Deciphering the role of FUS::DDIT3 expression and tumor microenvironment in myxoid liposarcoma development.

BACKGROUND: Myxoid liposarcoma (MLS) displays a distinctive tumor microenvironment and is characterized by the FUS::DDIT3 fusion oncogene, however, the precise functional contributions of these two elements remain enigmatic in tumor development. METHODS: To study the cell-free microenvironment in MLS, we developed an experimental model system based on decellularized patient-derived xenograft tumors. We characterized the cell-free scaffold using mass spectrometry. Subsequently, scaffolds were repopulated using sarcoma cells with or without FUS::DDIT3 expression that were analyzed with histology and RNA sequencing. RESULTS: Characterization of cell-free MLS scaffolds revealed intact structure and a large variation of protein types remaining after decellularization. We demonstrated an optimal culture time of 3 weeks and showed that FUS::DDIT3 expression decreased cell proliferation and scaffold invasiveness. The cell-free MLS microenvironment and FUS::DDIT3 expression both induced biological processes related to cell-to-cell and cell-to-extracellular matrix interactions, as well as chromatin remodeling, immune response, and metabolism. Data indicated that FUS::DDIT3 expression more than the microenvironment determined the pre-adipocytic phenotype that is typical for MLS. CONCLUSIONS: Our experimental approach opens new means to study the tumor microenvironment in detail and our findings suggest that FUS::DDIT3-expressing tumor cells can create their own extracellular niche.

Characteristics of traumatic major haemorrhage in a tertiary trauma center.

BACKGROUND: Major traumatic haemorrhage is potentially preventable with rapid haemorrhage control and improved resuscitation techniques. Although advances in prehospital trauma management, haemorrhage is still associated with high mortality. The aim of this study was to use a recent pragmatic transfusion-based definition of major bleeding to characterize patients at risk of major bleeding and associated outcomes in this cohort after trauma. METHODS: This was a retrospective cohort study including all trauma patients (n = 7020) admitted to a tertiary trauma center from January 2015 to June 2020. The major bleeding cohort (n = 145) was defined as transfusion of 4 units of any blood components (red blood cells, plasma, or platelets) within 2 h of injury. Univariate and multivariable logistic regression analyses were performed to identify risk factors for 24-hour and 30-day mortality post trauma admission. RESULTS: In the major bleeding cohort (n = 145; 145/7020, 2.1% of the trauma population), there were 77% men (n = 112) and 23% women (n = 33), median age 39 years [IQR 26-53] and median Injury Severity Score (ISS) was 22 [IQR 13-34]. Blunt trauma dominated over penetrating trauma (58% vs. 42%) where high-energy fall was the most common blunt mechanism and knife injury was the most common penetrating mechanism. The major bleeding cohort was younger (OR 0.99; 95% CI 0.98 to 0.998, P = 0.012), less female gender (OR 0.66; 95% CI 0.45 to 0.98, P = 0.04), and had more penetrating trauma (OR 4.54; 95% CI 3.24 to 6.36, P = 0.001) than the rest of the trauma cohort. A prehospital (OR 2.39; 95% CI 1.34 to 4.28; P = 0.003) and emergency department (ED) (OR 6.91; 95% CI 4.49 to 10.66, P = 0.001) systolic blood pressure < 90 mmHg was associated with the major bleeding cohort as well as ED blood gas base excess < -3 (OR 7.72; 95% CI 5.37 to 11.11; P < 0.001) and INR > 1.2 (OR 3.09; 95% CI 2.16 to 4.43; P = 0.001). Emergency damage control laparotomy was performed more frequently in the major bleeding cohort (21.4% [n = 31] vs. 1.5% [n = 106]; OR 3.90; 95% CI 2.50 to 6.08; P < 0.001). There was no difference in transportation time from alarm to hospital arrival between the major bleeding cohort and the rest of the trauma cohort (47 [IQR 38;59] vs. 49 [IQR 40;62] minutes; P = 0.17). However, the major bleeding cohort had a shorter time from ED to first emergency procedure (71.5 [IQR 10.0;129.0] vs. 109.00 [IQR 54.0; 259.0] minutes, P < 0.001). In the major bleeding cohort, patients with penetrating trauma, compared to blunt trauma, had a shorter alarm to hospital arrival time (44.0 [IQR 35.5;54.0] vs. 50.0 [IQR 41.5;61.0], P = 0.013). The 24-hour mortality in the major bleeding cohort was 6.9% (10/145). All fatalities were due to blunt trauma; 40% (4/10) high energy fall, 20% (2/10) motor vehicle accident, 10% (1/10) motorcycle accident, 10% (1/10) traffic pedestrian, 10% (1/10) traffic other, and 10% (1/10) struck/hit by blunt object. In the logistic regression model, prehospital cardiac arrest (OR 83.4; 95% CI 3.37 to 2063; P = 0.007) and transportation time (OR 0.95, 95% CI 0.91 to 0.99, P = 0.02) were associated with 24-hour mortality. RESULTS: Early identification of patients at high risk of major bleeding is challenging but essential for rapid definitive haemorrhage control. The major bleeding trauma cohort is a small part of the entire trauma population, and is characterized of being younger, male gender, higher ISS, and exposed to more penetrating trauma. Early identification of patients at high risk of major bleeding is challenging but essential for rapid definitive haemorrhage control.

