Land use change threatens global biodiversity and compromises ecosystem functions, including pollination and food production. Reduced taxonomic α-diversity is often reported under land use change, yet the impacts could be different at larger spatial scales (i.e.
View Article and Find Full Text PDFThe Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNALP) is essential for the immortalization of naive B lymphocytes (NBLs). However, the mechanisms remain elusive. To understand EBNALP's role in B-cell transformation, we compare NBLs infected with wild-type EBV and an EBNALP-null mutant EBV using multi-omics techniques.
View Article and Find Full Text PDFFront Pharmacol
November 2024
The clinical drug-drug interaction side-effects of Ritonavir, an ingredient in Paxlovid™, have been documented, highlighting the need to explore alternative administration methods for Nirmatrelvir, another drug in the Paxlovid™ combination. In this study, the skin permeability potential of Nirmatrelvir was assessed using various models. The prediction results suggest that Nirmatrelvir could be administrated via the transdermal route, offering a promising avenue to enhance the efficacy of anti-COVID-19 agents.
View Article and Find Full Text PDFPurpose: Intravitreal delivery of therapeutic transgenes to the retina via engineered viral vectors can provide sustained local concentrations of therapeutic proteins and thus potentially reduce the treatment burden and improve long-term vision outcomes for patients with neovascular (wet) age-related macular degeneration (AMD), diabetic macular edema (DME), and diabetic retinopathy.
Methods: We performed directed evolution in nonhuman primates (NHP) to invent an adeno-associated viral (AAV) variant (R100) with the capacity to cross vitreoretinal barriers and transduce all regions and layers of the retina following intravitreal injection. We then engineered 4D-150, an R100-based genetic medicine carrying 2 therapeutic transgenes: a codon-optimized sequence encoding aflibercept, a recombinant protein that inhibits VEGF-A, VEGF-B, and PlGF, and a microRNA sequence that inhibits expression of VEGF-C.
Background: Karyomegalic interstitial nephritis (KIN) is a rare renal diagnosis associated with both genetic and medication etiologies. The primary gene associated with KIN is the FAN1 gene which encodes a protein responsible for DNA interstrand repair. Common medication triggers of KIN are chemotherapeutic agents, especially those which disrupt DNA structure such as carboplatin.
View Article and Find Full Text PDFDelayed gastric emptying increases the risk of pulmonary aspiration during anaesthesia for Caesarean delivery. Our aim in conducting this narrative review was to consider the effect of pregnancy on gastric emptying. The indices of gastric emptying after liquids, solids, or both and when fasted in the various trimesters of pregnancy, at the time of Caesarean delivery, in labour, and the postpartum period were assessed.
View Article and Find Full Text PDFBörjeson-Forssman-Lehmann syndrome (BFLS) is an X-linked intellectual disability and endocrine disorder caused by pathogenic variants of plant homeodomain finger gene 6 (PHF6). An understanding of the role of PHF6 in vivo in the development of the mammalian nervous system is required to advance our knowledge of how PHF6 mutations cause BFLS. Here, we show that PHF6 protein levels are greatly reduced in cells derived from a subset of patients with BFLS.
View Article and Find Full Text PDFBackground: Adolescent idiopathic scoliosis (AIS) corrective surgery may involve significant blood loss and blood transfusion requirements. Antifibrinolytic agents such as tranexamic acid (TXA) have been used to reduce blood loss, but its optimal dose is uncertain. The objective of this study is to determine the estimated blood loss and rate of blood transfusion between two groups of AIS patients receiving TXA as a single bolus versus bolus followed by infusion in scoliosis surgery.
View Article and Find Full Text PDFBackground: Comprehensive infection prevention and control (IPC) programmes are proven to reduce the spread of healthcare-associated infections (HAIs) and antimicrobial resistance (AMR). However, published assessments of IPC programmes against the World Health Organization (WHO) IPC Core Components in Pacific Island Countries and Territories (PICTs) at the national and acute healthcare facility level are currently unavailable.
Methods: From January 2022 to April 2023, a multi-country, cross-sectional study was conducted in PICTs.
Time-restricted feeding (TRF) is a popular dietary strategy whereby daily food intake is limited to a <12h window. As little is known about the effects of TRF on cognitive and behavioral measures, the present study examined the effects of time-restricted (8h/day; zeitgeber time [ZT]12-20) or continuous access to a high-fat, high-sugar cafeteria-style diet (Caf; Caf and Caf-TRF groups; n=12 adult male Sprague-Dawley rats) or standard chow (Chow and Chow-TRF groups) on short-term memory, anxiety-like behavior, adiposity and gut microbiota composition over 13-weeks with daily food intake measures. TRF significantly reduced daily energy intake in Caf- but not chow-fed groups.
View Article and Find Full Text PDFObjectives: Continuous subcutaneous infusions (CSCIs) are indicated as an alternative therapy when the oral route is not viable. However, despite their widespread use in palliative care, the evidence for admixture compatibility remains a limitation. It is estimated that a significant number of admixtures used in practice are not supported by laboratory studies, which may lead to suboptimal clinical outcomes.
