Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection.

The extent of lung regeneration following catastrophic damage and the potential role of adult stem cells in such a process remains obscure. Sublethal infection of mice with an H1N1 influenza virus related to that of the 1918 pandemic triggers massive airway damage followed by apparent regeneration. We show here that p63-expressing stem cells in the bronchiolar epithelium undergo rapid proliferation after infection and radiate to interbronchiolar regions of alveolar ablation. Once there, these cells assemble into discrete, Krt5+ pods and initiate expression of markers typical of alveoli. Gene expression profiles of these pods suggest that they are intermediates in the reconstitution of the alveolar-capillary network eradicated by viral infection. The dynamics of this p63-expressing stem cell in lung regeneration mirrors our parallel finding that defined pedigrees of human distal airway stem cells assemble alveoli-like structures in vitro and suggests new therapeutic avenues to acute and chronic airway disease.

Quinoline, Indole, and Isogranatanine Alkaloids from Malayan Leuconotis eugeniifolia.

Nine new alkaloids, eugeniinalines A-H (1-8) and (+)-eburnamenine N-oxide (9), comprising one quinoline, six indole, and two isogranatanine alkaloids, were isolated from the stem-bark extract of the Malayan Leuconotis eugeniifolia. The structures and absolute configurations of these alkaloids were established based on the analysis of the spectroscopic data, GIAO NMR calculations, DP4+ probability analysis, TDDFT-ECD method, and X-ray diffraction analysis. Eugeniinaline A (1) represents a new pentacyclic quinoline alkaloid with a 6/6/5/6/7 ring system. Eugeniinaline G (7) and its seco-derivative, eugeniinaline H (8), were the first isogranatanine alkaloids isolated as natural products. The known alkaloids leucolusine (10) and melokhanine A (11) were found to be the same compound, based on comparison of the spectroscopic data of both compounds, with the absolute configuration of (7R, 20R, 21S). Eugeniinalines A and G (1 and 7) showed cytotoxic activity against the HT-29 cancer cell line with IC50 values of 7.1 and 7.2 µM, respectively.

Translating evidence into practice in primary care management of adolescents and women with polycystic ovary syndrome: a mixed-methods study.

BACKGROUND: The international guideline on polycystic ovary syndrome (PCOS) provides evidence-based recommendations on the management of PCOS. Guideline implementation tools (GItools) were developed for general practitioner (GP) use to aid rapid translation of guidelines into practice. This mixed-methods study aimed to evaluate barriers and enablers of the uptake of PCOS GItools in general practice. DESIGN AND SETTING: A cross-sectional survey was distributed through professional networks and social media to GPs and GPs in training in Australia. Survey respondents were invited to contribute to semi-structured interviews. Interviews were audio-recorded and transcribed verbatim. Qualitative data were thematically analysed and mapped deductively to the Theoretical Domains Framework and Capability, Opportunity, Motivation and Behaviour model. RESULTS: The study engaged 146 GPs through surveys, supplemented by interviews with 14 participants. A key enabler to capability was reflective practice. Barriers relating to opportunity included limited awareness and difficulty locating and using GItools due to length and lack of integration into practice software, while enablers included ensuring recommendations were relevant to GP scope of practice. Enablers relevant to motivation included co-use with patients, and evidence of improved outcomes with the use of GItools. DISCUSSION: This study highlights inherent barriers within the Australian healthcare system that hinder GPs from integrating evidence for PCOS. Findings will underpin behaviour change interventions to assist GPs in effectively utilising guidelines in clinical practice, therefore minimising variations in care. While our findings will have a direct influence on guideline translation initiatives, changes at organisational and policy levels are also needed to address identified barriers.

Evaluation of nurse-reported missed care in a post-anesthesia care unit: A mixed-methods study.