Facilitating children's in-session involvement in child and family therapies: A dynamic framework of clinical practices.

Children's in-session involvement in child and family therapies correlates with both positive and negative treatment outcomes. Thus, it is important to gain a better understanding of the clinical practices that facilitate children's involvement in therapy sessions so that practitioners can employ them with greater precision. To address this need, we conducted a study to answer the following question: What clinical practices facilitate children's in-session involvement in child and family therapies? The data consisted of 16 extant audiovisual recordings of child and family therapy sessions and 24 stimulated-recall interviews with the participants in the recordings. Following constructivist grounded theory and incorporating storyline as an additional analytical technique, we have constructed a framework consisting of four involvement-enhancing practices: managing time, staying relevant, adjusting intensity, and facilitating inclusion. Furthermore, by detailing some of the complex processes that practitioners navigate when they facilitate children's involvement, our study adds a multilayered and dynamic dimension to the list of already established involvement facilitators. It may be used to moderate an overstandardized work culture that continues to characterize services that address children's needs. The results may be applied to other institutional encounters, providing resonance beyond the analyzed therapy sessions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Investigation of tryptophan to kynurenine degradation in response to interferon-γ in melanoma cell lines.

Background and aim: Melanoma is a fatal form of skin cancer that carries a grave prognosis if the cancer cells spread and form metastases. The Kynurenine (Kyn) pathway is activated by the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1) and has been shown to have a role in tumour progression. We have previously shown that interferon-γ (IFN-γ) acts as an inducer of tryptophan (Trp) degradation to Kyn in keratinocytes of the basal layer in a 3D epidermis model. Before extending our reconstructed human epidermis model to not only contain keratinocytes but also fibroblasts and melanocytes/melanoma cells, we have in this study set out to investigate possible differences between primary adult melanocytes and six melanoma cell lines regarding the expression of the immune checkpoint inhibitors IDO-1 and programmed death ligand 1 (PD-L1) together with Kyn production. Methods: The melanocytes and melanoma cells were stimulated with 1-20 ng/ml of IFN-γ and the levels of Trp to Kyn degradation were monitored with high-performance liquid chromatography (HPLC). To analyze the viability of the cell types after IFN-γ treatment, an MTT assay was performed. mRNA quantity of IDO-1, PD-L1 and IFN-γ receptor (IFN-GR1) was analyzed with qPCR. Results: After 24 h, only the metastatic cell line WM-266-4 was affected by all concentrations of IFN-γ, whereas at 48 h, the higher IFN-γ concentrations gave a more pronounced effect on the viability in all cell types. Trp was detected at various levels in the culture medium from all cell types before and after IFN-γ treatment. The degradation to Kyn was detected in primary melanocytes, Mel Juso, and Mel Ho cell lines after 24 h of treatment and low levels of IFN-γ. However, the higher concentration of IFN-γ, 20 ng/ml, induced Kyn to various degrees in all cell types after 24 h. The change in mRNA quantity of IDO-1 and PD-L1 was similar in all cell types. Conclusion: To conclude, no significant difference in upregulation of the immune checkpoint inhibitors PD-L1 and IDO-1 was seen between primary tumour and metastatic melanoma. IFN-γ stimulation of melanocytes and different stages of melanoma cell lines resulted in an increased Kyn/Trp ratio in the more aggressive melanoma cells when a high concentration was used (20 ng/ml) but when a lower concentration of IFN-γ (5 ng/ml) was used an increased Kyn/Trp ratio were detected in media from primary melanocytes and early-stage melanoma.

