Care Pathway Research Articles

Parasport medicine and its challenges

Introduction: The field of Paralympic medicine examines the healthcare issues that are specific to athletes with disabilities. This article presents a historical phenomenon in which the introduction of further activities for patients with neurological conditions led to the hosting of the Paralympic Games. The article describes the complexity of inclusivity in disability health research and outlines the historical context of the emergence of this field of sports medicine. It also presents the main challenges posed by the developing parasport. One of the most significant issues is to guarantee that competition is conducted with the greatest degree of equity possible. This entails ensuring the precision of classification, preventing the over-medicalisation of athletes. It is also imperative that athletes with special requirements are provided with the appropriate support and equipment. The creation of adequate care pathways requires a challenging process, largely due to the inconclusive nature of research findings over the years. Further investigation is necessary to gain a more nuanced understanding of this relatively new area of study. Purpose of work: The aim of this article is to provide an overview of the broader challenges that paramedicine is facing in relation to the rapid development of this branch of sports medicine. Materials and methods: This article is based on the literature found in Pubmed database and other scientific databases. References were researched using following keywords: paralympic games, persons with disabilities, paramedicine, para-athletes, Conclusions: The advancement of Paralympic medicine is markedly expedited by a synthesis of qualitative and quantitative research methodologies. The integration of these two approaches yields invaluable insights into the personal perspectives of athletes on their health, while also facilitating statistically significant, evidence-based results on the analysis of large groups of athletes.

A nurse-led multidisciplinary service for Nipple-Areola complex tattooing after breast cancer: reporting on a complex intervention with TIDieR analysis

BackgroundThe Nipple-Areola Complex (NAC) tattooing can restore physical and mental integrity after breast cancer, but it is not always easily accessible for women. This paper aims to report on the development of a multidisciplinary nurse-led service for NAC tattooing for women who underwent breast cancer surgery with NAC removal to allow its thorough review and replication.MethodsThe Medical Research Council’s framework for developing complex healthcare interventions was followed. According to the results of a literature review, and the context analysis, an initial intervention was planned. The Template for Intervention Description and Replication checklist was chosen to ensure the quality and completeness of the intervention description.ResultsThe Breast Unit and the Research departments were engaged; three nurse-tattooists were selected; the informative material was created and shared with patients, families and local associations, involving them actively. Finally, the setting and the materials were defined. A monthly schedule of activities was set: patients with the indication for NAC tattooing were contacted by the nurse case manager. Each treatment involves 3–4 sessions, 30–40 days apart, in an ambulatory setting. It consists of NAC shaping and tattooing with a dermographer and sterile needles.ConclusionImplementing freely and equally multidisciplinary nurse-led clinics might provide this treatment ensuring the patient’s quality of life and nurse competence. The NAC tattooing is a complex intervention that represents the final part of the breast cancer surgical care pathway.

Exploring Implementation of Reasonable Adjustments in Hospitals for People With Intellectual Disability: Using a Realist Lens.

To explore the factors influencing the implementation of reasonable adjustments in hospitals for people with intellectual disability: using a realist lens. A qualitative study using a realist lens. Data collection involved one focus group interview and three semi-structured interviews with healthcare professionals working in hospital or community settings in September 2023. Data were analysed using qualitative content analysis and findings were mapped to the Context and Implementation of Complex Interventions (CICI) framework across the dimension's context, implementation and setting. Healthcare professionals support the provision of reasonable adjustments in acute hospitals as a person-centred approach to caring for people with intellectual disability. While reasonable adjustments are evident in practice, they are mostly individual-level cases with little evidence of strategic system-level implementation. The factors influencing the implementation of reasonable adjustments in practice were conceptualised using the CICI framework. Context factors spanned the domains of epidemiological (e.g., ageing population), socio-cultural (e.g., historical healthcare), political (e.g., lack of integrated care pathways) and ethical (e.g., provision of person-centred care). Implementation factors spanned the domains of strategies (e.g., leadership strategies), agents (e.g., liaison and advocacy roles) and outcomes (e.g., individual-level reasonable adjustments). The setting for the complex intervention was the acute hospital. System-level indicators for successful implementation include intellectual disability specific policies/procedures for integrated care pathways, education and awareness training for hospital staff, and leadership strategies such as the development of liaison nursing roles and the appropriate allocation of physical and human resources. A radical change is needed where implementation of reasonable adjustments in acute hospitals are broadened beyond isolated individual-level cases to system-level healthcare. This research highlights the importance of exploring the integrated dimensions of context, implementation and setting in complex interventions such as reasonable adjustments and sets foundation for further implementation research in this area. Reasonable adjustments at the system-level within acute hospitals would promote person-centred care and help address the inequities and health disparities experienced by people with intellectual disability. This research uses a realist lens to explore the factors influencing the implementation of reasonable adjustments in acute hospitals for people with intellectual disability. The factors influencing the implementation of reasonable adjustments in practice were conceptualised using the CICI framework across the dimensions of context (domains epidemiological, socio-cultural, political and ethical), implementation (domains strategies, agents and outcomes) and setting. System-level indicators for successful implementation include intellectual disability specific policies/procedures for integrated care pathways, education and awareness training for hospital staff, and leadership strategies such as the development of liaison nursing roles and the appropriate allocation of physical and human resources. This research highlights the importance of exploring the integrated dimensions of context, implementation and setting of complex interventions such as reasonable adjustments and sets a foundation for further implementation research in this area. This research adhered to the Equator research reporting guideline: standards for reporting qualitative research. A parent of a child with intellectual disability was involved in the conduct of this research, specifically in the design, data collection and preparation of the manuscript.

