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Background: Mother's own milk (MOM) is important as the first nutrition for preterm infants, but mothers often struggle to initiate milk production right after preterm birth. If antenatal breastmilk expression (aBME) does not induce preterm labor when performed before term age, it could promote nutrition with MOM right after preterm birth. In this pilot study, we aimed to investigate whether aBME induces preterm labor among healthy nulliparous women from week 34 of pregnancy, to examine if aBME promotes the availability of MOM right after birth and affects breastfeeding outcomes., Methods: Women were randomized to aBME (10 min 2 × daily) from week 34 of pregnancy until birth or to the control group. Both groups had a breastfeeding consultation between week 33 and 34 of pregnancy and were followed until eight weeks after birth. The primary outcome was gestational age (GA) at birth. Secondary outcomes were the availability of MOM and exclusive breastfeeding rates from 24 h to eight weeks after birth. Ranksum test and a posterior plot for the probability of non-inferiority were applied to the primary outcome. The availability of MOM is reported as medians and IQR. Breastfeeding outcomes were analyzed with mixed effects logistic regression., Results: One hundred forty-four pregnant women were eligible for participation, 51 were excluded, and 33 declined participation/did not answer inclusion phone calls. 60 women were included and randomized. Primary outcome data were available in 55 women (28 in intervention, 27 in control). We found no difference in GA at birth between the two groups: median (IQR), 40 + 1(39 + 5:41 + 2) in intervention vs. 40 + 2 (39 + 4:41 + 1) in control, p = 0.98. Antenatal expressed MOM was available at birth in most women in the intervention group (23/28, 82%), with a median of 52 mL during pregnancy. There was no statistically significant difference in breastfeeding outcomes. No adverse events were reported., Conclusions: aBME performed by healthy nulliparous women from gestational week 34 did not induce preterm labor. In most women in the intervention group, MOM was available right after birth. The study results provide the basis for a trial among women at high risk for preterm birth., Clinicaltrials: gov (NCT05516199)., Competing Interests: Declarations. Ethics approval and consent to participate: The Research Ethical Committee of the University of Southern Denmark approved the study (22/2533). The study gained approval from the Data Protection Agency of the Region of Southern Denmark (21/59493). All participants signed written consent before participation in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Breastfeeding establishment can be challenging due to several factors including women's emotional and physical perception of breastfeeding. This study examines the bodily experiences of healthy women performing antenatal breastmilk expression (aBME) from gestational week 34 until term and whether aBME can support women during breastfeeding establishment., Methods: A qualitative phenological-hermeneutic approach was applied. In-depth semi-structured interviews were conducted from December 2022 to March 2023, and women were recruited from the Express-MOM Study, which examined aBME before term. Interviews were conducted 2-4 weeks after birth. Questions concerned body image, bodily experience of aBME, and whether aBME supported their confidence during breastfeeding establishment. Interviews were audio recorded, verbatim transcribed, coded by the first and last author, and subjected to thematic analysis., Results: Seven women participated in the interviews. Three themes were identified: 1) A desire to be prepared, which identified how women had a deep-felt wish to provide their infants with their milk; 2) Bodily confident, which covered how women trusted their body when expressing milk through aBME, and how this increased their confidence in breastfeeding; and 3) Being confident in the storm, which addressed how knowledge about women's own body obtained from aBME was valuable in the vulnerable breastfeeding establishment., Conclusions: aBME from 34 weeks of gestation can contribute to women feeling more bodily confident and prepared for breastfeeding establishment. This study provides a basis for future research on aBME in women at risk of breastfeeding difficulties (e.g. preterm delivery) to identify if aBME can increase breastfeeding confidence and also breastfeeding initiation and rates., Clinical Trial Registration: The study is registered on the official website of ClinicalTrials.gov., Identifier: ID NCT05516199., Competing Interests: The authors have completed and submitted the ICMJE Form for disclosure of Potential Conflicts of Interest and none was reported., (© 2024 Bentzen S.B. et al.)