BACKGROUND: Nurse-reported missed care (NRMC) is considered as any significant delay or omission in provision of nursing care. AIM: (i) Evaluate the frequency, types, and reasons for NRMC in the Post-anesthesia Care Unit (PACU). (ii) Evaluate associations between nurse demographic and workload factors with NRMC. (iii) Explore nurses' perception of NRMC in the PACU. METHODS: A cross-sectional study was conducted in the PACU in a tertiary acute care hospital over 3 months. Full-time PACU nurses were conveniently sampled to complete an anonymous survey after their daily shift over different shifts. It contained three sections: (i) nurse demographics; (ii) elements of NRMC; and (iii) reasons for NRMC. Qualitative interviews employed a semi-structured guide to explore perceptions and experiences of NRMC. Descriptive, inferential statistics, and thematic analyses were applied. RESULTS: Sixty-six survey responses were collected. 48.5% of respondents indicated at least one NRMC activity. Activities more clinically sensitive were less missed. Eight nurses were interviewed. Four main themes were identified: (i) communication with patients; (ii) communication and teamwork with colleagues; (iii) dual role of documentation; and (iv) staffing inadequacy. Language barriers made communication challenging. Staff shortage exacerbates workload but effective teamwork and documentation facilitates nursing care. CONCLUSION: Communication and staffing concerns aggravate NRMC. Teamwork and personal contentment were satisfactory. Nurses' turnover intention may worsen staffing. CLINICAL RELEVANCE: Timeliness and quality of nursing care is impacted by elements such as manpower, allocation of resources, work processes, and workplace environmental or interpersonal factors such as culture and language fit. Re-evaluation of nursing resources and work processes may assist post-anesthesia care unit nurses in fulfilling their role, decreasing the prevalence of nurse-reported missed care.

'Been there, experienced that': A qualitative study on the experiences and perceptions of online peer volunteers in supporting Singaporean mothers at risk of depression.

BACKGROUND: Online peer support is a useful source of support for parents during the perinatal period, associated with improved psychological outcomes. Past research has found that peer support providers themselves gain from providing peer support as well, making it mutually beneficial. As current maternity care services are insufficient to meet the support needs of parents, the Supportive Parenting App (SPA) intervention was developed to offer them informational, appraisal and emotional support during the perinatal period. It consists of mobile health application-based educational support and online peer support provided by trained peer volunteers, to prevent the development of postnatal depression. OBJECTIVE: To explore the experiences of peer volunteers with providing online peer support to parents during the perinatal period, as well as to identify areas of improvement for the SPA intervention. METHODS: A qualitative descriptive design was adopted. This study took place from October 2020 to August 2021 in two tertiary public healthcare institutions in Singapore. A total of 18 peer volunteers were invited for individual semi-structured interviews. The interviews were audio recorded and transcribed verbatim, and thematic analysis was used to analyse the data. RESULTS: Four themes were emerged as follows: (1) 'Being there': Reminiscing about and healing of own postnatal depression experience; (2) Building rapport with parents; (3) Parents in mind: Mutual sharing of knowledge and how to support new parents better; (4) Ensuring good quality peer support. CONCLUSIONS: The peer volunteers felt that their experience was fulfilling and healing. Frequent contact, sharing of SPA resources and self-disclosure were found to help engage the new parents and build rapport between peer volunteers and parents. Challenges described by the peer volunteers have identified possible areas in which the SPA intervention can be improved. IMPLICATIONS FOR CARE: Communication between peer program facilitators, managers and peer volunteers can be enhanced to ensure that peer volunteers are more sensitive and precise when providing support or information. This can improve rapport building between parents and peer volunteers, which will in turn maximize the benefits that parents can reap through online peer-to-peer support. IMPACT: This study explored the perceptions of peer volunteers who provided online peer support to parents across the perinatal period. Peer volunteers felt that the SPA intervention was meaningful and that providing peer support was a healing experience. They were able to learn about the experiences of other mothers with postpartum depression while sharing their own past experiences. Thus, both parents and peer volunteers can benefit from engaging in online peer support programs. Technology-based interventions like the Supportive Parenting App (SPA) can be a suitable complement to maternity care services by providing parents access to medically accurate information and social support. Additionally, more experienced mothers can engage in fulfilling experiences through volunteering for new mothers who may benefit from informational, appraisal and emotional support. REPORTING METHOD: This study follows the reporting guidelines as stated by the Consolidated criteria for reporting qualitative research (COREQ) checklist. PATIENT OR PUBLIC CONTRIBUTION: Parents and peer volunteers contributed ideas that aided with the design of the mobile app. Many topics added to the educational materials were suggested by these parents as well. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: This study showed that sufficient training can be provided to lay peer volunteers to help them support other parents, buffering the pressure exerted on the healthcare industry due to the rising demand for healthcare services. The provision of such support is also beneficial for the peer volunteers themselves, as they find it meaningful and educational. Program developers of parenting and peer volunteering interventions can draw on the findings of this study to improve the effectiveness of these programs.