Identification of nitric oxide-mediated necroptosis as the predominant death route in Parkinson’s disease

Parkinson's disease (PD) involves multiple forms of neuronal cell death, but the dominant pathway involved in disease progression remains unclear. This study employed RNA sequencing (RNA-seq) of brain tissue to explore gene expression patterns across different stages of PD. Using the Scaden deep learning algorithm, we predicted neurocyte subtypes and modelled dynamic interactions for five classic cell death pathways to identify the predominant routes of neuronal death during PD progression. Our cell type-specific analysis revealed an increasing shift towards necroptosis, which was strongly correlated with nitric oxide synthase (NOS) expression across most neuronal subtypes. In vitro experiments confirmed that nitric oxide (NO) is a key mediator of necroptosis, leading to nuclear shrinkage and decreased mitochondrial membrane potential via phosphorylation of the PIP1/PIP3/MLKL signalling cascade. Importantly, specific necroptosis inhibitors significantly mitigated neuronal damage in both in vitro and in vivo PD models. Further analysis revealed that NO-mediated necroptosis is prevalent in early-onset Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) and across multiple brain regions but not in brain tumours. Our findings suggest that NO-mediated necroptosis is a critical pathway in PD and other neurodegenerative disorders, providing potential targets for therapeutic intervention.

Inadequate sleep as a limiting factor in achieving remission in patients with rheumatoid arthritis

IntroductionGood sleep has a restorative effect at the cellular level and helps maintain the body's homeostasis. ObjectivesGiven our clinical experiences, we propose that sleep quality should be evaluated in patients with rheumatoid arthritis. Poor sleep quality should be considered as a factor that may impact clinical outcomes in patients with rheumatoid arthritis. Materials and methodsWe researched medical literature on clinical and physiological pathways associated with sleep quality. ResultsThere is evidence that interleukin-6 and tumor necrosis factor have a role in inflammatory and immune imbalance as well as in sleep disturbance in patients with rheumatoid arthritis, which leads to the chronic inflammatory process seen in these patients. Most patients with rheumatoid arthritis report sleep problems, be it insomnia or other complaints of non-refreshing sleep. Lack of sleep or poor sleep patterns in these patients further compromise their quality of life. In patients with RA, aetiologies such as restless leg syndrome (RLS), sleep apnoea syndrome, and Temporomandibular Joint Dysfunction (TMJ) syndromes might contribute to sleep disturbances. This lack of restful sleep might limit our goal, as treating physicians, to achieve remission states in these patients. ConclusionsIt is our opinion that sleep quality evaluation must be addressed, monitored, and treated as part of the management of patients with RA. Bad sleep adds an additional burden to disease activity in patients with RA, besides, it limits patients’ possibility of achieving disease remission.

Chaetocin inhibits the progression of neuroblastoma by targeting JAK2/STAT3 signaling pathway in SH-SY5Y cells.

