Locoregional CAR T Cells for the Treatment of CNS Tumors in Children: Investigational Drug Service Pharmacy Activities.

BACKGROUND: A major obstacle in translating the therapeutic potential of chimeric antigen receptor (CAR) T cells to children with central nervous system (CNS) tumors is the blood-brain barrier. To overcome this limitation, preclinical and clinical studies have supported the use of repeated, locoregional intracranial CAR T-cell delivery. However, there is limited literature available describing the process for the involvement of an investigational drug service (IDS) pharmacy, particularly in the setting of a children's hospital with outpatient dosing for CNS tumors. OBJECTIVES: To describe Seattle Children's Hospital's experience in clinically producing CAR T cells and the implementation of IDS pharmacy practices used to deliver more than 300 intracranial CAR T-cell doses to children, as well as to share how we refined the processing techniques from CAR T-cell generation to the thawing of fractionated doses for intracranial delivery. METHODS: Autologous CD4+ and CD8+ T cells were collected and transduced to express HER2, EGFR, or B7-H3-specific CAR T cells. Cryopreserved CAR T cells were thawed by the IDS pharmacy before intracranial delivery to patients with recurrent/refractory CNS tumors or with diffuse intrinsic pontine glioma/diffuse midline glioma. RESULTS: The use of a thaw-and-dilute procedure for cryopreserved individual CAR T-cell doses provides reliable viability and is more efficient than typical thaw-and-wash protocols. Cell viability with the thaw-and-dilute protocol was approximately 75% and was always within 10% of the viability assessed at cryopreservation. Cell viability was preserved through 6 hours after thawing, which exceeded the 1-hour time frame from thawing to infusion. CONCLUSION: As the field of adoptive immunotherapy grows and continues to bring hope to patients with fatal CNS malignancies, it is critical to focus on improving the preparatory steps for CAR T-cell delivery.

Emerging Evidence and Critical Issues with the Use of Single-Drop Capillary Blood for the Measurement of Hemoglobin Concentration in Population-Level Anemia Surveys.

Accurate and precise measurement of hemoglobin concentration is critical for reliable estimations of anemia prevalence at the population level. When systematic and/or random error are introduced in hemoglobin measurement, estimates of anemia prevalence might be significantly erroneous and, hence, limit their usefulness. For decades, single-drop capillary blood has been the most common blood source used for the measurement of hemoglobin concentration in surveys, especially in low-income and middle-income countries. In this study, we highlight historical and emerging evidence that single-drop capillary blood introduces a high degree of random error (variability) to hemoglobin estimates, leading to less reliable estimates of anemia prevalence at the population level. At present, the best practice is to collect and use venous blood for measurement of hemoglobin with an automated hematology analyzer, following standard operating procedures and quality assurance measures. Where use of an automated analyzer is not possible, the analysis of venous blood in a point-of-care hemoglobinometer by trained phlebotomists or specimen collectors should be considered. A forthcoming systematic review will provide additional evidence on the accuracy and precision of single-drop capillary blood for hemoglobin assessment. In the meantime, we raise caution when using single-drop capillary blood for hemoglobin measurement as it can result in inaccurate hemoglobin estimates and less reliable anemia prevalence estimates.

Palmitate and group B Streptococcus synergistically and differentially induce IL-1ß from human gestational membranes.