Impact of storage time prior to cryopreservation on mechanical properties of aortic homografts.

Optimal time spans in homograft procurement are still debatable among tissue banks and needs to be further investigated. Cell viability decreases at longer preparation intervals, but the effect on collagen and elastic fibers has not been investigated to the same extent. These fibers are of importance to the homograft elasticity and strength. The objective of this study was to analyze the mechanical properties of homograft tissue at different time spans in the procurement process. Ten aortic homografts were collected at the Tissue Bank in Lund. Twelve samples were obtained from each homograft, cryopreserved in groups of three after 2-4 days, 7-9 days, 28-30 days, and 60-62 days in antibiotic decontamination. Mechanical testing was performed with uniaxial tensile tests, calculating elastic modulus, yield stress and energy at yield stress. Two randomly selected samples were assessed with light microscopy. Procurement generated a total of 120 samples, with 30 samples in each time group. Elastic modulus and yield stress was significantly higher in samples cryopreserved after 2-4 days (2.7 MPa (2.5-5.0) and 0.78 MPa (0.68-1.0)) compared to 7-9 days (2.2 MPa (2.0-2.6) and 0.53 MPa (0.46-0.69)), p = 0.008 and 0.011 respectively. Light microscopy did not show any difference in collagen and elastin at different time spans. There was a significant decrease in elastic modulus and yield stress after 7 days of decontamination at 4 °C compared to 2-4 days. This could indicate some deterioration of elastin and collagen at longer decontamination intervals. Clinical significance of these findings remains to be clarified.

Antisecretory factor in breastmilk is associated with reduced incidence of sepsis in preterm infants.

BACKGROUND: Antisecretory Factor (AF) is a protein present in breastmilk that regulates inflammatory processes. We aimed to investigate the level of AF in mothers' own milk (MOM) in relation to sepsis and other neonatal morbidities in preterm infants. METHODS: Samples of breastmilk and infant plasma were collected at 1, 4, and 12 weeks after birth from 38 mothers and their 49 infants born before 30 weeks gestation. AF-compleasome in MOM was determined by a sandwich enzyme-linked immunosorbent assay (ELISA) and inflammatory markers in infant plasma by a panel of 92 inflammatory proteins. Neonatal treatments and outcomes were recorded. RESULTS: The level of AF in MOM week 1 was lower for infants with later sepsis compared to no sepsis (p = 0.005). Corrected for nutritional intake of MOM, higher levels of AF decreased the risk for sepsis, OR 0.24. AF in MOM week 1 was negatively correlated to inflammatory proteins in infant plasma week 4, markedly IL-8, which was also associated with infant sepsis. Overall, higher AF levels in MOM was associated with fewer major morbidities of prematurity. CONCLUSION: Mother's milk containing high levels of antisecretory factor is associated with reduced risk for sepsis and inflammation in preterm infants. IMPACT: High level of antisecretory factor (AF) in mothers' own milk is associated with less risk for later sepsis in preterm infants. Receiving mothers' milk with low AF levels during the first week after birth is correlated with more inflammatory proteins in infant's plasma 2-4 weeks later. Human breastmilk has anti-inflammatory properties, and antisecretory factor in mothers' own milk is a component of potential importance for infants born preterm. The findings suggest that food supplementation with AF to mothers of preterm infants to increase AF-levels in breastmilk may be a means to decrease the risk of inflammatory morbidities of prematurity.

Patient-derived scaffolds representing breast cancer microenvironments influence chemotherapy responses in adapted cancer cells consistent with clinical features.