Chaetocin is a fungal mycotoxin that extensively found in various natural products and has anticancer and anti‑inflammatory activities. Herein, the anticancer effects of chaetocin against the progression of neuroblastoma were studied with SHSY-5Y human neuroblastoma cells and examined the underlying molecular mechanisms. The effects of chaetocin on cellular viability, apoptosis, cell migration, and invasion were investigated. The underlying mechanism of anticancer effects of chaetocin was found to mediate via activating JAK2/STAT3 signaling pathway. Furthermore, when SHSY-5Y cells were exposed to a higher concentration of chaetocin, the induction of cell apoptosis significantly increased by enhancing the expression of pro-apoptotic protein Bcl-2, resulting in anticancer activity against neuroblastoma. In addition, chaetocin significantly decreased the SHSY-5Y cell invasion and migration at 50μM treatment. Moreover, it was shown that increasing chaetocin treatments greatly decreased the activity of proteins connected to the JAK2/STAT3 signaling pathway. In conclusion, chaetocin exhibits a diverse range of actions on neuroblastoma cells, including the inhibition of proliferation, induction of apoptosis, perturbation of cellular morphology, and modulation of critical signaling pathways, with a specific focus on the JAK/STAT3 pathway. These results contribute valuable insights that underscore the potential therapeutic utility of chaetocin in the context of neuroblastoma treatment, suggesting its multifaceted impact on key cellular processes involved in cancer progression.

Decoding Critical Targets and Signaling Pathways in EBV-Mediated Diseases Using Large Language Models

Decoding Critical Targets and Signaling Pathways in EBV-Mediated Diseases Using Large Language Models

The hidden costs: a qualitative analysis exploring the experience of prostate cancer treatment-related side effects on sexual function and urinary incontinence among Black survivors and their caregivers.

Prostate cancer (PCa) disproportionately affects Black men in the U.S., leading to high incidence and mortality rates. Post-treatment challenges, such as sexual dysfunction and urinary incontinence, significantly impact quality of life yet are frequently overlooked. The purpose of this study was to characterize the experience of treatment-related side effects around sexual function and urinary incontinence among Black survivors of PCa and their caregivers. We conducted semi-structured virtual interviews with 11 Black survivors of PCa and 11 caregivers (22 total participants). Survivors were eligible if they were diagnosed and treated for PCa within the last decade and caregivers were eligible if they self-identified as a caregiver for a Black survivor. Interviews were transcribed verbatim and analyzed using a qualitative descriptive approach. During interviews, participants spontaneously discussed topics covering sexual dysfunction and urinary incontinence. Key themes identified from interview discussions included the physical experience of PCa treatment, knowledge of the impact of PCa treatment on life quality, and the process of navigating survivorship care. Although they received peer and familial support, survivors expressed a desire for clinicians to initiate discussions on sexual dysfunction and urinary incontinence. Caregivers recounted their experiences while providing support to the survivor. The findings underscore the need for clinicians to prioritize discussions on sexual dysfunction and urinary incontinence with patients, and for enhancement of care pathways and resources for these issues in survivorship care. Trained professionals, such as occupational and physical therapists, social workers, genetic counselors, and psychologists, have the potential to fill this survivorship care gap.

Use and impact of clinical pathways across various healthcare settings: A protocol for an umbrella review of global evidence.

The proposed umbrella review aims to assess the use and impact of clinical pathways on professional practice, patient outcomes, length of hospital stay, hospital costs, patient satisfaction, and hospital staff satisfaction through a synthesis of existing systematic reviews and meta-analyses. Following PRIOR guidelines, a systematic search will be conducted in MEDLINE, Epistemonikos, and the Cochrane Library to identify relevant systematic reviews and meta-analyses, from inception till March 2024. Two reviewers will independently screen titles and abstracts, with a third resolving any disagreements. Full-text articles considered potentially relevant will be assessed for eligibility by the same process. The data extraction form will cover information about the review methods, characteristics of the included primary studies, the types of interventions evaluated, and the reported outcomes. This standardized data extraction form will be piloted by the review team on five to ten articles to ensure all relevant information is recorded. The quality of included systematic reviews and meta-analyses will be evaluated using AMSTAR 2. PROSPERO registration number is CRD42024529371. The study will present a narrative synthesis of the findings, addressing the clinical and methodological heterogeneity and assessing the impact of clinical pathways on various healthcare outcomes. This umbrella review will provide evidence-based insights into the effectiveness, challenges, and best practices of clinical pathways, guiding healthcare decision-making and identifying areas for future research. Results will be disseminated widely to inform policy and improve healthcare service delivery. No patient or public contribution, as this paper is a protocol of an umbrella review.