Introduction: Rupture of the gestational membranes often precedes major pregnancy complications, including preterm labor and preterm birth. One major cause of inflammation in the gestational membranes, chorioamnionitis (CAM) is often a result of bacterial infection. The commensal bacterium Streptococcus agalactiae, or Group B Streptococcus (GBS) is a leading infectious cause of CAM. Obesity is on the rise worldwide and roughly 1 in 4 pregnancy complications is related to obesity, and individuals with obesity are also more likely to be colonized by GBS. The gestational membranes are comprised of several distinct cell layers which are, from outermost to innermost: maternally-derived decidual stromal cells (DSCs), fetal cytotrophoblasts (CTBs), fetal mesenchymal cells, and fetal amnion epithelial cells (AECs). In addition, the gestational membranes have several immune cell populations; macrophages are the most common phagocyte. Here we characterize the effects of palmitate, the most common long-chain saturated fatty acid, on the inflammatory response of each layer of the gestational membranes when infected with GBS, using human cell lines and primary human tissue. Results: Palmitate itself slightly but significantly augments GBS proliferation. Palmitate and GBS co-stimulation synergized to induce many inflammatory proteins and cytokines, particularly IL-1ß and matrix metalloproteinase 9 from DSCs, CTBs, and macrophages, but not from AECs. Many of these findings are recapitulated when treating cells with palmitate and a TLR2 or TLR4 agonist, suggesting broad applicability of palmitate-pathogen synergy. Co-culture of macrophages with DSCs or CTBs, upon co-stimulation with GBS and palmitate, resulted in increased inflammatory responses, contrary to previous work in the absence of palmitate. In whole gestational membrane biopsies, the amnion layer appeared to dampen immune responses from the DSC and CTB layers (the choriodecidua) to GBS and palmitate co-stimulation. Addition of the monounsaturated fatty acid oleate, the most abundant monounsaturated fatty acid in circulation, dampened the proinflammatory effect of palmitate. Discussion: These studies reveal a complex interplay between the immunological response of the distinct layers of the gestational membrane to GBS infection and that such responses can be altered by exposure to long-chain saturated fatty acids. These data provide insight into how metabolic syndromes such as obesity might contribute to an increased risk for GBS disease during pregnancy.

Evaluating the Base Excision Repair Inhibitor TRC102 and Temozolomide for Patients with Recurrent Glioblastoma in the Phase 2 Adult Brain Tumor Consortium Trial BERT.

PURPOSE: Patients with glioblastoma (GBM) have a dismal prognosis. Although the DNA alkylating agent temozolomide (TMZ) is the mainstay of chemotherapy, therapeutic resistance rapidly develops in patients. Base excision repair inhibitor TRC102 (methoxyamine) reverses TMZ resistance in preclinical glioma models. We aimed to investigate the efficacy and safety of oral TRC102+TMZ in recurrent GBM (rGBM). PATIENTS AND METHODS: A preregistered (NCT02395692), nonrandomized, multicenter, phase 2 clinical trial (BERT) was planned and conducted through the Adult Brain Tumor Consortium (ABTC-1402). Arm 1 included patients with bevacizumab-naïve GBM at the first recurrence, with the primary endpoint of response rates. If sufficient activity was identified, a second arm was planned for the bevacizumab-refractory patients. The secondary endpoints were overall survival (OS), progression-free survival (PFS), PFS at 6 months (PFS6), and toxicity. RESULTS: Arm 1 enrolled 19 patients with a median of two treatment cycles. Objective responses were not observed; hence, arm 2 did not open. The median OS was 11.1 months [95% confidence interval (CI), 8.2-17.9]. The median PFS was 1.9 months (95% CI, 1.8-3.7). The PFS6 was 10.5% (95% CI, 1.3%-33.1%). Most toxicities were grades 1 and 2, with two grade 3 lymphopenias and one grade 4 thrombocytopenia. Two patients with PFS ≥ 17 months and OS > 32 months were deemed "extended survivors." RNA sequencing of tumor tissue, obtained at diagnosis, demonstrated significantly enriched signatures of DNA damage response (DDR), chromosomal instability (CIN70, CIN25), and cellular proliferation (PCNA25) in "extended survivors." CONCLUSIONS: These findings confirm the safety and feasibility of TRC102+TMZ in patients with rGBM. They also warrant further evaluation of combination therapy in biomarker-enriched trials enrolling GBM patients with baseline hyperactivated DDR pathways.

Systematic review on the frequency and quality of reporting patient and public involvement in patient safety research.