Exploring perceptions of frailty, resilience, and self-efficacy in older adults and caregivers in acute care context.

This study aimed to explore the experience and perceptions of frailty in hospitalized older adults and caregivers caring for older adults, in relation to resilience and self-efficacy. A qualitative explorative descriptive study design was utilized. Face to face interviews were conducted from September 2020 to July 2021 with 24 older adults who were 65 years and above and hospitalized in the acute care hospital. Ten informal family caregivers were also recruited. Data were analysed using an inductive content analysis approach. Frailty encompassed physical elements as well as manifestations of psychological traits, fear of the unknown, and being in control. Resilience was determined by individual psychological traits and mindset, and the possession of a coping mechanism. Self-efficacy could influence both frailty and resilience through inner motivation and assistance received. Older adults and family caregivers reported that considerable decline in physical health with age and level of perseverance can determine the level of frailty. Resilience and self-efficacy play a pivotal role in the context of frailty. Understanding resilience in this context will assist nurses to facilitate the use of individual and sociocultural resources to improve the way resilience is experienced by older adults. Various coping strategies can enhance self-efficacy and build greater resilience in older adults, including maintaining their active involvement in health management and social life.

An SNP Marker Predicts Colorectal Cancer Outcomes with 5-Fluorouracil-Based Adjuvant Chemotherapy Post-Resection.

Colorectal cancer (CRC) is a global health concern, necessitating adjuvant chemotherapy post-curative surgery to mitigate recurrence and enhance survival, particularly in intermediate-stage patients. However, existing therapeutic disparities highlight the need for biomarker-guided adjuvant chemotherapy to achieve better CRC inhibition. This study explores the molecular mechanisms underlying the inhibition of CRC through a genome-wide association study (GWAS) focused on 5-fluorouracil (5-FU)-based adjuvant therapy in intermediate-stage CRC patients, a domain previously unexplored. We retrospectively included 226 intermediate-stage CRC patients undergoing surgical resection followed by 5-FU-based adjuvant chemotherapy. The exploration cohort comprised 31 patients, and the validation cohort included 195 individuals. Genotyping was carried out using either Axiom Genome-Wide TWB 2.0 Array Plate-based or polymerase chain reaction-based methods on genomic DNA derived from collected tissue samples. Statistical analyses involved descriptive statistics, Kaplan-Meier analyses, and Cox proportional hazard analyses. From the GWAS, potential genetic predictors, GALNT14-rs62139523 and DNMBP-rs10786578 genotypes, of 5-FU-based adjuvant therapy following surgery in intermediate-stage CRC patients were identified. Validation in a larger cohort of 195 patients emphasized the predictive significance of GALNT14-rs62139523 genotypes, especially the "A/G" genotype, for improved overall and progression-free survival. This predictive association remained robust across various subgroups, with exceptions for specific demographic and clinical parameters such as age < 58 years old, CEA ≤ 2.5 ng/mL, tumor diameter > 44.0 mm, and tumor-free margin ≥ 50 mm. This study identifies that the GALNT14-rs62139523 "A/G" genotype modulates therapeutic outcomes, establishing it as a promising biomarker for predicting favorable responses to 5-FU-based adjuvant chemotherapy in intermediate-stage CRC patients, although further investigations are needed to detail these mechanisms.

Socio-economic and environmental factors associated with community-acquired pressure injuries: A mixed method study.