Dan'e fukang decoction reduces hemorrhage in a rat model of mifepristone induced incomplete abortion and may correlate with cell adhesion molecule signaling interference

Ethnopharmacological relevanceDan'e fukang decoction(DFD) is a traditional Chinese medicine formula. DFD obtains 10 herbs, including Salvia yunnanensis C.H.Wright (Zidanshen) , Curcuma zedoaria (Christm.) Roscoe (Ezhu), Angelica sinensis (Oliv.) Diels (Danggui), Cyperus rotundus L. (Xiangfuzi), Corydalis yanhusuo (Y.H.Chou & Chun C.Hsu) W.T.Wang ex Z.Y.Su & C.Y.Wu, Bupleurum marginatum Wall. ex DC. (Yanhusuo), Sparganium stoloniferum (Buch.-Ham. ex Graebn.) Buch.-Ham. ex Juz. (Sanleng), Panax notoginseng (Burkill) F.H.Chen (Sanqi), Paeonia lactiflora Pall. (Shaoyao) and Glycyrrhiza uralensis Fisch. (Gancao). DFD is now clinically used for the treatment of menstrual irregularities, dysmenorrhea and menstrual discomfort caused by blood stasis and easing of endometriosis. Based on this, it is reasonable to presume that DFD may be effective in treating incomplete abortion and reducing postpartum bleeding, but no specific studies have been reported so far. Aim of the studyTo investigate the efficacy of Dan'e fukang decoction (DFD) in reducing prolonged vaginal bleeding followed by mifepristone induced incomplete abortion and explore the mechanisms of action of DFD in treating incomplete abortion. MethodsAn incomplete abortion model of rat was established by single intragastrically administered 8.5 mg/kg mifepristone on the 7th day of pregnancy. From the 8th day of pregnancy, the abortive rats were administered solvent, a positive control drug, or different doses of DFD, respectively for seven consecutive days. The efficacy of DFD was assessed by measuring the vaginal bleeding volume of the rats. Four coagulation parameters and platelet counts were measured. Hematoxylin and eosin (HE) staining was performed to evaluate pathological changes in the uterine embryos. Serum levels of progesterone and estrogen were measured using ELISA. Network pharmacology and transcriptomics were used to predict potential targets and pathways for DFD to reduce hemorrhage. The levels of mRNA related to cell adhesion molecules (CAMs) were detected by RT-qPCR. The levels of progesterone and estrogen receptors and the proteins associated with CAMs pathway in uterine tissues were detected by Western Blot. ResultsDFD significantly reduced the volume of vaginal bleeding of the abortive rats and significantly downgraded the pathological scores of uterine embryos. DFD significantly increased serum levels of E2, and had no impact on serum levels of P4 and the protein expression of ER and PR in the uteri of the abortive rats. Pathways in cancer, lipid, focal adhesion and immune-related signaling were predicted to be influenced by DFD via the analysis of network pharmacology. The CAMs signaling was found the most critical pathway regulated by both mifepristone and DFD via RNA-seq assay, followed by axon guidance, basal cell carcinoma, hippo signaling pathway and neuroactive ligand-receptor interaction. Combining the two analytical methods, ICAM-1 was predicted likely the key targeted gene by DFD. Finally, DFD was validated to decrease the protein expression of ICAM-1, ITGB2, ITGB7 and RASSF5 in the uterine tissues, which correlated to suppress the CAMs signaling pathway. ConclusionDFD significantly reduced hemorrhage. DFD significantly increased the serum levels of E2 and inhibited CAMs signaling pathway, which was likely to be involved in the mechanism of action of DFD facilitating residual uterine embryo expulsion in the rat model of incomplete abortion.

Transforming care: Optimizing ERAS pathway in breast cancer surgery with latissimus dorsi flap.