BACKGROUND: In recent years, patient and public involvement (PPI) in research has significantly increased; however, the reporting of PPI remains poor. The Guidance for Reporting Involvement of Patients and the Public (GRIPP2) was developed to enhance the quality and consistency of PPI reporting. The objective of this systematic review is to identify the frequency and quality of PPI reporting in patient safety (PS) research using the GRIPP2 checklist. METHODS: Searches were performed in Ovid MEDLINE, EMBASE, PsycINFO, and CINAHL from 2018 to December, 2023. Studies on PPI in PS research were included. We included empirical qualitative, quantitative, mixed methods, and case studies. Only articles published in peer-reviewed journals in English were included. The quality of PPI reporting was assessed using the short form of the (GRIPP2-SF) checklist. RESULTS: A total of 8561 studies were retrieved from database searches, updates, and reference checks, of which 82 met the eligibility criteria and were included in this review. Major PS topics were related to medication safety, general PS, and fall prevention. Patient representatives, advocates, patient advisory groups, patients, service users, and health consumers were the most involved. The main involvement across the studies was in commenting on or developing research materials. Only 6.1% (n = 5) of the studies reported PPI as per the GRIPP2 checklist. Regarding the quality of reporting following the GRIPP2-SF criteria, our findings show sub-optimal reporting mainly due to failures in: critically reflecting on PPI in the study; reporting the aim of PPI in the study; and reporting the extent to which PPI influenced the study overall. CONCLUSIONS: Our review shows a low frequency of PPI reporting in PS research using the GRIPP2 checklist. Furthermore, it reveals a sub-optimal quality in PPI reporting following GRIPP2-SF items. Researchers, funders, publishers, and journals need to promote consistent and transparent PPI reporting following internationally developed reporting guidelines such as the GRIPP2. Evidence-based guidelines for reporting PPI should be encouraged and supported as it helps future researchers to plan and report PPI more effectively. TRIAL REGISTRATION: The review protocol is registered with PROSPERO (CRD42023450715).

Folate Receptor Beta Signaling in the Regulation of Macrophage Antimicrobial Immune Response: A Scoping Review.

Introduction: Folate, vitamin B9, is a water-soluble vitamin that is essential to cellular proliferation and division. In addition to the reduced folate carrier, eukaryotic cells take up folate through endocytosis mediated by one of two GPI-anchored folate receptors (FRs), FRα or FRß. Two other isoforms of FR exist, FRγ and FRδ, neither of which support endocytic activities of FR signaling. FRß is expressed primarily by monocytes and macrophages and highly expressed on activated macrophages. Macrophage expression of FRß suggests a role for this receptor in modulating function of these immune sentinels, particularly as they engage in inflammatory processes. Despite several studies suggesting that folates can suppress inflammatory responses of macrophages to proinflammatory stimuli, there appears to be a lack of basic research examining the role of FRß in modulating macrophage responses to microbial sensing. We therefore conducted a scoping review to assess evidence within the published literature addressing the question, "what is known about the extent to which FRß regulates macrophage responses to sensing, and responding to, microorganisms?". Methods: As a strategy for the study selection, we queried articles indexed in the research database PubMed and the search engine Google Scholar (up until August 12, 2023), including combinations of the research words: macrophage, folate receptor beta, FOLR2. Results: We identified 2 relevant articles out of 153 that are worth discussing here, none of which directly addressed our research question. Conclusion: There is an unmet need to better define the contribution of FRß to regulating the macrophage response to microbes.

A systematic review critically appraising quantitative survey measures assessing power dynamics among multidisciplinary teams in acute care settings.

By valuing the knowledge of each discipline holistic patient-centered care can be achieved as decisions arise from expertise rather than established hierarchies. While healthcare has historically operated as a hierarchical power structure (i.e., some voices have more influence), these dynamics are rarely discussed. This review addresses this issue by appraising extant quantitative measures that assess multidisciplinary team (MDT) power dynamics. By identifying psychometrically sound measures, change agents can uncover the collective thought processes informing power structures in practice and develop strategies to mitigate power disparities. Several databases were searched. English language articles were included if they reported on quantitative measures assessing power dynamics among MDTs in acute/hospital settings. Results were synthesized using a narrative approach. In total, 6,202 search records were obtained of which 62 met the eligibility criteria. The review reveals some promising measures to assess power dynamics (e.g., Interprofessional Collaboration Scale). However, the findings also confirm several gaps in the current evidence base: 1) need for further psychometric and pragmatic testing of measures; 2) inclusion of more representative MDT samples; 3) further evaluation of unmatured power dimensions. Addressing these gaps will support the development of future interventions aimed at mitigating power imbalances and ultimately improve collaborative working within MDTs.

Environmental Toxicant Exposure Paralyzes Human Placental Macrophage Responses to Microbial Threat.