Objectives: The safety and feasibility of human milk fortification with bovine colostrum (BC) were investigated in very preterm infants (FortiColos trial, NCT03537365). The BC product contained lower calcium, phosphate, and iron levels compared to the conventional fortifier (CF). We tested whether fortification with BC plus extra phosphate was sufficient to support the infants' mineral status assessed by blood biochemistry., Methods: In a randomised controlled trial (FortiColos, NCT03537365), mineral status was compared after fortification with BC versus CF. Blood calcium, phosphate, and haemoglobin were determined before and up to 3 weeks after the start of fortification (at the mean age of 8-9 days). The maximum supplemental doses of calcium, phosphate, and iron given were retrieved from patient medical records. Results were adjusted for gestational age, birth weight, and enteral nutrition with the mother's own milk and/or donor human milk., Results: Blood values of calcium, phosphate, and haemoglobin were similar between groups. Infants in both groups required supplementation with calcium and phosphate, but infants fed BC required higher maximum doses of phosphate and calcium (p < 0.05) to maintain acceptable blood values. Regardless of fortification groups, the most immature (<29 weeks of gestation) and small for gestational age infants showed a higher risk for requiring additional phosphate (odds ratio [OR]: 3.9, p < 0.001; OR: 2.14, p = 0.07, respectively)., Conclusions: The use of BC as a fortifier for human milk requires additional phosphate and calcium relative to a CF. Regardless of the fortification product, the most immature and small infants require additional mineral supplementation., (© 2024 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Rusty pipe syndrome (RPS) is a benign, self-limiting condition characterized by bloody milk secretion, and is primarily seen among primiparous women. This case report highlights the clinical presentation of a 31-year-old primiparous woman with bloody milk secretion from gestational week 31. This persisted throughout pregnancy until seven days after birth. RPS should be considered in pregnant women with painless bilateral bloody milk secretion during pregnancy and/or the early days post-partum. The milk can safely be provided to the infant, and RPS is not an indication for formula feeding., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Electrochemotherapy (ECT) is becoming an established therapy for melanoma and is under investigation for application in additional cancer types. One potential cancer type that may benefit from ECT is lung cancer as lung cancer treatments remain unable to deliver long-lasting treatment responses. Given the importance of the immune system in lung cancer, here we have also examined the impact of ECT on immune populations. The impact of electroporation and ECT on three human lung cancer cell lines (A549, H460, SK-MES 1), one murine cell line (LLC) and murine T cells, dendritic cells and macrophages was examined. The viability, metabolic activity and recovery potential post-treatment of all cell types was determined to evaluate the potential utility of ECT as a lung cancer treatment. Our findings demonstrate that cisplatin at 11 µM would be the suggested drug of choice when using ECT for lung cancer treatment. Our study also shows that T cells are not impacted by any tested condition, whilst dendritic cells and macrophages are significantly negatively impacted by electric field strengths surpassing 800 V/cm in vitro. Therefore, current ECT protocols (using 1000 V/cm in vivo) might need to adapted to improve viability of the immune population, thus improving therapy outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Electrochemotherapy (ECT), the application of an electric impulse to deliver chemotherapy drugs into cells, has been in clinical trials since the early 1990s and has been used for a variety of different malignancies including melanoma and sarcoma. A standard operating procedure for the use of ECT in clinical settings has been established since 2006. ECT is very effective in reducing the local tumour burden via T-cell dependent killing of the cancer cells; however abscopal effects are not consistently observed. Currently little is known or understood about how ECT affects the immune cell population within the treated tumour and how these changes could impact the immune response. In this manuscript, we will review the current knowledge on ECT in the context of its interactions with the immune system and discuss how the gained knowledge could be harnessed to develop a potent ECT-immune co-treatment combination (Electroimmunotherapy)., Competing Interests: Declaration of competing interest The Authors have no conflicts of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Person-centred care based on systematic and comprehensive patient-engagement is gaining momentum across healthcare systems. Providing care that is responsive to the needs, values and priorities of each patient is important for patients, relatives and providers alike, not least for the growing population of older patients living with multi-morbidity and associated complex care trajectories., Objectives: The aim of this systematic review is to investigate the effects of patient engagement interventions for older patients with multimorbidity., Methods: Systematic review conducted in August 2021. Two reviewers independently screened the international databases Embase and PubMed. Reviewers carried out duplicate and independent data extraction and assessment of study quality. Grading of Recommendations Assessment, Development and Evaluation was used to assess the quality of the evidence for each study., Results: We included twelve studies from primary care setting and hospitals. The included studies were heterogeneous in terms of characteristics of populations, types of interventions to enhance patient-engagement, outcome measures and length of follow-up. Nine of the 12 included studies found significant improvements in health and patient-reported outcomes such as higher quality-adjusted life-years, fewer hospital visits and disease specific symptoms. Quality of the included studies was of low to moderate., Conclusion: This review identifies potential beneficial effects of interventions to enhance patient-engagement in older adults with multimorbidity. Nevertheless, the limited and very diverse evidence-based calls for more robust studies into efficient approaches to engaging older adults with multimorbidity in care trajectories., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