This study aims to establish, execute, and assess the effectiveness of a perioperative enhanced recovery after surgery (ERAS) clinical care pathway in breast reconstruction patients with LD flap breast cancer treatment. The goal is to improve early recovery outcomes, reduce hospitalization time, and enhance patient satisfaction by implementing a standardized approach to postoperative care. This study was conducted at the University of Malaya Medical Center. The outcomes of 21 breast cancer patients who underwent autologous reconstructive breast surgery with the latissimus dorsi (LD) flap within six months before the implementation of the ERAS pathway (pre-ERAS) were compared with 26 patients who underwent the same surgery with the ultrasound-guided erector spinae plane (ESP) block for the (ERAS protocol implementation) cohort. The study was conducted from November 2019 to October 2020. The length of hospital stay, amount of analgesic usage, and incidence of postoperative nausea vomiting (PONV) were recorded. The implementation of the ERAS clinical care pathway resulted in shorter hospital stays compared with the preceding care. On average, ERAS patients were mostly discharged on Day 2 post-surgery, whereas pre-ERAS patients were mostly discharged on Day 7. ERAS patients had a lower incidence of PONV from Days 1 to 5, starting with 88.5% not experiencing the condition on Days 1 and 2 and increasing to 100% on Day 5. All pre-ERAS patients experienced PONV in the first 5days post-surgery. Fewer ERAS patients required antiemetics post-surgery (88.5%) compared with pre-ERAS patients (42.9%). The implementation of the ERAS protocol as part of clinical care in autologous reconstructive breast surgery with the LD flap can improve recovery by shortening hospital stay, decreasing the use of analgesia, and alleviating PONV.

Using the Candidacy Framework to understand individual, interpersonal, and system level factors driving inequities in women with breast cancer: a cross-sectional study

BackgroundPersistent inequities in breast cancer outcomes exist. Understanding women’s experiences along the care pathway is the first step to finding solutions to tackle these inequities.MethodsSecondary data analysis of the 2017/2018 English National Cancer Patient Experience Survey (n = 25,408) using logistic regression to explore inequities in care experience by sociodemographic factors (age, ethnicity, socioeconomic position, sexual orientation) across 59 survey questions. We used the Candidacy Framework to interpret and organise our findings.ResultsCompared to older (65–74) and White British women, young (35-44, OR = 0.55 [0.44, 0.69]), Asian (OR = 0.52 [0.41, 0.67]), Black (OR = 0.67 [0.46, 0.97]) and White Other (OR = 0.63 [0.49, 0.81]) women were more likely to rate their overall care experience less positively, respectively. Similar findings were observed along all domains of the cancer pathway. Through a candidacy lens, we identified multilevel factors related to this variation including prolonged help-seeking behaviours (individual), poor patient-provider communication (interpersonal), and variation in access to healthcare professionals and resources (system level).ConclusionMultilevel factors influence inequities in the experience of care along the breast cancer pathway for young women and women from minoritised groups. Interventions are necessary to ensure cancer care systems are responsive to women’s health needs and provide equity of care to all patients.

27 Our journey, our stories: The lived experiences of parents and caregivers of children with severe neurodevelopmental disorders and behavioural complexity requiring sedation

Abstract Background 40% of children with severe neurodevelopmental disorders (NDD) in British Columbia (BC) are unable to access recommended medical evaluations due to behavioural complexity (aggression/self-injury). Medical evaluations under anesthesia (EUA) are thus often required, however, difficulties in coordination result in inequities and repeated traumatic sedations. Objectives We aim to describe the experiences of parents/caregivers of children with NDD and behavioural complexity undergoing EUA at BC Children’s Hospital (BCCH). Using thematic analysis we aim to identify leverage points for action to address health inequity. Design/Methods Patient oriented research (POR) principles guided study design, with parent partners involved throughout phases of the project including identification of study area, recruitment, development of interviews, data analysis and knowledge translation. Semi-structured interviews were conducted to explore families’ experiences of EUAs. Data collected included the child’s demographics/diagnoses, their experiences of previous EUA, and facilitators and barriers towards this. Results 11 families participated in the study. Key stakeholders involved in care coordination of EUA were identified (Figure 1). An illustration was developed by a parent partner as a more accessible means of presenting families’ narratives (Figure 2), integrated within five emerging themes: 1) The cumulative physical/psychological trauma experienced by families when accessing care (represented by the river which deepens and widens over time); 2) The need for an awareness and understanding from providers of behavioural complexity (represented by child being left behind); 3) Requirement of equitable and not equal care, tailored towards specific needs (represented by the precarious raft and boat); 4) Communication being key (represented by the walky-talky and map); 5) Providers being willing to undertake the role of care coordination (represented by the rescue workers, with safety gear and a rope, representing resources and role of care coordination respectively). Details within each scene (e.g. dad holding up his younger son on his shoulders to shield him from the trauma vs mum holding the hand of her older daughter now immersed in the water due to repeated traumatic experiences with age) attempt to capture the nuanced experiences encountered by families over time. Conclusion Our results highlight the complex journey coordinating EUA for this specific population. Due to resource constraints and lack of formalised pathways, current processes are traumatic and result in missed opportunities. Next steps include advocacy by the EUA Project Group at BCCH for 1) A centralized intake process with a hospital-based coordinator role and 2) Implementation of integrated EUA algorithms and care pathways between services, to improve equitable access and minimise trauma for all involved in EUA.