Exposure to environmental toxicants (such as dioxins) has been epidemiologically linked to adverse reproductive health outcomes, including placental inflammation and preterm birth. However, the molecular underpinnings that govern these outcomes in gravid reproductive tissues remain largely unclear. Placental macrophages (also known as Hofbauer cells) are crucial innate immune cells that defend the gravid reproductive tract and help promote maternal-fetal tolerance. We hypothesized that exposure to environmental toxicants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) could alter placental macrophage responses to inflammatory insults such as infection. To test this, placental macrophages were cultured in the presence or absence of TCDD and then infected with the perinatal pathogen Group B Streptococcus (GBS). Our results indicate that TCDD is lethal to placental macrophages at and above a 5 nM concentration and that sublethal dioxin exposure inhibits phagocytosis and cytokine production. Taken together, these results indicate that TCDD paralyzes placental macrophage responses to bacterial infection.

Impact of Metabolic Stress on BeWo Syncytiotrophoblast Function.

During placental formation, cytotrophoblasts (CTBs) fuse into multinucleate, microvilli-coated syncytiotrophoblasts (STBs), which contact maternal blood, mediating nutrient, metabolite, and gas exchange between mother and fetus, and providing a barrier against fetal infection. Trophoblasts remodel the surrounding extracellular matrix through the secretion of matrix metalloproteinases (MMPs). Maternal obesity and diabetes mellitus can negatively impact fetal development and may impair trophoblast function. We sought to model the impact of metabolic stress on STB function by examining MMP and hormone secretion. The BeWo CTB cell line was syncytialized to STB-like cells with forskolin. Cell morphology was examined by electron microscopy and immunofluorescence; phenotype was further assessed by ELISA and RT-qPCR. STBs were exposed to a metabolic stress cocktail (MetaC: 30 mM glucose, 10 nM insulin, and 0.1 mM palmitic acid). BeWo syncytialization was demonstrated by increased secretion of HCGß and progesterone, elevated syncytin gene expression (ERVW-1 and ERVFRD-1), loss of tight junctions, and increased surface microvilli. MetaC strongly suppressed syncytin gene expression (ERVW-1 and ERVFRD-1), suppressed HCGß and progesterone secretion, and altered both MMP-9 and MMP-2 production. Metabolic stress modeling diabetes and obesity altered BeWo STB hormone and MMP production in vitro.

A resilient workforce: patient safety and the workforce response to a cyber-attack on the ICT systems of the national health service in Ireland.

BACKGROUND: In May 2021, the Irish public health service was the target of a cyber-attack. The response by the health service resulted in the widespread removal of access to ICT systems. While services including radiology, diagnostics, maternity, and oncology were prioritised for reinstatement, recovery efforts continued for over four months. This study describes the response of health service staff to the loss of ICT systems, and the risk mitigation measures introduced to safely continue health services. The resilience displayed by frontline staff whose rapid and innovative response ensured continuity of safe patient care is explored. METHODS: To gain an in-depth understanding of staff experiences of the cyber-attack, eight focus groups (n = 36) were conducted. Participants from a diverse range of health services were recruited, including staff from radiology, pathology/laboratories, radiotherapy, maternity, primary care dental services, health and wellbeing, COVID testing, older person's care, and disability services. Thematic Analysis was applied to the data to identify key themes. RESULTS: The impact of the cyber-attack varied across services depending on the type of care being offered, the reliance on IT systems, and the extent of local IT support. Staff stepped-up to the challenges and quickly developed and implemented innovative solutions, exhibiting great resilience, teamwork and adaptability, with a sharp focus on ensuring patient safety. The cyber-attack resulted in a flattening of the healthcare hierarchy, with shared decision-making at local levels leading to an empowered frontline workforce. However, participants in this study felt the stress placed on staff by the attack was more severe than the cumulative effect of the COVID-19 pandemic. CONCLUSIONS: Limited contingencies within the health system IT infrastructure - what we call a lack of system resilience - was compensated for by a resilient workforce. Within the context of the prevailing COVID-19 pandemic, this was an enormous burden on a dedicated workforce. The adverse impact of this attack may have long-term and far-reaching consequences for staff wellbeing. Design and investment in a resilient health system must be prioritised.

Endoglin inhibitor TRC105 with or without bevacizumab for bevacizumab-refractory glioblastoma (ENDOT): a multicenter phase II trial.