AIMS: To: (1) report on the prevalence of community-acquired pressure injuries (CAPIs) in patients admitted into the acute care setting; (2) examine the socio-economic and home environment associated with CAPIs; and (3) understand the challenges of caring for patients with CAPIs at home. METHODS: This mixed-method study recruited patients admitted with CAPIs in the acute care hospital between March 2021 to June 2022. The hospital's pressure injury (PI) database was used to screen patients admitted with CAPIs. A purposive sample of CAPI patients and their caregivers participated in this study. A cross-sectional survey study was first performed to examine the prevalence of CAPIs and the socio-economic and home environment factors. Semi-structured interviews were conducted to understand the caregivers' challenges in caring for patients with CAPIs at home. RESULTS: The CAPI prevalence was reported at 1.1 % during the study period (1039 had CAPIs out of 97 912 patients admitted to the hospital). A total of 70 caregivers and patients consented to participate in the study. The mean age of patients was 84.2 (SD = 10.4) years old; 68.6 % (n = 48) were females. Majority presented with a deep tissue injury (DTI) (37.1 %; n = 26) or unstageable PI (31.4 %; n = 22). More than half of the patients had alternating air mattresses at home (54.3 %; n = 38), and only 10 % (n = 7) had positioning wedges and used a sliding sheet for turning. The mean age of the caregivers was 43.4 years old (SD = 13.1), and 84.3 % (n = 59) were female. Continuous data were summarised using means and standard deviations, and categorical data were summarised using frequencies and percentages. Logistic regression found no significant socio-demographic and clinical predictors of patients having PI stages 2, 3, and 4 compared to patients with DTI and unstageable PI. Challenges to caring for PI at home included high financial burden, physical limitations, and personal challenges in CAPIs management. CONCLUSION: CAPIs are prevalent among older patients admitted to the acute care setting. Understanding the influence of socio-economic factors is crucial for developing comprehensive strategies to mitigate the occurrence and impact of PIs. Ongoing support and education to the caregivers in the community is essential to address the reported challenges in PI care.

Second victim experiences and impact among acute care nurses: An exploratory study.

AIM: To explore the experience of second victim symptoms and adverse outcomes among nurses working in public healthcare institutions; understand the preferred components of a structured support programme; and explore the barriers to accessing existing support strategies. BACKGROUND: The second victim phenomenon is experienced by nurses during patient-related adverse events, requiring further exploration. METHODS: A mixed-methods design. Second Victim Experience and Support Tool and semi-structured individual interviews were used among nurses involved in adverse events that occurred from January 2022 to April 2023. Descriptive statistics was used to describe sociodemographic characteristics and survey responses. Thematic analysis was used to analyse qualitative data. RESULTS: Nurses (n = 12) experienced second victim-related physical, psychological and professional distress (58.3% to 83.3%) within one month after the event. Nurses continued to experience second victim-related distress (58.3%) three months after and turnover intentions (58.4%). Having a respected peer to discuss what happened was the most desired component of a support programme (75.0%). Five qualitative themes: (i) whirlwind of immediate emotions, (ii) lasting impact of adverse events, (iii) organisational barriers, (iv) coping resources at organisational level and (v) positive individual coping strategies. DISCUSSION: Nurses experienced immediate and profound distress, highlighting the pervasive and distressing nature of the second victim phenomenon. CONCLUSION: It is critical to recognise the second victim phenomenon and improve organisational climate to provide adequate support to affected nurses. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Organisations can establish a structured second victim support system, allowing nurses to seek emotional aid during the occurrence of adverse events. Establishing national policies as guidelines for organisations to refer to, raise awareness of the second victim phenomenon, and provide a standardised approach for identification and intervention for affected nurses.

Lifestyle management in polycystic ovary syndrome - beyond diet and physical activity.

Polycystic ovary syndrome (PCOS) is a common condition affecting reproductive-aged women with reproductive, metabolic and psychological consequences. Weight and lifestyle (diet, physical activity and behavioural) management are first-line therapy in international evidence-based guidelines for PCOS. While these recommend following population-level diet and physical activity guidelines, there is ongoing interest and research in the potential benefit of including psychological and sleep interventions, as well as a range of traditional, complimentary and integrative medicine (TCIM) approaches, for optimal management of PCOS. There is limited evidence to recommend a specific diet composition for PCOS with approaches including modifying protein, carbohydrate or fat quality or quantity generally having similar effects on the presentations of PCOS. With regards to physical activity, promising evidence supports the provision of vigorous aerobic exercise, which has been shown to improve body composition, cardiorespiratory fitness and insulin resistance. Psychological and sleep interventions are also important considerations, with women displaying poor emotional wellbeing and higher rates of clinical and subclinical sleep disturbance, potentially limiting their ability to make positive lifestyle change. While optimising sleep and emotional wellbeing may aid symptom management in PCOS, research exploring the efficacy of clinical interventions is lacking. Uptake of TCIM approaches, in particular supplement and herbal medicine use, by women with PCOS is growing. However, there is currently insufficient evidence to support integration into routine clinical practice. Research investigating inositol supplementation have produced the most promising findings, showing improved metabolic profiles and reduced hyperandrogenism. Findings for other supplements, herbal medicines, acupuncture and yoga is so far inconsistent, and to reduce heterogeneity more research in specific PCOS populations, (e.g. defined age and BMI ranges) and consistent approaches to intervention delivery, duration and comparators are needed. While there are a range of lifestyle components in addition to population-recommendations for diet and physical activity of potential benefit in PCOS, robust clinical trials are warranted to expand the relatively limited evidence-base regarding holistic lifestyle management. With consumer interest in holistic healthcare rising, healthcare providers will be required to broaden their knowledge pertaining to how these therapies can be safely and appropriately utilised as adjuncts to conventional medical management.

