated with a dose-dependent increase in the exposure variables of interest (Σ28 MVOCs) per quartile increase in AH (P < 0.0001 for the cases; P = 0.780 for the controls). Only among the children who live in a high AH homes, a natural log (ln)-unit of Σ 28 MVOCs was associated with 2.5-times greater odds of the case status (95% CI, 1.0–6.2; P = 0.046), compared to 0.7-times the odds (95% CI, 0.4–1.0; P = 0.074) of the same outcome among the low AH homes. Specifically, joint exposure to a high MVOCs and high AH was associated with 2.6-times greater odds of the doctor-diagnosed asthma status (95% CI, 0.7–8.91; P = 0.137). Conclusion Joint occurrence of high Σ28 MVOCs and AH was associated with a significant increase in the case status and asthma risks in an additive scale.

There is a strong need for innovative and efficient drug delivery systems for ocular therapy development. However, testing intravitreal drug delivery systems without using live animals is challenging. Ex vivo animal models offer an interesting alternative. We analyzed the potential of using fresh porcine eyes obtained from the local slaughterhouse as a model for testing the intravitreal biodistribution and retention of liposomes with or without polyethylene glycol (PEG) conjugation and with different surface charges. The histology of the eyes was analyzed to localize the liposomes, and it was found that liposomes with PEG absorbed rapidly on the retina (within 1 h), with positively charged and PEG-coated liposomes being retained for at least 24 h. In parallel, fluorophotometry was employed on intact eyes, to determine the pharmacokinetics of the fluorophore calcein, as a substitute for a small hydrophilic therapeutic compound. We found a 4.5-fold increase in the vitreous half-life of calcein loaded in liposomes, compared with the free solution. Retinal toxicity was addressed using murine-derived retinal explant cultures. Liposomes were non-toxic up to 500 µg/mL. Toxicity was observed at 5 mg/mL for anionic and cationic liposomes, with 2-fold and 2.5-fold increased photoreceptor cell death, respectively. Overall, we could show that important ocular drug delivery considerations such as pharmacokinetics and biodistribution can be estimated in ex vivo porcine eyes, and may guide subsequent in vivo experiments.

Despite several promising candidates, there is a paucity of drug treatments available for patients suffering from retinal diseases. An important reason for this is the lack of suitable delivery systems that can achieve sufficiently high drug uptake in the retina and its photoreceptors. A promising and versatile method for drug delivery to specific cell types involves transporter-targeted liposomes, i.e., liposomes surface-coated with substrates for transporter proteins highly expressed on the target cell. We identified strong lactate transporter (monocarboxylate transporter, MCT) expression on photoreceptors as a potential target for drug delivery vehicles. To evaluate MCT suitability for drug targeting, we used PEG-coated liposomes and conjugated these with different monocarboxylates, including lactate, pyruvate, and cysteine. Monocarboxylate-conjugated and dye-loaded liposomes were tested on both human-derived cell-lines and murine retinal explant cultures. We found that liposomes conjugated with pyruvate consistently displayed higher cell uptake than unconjugated liposomes or liposomes conjugated with lactate or cysteine. Pharmacological inhibition of MCT1 and MCT2 reduced internalization, suggesting an MCT-dependent uptake mechanism. Notably, pyruvate-conjugated liposomes loaded with the drug candidate CN04 reduced photoreceptor cell death in the murine rd1 retinal degeneration model while free drug solutions could not achieve the same therapeutic effect. Our study thus highlights pyruvate-conjugated liposomes as a promising system for drug delivery to retinal photoreceptors, as well as other neuronal cell types displaying high expression of MCT-type proteins. © 2023 The Authors

Recently, cGMP analogues have been investigated for the treatment of inherited retinal degenerations (IRD) using intravitreal injections. However, higher vitreous elimination rates limit the possibility to treat the retina with small molecule drugs. Here, we investigated the potential of lipid nanocapsules (LNCs) as vehicles to reduce clearance and prolong the delivery of cGMP analogue, CN03 to the retinal photoreceptors. Initially LNCs were investigated for both topical/periocular and intravitreal administration routes. While LNC-mediated drug permeation through the cornea proved to be too low for clinical applications, intravitreal application showed significant promise. Intravitreally administered LNCs containing fluorescent tracer in ex vivo porcine eyes showed complete intravitreal dispersal within 24 h. Ocular bio-distribution on histological sections showed that around 10 % of the LNCs had reached the retina, and 40 % accumulated in the ciliary body. For comparison, we used fluorescently labeled liposomes and these showed a different intraocular distribution with 48 % accumulated in the retina, and almost none were in the ciliary body. LNCs were then tested in retinal explants prepared from wild-type (WT) and rd1 mouse. In WT retina LNCs showed no significant toxic effects up to a concentration of 5 mg/mL. In rd1 retina, the LNC/CN03 formulation protected rd1 photoreceptors with similar efficacy to that of free CN03, demonstrating the usefulness of LNC/CN03 formulation in the treatment of IRD. Overall, our results indicate the suitability of LNCs for intraocular administration and drug delivery to both the retina and the ciliary body. © 2023 The Author(s)

In this work, we present a quantitative (statistical) 3D morphological characterization of optical fibers used in electric-field sensing. The characterization technique employs propagation-based x-ray phase-contrast microcomputed tomography (micro-CT). In particular, we investigate specialty optical fibers that contain microstructured holes that are electro-optically modified by thermal poling to induce second-order nonlinear effects (SONE). The efficiency of the SONE is reflected in the characterization parameter, Vπ, which is highly dependent on the dimensions of the fiber. The fiber microstructures must be uniform to support the fabrication of reproducible devices. The results obtained using the micro-CT technique show that uncertainty of ±1.7% arises in the determination of the expected value of the voltage that causes a change in the phase of the electromagnetic wave equal to π rad (Vπ ), demonstrating a great advantage, compared with other techniques e.g. SEM, which would need at least 1000 images of the cross-section of an optical fiber, taken at different points, making the process more expensive and time-consuming.