To make in vitro single cell electroporation protocols more comparable between various cancer types and groups, we propose a set of assays to test a range of electric field strengths at the start of any new project to determine the optimal electric field strength for a given cell line. While testing a range of electric field strengths, we kept the other ESOPE parameters constant (8 pulses, 100 µs pulse duration, 1 Hz pulse frequency). Basic assays were employed to measure short-term viability, effectiveness of treatment, metabolic activity, and recovery potential post-treatment to determine the optimal field strength for a particular cell line. Six cancer cell lines were tested, three of human (A549, A375 and Pan02) and three murine (LLC, B16F10 and MIA-PACA2). Our findings demonstrate that the optimal electroporation setting while keeping with all other ESOPE parameters are 800 V/cm for A549 and Pan02, 700 V/cm for A375, Mia-PACA2, and B16F10, and 1300 V/cm for LLC. Having an agreed upon set of assays to determine each cell lines optimal electric field strength should allow an improve translation of findings between cell lines for in vitro work from various groups and potentially improve translation into the clinic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Cytokines of the common γ-chain receptor family such as IL-15 are vital with respect to activating immune cells, sustaining healthy immune functions, and augmenting the anti-tumor activity of effector cells, making them ideal candidates for cancer immunotherapy. IL-15, either in its soluble form (IL-15sol) or complexed with IL-15Rα (IL-15Rc), has been shown to exhibit potent anti-tumor activities in various experimental cancer studies. Here we describe the impact of intraperitoneal IL-15 in a cancer cell-delivered IL-15 immunotherapy approach using the 70Z/3-L leukemia mouse model. Whereas both forms of IL-15 led to significantly improved survival rates compared to the parent cell line, there were striking differences in the extent of the improved survival: mice receiving cancer cells secreting IL-15sol showed significantly longer survival and protective long-term immunity compared to those producing IL-15Rc. Interestingly, injection of leukemia cells secreting IL-15sol lead to heightened expansion of CD4 + and CD8 + T-cell populations in the peritoneum compared to IL-15Rc. Cell-secreted IL-15Rc resulted in an influx and/or expansion of NK1.1 + cells in the peritoneum which was much less pronounced in the IL-15sol model. Furthermore, IL-15Rc but not IL-15sol lead to T-cell exhaustion and disease progression. To our knowledge, this is the first study detailing a significantly different biological effect of cell-delivered IL-15sol versus IL-15Rc in a mouse cancer immunotherapy study.

Background: Mother's own milk (MOM) is preferred when feeding preterm infants. When expressed mother's milk is stored and handled, there is a risk of bacterial contamination, decreased immunological activity, and less nutritional potential., Purpose: The aim of this study was to investigate current routines when handling MOM in Danish neonatal intensive care units (NICUs)., Methods: A survey was sent to all 17 NICUs in Denmark in which current practices regarding human milk handling, storage, and preparation were evaluated. Furthermore, one question sought to establish when mother's milk was believed to be colostrum. Respondents of the survey were neonatal nurses., Results: All 17 units responded to the survey. Only 5 of 17 units answered that human colostrum was defined as milk from the first week after birth. Refrigerator storage time varied between 24 and 72 hours. In 6 of 17 units, parents were in charge of mixing milk and fortifier. Heating of human milk was done by using microwave ovens in 4 of 17 of the units., Implications for Practice: This national survey established that there is significant variability in the way mother's milk is handled. Some of the procedures performed may affect the quality of the milk. It is important to implement evidence-based practice regarding storage and handling of expressed mother's milk to ensure that the quality of the milk is the best possible alternative for all preterm infants., Implications for Research: Prospective studies are needed to examine the association between handling of human milk and changes in composition and nutritional potential of the milk.

Dendritic cells (DCs) constantly sample peripheral tissues for antigens, which are subsequently ingested to derive peptides for presentation to T cells in lymph nodes. To do so, DCs have to traverse many different tissues with varying oxygen tensions. Additionally, DCs are often exposed to low oxygen tensions in tumors, where vascularization is lacking, as well as in inflammatory foci, where oxygen is rapidly consumed by inflammatory cells during the respiratory burst. DCs respond to oxygen levels to tailor immune responses to such low-oxygen environments. In the present study, we identified a mechanism of hypoxia-mediated potentiation of release of tumor necrosis factor α (TNF-α), a pro-inflammatory cytokine with important roles in both anti-cancer immunity and autoimmune disease. We show in human monocyte-derived DCs (moDCs) that this potentiation is controlled exclusively via the p38/mitogen-activated protein kinase (MAPK) pathway. We identified MAPK kinase kinase 8 (MAP3K8) as a target gene of hypoxia-induced factor (HIF), a transcription factor controlled by oxygen tension, upstream of the p38/MAPK pathway. Hypoxia increased expression of MAP3K8 concomitant with the potentiation of TNF-α secretion. This potentiation was no longer observed upon siRNA silencing of MAP3K8 or with a small molecule inhibitor of this kinase, and this also decreased p38/MAPK phosphorylation. However, expression of DC maturation markers CD83, CD86, and HLA-DR were not changed by hypoxia. Since DCs play an important role in controlling T-cell activation and differentiation, our results provide novel insight in understanding T-cell responses in inflammation, cancer, autoimmune disease and other diseases where hypoxia is involved., (© 2018 The Author(s).)

