Acute confusion in pregnancy.

If a woman is acutely confused in pregnancy, she will most likely present to an unscheduled care setting outside of maternity services. It is therefore essential that all clinicians working within general medicine are comfortable assessing pregnant women in this context. Useful resources are available to support assessing pregnant women who present acutely; however, confusion is beyond their scope.

Medical Diseases in Pregnancy: An Acute on Chronic Focus.

In the last decade or so obstetric care has evolved and become more complex. This can be attributed to a combination of factors including rising obesity rates, maternal age and medical treatment advances. Clinicians are caring for more pregnant women with chronic medical disease in addition to any de novo presentations which may occur, emphasising the need for the general medicine body to feel confident and skilled in the management of medical problems before, during and after pregnancy.

Benchmarking for healthy food stores: protocol for a randomised controlled trial with remote Aboriginal and Torres Strait Islander communities in Australia to enhance adoption of health-enabling store policy and practice.

Background: Aboriginal and Torres Strait Islander communities in remote Australia have initiated bold policies for health-enabling stores. Benchmarking, a data-driven and facilitated 'audit and feedback' with action planning process, provides a potential strategy to strengthen and scale health-enabling best-practice adoption by remote community store directors/owners. We aim to co-design a benchmarking model with five partner organisations and test its effectiveness with Aboriginal and Torres Strait Islander community stores in remote Australia.

JAK inhibition decreases the autoimmune burden in Down syndrome.

Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmune disorders and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined. Here, we report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS.

A gene edited pig model for studying LGR5 stem cells: implications for future applications in tissue regeneration and biomedical research.

Recent advancements in genome editing techniques, notably CRISPR-Cas9 and TALENs, have marked a transformative era in biomedical research, significantly enhancing our understanding of disease mechanisms and helping develop novel therapies. These technologies have been instrumental in creating precise animal models for use in stem cell research and regenerative medicine. For instance, we have developed a transgenic pig model to enable the investigation of LGR5-expressing cells.

Development of a survey tool to assess the environmental determinants of health-enabling food retail practice in Aboriginal and Torres Strait Islander communities of remote Australia.

Background: Environmental factors can impact the ability of food retail businesses to implement best practice health-enabling food retail.

Methods: We co-designed a short-item survey on factors influencing food retail health-enabling practice in a remote Australian setting. Publicly available submissions to an Australian Parliamentary Inquiry into food pricing and food security in remote Indigenous communities were coded using an existing remote community food systems assessment tool and thematically analysed.

Corrigendum: Genome-wide association study of motor coordination.

[This corrects the article DOI: 10.3389/fnhum.2021.

Proteasome Inhibition Sensitizes Liposarcoma to MDM2 Inhibition with Nutlin-3 by Activating the ATF4/CHOP Stress Response Pathway.

Unlabelled: Liposarcoma is the most commonly occurring soft-tissue sarcoma and is frequently characterized by amplification of chromosome region 12q13-15 harboring the oncogenes MDM2 and CDK4. This unique genetic profile makes liposarcoma an attractive candidate for targeted therapeutics. While CDK4/6 inhibitors are currently employed for treatment of several cancers, MDM2 inhibitors have yet to attain clinical approval.

Efficacious cellular therapy of descemetocele in a dog.

The cornea is comprised of 4 layers; the outermost layer is the epithelium, followed by the stroma, Descemet's membrane, and endothelium. Corneal descemetocele is a serious consequence of progressive corneal ulceration, characterized by a herniation of the Descemet membrane through an overlying stromal defect. It requires urgent intervention due to the risk of perforation.

Mertk: An emerging target in cancer biology and immuno-oncology.

Mertk, a type I Receptor Tyrosine Kinase (RTK) and member of the TAM (Tyro3, Axl, and Mertk) family of homologous tyrosine kinases, has important roles in signal transduction both homeostatically on normal cells as well as patho-physiologically on both tumor-associated macrophages and malignant cells by its overexpression in a wide array of cancers. The main ligands of Mertk are Vitamin K-modified endogenous proteins Gas6 and Protein S (ProS1), heterobifunctional modular proteins that bind Mertk via two carboxyl-terminal laminin-like globular (LG) domains, and an N-terminal Gla domain that binds anionic phospholipids, whereby externalized phosphatidylserine (PS) on stressed viable and caspase-activated apoptotic cells is most emblematic. Recent studies indicate that Vitamin K-dependent γ-carboxylation on the N-terminal Gla domain of Gas6 and Protein S is necessary for PS binding and Mertk activation, implying that Mertk is preferentially active in tissues where there is high externalized PS, such as the tumor microenvironment (TME) and acute virally infected tissues.

The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Home-based antibody testing results, October 2020. An emphasis on self-screening at a population level.

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992 and has followed these women, their partners (Generation 0; G0) and offspring (Generation 1; G1) ever since. The study reacted rapidly to the COVID-19 pandemic, deploying online questionnaires in March and May 2020. Home-based antibody tests and a further questionnaire were sent to 5220 participants during a two-week period of October 2020.

The Pasifika Veilomani Project: a pilot online training programme for healthcare workers in managing gender-based violence and family violence and sharing experiences.