BACKGROUND: The tumor microenvironment clearly influences cancer progressing properties but less is known about how individual cancer microenvironments potentially moderate cancer treatment effects. By cultivating and treating cancer cell lines in patient-derived scaffolds (PDS), the impact of specific characteristics of individual cancer microenvironments can be incorporated in human-like growth modelling and cancer drug treatment testing. METHODS: PDSs from 78 biobanked primary breast cancer samples with known patient outcomes, were prepared and repopulated with donor breast cancer cell lines, followed by treatment with 5-fluorouracil or doxorubicin after cellular adaption to the various microenvironments. Cancer cell responses to the treatments were monitored by RNA-analyses, highlighting changes in gene sets representative for crucial tumor biological processes such as proliferation, cancer stem cell features, differentiation and epithelial-to-mesenchymal transition. RESULTS: The chemotherapy treatments induced distinct gene expression patterns in adapted cancer cells with clusters of similar treatment responses depending on the patient-derived cancer microenvironment used as growth substrate. The doxorubicin treatment displayed a favorable gene signature among surviving cancer cells with low proliferation (MKI67) and pluripotency features (NANOG, POU5F1), in comparison to 5-fluorouracil showing low proliferation but increased pluripotency. Specific gene changes monitored post-treatment were also significantly correlated with clinical data, including histological grade (NANOG), lymph node metastasis (SLUG) and disease-free patient survival (CD44). CONCLUSIONS: This laboratory-based treatment study using patient-derived scaffolds repopulated with cancer cell lines, clearly illustrates that the human cancer microenvironment influences chemotherapy responses. The differences in treatment responses defined by scaffold-cultures have potential prognostic and treatment predictive values.

In vitro effects of undifferentiated callus extracts from Plantago major L, Rhodiola rosea L and Silybum marianum L in normal and malignant human skin cells.

Background and objectives: The occurrence of non-melanoma and melanoma skin cancers is currently increasing rapidly with one in every three cancers diagnosed as a skin cancer. A useful strategy to control the progression of skin cancer could be the use of plant flavonoids that suppress pro-inflammatory cytokines involved in tumor initiation and progression. In this study, the anti-inflammatory and antioxidant activity of undifferentiated callus extracts from Plantago major L, Silybum marianum L and Rhodiola rosea L was investigated both in normal and malignant skin cells. Methods: Antioxidant activity of the extracts was analyzed by using the Trolox Equivalent Antioxidant Capacity (TEAC) assay. High-Performance Thin-Layer Chromatography (HPTLC) was performed to demonstrate the phytochemical profile, and the total flavonoid content was analyzed with an aluminum chloride colorimetric method. The anti-inflammatory effect was investigated by cell treatments using the plant extracts. Thereafter, the possible suppression of induced IL-6 response was measured from the cultured skin cancer cell lines A2058 and A431, and normal primary keratinocytes with Enzyme-Linked Immunosorbent Assay (ELISA). Results: The HPTLC analysis assessed that the extracts contained a complex phytochemical profile that was rich in phenolic and flavonoid compounds. Dose response assays showed that concentrations between 15 and 125 µg/mL of all three plant extracts could be used to investigate an effect on the IL-6 production. The S. marianum extract had the most pronounced anti-inflammatory effect, which significantly inhibited induced IL-6 production in both normal keratinocytes and skin cells derived from epidermal carcinoma. The extract from S. marianum also had the highest flavonoid content and showed the highest antioxidant activity of the three extracts tested. Conclusion: All in all, we have confirmed that undifferentiated callus extracts of S. marianum possess properties such as antioxidant and anti-inflammatory activities in both normal and malignant keratinocytes, and thus could be a promising agent controlling the pro-inflammatory IL-6 production.

Selective transfer of maternal antibodies in preterm and fullterm children.

Preterm newborns are more likely to suffer from infectious diseases at birth compared to children delivered at term. Whether this is due to compromised cellular, humoral, or organ-specific development remains unclear. To begin to define whether maternal-fetal antibody transfer profiles differ across preterm (PT) and fullterm (FT) infants, the overall quantity and functional quality of an array of 24 vaccine-, endemic pathogen-, and common antigen-specific antibodies were assessed across a cohort of 11 PT and 12 term-delivered maternal:infant pairs from birth through week 12. While total IgG levels to influenza, pneumo, measles, rubella, EBV, and RSV were higher in FT newborns, selective Fc-receptor binding antibodies was noted in PT newborns. In fact, near equivalent antibody-effector functions were observed across PT and FT infants, despite significant quantitative differences in transferred antibody levels. Moreover, temporal transfer analysis revealed the selective early transfer of FcRn, FcγR2, and FcγR3 binding antibodies, pointing to differential placental sieving mechanisms across gestation. These data point to selectivity in placental transfer at distinct gestational ages, to ensure that children are endowed with the most robust humoral immunity even if born preterm.

Core competencies for a biomedical laboratory scientist - a Delphi study.

