Every repeat is unique: Exploring the genomic impact of human L1 retrotransposons at locus-specific resolution.

Fully understanding the impact of the human retrotransposon L1 requires that each of ∼500,000 L1 copies be evaluated as a potentially unique genomic entity. In this issue of Cell Genomics, Lanciano et al. strive toward this goal, illuminating the reciprocal regulatory influence between individual L1s and their genomic integration sites.

Microtissue Culture Provides Clarity on the Relative Chondrogenic and Hypertrophic Response of Bone-Marrow-Derived Stromal Cells to TGF-β1, BMP-2, and GDF-5.

Chondrogenic induction of bone-marrow-derived stromal cells (BMSCs) is typically accomplished with medium supplemented with growth factors (GF) from the transforming growth factor-beta (TGF-β)/bone morphogenetic factor (BMP) superfamily. In a previous study, we demonstrated that brief (1-3 days) stimulation with TGF-β1 was sufficient to drive chondrogenesis and hypertrophy using small-diameter microtissues generated from 5000 BMSC each. This biology is obfuscated in typical large-diameter pellet cultures, which suffer radial heterogeneity.

A systematic review of the cost-effectiveness of maternity models of care.

Objectives: In this systematic review, we aimed to identify the full extent of cost-effectiveness evidence available for evaluating alternative Maternity Models of Care (MMC) and to summarize findings narratively.

Methods: Articles that included a decision tree or state-based (Markov) model to explore the cost-effectiveness of an MMC, and at least one comparator MMC, were identified from a systematic literature review. The MEDLINE, Embase, Web of Science, CINAHL and Google Scholar databases were searched for papers published in English, Arabic, and French.

Effectiveness and cost-effectiveness of an electronic mindfulness-based intervention to improve maternal mental health in the peripartum: study protocol for a randomised controlled trial.

Background: Perinatal women are highly vulnerable to developing mental health issues and particularly susceptible to a recurrence of psychiatric illness. Poor mental health during the perinatal period can have long-term impacts on the physical and psychiatric health of both mother and child. A potentially useful strategy to improve women's mental health is through a mobile application teaching mindfulness, an evidence-based technique helping individuals focus on the present moment.

A novel monoclonal antibody against porcine macrophage colony-stimulating factor (CSF1) detects expression on the cell surface of macrophages.

Macrophage colony-stimulating factor (CSF1) controls the proliferation and differentiation of cells of the mononuclear phagocyte system through binding to the receptor CSF1R. The expression and function of CSF1 has been well-studied in rodents and humans, but knowledge is lacking in other veterinary species. The development of a novel mouse anti-porcine CSF1 monoclonal antibody (mAb) facilitates the characterisation of this growth factor in pigs.

Genetic models of fibrillinopathies.

The fibrillinopathies represent a group of diseases in which the 10-12 nm extracellular microfibrils are disrupted by genetic variants in one of the genes encoding fibrillin molecules, large glycoproteins of the extracellular matrix. The best-known fibrillinopathy is Marfan syndrome, an autosomal dominant condition affecting the cardiovascular, ocular, skeletal, and other systems, with a prevalence of around 1 in 3,000 across all ethnic groups. It is caused by variants of the FBN1 gene, encoding fibrillin-1, which interacts with elastin to provide strength and elasticity to connective tissues.

Locus-resolution analysis of L1 regulation and retrotransposition potential in mouse embryonic development.

Mice harbor ∼2800 intact copies of the retrotransposon Long Interspersed Element 1 (L1). The in vivo retrotransposition capacity of an L1 copy is defined by both its sequence integrity and epigenetic status, including DNA methylation of the monomeric units constituting young mouse L1 promoters. Locus-specific L1 methylation dynamics during development may therefore elucidate and explain spatiotemporal niches of endogenous retrotransposition but remain unresolved.

Recent developments in frailty identification, management, risk factors and prevention: A narrative review of leading journals in geriatrics and gerontology.

Frailty is an age-related clinical condition characterised by an increased susceptibility to stressors and an elevated risk of adverse outcomes such as mortality. In the light of global population ageing, the prevalence of frailty is expected to soar in coming decades. This narrative review provides critical insights into recent developments and emerging practices in frailty research regarding identification, management, risk factors, and prevention.

Reasons for Encounters and Comorbidities in Adolescents with Intellectual Disability in General Practice: A Retrospective Analysis of Data from the Ask Study.

Adolescents with intellectual disability have substantial health needs. This retrospective analysis of data from the Ask Study describes reasons for primary care encounters and the prevalence and incidence of chronic physical and mental conditions among a cohort of community-dwelling adolescents with intellectual disability. Participants attended secondary schools in southern Queensland, Australia.

MUC13 Cell Surface Mucin Limits Salmonella Typhimurium Infection by Protecting the Mucosal Epithelial Barrier.

Background & Aims: MUC13 cell surface mucin is highly expressed on the mucosal surface throughout the intestine, yet its role against bacterial infection is unknown. We investigated how MUC13 impacts Salmonella typhimurium (S Tm) infection and elucidated its mechanisms of action.

Methods: Muc13 and wild-type littermate mice were gavaged with 2 isogenic strains of S Tm after pre-conditioning with streptomycin.

