Evaluation of subretinally delivered Cas9 ribonucleoproteins in murine and porcine animal models highlights key considerations for therapeutic translation of genetic medicines.

Genetic medicines, including CRISPR/Cas technologies, extend tremendous promise for addressing unmet medical need in inherited retinal disorders and other indications; however, there remain challenges for the development of therapeutics. Herein, we evaluate genome editing by engineered Cas9 ribonucleoproteins (eRNP) in vivo via subretinal administration using mouse and pig animal models. Subretinal administration of adenine base editor and double strand break-inducing Cas9 nuclease eRNPs mediate genome editing in both species.

Multi-omic Biomarkers Distinguish Rheumatoid Arthritis in Discordant Monozygotic Twins.

Background: Although genetic factors have been identified in the pathogenesis of rheumatoid arthritis (RA), the concordance rate in monozygotic (MZ) twins is low, suggesting that other features contribute to disease development. Further, the relative contribution of such non-genetic elements in identical twins have not been characterized. Here, we aimed to measure differentiating host and microbial biomarkers of RA by studying MZ twins discordant for disease using a multi-omics approach.

Stratifying Risk for Cognitive Decline in Older Adult Populations using the Geriatric Depression Scale.

Objectives: Late-life psychological symptoms in older adults such as depression and apathy have been increasingly associated with increased risk of cognitive and functional decline. The goal of this study was to conduct a confirmatory factor analysis of the Geriatric Depression Scale (GDS), pooling 3 unique cohorts of older adults to 1) develop a novel measurement model that distinguishes apathy from other domains of depression including dysphoria and cognitive concern and 2) evaluate if the measurement model distinguishes older adult populations with varied risk for cognitive decline.

Methods: We pooled the baseline waves of three older adult cohorts (N=1421).

Postoperative Opioid Reduction Using a Multimodal Pain Protocol for Outpatient Orthopaedic Sports Medicine Surgery.

Background: Orthopaedic surgery regularly employs opioids for postoperative pain management. Multimodal pain protocols have been shown to reduce opioid prescriptions in orthopaedic surgery.

Purpose: To analyze the impact of a division-level multimodal pain protocol for orthopaedic sports medicine surgery on opioid prescription reduction and pain level postoperatively.

One Hundred Years of Seeking Respectful Maternity Care: History and Evolution.

Growing awareness of poor maternal health outcomes and maternal health disparities in the United States has heightened urgency around the need to promote Respectful Maternity Care (RMC) as a fundamental tenet of obstetric/midwifery care and standardize efforts to improve safety, eliminate obstetric violence and racism, and optimize health outcomes for all birthing people. The historical context of prior and contemporary perspectives around childbirth influences our understanding of RMC and are shaped by varying scholarly, clinical, and community standards (e.g.

Screening and Supplementation for Iron Deficiency and Iron Deficiency Anemia During Pregnancy: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: In 2015 the US Preventive Services Task Force (USPSTF) found insufficient evidence to assess the balance of benefits and harms of routine screening and supplementation for iron deficiency anemia during pregnancy.

Objective: To update the 2015 review on screening for iron deficiency anemia, in addition to iron deficiency during pregnancy, to inform the USPSTF.

Data Sources: Ovid MEDLINE and Cochrane databases through May 24, 2023; surveillance through May 24, 2024.

LGBTQ-competent obesity prevention and management.

Obesity is a complex and largely preventable disease that is an enormous burden to patient health and to the healthcare system. Lesbian, gay, bisexual, transgender, and queer (LGBTQ) patients and their healthcare providers should be aware of their personal risks and causes of weight gain and obesity. Sensitive, comprehensive, and competent LGBTQ preventive care and treatment are needed to address the needs of this population, improve patient outcomes, and reduce healthcare inequalities.

Respectful Maternity Care : A Systematic Review.

Background: Severe maternal morbidity and mortality are worse in the United States than in all similar countries, with the greatest effect on Black women. Emerging research suggests that disrespectful care during childbirth contributes to this problem.