BACKGROUND: After completing university education, biomedical laboratory scientists work in clinical laboratories, in biomedical research laboratories, in biotech, and in pharmaceutical companies. Laboratory diagnostics have undergone rapid development over the recent years, with the pace showing no signs of abatement. This rapid development challenges the competence of the staff and will most certainly influence the education of future staff. This study aimed to examine what was considered the necessary competencies needed to pursue a career as a biomedical laboratory scientist. METHODS: A modified Delphi technique was used, with the panel of experts expressing their views in a series of three questionnaire. Consensus was defined as the point which 75 % or more of the panel participants agreed that a particular competency was necessary. RESULTS: The study highlights the perceived importance of mostly generic competencies that relate to quality, quality assurance, and accuracy, as well as different aspects of safety, respect, trustworthiness (towards patients/clients and colleagues), and communication skills. The results also stress the significance of self-awareness and professionality. CONCLUSIONS: We identified important competencies for biomedical laboratory scientists. Together with complementary information from other sources, i.e., guidelines, laws, and scientific publications, the competencies identified can be used as learning outcomes in a competency-based education to provide students with all the competencies needed to work as professional biomedical laboratory scientists.

Cord clamping beyond 3 minutes: Neonatal short-term outcomes and maternal postpartum hemorrhage.

BACKGROUND: Delaying cord clamping (CC) for 3-5 minutes reduces iron deficiency and improves neurodevelopment. Data on the effects of CC beyond 3 minutes in relation to short-term neonatal outcomes and maternal risk of postpartum hemorrhage are scarce. METHODS: This was a prospective observational study performed in two delivery departments. Pregnant women with vaginal deliveries were included. Time to CC, estimated postpartum blood loss, and perinatal data were recorded. Spearman's correlation analysis and comparisons between newborns clamped before and after 3 minutes were performed. RESULTS: In total, 904 dyads were included. The mean gestational age ± standard deviation was 40.1 ± 1.2 weeks. CC was performed at a median time of 6 minutes (range 0-23.5). Apgar scores at 5 and 10 minutes were positively correlated with time to CC (correlation coefficient .140, P < .001 and .161, < .001). There was no correlation between CC time and bilirubin level (correlation coefficient .021, P = .54). The median postpartum blood loss was 300 mL (70-2550 mL), with a negative correlation between CC time and postpartum blood loss (-0.115, P = .001). The postpartum blood loss was larger in the group clamped at ≤3 minutes (median [interquartile range] 400 mL [300-600] vs 300 mL [250-450], [P = .003]]. CONCLUSIONS: Umbilical CC times beyond 3 minutes in vaginal deliveries were not associated with negative short-term outcomes in newborns and were associated with a smaller maternal postpartum blood loss. Although CC time as long as 6 minutes could be considered as safe, further research is needed to decide the optimal timing.

Breast Cancer Patient-Derived Scaffolds Can Expose Unique Individual Cancer Progressing Properties of the Cancer Microenvironment Associated with Clinical Characteristics.

Breast cancer is a heterogeneous disease in terms of cellular and structural composition, and besides acquired aggressive properties in the cancer cell population, the surrounding tumor microenvironment can affect disease progression and clinical behaviours. To specifically decode the clinical relevance of the cancer promoting effects of individual tumor microenvironments, we performed a comprehensive test of 110 breast cancer samples using a recently established in vivo-like 3D cell culture platform based on patient-derived scaffolds (PDSs). Cell-free PDSs were recellularized with three breast cancer cell lines and adaptation to the different patient-based microenvironments was monitored by quantitative PCR. Substantial variability in gene expression between individual PDS cultures from different patients was observed, as well as between different cell lines. Interestingly, specific gene expression changes in the PDS cultures were significantly linked to prognostic features and clinical information from the original cancer. This link was even more pronounced when ERα-status of cell lines and PDSs matched. The results support that PDSs cultures, including a cancer cell line of relevant origin, can monitor the activity of the tumor microenvironment and reveal unique information about the malignancy-inducing properties of the individual cancer niche and serve as a future complementary diagnostic tool for breast cancer.

Non-Invasive, Topical Sampling of Potential, Low-Molecular Weight, Skin Cancer Biomarkers: A Study on Healthy Volunteers.