Human transforming growth factor β type I receptor in complex with kinase inhibitor SB505124.

The crystal structure of the intracellular domain of transforming growth factor β type I receptor (TβR1) in complex with the competitive inhibitor SB505124 is presented. The study provides insights into the structure and function of TβR1 in complex with SB505124, and as such offers molecular-level understanding of the inhibition of this critical signalling pathway. The potential of SB505124 as an avenue for therapy in cancer treatment is discussed on basis of the results.

Expanding the therapeutic horizon in acute myeloid leukemia: The role of phosphoinositide-3-kinase-γ inhibition

Abstract Acute myeloid leukemia (AML) remains a formidable challenge due to its high relapse rate and limited therapeutic options. This study investigates the role of phosphoinositide-3-kinase-γ (PI3Kγ) in AML and explores the therapeutic potential of the PI3Kγ inhibitor, eganelisib, in preclinical models. Using genome-wide CRISPR interference screening, we identified PI3Kγ as a critical survival pathway in certain AML subsets. We demonstrated that inhibition of PI3Kγ with eganelisib disrupts oxidative phosphorylation, thereby impeding AML cell survival and proliferation. Notably, the combination of eganelisib with cytarabine showed enhanced efficacy, suggesting a synergistic interaction that improves treatment outcomes. These findings indicate that PI3Kγ is a viable therapeutic target in AML and that PI3Kγ inhibitors could be pivotal in overcoming treatment resistance and reducing relapse.

Deciphering the role of lipid metabolism-related genes in Alzheimer’s disease: a machine learning approach integrating Traditional Chinese Medicine

BackgroundAlzheimer’s disease (AD) represents a progressive neurodegenerative disorder characterized by the accumulation of misfolded amyloid beta protein, leading to the formation of amyloid plaques and the aggregation of tau protein into neurofibrillary tangles within the cerebral cortex. The role of carbohydrates, particularly apolipoprotein E (ApoE), is pivotal in AD pathogenesis due to its involvement in lipid and cholesterol metabolism, and its status as a genetic predisposition factor for the disease. Despite its significance, the mechanistic contributions of Lipid Metabolism-related Genes (LMGs) to AD remain inadequately elucidated. This research endeavor seeks to bridge this gap by pinpointing biomarkers indicative of early-stage AD, with an emphasis on those linked to immune cell infiltration. To this end, advanced machine-learning algorithms and data derived from the Gene Expression Omnibus (GEO) database have been employed to facilitate the identification of these biomarkers.MethodsDifferentially expressed genes (DEGs) were identified by comparing gene expression profiles between healthy individuals and Alzheimer’s disease (AD) patients, using data from two Gene Expression Omnibus (GEO) datasets: GSE5281 and GSE138260. Functional enrichment analysis was conducted to elucidate the biological relevance of the DEGs. To ensure the reliability of the results, samples were randomly divided into training and validation sets. The analysis focused on lipid metabolism-related DEGs (LMDEGs) to explore potential biomarkers for AD. Machine learning algorithms, including Support Vector Machine-Recursive Feature Elimination (SVM-RFE) and the Least Absolute Shrinkage and Selection Operator (LASSO) regression model, were applied to identify a key gene biomarker. Additionally, immune cell infiltration and its relationship with the gene biomarker were assessed using the CIBERSORT algorithm. The Integrated Traditional Chinese Medicine (ITCM) database was also referenced to identify Chinese medicines related to lipid metabolism and their possible connection to AD. This comprehensive strategy aims to integrate modern computational methods with traditional medicine to deepen our understanding of AD and its underlying mechanisms.ResultsThe study identified 137 genes from a pool of 751 lipid metabolism-related genes (LMGs) significantly associated with autophagy and immune response mechanisms. Through the application of LASSO and SVM-RFE machine-learning techniques, four genes—choline acetyl transferase (CHAT), member RAS oncogene family (RAB4A), acyl-CoA binding domain-containing protein 6 (ACBD6), and alpha-galactosidase A (GLA)—emerged as potential biomarkers for Alzheimer’s disease (AD). These genes demonstrated strong therapeutic potential due to their involvement in critical biological pathways. Notably, nine Chinese medicine compounds were identified to target these marker genes, offering a novel treatment approach for AD. Further, ceRNA network analysis revealed complex regulatory interactions involving these genes, underscoring their importance in AD pathology. CIBERSORT analysis highlighted a potential link between changes in the immune microenvironment and CHAT expression levels in AD patients, providing new insights into the immunological dimensions of the disease.ConclusionThe discovery of these gene markers offers substantial promise for the diagnosis and understanding of Alzheimer’s disease (AD). However, further investigation is necessary to validate their clinical utility. This study illuminates the role of Lipid Metabolism-related Genes (LMGs) in AD pathogenesis, offering potential targets for therapeutic intervention. It enhances our grasp of AD’s complex mechanisms and paves the way for future research aimed at refining diagnostic and treatment strategies.