Eugeniifoline, a Pentacyclic Indole Alkaloid from Leuconotis eugeniifolia, and Configurational Revision of Synthetic Eugeniifoline Isolated from a Diversity-Enhanced Extract.

Eugeniifoline (1), a pentacyclic indole alkaloid with a five-membered ring E, was isolated for the first time as a natural product from the stem-bark extract of Leuconotis eugeniifolia. Eugeniifoline (1) was previously reported as a synthetic product from a diversity-enhanced extract, but with the configuration at C-21 reported as S (1a). The configuration at C-21 was revised to R as shown in 1, based on the NOE data, GIAO NMR calculations, and DP4+ probability analysis, as well as the TDDFT-ECD method.

Co-designing a community lifestyle intervention program to reduce postpartum weight retention.

BACKGROUND: Postpartum weight retention is a major contributor to obesity in later life resulting in long-term health consequences in women. Postpartum lifestyle interventions are known to be effective in reducing postpartum weight retention and improving the overall health and wellbeing of mothers but have poor reach and engagement. This study describes the engagement of mothers with young children in the development of a theory- and evidence-based intervention to reduce postpartum weight retention. METHODS: A participatory design methodology with input from a community mothers' group, literature reviews and an expert advisory group was applied. Mothers who were members of 'Mothers of Preschoolers' (MOPS) were invited to participate in a focus group discussion and two co-design workshop sessions. RESULTS: Thirteen women participated in a focus group discussion and 12 women in each co-design workshop. We found that mothers valued having social support from their peers, practical support such as meal delivery, and learning opportunities that focus on the mother's health and wellbeing. The advisory group suggested leveraging the unique skills and prior experiences of mothers within the group and developing a curriculum that mothers can be trained to deliver. CONCLUSION: A program that emphasizes the strengths and value of mothers can increase their self-worth and self-confidence resulting in intrinsic motivation to improve lifestyle behaviours. An intervention designed to be implemented by MOPS for its members and incorporated into their regular sessions has the potential for feasibility and acceptability among mothers with young children. PATIENT OR PUBLIC CONTRIBUTION: Mothers with young children were part of the program planners and were involved in the design and conduct of this study and in the interpretation of the findings. A member of a community mothers' group recruited other mothers with young children within the group to participate in a series of sessions to discuss their experiences of the postpartum period and preferences for a lifestyle program. The mothers identified the behavioural outcomes and program goals for a postpartum lifestyle program and then generated the program ideas based on these.

Facilitators and barriers to the implementation of surgical safety checklist: an integrative review.

Surgical procedures pose an immense risk to patients, which can lead to various complications and adverse events. In order to safeguard patients' safety, the World Health Organization initiated the implementation of the Surgical Safety Checklist (SSC) in operating theatres worldwide. The aim of this integrative review was to summarize and evaluate the use and implementation of SSC, focusing on facilitators and barriers at the individual, professional, and organizational levels. This review followed closely the integrative review method by Whittemore and Knafl. An English literature search was conducted across three electronic databases (PubMed, CINAHL, and EMBASE) and other hand search references. Keywords search included: 'acute care', 'surgical', 'adult patients', 'pre-operative', 'intra-operative', and 'post-operative'. A total of 816 articles were screened by two reviewers independently and all articles that met the pre-specified inclusion criteria were retained. Data extracted from the articles were categorized, compared, and further analysed. A total of 34 articles were included with the majority being observational studies in developed and European countries. Checklists had been adopted in various surgical specialities. Findings indicated that safety checklists improved team cohesion and communication, resulting in enhanced patient safety. This resulted in high compliance rates as healthcare workers expressed the benefits of SSC to facilitate safety within operating theatres. Barriers included manpower limitations, hierarchical culture, lack of staff involvement and training, staff resistance, and appropriateness of checklist. Common facilitators and barriers at individual, professional, and organizational levels have been identified. Staff training and education, conducive workplace culture, timely audits, and appropriate checklist adaptations are crucial components for a successful implementation of the SSC. Methods have also been introduced to counter barriers of SSC.