View Article and Find Full Text PDFNanoparticle-mediated mRNA delivery has emerged as a promising therapeutic modality, but its growth is still limited by the discovery and optimization of effective and well-tolerated delivery strategies. Lipid nanoparticles containing charged or ionizable lipids are an emerging standard for in vivo mRNA delivery, so creating facile, tunable strategies to synthesize these key lipid-like molecules is essential to advance the field. Here, we generate a library of N-substituted glycine oligomers, peptoids, and undertake a multistage down-selection process to identify lead candidate peptoids as the ionizable component in our Nutshell nanoparticle platform.
View Article and Find Full Text PDFBMC Complement Med Ther
July 2024
Wound is defined as the damage to biological tissues including skin, mucous membranes and organ tissues. The acute wound heals in less than 4 weeks without complications, while a chronic wound takes longer than 6 weeks to heal. Wound healing occurs in 4 phases, namely, coagulation, inflammatory, proliferative and remodeling phases.
View Article and Find Full Text PDFBackground: Post-Transplant Diabetes Mellitus (PTDM) affects 20%-40% of lung transplant recipients within five years, impacting rejection, infection, cardiovascular events, and mortality. Continuous glucose monitoring (CGM) is used in diabetes but not well-studied in PTDM.
Objective: This study assessed CGM performance in detecting hypoglycemia and hyperglycemia post-lung transplantation, compared to self-monitoring blood glucose.
Western Pac Surveill Response J
July 2024
Problem: In January 2022, Kiribati experienced widespread community transmission of COVID-19, leading to high rates of infection among health-care workers (HCWs), which reduced essential HCWs during a period of increased hospital admissions.
Context: Kiribati, a Pacific island country made up of a remote group of 33 low-lying atolls in the Pacific Ocean, experienced its first surge of COVID-19 cases beginning on 24 January 2022.
Action: Reports of increasing numbers of COVID-19 cases in South Tarawa prompted the Kiribati Ministry of Health and Medical Services to request assistance from the international community, including the World Health Organization's Global Outbreak Alert and Response Network (GOARN), to support national COVID-19 response operations.
Purpose: Cancer center clinical trial offices (CCTOs) support trial development, activation, conduct, regulatory adherence, data integrity, and compliance. In 2018, the Association of American Cancer Institutes (AACI) Clinical Research Innovation (CRI) Steering Committee conducted and published survey results to benchmark North American CCTOs, including trial volume, accrual, full time equivalents (FTEs), and budget. The survey was readministered in 2023 to assess contemporary CCTO performance and capacity with results presented here.
View Article and Find Full Text PDFBackground And Objectives: Endovascular therapy (EVT) for stroke has emerged as an important therapy for selected stroke patients, and shorter times to clot removal improve functional outcomes. EVT requires the close coordination of multiple departments and poses unique challenges to care coordination in large hospitals. We present the results of our quality improvement project that aimed to improve our door-to-groin puncture (DTP) times for patients who undergo EVT after direct presentation to our emergency department.
View Article and Find Full Text PDFProblem: Coronavirus disease (COVID-19) reached Tuvalu's shores in November 2022, making Tuvalu one of the last countries in the world to experience community transmission of the disease. With minimal capacity to deliver critical care and a small health workforce that had been further depleted by COVID-19 infection, response priorities rapidly shifted to the outer islands.
Context: The outer islands are accessible only by boat, with travel taking from 6 to 24 hours.
Tetralogy of Fallot is the most prevalent cyanotic congenital heart disease, requiring lifelong multimodality non-invasive cardiac imaging, such as echocardiography, cardiothoracic computed tomography, and cardiac magnetic resonance imaging. As imaging techniques continuously evolve and are gradually integrated into clinical practice, there is a critical need to update multimodality imaging protocols. Over the last two decades, cardiothoracic computed tomography imaging techniques have advanced remarkably, significantly enhancing its role in evaluating patients with tetralogy of Fallot.
View Article and Find Full Text PDFHuman cytomegalovirus (HCMV) infects up to 80% of the world's population. Here, we show that HCMV infection leads to widespread changes in human chromatin accessibility and chromatin looping, with hundreds of thousands of genomic regions affected 48 hours after infection. Integrative analyses reveal HCMV-induced perturbation of Hippo signaling through drastic reduction of TEAD1 transcription factor activity.
View Article and Find Full Text PDFUnlabelled: The coronavirus disease 2019 pandemic illustrates the importance of understanding the behavior and control of human pathogenic viruses in the environment. Exposure via water (drinking, bathing, and recreation) is a known route of transmission of viruses to humans, but the literature is relatively void of studies on the persistence of many viruses, especially coronaviruses, in water and their susceptibility to chlorine disinfection. To fill that knowledge gap, we evaluated the persistence and free chlorine disinfection of human coronavirus OC43 (HCoV-OC43) and its surrogates, murine hepatitis virus (MHV) and porcine transmissible gastroenteritis virus (TGEV), in drinking water and laboratory buffer using cell culture methods.
View Article and Find Full Text PDFBackground: There are two major genetic types of Epstein-Barr Virus (EBV): type 1 (EBV-1) and type 2 (EBV-2). EBV functions by manipulating gene expression in host B cells, using virus-encoded gene regulatory proteins including Epstein-Barr Nuclear Antigen 2 (EBNA2). While type 1 EBNA2 is known to interact with human transcription factors (hTFs) such as RBPJ, EBF1, and SPI1 (PU.
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