Evaluation of moderate periorbital cellulitis and home-based therapy in children (EPOCH study, Part 2): A prospective single centre cohort study.

Paediatric periorbital cellulitis, a common eye condition, typically requires inpatient admission for intravenous antibiotics due to concerns about orbital spread. This study aimed to assess the safety and effectiveness of ambulatory management for children with moderate periorbital cellulitis. Over a 24-month period, we prospectively enrolled 84 children aged 1 to 16 years who presented with moderate periorbital cellulitis to the emergency department. Demographic and clinical data were collected. Following a guideline-based decision tree, eligible children received intravenous antibiotics and were discharged with a peripheral cannula for follow-up in ambulatory care and ophthalmology clinics. Descriptive statistics were used for data presentation. Among the 84 children, 62 (73.8%) were managed through the ambulatory care model. Within the category of moderate POC, those who were admitted to the hospital did not have higher CRP or White Cell counts and received IV antibiotics for the same length of time. The ambulatory care clinic provided a total of 132 daily doses of intravenous antibiotics. Two children treated on this pathway required inpatient admission due to clinical deterioration, one of whom required ophthalmic surgical intervention. There was no mortality or sight-threatening complications in this study. Implementing a directed ambulatory care pathway for children with moderate periorbital cellulitis proved to be an effective and safe management strategy. This approach reduces the strain on hospital bed occupancy while promoting community-based patient care.

Current Insights into Therapeutic Potential of Terpenoids as Anticancer Agents.

Cancer is regarded as one of the main causes of death globally. Future predictions indicate that the death rate from cancer will keep rising, which may reach 11.4 million in 2030. Carcinogenesis refers to the phenomenon of transforming a normal cell into a cancer cell. Cancer is characterized by unregulated and uncontrolled cell division due to alterations at the molecular and genetic levels. Gene mutations can speed up the rate of cell division, which leads to cancer. Metastasis entails the dissemination of cancer cells from the primary site to distant regions of the body via the circulatory or lymphatic systems. This review is mainly focusing on the anticancer properties of terpenoids. In the case of human beings, several types of cancers can be treated clinically based on the form and phase of the cancer. So, there are different types of treatment regimens available for the management of cancer, such as immunotherapy, hormonal therapy, radiation therapy, and chemotherapy. Several problems are associated with cancer therapy, including chemoresistance, severe toxicity, relapse, and metastasis. To minimize these complications, natural products like terpenoids seem to be beneficial for the effective management of cancer. Experimental results revealed that the anticancer potential of terpenoids is due to activation of apoptosis and stimulation of cell cycle arrest. Some of the terpenoids exhibit anticancer effects by inhibiting angiogenesis and metastasis via the regulation of several signaling pathways intracellularly. Certain terpenoids have been shown to work in concert with anticancer medications (doxorubicin, cisplatin, paclitaxel, and 5-fluorouracil) to provide synergistic effects. These terpenoids have also been shown to be effective against cancer cells that are resistant to several drug therapies. The current study will focus on signaling pathways and mode of action of several types of terpenoids as anticancer agents. Further, it will provide insights into the ongoing clinical trials and prospective pathways for the advancement of terpenoids as possible anti-cancer agents.