Evaluating the Effectiveness of the Supportive Parenting App on Parental Outcomes: Randomized Controlled Trial.

BACKGROUND: Adjusting to new or additional parenting responsibilities increases stress and affects parental well-being. Existing research has highlighted both parents' desire to receive more support. It has also been found that receiving sufficient social support enhances parenting outcomes. With the increasing popularity of mobile health apps, a Supportive Parenting App (SPA) intervention was developed to fulfill the support needs of parents during the perinatal period. OBJECTIVE: This study aimed to examine the effectiveness of the SPA on parental outcomes during the perinatal period. METHODS: A 2-group pretest and repeated posttest randomized controlled trial was conducted wherein 200 couples (N=400 mothers and fathers) were recruited from 2 public health care institutions in Singapore. Parents were randomly assigned to intervention (100/200, 50%) or control (100/200, 50%) groups. The SPA intervention consisted of a mobile app-based psychoeducation and peer support program to support parents from pregnancy to 6 months post partum. The outcome measures included postnatal depression, anxiety, parental bonding, parental self-efficacy, perceived social support, and parenting satisfaction. Data were collected at baseline (at >24 weeks of gestation-age of viability in Singapore) and at the first, second, fourth, sixth, ninth, and 12th month post partum. Linear mixed models were used to compare parental outcomes between the groups, and a linear mixed model for repeated measures was used to examine within-group changes. RESULTS: Parents in the intervention group mostly showed better outcomes compared with those in the control group. Parents in the intervention group had higher perceived social support than those in the control group at the first (effect size=1.59, 95% CI 0.38-2.80; Cohen standardized effect size=1.31; P=.01), second (effect size=1.98, 95% CI 1.09-2.88; Cohen standardized effect size=2.21; P=.003), and fourth (effect size=2.57, 95% CI 1.62-3.51; Cohen standardized effect size=2.72; P=.048) months post partum. However, parents in the intervention group showed significantly poorer parental bonding (effect size=1.67, 95% CI 0.24-3.11; Cohen standardized effect size=1.16; P=.02). The other parental outcomes did not differ significantly between groups. The scores of mothers and fathers also differed significantly for all outcomes except parental self-efficacy. CONCLUSIONS: Parents in the intervention group generally fared better, especially regarding perceived social support. However, the lack of statistical significance in most outcomes showed the limited effectiveness of the SPA intervention, which may be because of the COVID-19 pandemic. Parental differences in outcome scores suggest that mothers and fathers have different support needs; therefore, interventions should be tailored accordingly. Further improvements and evaluations are needed to examine the effectiveness of the SPA intervention in enhancing parental outcomes. Despite statistically insignificant results, limitations should be considered to further improve mobile health app-based interventions such as SPA, as they could serve as reliable and convenient sources of support for parents. TRIAL REGISTRATION: Clinicaltrails.gov NCT4706442; https://clinicaltrials.gov/ct2/show/NCT04706442.

Perinatal support for couples during COVID-19: A descriptive qualitative study.

AIMS AND OBJECTIVES: To explore the perspectives of parents during the perinatal period amid the COVID-19 pandemic and explore the experiences of Singaporean parents receiving perinatal support via the Supportive Parenting App (SPA). BACKGROUND: The stressors accompanying parenting responsibilities often affect the overall well-being of the family unit. With the emergence of the COVID-19 pandemic, Singaporean parents are forced to shoulder childcare responsibilities with minimal support due to safety restrictions. The Supportive Parenting Application (SPA) was introduced to parents during the start of the pandemic to offer timely additional support. It is a mobile health application-based educational support for parents across the perinatal period, consisting of features such as peer support, expert advice and discussion forums. DESIGN: Descriptive qualitative study. METHODS: Semi-structured one-to-one interviews were conducted with 33 parents (16 from the control group, 17 from the intervention group) in an ongoing randomised controlled trial between June 2021 and February 2022. The COREQ checklist was used to guide the reporting of the data. RESULTS: Four themes with 10 subthemes describing the perinatal experiences of parents were identified. The themes include 'Ups and downs' of parenting experiences; Perinatal care from 'best care' to 'flying blind'; What kept couples going and Use of technology-a way forward. CONCLUSION: Although COVID-19 negatively affected parents' availability of care and support, most could still access other support sources to help them. Additionally, the SPA was found to be a dependable information source for the intervention group parents. Future research could work on improving technology-based support based on the feedback given to offer better quality perinatal care for parents. RELEVANCE TO CLINICAL PRACTICE: Technology-based support provided by healthcare professionals helps provide reliable perinatal information and support for parents. More efforts should be directed towards developing quality informational resources and support to improve perinatal care. PATIENT OR PUBLIC CONTRIBUTION: Patients/members of the public contributed to the data collected and were involved in member checking to ensure the rigour of the study. CLINICAL TRIAL REGISTRATION NUMBER: NHG DSRB: 2019/00875.