BACKGROUND: Glioblastoma (GBM), the most lethal primary brain tumor, has limited treatment options upon recurrence after chemoradiation and bevacizumab. TRC105 (carotuximab), a chimeric anti-endoglin (CD105) antibody, inhibits angiogenesis and potentiates activity of VEGF inhibitor bevacizumab in preclinical models. This study sought to assess safety, pharmacokinetics, and efficacy of TRC105 for bevacizumab-refractory GBM. METHODS: We conducted a pre-registered (NCT01564914), multicenter, open-label phase II clinical trial (ENDOT). We administered 10 mg/kg TRC105 monotherapy (first cohort) in adults with GBM and radiographic progression following radiation, temozolomide and bevacizumab therapy. Primary outcome was median time-to-progression (TTP), amended after first cohort's enrollment to median overall survival (mOS). Secondary outcomes were objective response rate, safety and tolerability, and progression-free survival (PFS). RESULTS: 6 patients were enrolled in TRC105 monotherapy cohort. Median TTP and PFS of 5 evaluable patients receiving monotherapy was 1.4 months, in whom plasma VEGF-A levels were elevated post-therapy. Lack of response led to protocol amendment, and second cohort's addition of bevacizumab+TRC105 with primary endpoint of mOS. 16 patients were enrolled in bevacizumab+TRC105 cohort. mOS of 15 evaluable patients was 5.7 (95%CI: 4.2-9.8) months. All 22 patients had measurable disease at baseline. Median PFS of 14 evaluable patients receiving bevacizumab+TRC105 was 1.8 months (95%CI 1.2-2.1). Serum TRC105 was measurable above target concentration of 25 ug/mL in all evaluable patients. Study medications were well-tolerated in both cohorts. Combined administration did not potentiate known toxicities of either medication, with cerebral hemorrhage not observed. CONCLUSIONS: Single-agent TRC105 lacks activity in bevacizumab-refractory GBM, possibly secondary to upregulated VEGF-A expression. Meaningful mOS in bevacizumab+TRC105 cohort warrants further trials to investigate efficacy of combination therapy.

Glioblastoma is an aggressive and lethal brain tumor, with patients typically expected to survive for 14 to 16 months after diagnosis. Nearly all patients experience tumor recurrence once conventional treatment strategies fail, after which a drug called bevacizumab is used. However, subsequent treatment options are extremely limited. We performed a clinical trial in which we investigated how safe and effective a new drug called TRC105 (carotuximab) is in patients who no longer respond to chemotherapy, radiotherapy or bevacizumab. We tested TRC105 both with and without bevacizumab, since TRC105 might enhance the activity of bevacizumab. We found that patients survived for an average of 5.7 months when given TRC105 and bevacizumab in combination. These findings suggest that further clinical trials are needed to confirm whether or not this combination therapy is a useful approach in patients with glioblastoma recurrence.

Review of intervention products for use in the prevention and control of anemia.

Anemia remains a major public health problem, especially in low- and middle-income countries. The World Health Organization recommends several interventions to prevent and manage anemia in vulnerable population groups, including young children, menstruating adolescent girls and women, and pregnant and postpartum women. Daily iron supplementation reduces the risk of anemia in infants, children, and pregnant women, and intermittent iron supplementation reduces anemia risk in menstruating girls and women. Micronutrient powders reduce the risk of anemia in children. Fortifying wheat flour with iron reduces the risk of anemia in the overall population, whereas the effect of fortifying maize flour and rice is still uncertain. Regarding non-nutrition-related interventions, malaria treatment and deworming have been reported to decrease anemia prevalence. Promising interventions to prevent anemia include vitamin A supplementation, multiple micronutrient supplementation for pregnant women, small-quantity lipid-based supplements, and fortification of salt with iodine and iron. Future research could address the efficacy and safety of different iron supplementation formulations, identify the most bioavailable form of iron for fortification, examine adherence to supplementation regimens and fortification standards, and investigate the effectiveness of integrating micronutrient, helminth, and malaria control programs.

Comparison of Published Estimates of the National Prevalence of Iron, Vitamin A, and Zinc Deficiency and Sources of Inconsistencies.