Objective: Pacific Island Countries (PICs) record high rates of gender-based violence (GBV). COVID-19 has significantly increased the number of GBV cases globally. This research aims to understand educational pathways for PICs' healthcare workers (HCWs) to strengthen GBV clinical practices in the Pasifika Veilomani (sharing the love) project.

Genome-Wide Association Study of Motor Coordination.

The ability to finely control our movement is key to achieving many of the educational milestones and life-skills we develop throughout our lives. Despite the centrality of coordination to early development, there is a vast gap in our understanding of the underlying biology. Like most complex traits, both genetics and environment influence motor coordination, however, the specific genes, early environmental risk factors and molecular pathways are unknown.

Dysregulated Gene Expression of Imprinted and X-Linked Genes: A Link to Poor Development of Bovine Haploid Androgenetic Embryos.

Mammalian uniparental embryos are efficient models for genome imprinting research and allow studies on the contribution of the paternal and maternal genomes to early embryonic development. In this study, we analyzed different methods for production of bovine haploid androgenetic embryos (hAE) to elucidate the causes behind their poor developmental potential. Results indicate that hAE can be efficiently generated by using intracytoplasmic sperm injection and oocyte enucleation at telophase II.

If it ain't broke don't fix it: Lack of review of antimicrobials in 'well' patients - time for a CRP change.

Introduction: The rising prevalence of multi-resistant organisms threatens the efficacy of current antimicrobial treatments. Antibiotic stewardship is a key factor in slowing the development of resistance and must become part of a clinician's regular practice. National guidance unanimously emphasises the importance of a 48-hour review of antimicrobial prescriptions.

Multi-level evidence of an allelic hierarchy of USH2A variants in hearing, auditory processing and speech/language outcomes.

Language development builds upon a complex network of interacting subservient systems. It therefore follows that variations in, and subclinical disruptions of, these systems may have secondary effects on emergent language. In this paper, we consider the relationship between genetic variants, hearing, auditory processing and language development.

PIP4Ks Suppress Insulin Signaling through a Catalytic-Independent Mechanism.

Insulin stimulates the conversion of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P) to phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P), which mediates downstream cellular responses. PI(4,5)P is produced by phosphatidylinositol-4-phosphate 5-kinases (PIP5Ks) and by phosphatidylinositol-5-phosphate 4-kinases (PIP4Ks). Here, we show that the loss of PIP4Ks (PIP4K2A, PIP4K2B, and PIP4K2C) in vitro results in a paradoxical increase in PI(4,5)P and a concomitant increase in insulin-stimulated production of PI(3,4,5)P.

Applications of mesenchymal stem cell technology in bovine species.

Mesenchymal stem cells (MSCs) have received a great deal of attention over the past 20 years mainly because of the results that showed regeneration potential and plasticity that were much stronger than expected in prior decades. Recent findings in this field have contributed to progress in the establishment of cell differentiation methods, which have made stem cell therapy more clinically attractive. In addition, MSCs are easy to isolate and have anti-inflammatory and angiogenic capabilities.

Derivation and Differentiation of Canine Ovarian Mesenchymal Stem Cells.

Interest in mesenchymal stem cells (MSCs) has increased over the past decade due to their ease of isolation, expansion, and culture. Recently, studies have demonstrated the wide differentiation capacity that these cells possess. The ovary represents a promising candidate for cell-based therapies due to the fact that it is rich in MSCs and that it is frequently discarded after ovariectomy surgeries as biological waste.

MERTK inhibition alters the PD-1 axis and promotes anti-leukemia immunity.

MERTK is ectopically expressed and promotes survival in acute lymphoblastic leukemia (ALL) cells and is thus a potential therapeutic target. Here we demonstrate both direct therapeutic effects of MERTK inhibition on leukemia cells and induction of anti-leukemia immunity via suppression of the coinhibitory PD-1 axis. A MERTK-selective tyrosine kinase inhibitor, MRX-2843, mediated therapeutic anti-leukemia effects in immunocompromised mice bearing a MERTK-expressing human leukemia xenograft.

Bazedoxifene/conjugated estrogens in combination with leuprolide for the treatment of endometriosis.

Bazedoxifene/conjugated estrogens can be used with leuprolide as effective add-back therapy in premenopausal women with endometriosis without unwanted stimulation of the breasts, CNS (Central Nervous System), or endometrium. Bazedoxifene/conjugated estrogens may be an effective progestin-free alternative to traditional add-back therapies.

CDK8 Kinase Activity Promotes Glycolysis.

Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancerous tissues. Despite its importance in cancer development, our understanding of mechanisms driving this form of metabolic reprogramming is incomplete. We report here an analysis of colorectal cancer cells engineered to carry a single point mutation in the active site of the Mediator-associated kinase CDK8, creating hypomorphic alleles sensitive to bulky ATP analogs.

LEAN SIX SIGMA TECHNIQUES TO IMPROVE OPHTHALMOLOGY CLINIC EFFICIENCY.

Purpose: Ophthalmologists serve an increasing volume of a growing elderly population undergoing increasingly complex outpatient medical care, including extensive diagnostic testing and treatment. The resulting prolonged patient visit times ("patient flow times") limit quality, patient and employee satisfaction, and represent waste. Lean Six Sigma process improvement was used in a vitreoretinal practice to decrease patient flow time, demonstrating that this approach can yield significant improvement in health care.