Weighted Gene Co-Expression Network Analysis Uncovers Critical Genes and Pathways Involved in Soybean Response to Soybean Mosaic Virus

Background: Soybean mosaic virus (SMV) is a globally prevalent and detrimental virus that belongs to the Potyvirus genus. Pathogenic viruses of this genus are typically linear in shape, with dimensions ranging between 630 and 750 nm, and are composed of single-stranded RNA and proteins. We have developed an SMV-resistant soybean line, Dongnong 93-046, which has no significant changes in disease resistance identification in the adult plants and has neat grains with no obvious brown or black markings. To explore the defense mechanisms of soybean against SMV, we performed comparative transcriptomic sequencing of the leaves between the Dongnong 93-046 inoculated with SMV at 8 h (T) and the non-inoculated control (C) on the HiSeq2000 platform. In addition, we performed non-targeted metabolomic sequencing of leaves from the treatment and control groups. Results: We identified a total of 41,189 differentially expressed genes (DEGs). A total of 9809 differentially expressed genes (DEGs) met the criteria of |Log2FC (Fold Change)| ≥ 1 and adjusted p-value ≤ 0.001. Among the 41,189 DEGs identified, 9196 exhibited FPKM values greater than 10. KEGG pathway enrichment analysis of the 9809 DEGs revealed significant enrichment of genes involved in resistance-related pathways such as plant–pathogen interaction, linoleic acid metabolism, mitogen-activated protein kinase (MAPK) signaling pathway, and plant hormone signaling transduction. Functional analysis using MapMan software identified multiple DEGs that were associated with pathways such as jasmonate synthesis and phenylpropanoid biosynthesis. Weighted gene co-expression network analysis (WGCNA) using the differential metabolites and the 9196 DEGs revealed a strong correlation between gene clusters within the Turquoise module and the content of jasmonate-related metabolites. Further functional enrichment analysis of the 894 genes within the gene clusters showed a significant and repeated enrichment of pathways related to plant–pathogen interaction, linoleic acid metabolism, and plant hormone signaling transduction. Subsequent focused pathway analysis identified key genes involved in plant hormone signaling transduction pathways, such as the jasmonate ZIM domain protein Glyma.16G010000, the gene Glyma.01G235600 encoding the essential diterpene reductase required for jasmonate synthesis in the jasmonate biosynthesis pathway, and the transcription factor Glyma.02G232600 involved in the plant–pathogen interaction pathway, among others. This study provides a theoretical framework for understanding the resistance mechanism of soybean cultivar Dongnong 93-046 against the SMV N1 strain, offers potential gene resources for breeding soybean varieties with resistance to SMV, and paves the way for new strategies to control SMV infection, enhance resistance, and improve crop yield and quality.

What Outcomes Matter Most to Paediatric Burn Patients and Their Caregivers: A Comparison of Short-Term and Long-Term Priorities

Identifying outcomes that matter most is key in driving specialized paediatric burn care. The aim of this study was to discover the most important outcomes for paediatric burns. Parents of children (0–3 year and 4–11 years old) and adolescents (12–17 yearss old) completed surveys to identify outcomes that matter most in the short-term (<6 months postburn) and long-term (6–24 months postburn). The percentage of patients scoring an outcome as ‘very important’ was used to rank the outcomes. Fifty-four parents/adolescents participated (response rate: 27%). Children had a median TBSA burned of 5.0% (IQR: 2.0–7.0%). In the short-term, ‘good wound healing’ and ‘no wound infection’ (both at 71.4–100%) were very important for all children. ‘Not having pain’ (90.3–93.8%) was ranked highest for children ≤11 years old, whereas ‘walking or moving around’ (85.7%) was most important for older children. In the long-term, more variation was seen in outcome priorities; however, both ‘not having pain’ (53.6–85.7%) and ‘flexibility of scar(s)’ (60.7–71.4%) were considered very important by all three groups. Patient- and parent-derived priorities are important for developing consumer-centric, highest-value care pathways. The priority of the outcomes identified is a starting point to discuss treatment options and recovery priorities in a family-centric approach to guide high-value, individualized care.