Micronutrient deficiencies result in a broad range of adverse health and functional consequences, but the true prevalence of specific deficiencies remains uncertain because limited information is available from nationally representative surveys using recommended biomarkers. The present review compares various reported national deficiency prevalence estimates for nutrients and years where the estimates overlap for individual countries that conducted nationally representative surveys and explores possible reasons for any discrepancies discovered. Nationally representative micronutrient status surveys that were conducted since 2000 among preschool-aged children or women of reproductive age and included assessment of iron, vitamin A, or zinc status based on recognized biomarkers were considered eligible for inclusion, along with any modeled deficiency prevalence estimates for these same countries and years. There was considerable variation across different published prevalence estimates, with larger inconsistencies when the prevalence estimate was based on proxies, such as hemoglobin for iron deficiency and dietary zinc availability for zinc deficiency. Numerous additional methodological issues affected the prevalence estimates, such as which biomarker and what cutoff was used to define deficiency, whether the biomarker was adjusted for inflammation, and what adjustment method was used. For some country-years, the various approaches resulted in fairly consistent prevalence estimates. For other country-years, however, the results differed markedly and changed the conclusions regarding the existence and severity of the micronutrient deficiency as a public health concern. In conclusion, to determine micronutrient status, we consider the assessment of one of the recommended biomarkers in a population representative survey as the best available information. If indicated, results should be adjusted for inflammation and generally acceptable cutoffs should be applied to facilitate comparisons, although individual countries may also apply nationally defined cutoffs to determine when and where to intervene. Global consensus is needed on best practices for presenting survey results and defining the prevalence of deficiency.

Propofol Inhibits Glioma Stem Cell Growth and Migration and Their Interaction with Microglia via BDNF-AS and Extracellular Vesicles.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. GBM contains a small subpopulation of glioma stem cells (GSCs) that are implicated in treatment resistance, tumor infiltration, and recurrence, and are thereby considered important therapeutic targets. Recent clinical studies have suggested that the choice of general anesthetic (GA), particularly propofol, during tumor resection, affects subsequent tumor response to treatments and patient prognosis. In this study, we investigated the molecular mechanisms underlying propofol's anti-tumor effects on GSCs and their interaction with microglia cells. Propofol exerted a dose-dependent inhibitory effect on the self-renewal, expression of mesenchymal markers, and migration of GSCs and sensitized them to both temozolomide (TMZ) and radiation. At higher concentrations, propofol induced a large degree of cell death, as demonstrated using microfluid chip technology. Propofol increased the expression of the lncRNA BDNF-AS, which acts as a tumor suppressor in GBM, and silencing of this lncRNA partially abrogated propofol's effects. Propofol also inhibited the pro-tumorigenic GSC-microglia crosstalk via extracellular vesicles (EVs) and delivery of BDNF-AS. In conclusion, propofol exerted anti-tumor effects on GSCs, sensitized these cells to radiation and TMZ, and inhibited their pro-tumorigenic interactions with microglia via transfer of BDNF-AS by EVs.

Setting a Patient-Driven Agenda for Cancer Research Priorities in Geriatric Oncology: A Qualitative Study.

OBJECTIVES: This study aims to explore older adults' perceptions of priorities for research in cancer and hematological malignancies and proposes an agenda of patient-driven priorities for cancer care research in the field of geriatric oncology. DATA SOURCES: Sixteen older adults (≥65 years) living with or after a diagnosis of cancer participated in a descriptive qualitative study. Participants were purposively recruited via a regional cancer center and cancer advocacy organizations. Semistructured telephone interviews explored participants' experiences of cancer and perceptions of priorities for future cancer-related research. CONCLUSION: Participants reported positive experiences of cancer care. However, positive and negative experiences of information, symptoms, and support both within and beyond the hospital setting were highlighted. Forty-two research priorities in six thematic areas were identified: 1) recognition of the signs and symptoms of cancer; 2) research about cancer treatment; 3) assessment and management of comorbidities; 4) unmet needs of older adults living with and after cancer; 5) impact of COVID-19; and 6) impact on caregivers and family members of people living with and after cancer. IMPLICATIONS FOR NURSING PRACTICE: The results of this study provide a basis for future priority-setting activities that are culturally and contextually sensitive to health care systems, resources, and needs of older adults living with and after cancer. Based on the findings of this study, we make recommendations for the development of interventions that can build awareness, capacity, and competence in geriatric oncology among cancer care professionals and consideration of the diverse needs of older adults in the development of interventions to address unmet information and supportive care needs.