Monitoring of low-molecular weight cancer biomarkers, such as tryptophan (Trp) and its derivative kynurenine (Kyn), might be advantageous to non-invasive skin cancer detection. Thus, we assessed several approaches of topical sampling of Trp and Kyn, in relation to phenylalanine (Phe) and tyrosine (Tyr), on the volar forearm of six healthy volunteers. The sampling was performed with three hydrogels (made of agarose or/and chitosan), hydrated starch films, cotton swabs, and tape stripping. The biomarkers were successfully sampled by all approaches, but the amount of collected Kyn was low, 20 ± 10 pmol/cm2. Kyn quantification was below LOQ, and thus, it was detected only in 20% of topical samples. To mitigate variability problems of absolute amounts of sampled amino acids, Tyr/Trp, Phe/Trp, and Phe/Tyr ratios were assessed, proving reduced inter-individual variation from 79 to 45% and intra-individual variation from 42 to 21%. Strong positive correlation was found between Phe and Trp, pointing to the Phe/Trp ratio (being in the 1.0-2.0 range, at 95% confidence) being least dependent on sampling materials, approaches, and sweating. This study leads to conclusion that due to the difficulty in quantifying less abundant Kyn, and thus the Trp/Kyn ratio, the Phe/Trp ratio might be a possible, alternative biomarker for detecting skin cancers.

Crack propagation in articular cartilage under cyclic loading using cohesive finite element modeling.

Severe joint injuries often involve cartilage defects that propagate after mechanical loading. The propagation of these lesions may contribute to the development of post-traumatic osteoarthritis (PTOA). However, the mechanisms behind their propagation remain unknown. Currently, no numerical predictive methods exist for estimating crack propagation in cartilage under cyclic loading, yet they would provide essential insights into crack growth in injured tissue after trauma. Here, we present a numerical approach to estimate crack propagation in articular cartilage under cyclic loading using a cohesive damage model. Four different material models for cartilage (hyperelastic, poro-hyperelastic, poro-hyper-viscoelastic, and fibril-reinforced poro-hyperelastic (FRPHE) with different collagen orientations) were implemented. Our numerical cohesive damage model was able to replicate the experimental crack length reported in the literature, showing greater crack length with an increasing number of loading cycles. Damage initiation stress (4.35-4.73 MPa) and fracture energy (0.97-1.55 N/mm) values obtained for the poro-hyperelastic, poro-hyper-viscoelastic, and parallel-FRPHE models were within the range of what has been reported previously. The crack growth predictions obtained by the FRPHE models showed the influence of anisotropy of the fibrillar matrix on the cartilage response. Our results indicate that our cohesive damage model could potentially be used to estimate the adverse conditions in injured soft tissue such as osteochondral lesions, menisci tears, or partial ligament ruptures under (ab)normal biomechanical scenarios.

Changes in Antisecretory Factor in Human Milk During the Postpartum and Length of Gestation.

BACKGROUND: Preterm infants are more susceptible to inflammatory complications than term infants. Human milk contains numerous bioactive components protecting the newborn infant. Antisecretory factor, a protein regulating secretory and inflammatory processes by complex binding with complement factors, is present in human milk. RESEARCH AIMS: To describe antisecretory factor (1) in mother's own milk in term and preterm infants; and (2) in donor milk before and after Holder pasteurization. METHODS: The study was prospective, longitudinal, explorative, and descriptive. Antisecretory factor-compleasome was determined using sandwich enzyme-linked immunosorbent assay in longitudinal human milk samples over 12 weeks from mothers (N = 87) of term (n = 41) and of preterm (n = 46) infants and 20 anonymized donor human milk samples before and after Holder pasteurization. RESULTS: Antisecretory factor-compleasome was overall higher in colostrum versus mature milk (p < .001) and no difference was found in term or preterm colostrum (p = .82). In mature milk, compleasome was higher and more variable in the preterm group (p = .01). After Holder pasteurization, compleasome levels increased (p < .001). CONCLUSION: Antisecretory factor followed the pattern of other immunological factors with high levels in colostrum. After preterm birth, levels of antisecretory factor were higher and more variable in mature milk. Holder pasteurization did not degrade antisecretory factor, indicating preserved anti-inflammatory properties in donor human milk.

Catalase Activity in Keratinocytes, Stratum Corneum, and Defatted Algae Biomass as a Potential Skin Care Ingredient.