Genetic Ablation of LAT1 Inhibits Growth of Liver Cancer Cells and Downregulates mTORC1 Signaling.

Through a comprehensive analysis of the gene expression and dependency in HCC patients and cell lines, LAT1 was identified as the top amino acid transporter candidate supporting HCC tumorigenesis. To assess the suitability of LAT1 as a HCC therapeutic target, we used CRISPR/Cas9 to knockout (KO) LAT1 in the epithelial HCC cell line, Huh7. Knockout of LAT1 diminished its branched chain amino acid (BCAA) transport activity and significantly reduced cell proliferation in Huh7. Consistent with in vitro studies, LAT1 ablation led to suppression of tumor growth in a xenograft model. To elucidate the mechanism underlying the observed inhibition of cell proliferation upon LAT1 KO, we performed RNA-sequencing analysis and investigated the changes in the mTORC1 signaling pathway. LAT1 ablation resulted in a notable reduction in phosphorylation of p70S6K, a downstream target of mTORC1, as well as its substrate S6RP. This reduced cell proliferation and mTORC1 activity were rescued when LAT1 was overexpressed. These findings imply an essential role of LAT1 for maintenance of tumor cell growth and additional therapeutic angles against liver cancer.

Risk factors, prevention and treatment of hypoglycaemia after hyperkalaemia in adult patients using intravenous insulin: An integrative review.

AIM: An integrative review was conducted to synthesize published evidence on the prevention and treatment of hypoglycaemia and patient risk factors, in adult patients treated for hyperkalaemia with intravenous insulin and dextrose. METHODS: This review followed the framework by Whittemore and Knafl. Papers included were limited to English language studies involving participants who were aged 18 years and above and admitted in the inpatient acute care and emergency departments. The literature search was performed using five electronic databases (CINAHL, Embase, PubMed, Proquest and Cochrane). RESULTS: A total of 22 studies were included. Two main themes were derived-patient risk factors and prevention-intervention strategies. Five main patient risk factors were lower pretreatment blood glucose (<7 mmol/L), lower weight, renal insufficiencies, older age and nondiabetic. The four subthemes in the prevention-intervention strategies included (i) methods of administration and dosing of intravenous insulin and dextrose, (ii) frequency of blood glucose monitoring, (iii) education to healthcare professionals and (iv) rescue agents. CONCLUSIONS: Standardized computerized order sets and integrated decision tool that can advise appropriate prescription of a higher volume of dextrose or lower insulin dose according to patient risk factors, regular monitoring and reinforced education may prevent and mitigate the risk of hypoglycaemia.

Evaluation of Care Outcomes of Patients Receiving Hyperkalemia Treatment With Insulin in Acute Care Tertiary Hospital Emergency Department.

INTRODUCTION: Treatment of hyperkalemia using intravenous insulin can result in severe hypoglycemia, but regular blood glucose monitoring is not standardized. This study aimed to (i) explore the demographics of adult patients receiving hyperkalemia treatment and (ii) identify the incidence rate of hypoglycemia and associated demographic or clinical characteristics. METHODS: A descriptive design with prospective data collection was used. This study recruited 135 patients who received hyperkalemia treatment in the emergency department. Structured blood glucose monitoring was conducted at 1, 2, 4, and 6 hours after receiving intravenous insulin. Univariate analyses of association between demographic and clinical variables and hypoglycemia outcome were performed. RESULTS: There were 31 hypoglycemic events, with 11.9%, 7.4%, 2.2%, and 1.5% occurring at the 1, 2, 4, and 6 hours after treatment. The logit regression showed no significantly increased risk of hypoglycemia in terms of the demographic and clinical variables. DISCUSSION: The variation in blood glucose response observed in this study combined with the high incidences of hypolycaemia indicated the need for frequent and longer duration of monitoring for patients who were being treated for hyperkalaemia with IDT.