Disparity in pseudohyphal morphogenic switching response to the quorum sensing molecule 2-phenylethanol in commercial brewing strains of Saccharomyces cerevisiae.

Saccharomyces cerevisiae can undergo filamentous growth in response to specific environmental stressors, particularly nitrogen-limitation, whereby cells undergo pseudohyphal differentiation, a process where cells transition from a singular ellipsoidal appearance to multicellular filamentous chains from the incomplete scission of the mother-daughter cells. Previously, it was demonstrated that filamentous growth in S. cerevisiae is co-regulated by multiple signaling networks, including the glucose-sensing RAS/cAMP-PKA and SNF pathways, the nutrient-sensing TOR pathway, the filamentous growth MAPK pathway, and the Rim101 pathway, and can be induced by quorum-sensing aromatic alcohols, such as 2-phenylethanol. However, the prevalent research on the yeast-pseudohyphal transition and its induction by aromatic alcohols in S. cerevisiae has been primarily limited to the strain Σ1278b. Due to the prospective influence of quorum sensing on commercial fermentation, the native variation of yeast-to-filamentous phenotypic transition and its induction by 2-phenylethanol in commercial brewing strains was investigated. Image analysis software was exploited to enumerate the magnitude of whole colony filamentation in 16 commercial strains cultured on nitrogen-limiting SLAD medium; some supplemented with exogenous 2-phenylethanol. The results demonstrate that phenotypic switching is a generalized, highly varied response occurring only in select brewing strains. Nevertheless, strains exhibiting switching behavior altered their filamentation response to exogenous concentrations of 2-phenylethanol.

Exploring healthcare staff narratives to gain an in-depth understanding of changing multidisciplinary team power dynamics during the COVID-19 pandemic.

BACKGROUND: Multidisciplinary teams (MDTs) are integral to healthcare provision. However, healthcare has historically adopted a hierarchical power structure meaning some voices within the MDT have more influence than others. While power dynamics can influence interprofessional communication and care coordination, the field's understanding of these power structures during the COVID-19 pandemic is limited. METHODS: Adopting a narrative inquiry methodology, this research addresses this knowledge gap and provides an in-depth understanding of MDT power dynamics during COVID-19. Using semi-structured interviews (n = 35) and inductive thematic analysis, this research explores staff perspectives of changing power dynamics in MDTs during the pandemic response. RESULTS: An in-depth analysis generated three overarching themes: (1) Healthcare: a deeply embedded hierarchy reveals that while a hierarchical culture prevails within the Irish health system, staff perceptions of influence in MDTs and 'real' experiences of autonomy differ significantly. (2) Team characteristics: the influence of team structure on MDT power dynamics highlights the impact of organisational structures (e.g., staff rotations) and local processes (e.g., MDT meeting structure) on collaborative practice. (3) Ongoing effort to stimulate true collaboration underscores the importance of ongoing interprofessional education to support collaborative care. CONCLUSION: By offering a greater understanding of MDT power dynamics throughout the COVID-19 pandemic, this research supports the development of more appropriate strategies to promote the provision of interprofessional care in practice.

Integrating and coordinating programs for the management of anemia across the life course.

Anemia is a major global public health concern with a complex etiology. The main determinants are nutritional factors, infection and inflammation, inherited blood disorders, and women's reproductive biology, but the relative role of each varies between settings. Effective anemia programming, therefore, requires evidence-based, data-driven, contextualized multisectoral strategies, with coordinated implementation. Priority population groups are preschool children, adolescent girls, and pregnant and nonpregnant women of reproductive age. Opportunities for comprehensive anemia programming include: (i) bundling interventions through shared delivery platforms, including antenatal care, community-based platforms, schools, and workplaces; (ii) integrating delivery platforms to extend reach; (iii) integrating anemia and malaria programs in endemic areas; and (iv) integrating anemia programming across the life course. Major barriers to effective anemia programming include weak delivery systems, lack of data or poor use of data, lack of financial and human resources, and poor coordination. Systems strengthening and implementation research approaches are needed to address critical gaps, explore promising platforms, and identify solutions to persistent barriers to high intervention coverage. Immediate priorities are to close the gap between access to service delivery platforms and coverage of anemia interventions, reduce subnational coverage disparities, and improve the collection and use of data to inform anemia strategies and programming.