The generation of reactive oxygen species presents a destructive challenge for the skin organ and there is a clear need to advance skin care formulations aiming at alleviating oxidative stress. The aim of this work was to characterize the activity of the antioxidative enzyme catalase in keratinocytes and in the skin barrier (i.e., the stratum corneum). Further, the goal was to compare the activity levels with the corresponding catalase activity found in defatted algae biomass, which may serve as a source of antioxidative enzymes, as well as other beneficial algae-derived molecules, to be employed in skin care products. For this, an oxygen electrode-based method was employed to determine the catalase activity and the apparent kinetic parameters for purified catalase, as well as catalase naturally present in HaCaT keratinocytes, excised stratum corneum samples collected from pig ears with various amounts of melanin, and defatted algae biomass from the diatom Phaeodactylum tricornutum. Taken together, this work illustrates the versatility of the oxygen electrode-based method for characterizing catalase function in samples with a high degree of complexity and enables the assessment of sample treatment protocols and comparisons between different biological systems related to the skin organ or algae-derived materials as a potential source of skin care ingredients for combating oxidative stress.

Oral health plays second fiddle in palliative care: an interview study with registered nurses in home healthcare.

BACKGROUND: Oral health is crucial to the experience of well-being, and symptoms from the mouth are common at the end of life. Palliative care aims to identify and treat symptoms early to avoid unnecessary suffering and is thus an important part of nursing in home healthcare. The aim of this study was to illustrate the professional reflections of registered nurses about oral health amongst patients in palliative care, who are being cared for in a home healthcare setting. RESULTS: The results showed oral health in end-of-life care, to be an area marked by responsibility and ethical considerations. This was seen in all four partly overlapping themes that emerged through the analysis: Oral health is easily overlooked in palliative care, Oral health is everybody's but in reality nobody's responsibility, Patient integrity can be an obstacle for oral health, and Focus on oral health is urgently needed. The mouth is often not included as part of the daily basic care routine, by the registered nurses and the home healthcare staff, until the patient is near end of life. Moreover, neither does the patient tell about symptoms from the mouth. The interpreted whole indicates that the registered nurses had a bad conscience about not doing what they are actually responsible for and ought to do. CONCLUSION: The oral health of patients at the end of life risks being forgotten or falling between the cracks, due to the nurses' scattered tasks and unclear delimitations between their, and other professionals' responsibilities. The responsibilities of registered nurses are also ethically demanding, since their intent to respect the patient's integrity could mean that in some cases the patients does not allow them to help with oral health. To reduce the risk that oral health is overlooked, clearer demarcation and guidelines on the division of responsibilities are required. Routines that clearly implement early and recurring oral health assessments in home healthcare as well as continuing education updates on oral health and oral care are also needed.

Patient-derived scaffolds influence secretion profiles in cancer cells mirroring clinical features and breast cancer subtypes.

BACKGROUND: Breast cancer is a common malignancy with varying clinical behaviors and for the more aggressive subtypes, novel and more efficient therapeutic approaches are needed. Qualities of the tumor microenvironment as well as cancer cell secretion have independently been associated with malignant clinical behaviors and a better understanding of the interplay between these two features could potentially reveal novel targetable key events linked to cancer progression. METHODS: A newly developed human derived in vivo-like growth system, consisting of decellularized patient-derived scaffolds (PDSs) recellularized with standardized breast cancer cell lines (MCF7 and MDA-MB-231), were used to analyze how 63 individual patient specific microenvironments influenced secretion determined by proximity extension assays including 184 proteins and how these relate to clinical outcome. RESULTS: The secretome from cancer cells in PDS cultures varied distinctly from cells grown as standard monolayers and besides a general increase in secretion from PDS cultures, several secreted proteins were only detectable in PDSs. Monolayer cells treated with conditioned media from PDS cultures, further showed increased mammosphere formation demonstrating a cancer stem cell activating function of the PDS culture induced secretion. The detailed secretomic profiles from MCF7s growing on 57 individual PDSs differed markedly but unsupervised clustering generated three separate groups having similar secretion profiles that significantly correlated to different clinical behaviors. The secretomic profile that associated with cancer relapse and high grade breast cancer showed induced secretion of the proteins IL-6, CCL2 and PAI-1, all linked to cancer stem cell activation, metastasis and priming of the pre-metastatic niche. Cancer promoting pathways such as "Suppress tumor immunity" and "Vascular and tissue remodeling" was also linked to this more malignant secretion cluster. CONCLUSION: PDSs repopulated with cancer cells can be used to assess how cancer secretion is effected by specific and varying microenvironments. More malignant secretion patterns induced by specific patient based cancer microenvironments could further be identified pinpointing novel therapeutic opportunities targeting micro environmentally induced cancer progression via secretion of potent cytokines. Video abstract.