Macrophage heterogeneity in the single-cell era: facts and artifacts.

In this spotlight, we review technical issues that compromise single-cell analysis of tissue macrophages, including limited and unrepresentative yields, fragmentation and generation of remnants, and activation during tissue disaggregation. These issues may lead to a misleading definition of subpopulations of macrophages and the expression of macrophage-specific transcripts by unrelated cells. Recognition of the technical limitations of single-cell approaches is required in order to map the full spectrum of tissue-resident macrophage heterogeneity and assess its biological significance.

Method for manufacture and cryopreservation of cartilage microtissues.

The financial viability of a cell and tissue-engineered therapy may depend on the compatibility of the therapy with mass production and cryopreservation. Herein, we developed a method for the mass production and cryopreservation of 3D cartilage microtissues. Cartilage microtissues were assembled from either 5000 human bone marrow-derived stromal cells (BMSC) or 5000 human articular chondrocytes (ACh) each using a customized microwell platform (the Microwell-mesh).

Self-control, limited willpower and decision fatigue in healthcare settings.

We argue that willpower as well as its depletion may, in some circumstances, adversely impact on clinical decision-making and patient care. This psychological phenomenon has been dubbed ego depletion in social psychology. Willpower and its depletion which is known as 'ego depletion' are well-established and validated theoretical constructs in social psychology and have been studied across a range of experimental contexts.

A Holistic Perspective on How Photobiomodulation May Influence Fatigue, Pain, and Depression in Inflammatory Bowel Disease: Beyond Molecular Mechanisms.

Background: Numerous mechanisms, mostly molecular, have been tested and proposed for photobiomodulation. Photobiomodulation is finding a niche in the treatment of conditions that have no gold-standard treatment or only partially effective pharmacological treatment. Many chronic conditions are characterised by symptoms for which there is no cure or control and for which pharmaceuticals may add to the disease burden through side effects.

Macrophage deficiency in CSF1R-knockout rat embryos does not compromise placental or embryo development.

Macrophages are an abundant cell population in the placenta and developing embryo and appear to be involved in processes of vascularization, morphogenesis, organogenesis, and hematopoiesis. The proliferation, differentiation, and survival are dependent on signals from the macrophage colony-stimulating factor receptor, CSF1R. Aside from the role in macrophages, Csf1r mRNA is highly expressed in placental trophoblasts.

Validation of a tool for determining the clinical utility of stillbirth investigations.

Background: Up to 20% of all stillbirths and 45% of term stillbirths are currently classified as unexplained. Many of these stillbirths do not undergo currently recommended investigations. This may leave questions unanswered and not identify stillbirths with a recurrence risk in subsequent pregnancies.

Endogenous retroviruses can propagate TDP-43 proteinopathy.

How does neurodegeneration spread in the brain? Leveraging TDP-43 fly models of amyotrophic lateral sclerosis (ALS), Chang and Dubnau recently reported that the endogenous retrovirus (ERV) mdg4 can trigger and transmit TDP-43 proteinopathy in vivo. Their results suggest that human ERVs could be targeted to develop future ALS therapies.

Fate-mapping studies in inbred mice: A model for understanding macrophage development and homeostasis?

The mononuclear phagocyte system (MPS) was defined in the early 1970s as a family of cells including progenitors, monocytes in the circulation, and resident tissue macrophages. They arise during development in three waves, in the yolk sac, fetal liver, and bone marrow. Fate-mapping studies using conditional reporter genes and regulated expression of cre recombinase have led to the view that most resident tissue macrophage populations are established during embryonic development and maintained in the adult by self-renewal with minimal input from bone marrow progenitors or blood monocytes.

Post-discharge consequences of protein-energy malnutrition, sarcopenia, and frailty in older adults admitted to rehabilitation: A systematic review.

Background & Aims: Malnutrition, sarcopenia, and frailty are three prevalent wasting conditions among older rehabilitation patients that lead to multiple health-related negative outcomes. This systematic review and meta-analysis aimed to determine the post-discharge consequences of malnutrition, sarcopenia, and frailty in older adults admitted to inpatient rehabilitation.

Methods: MEDLINE, Embase, Web of Science, and CINAHL databases were searched on 20 April, 2021 for longitudinal studies in older adults (≥65 years) admitted for inpatient rehabilitation.

Impact of retrotransposon protein L1 ORF1p expression on oncogenic pathways in hepatocellular carcinoma: the role of cytoplasmic PIN1 upregulation.

Background: Molecular characterisation of hepatocellular carcinoma (HCC) is central to the development of novel therapeutic strategies for the disease. We have previously demonstrated mutagenic consequences of Long-Interspersed Nuclear Element-1 (LINE1s/L1) retrotransposition. However, the role of L1 in HCC, besides somatic mutagenesis, is not well understood.

Use of psychotropic medications in adults with intellectual disability: A systematic review and meta-analysis.

Objective: This study presents the proportion of adults with intellectual disability using psychotropic medications including antipsychotics, antidepressants, anxiolytics, hypnotics and sedatives, and psychostimulants.

Methods: A search was performed in PubMed, Embase, PsycINFO, Web of Science, and Scopus up to 31 December 2021. Articles were included if they reported the proportion of adults with intellectual disability using psychotropic medications.