Immunohistochemistry study of tumor vascular normalization and anti-angiogenic effects of sunitinib versus bevacizumab prior to dose-dense doxorubicin/cyclophosphamide chemotherapy in HER2-negative breast cancer.

PURPOSE: Tumor angiogenesis controlled predominantly by vascular endothelial growth factor and its receptor (VEGF-VEGFR) interaction plays a key role in the growth and propagation of cancer cells. However, the newly formed network of blood vessels is disorganized and leaky. Pre-treatment with anti-angiogenic agents can "normalize" the tumor vasculature allowing effective intra-tumoral delivery of standard chemotherapy. Immunohistochemistry (IHC) analysis was applied to investigate and compare the vascular normalization and anti-angiogenic effects of two commonly used anti-angiogenic agents, Sunitinib and Bevacizumab, administered prior to chemotherapy in HER2-negative breast cancer patients. METHODS: This prospective clinical trial enrolled 38 patients into a sunitinib cohort and 24 into a bevacizumab cohort. All received 4 cycles of doxorubicin/cyclophosphamide chemotherapy and pre-treatment with either sunitinib or bevacizumab. Tumor biopsies were obtained at baseline, after cycle 1 (C1) and cycle 4 (C4) of chemotherapy. IHC was performed to assess the tumor vascular normalization index (VNI), lymphatic vessel density (LVD), Ki67 proliferation index and expression of tumor VEGFR2. RESULTS: In comparison to Bevacizumab, Sunitinib led to a significant increase in VNI post-C1 and C4 (p < 0.001 and 0.001) along with decrease in LVD post-C1 (p = 0.017). Both drugs when combined with chemotherapy resulted in significant decline in tumor proliferation after C1 and C4 (baseline vs post-C4 Ki67 index p = 0.006 for Sunitinib vs p = 0.021 for Bevacizumab). Bevacizumab resulted in a significant decrease in VEGFR2 expression post-C1 (p = 0.004). CONCLUSION: Sunitinib, in comparison to Bevacizumab showed a greater effect on tumor vessel modulation and lymphangiogenesis suggesting that its administration prior to chemotherapy might result in improved drug delivery. TRIAL REGISTRY: ClinicalTrials.gov: NCT02790580 (first posted June 6, 2016).

Anticoagulant drugs with or without proton pump inhibitor and colorectal cancer risk: a population-based, case-control study.

BACKGROUND: Low-dose aspirin and clopidogrel have demonstrated potential chemoprevention for colorectal cancer (CRC). Proton-pump inhibitors (PPI) are commonly prescribed with anticoagulation drugs, but the relationship between PPI and CRC is unclear. Moreover, evidence of CRC risk under direct oral anticoagulant (DOAC) is limited. This study aimed to investigate the effects of anticoagulation drugs combined with or without PPI on the risks of CRC in Taiwan. METHODS: A retrospective case-control study of 1,024,227 cases based on the Chang Gung Research Database from 2010 to 2017 was performed. Clinical characteristics, indications, duration of anticoagulation and PPI use, and CRC occurrence data were collected. Logistic regression was employed to adjust for known confounders of CRC risk. RESULTS: Monotherapy of clopidogrel decreased the risk of CRC (AOR 0.70; 95% CI 0.60-0.83), while no protective effect was observed in aspirin alone or aspirin plus clopidogrel. DOAC did not affect CRC significantly. The risk of CRC increased in patients with PPI (AOR 1.38; 95% CI 1.28-1.49) and PPI plus DOAC (OR 3.91; 95% CI 1.49-10.27), while PPI plus aspirin decreased the risk of CRC (OR 0.48; 95% CI 0.32-0.73). PPI plus clopidogrel showed no significant effect on the CRC. CONCLUSION: This study suggests clopidogrel alone and PPI plus aspirin offer a preventative benefit against CRC in the Taiwanese population studied. The same effect was not observed in DOAC. Moreover, a significant increase in CRC was observed in patients on PPI monotherapy and PPI plus DOAC, suggesting a possible risk.