Ethylene is a major plant hormone mediating developmental processes and stress responses to stimuli such as infection. We show here that ethylene is also produced during systemic inflammation in humans and is released in exhaled breath. Traces of ethylene were detected by laser spectroscopy both in vitro in isolated blood leukocytes exposed to bacterial lipopolysaccharide (LPS) as well as in vivo following LPS administration in healthy volunteers. Exposure to LPS triggers formation of ethylene as a product of lipid peroxidation induced by the respiratory burst. In humans, ethylene was detected prior to the increase of blood levels of inflammatory cytokines and stress-related hormones. Our results highlight that ethylene release is an early and integral component of in vivo lipid peroxidation with important clinical implications as a breath biomarker of bacterial infection.

Current plasma fractionation technology combines ethanol precipitation with packed bed chromatography. We have developed a novel core fractionation process comprising five expanded bed adsorption (EBA) chromatographic steps on high-density modified agarose/tungsten carbide beads. Plasma was first chromatographed on two diethyl amino-ethyl (DEAE)-tungsten carbide agarose adsorbents (respective mean particle diameters of d(v)(0.5)=190 and 37 microm) to isolate at 50 to 80% recovery a fraction containing 4 to 7 IU/ml factor II (FII), factor IX (FIX), and factor X (FX) (specific activity >1 IU/mg) and another enriched in FVIII and von Willebrand factor (vWF) (approximately 1 IU/ml and 0.6 IU/mg, respectively). The flow-through was adsorbed on 4% agarose-10% tungsten carbide beads coupled with an acidic mixed-mode ligand to isolate an 80% pure immunoglobulin G (IgG) at a 93% step recovery. A highly purified alpha1-antitrypsin was isolated at 95% step recovery by adsorbing the flow-through on 4% epoxy-crosslinked agarose-10% tungsten carbide adsorbent material coupled with a cationic ligand. Isolation of 98% pure albumin was achieved at a 99% step recovery by pH 4.5 adsorption of the flow-through on 6% agarose-10% tungsten carbide beads coupled with an acidic mixed-mode ligand. EBA may represent a feasible alternative core plasma fractionation tool., (Copyright 2009 Elsevier Inc. All rights reserved.)

Purpose: To characterize complex coacervates/flocculates of lysozyme and heparin in terms of binding stoichiometry and to determine the effect of complexation on protein structure and stability., Methods: Insoluble lysozyme-heparin complexes were formed at pH 7.2 and the binding stoichiometry determined using a solution depletion method. Protein structure was determined by infrared spectroscopy and intrinsic fluorescence. Protein stability was evaluated using differential scanning calorimetry and followed in a 12-weeks storage stability study at 37 degrees C., Results: Binding stoichiometry between heparin and lysozyme was found to be dependent on ionic strength of the solution. At low ionic strength (I approximately 0.01) about 11 lysozyme molecules could bind to a 17 kDa heparin chain, 3 to a 6 kDa chain, and less than 2 to a 3 kDa chain. At higher ionic strength (I approximately 0.1), only 7 lysozyme molecules could bind to a 18 kDa heparin chain.. Above ionic strengths of approximately 0.32 M, no insoluble complexes were observed. Infrared spectroscopy and intrinsic fluorescence did not show any major changes in protein structure upon complexation to heparin. In contrast, differential scanning calorimetry showed a large decrease in the melting temperature of the protein, from 77 degrees C to 61 degrees C. Moreover, after 12-weeks storage at 37 degrees C, only 60% protein recovery was observed for the complexes, with no loss of protein for the uncomplexed protein., Conclusions: Heparin has multiple binding sites for lysozyme, amounting to at most one lysozyme molecule per 3 disaccharide units of heparin. Complexation decreased lysozyme stability, suggesting that heparin has a higher affinity for the unfolded state than the native state. Similar destabilization may occur for other proteins upon interaction with highly charged polymeric compounds or surfaces.