Purpose: To conduct a systematic review on definitions and valid measurements of respectful maternity care (RMC), its effectiveness for improving maternal and infant health outcomes for those who are pregnant and postpartum, and strategies for implementation.

High-performance polyimine vitrimers from an aromatic bio-based scaffold.

Bio-based vitrimers represent a promising class of thermosetting polymer materials, pairing the recyclability of dynamic covalent networks with the renewability of non-fossil fuel feedstocks. Vanillin, a low-cost lignin derivative, enables facile construction of polyimine networks marked by rapid exchange and sensitivity to acid-catalyzed hydrolysis. Furthermore, the aromatic structure makes it a promising candidate for the design of highly aromatic networks capable of high-performance thermal and dimensional stability.

Oral vancomycin treatment suppresses gut trypsin activity and preserves intestinal barrier function during EAE.

Studies have reported increased intestinal permeability in multiple sclerosis (MS) patients and its mouse model experimental autoimmune encephalomyelitis (EAE). However, the mechanisms driving increased intestinal permeability that in turn exacerbate neuroinflammation during EAE remain unclear. Here we showed that vancomycin preserved the integrity of the intestinal barrier, while also suppressing gut trypsin activity, enhancing the relative abundance of specific and ameliorating disease during EAE.

Characterisation of a novel missense mutation in the gene leading to group G xeroderma pigmentosum/Cockayne syndrome overlap.

Xeroderma pigmentosum-Cockayne syndrome complex (XP-CS) is exceedingly rare, with 43 cases described over the past five decades; 21 of these cases exhibited mutations in the ERCC5 endonuclease associated with xeroderma pigmentosum, group G.We report the first known phenotypic characterisation of the homozygous chromosome 13 , Exon 11, c.2413G>A (p.

The effect of psychosocial stress on prenatal care among Hispanic immigrant women.

This article explores the effect of psychosocial stress on Hispanic immigrant women, including access to and use of prenatal care and birth outcomes. In addition to highlighting the health effects for this growing population, the article outlines strategies for clinicians to improve access to adequate prenatal care and to cultivate a supportive environment to promote use of prenatal services.

Gut and oral microbiome modulate molecular and clinical markers of schizophrenia-related symptoms: A transdiagnostic, multilevel pilot study.

Although increasing evidence links microbial dysbiosis with the risk for psychiatric symptoms through the microbiome-gut-brain axis (MGBA), the specific mechanisms remain poorly characterized. In a diagnostically heterogeneous group of treated psychiatric cases and nonpsychiatric controls, we characterized the gut and oral microbiome, plasma cytokines, and hippocampal inflammatory processes via proton magnetic resonance spectroscopic imaging (H-MRSI). Using a transdiagnostic approach, these data were examined in association with schizophrenia-related symptoms measured by the Positive and Negative Syndrome Scale (PANSS).

Risk of Gastroenteritis from Swimming at a Wastewater-Impacted Tropical Beach Varies across Localized Scales.

Population growth and changing climate are expected to increase human exposure to pathogens in tropical coastal waters. We examined microbiological water quality in three rivers within 2.3 km of each other that impact a Costa Rican beach and in the ocean outside their plumes during the rainy and dry seasons.

"": Rethinking Obstetric Violence in Costa Rica.

Obstetric violence is an emergent paradigm that uses gender-based violence to frame traumatic childbirth. Despite its growing popularity in the literature, it may not adequately address the nuanced ways that all actors experience these interactions. While Costa Rica adopted a nationally endorsed humane birthing policy, the semi-structured interviews on which I draw in this article show that health care personnel continue to dehumanize and objectify women; experiences considered characteristic of obstetric violence.

Telehealth for Women's Preventive Services for Reproductive Health and Intimate Partner Violence: a Comparative Effectiveness Review.

Background: Telehealth delivery of preventive health services may improve access to care; however, its effectiveness and adverse effects are unknown. We conducted a comparative effectiveness review on the effectiveness and harms of telehealth interventions for women's reproductive health and intimate partner violence (IPV) services.

Methods: We searched MEDLINE, Cochrane Library, CINAHL, and Scopus for English-language studies (July 2016 to May 2022) for randomized controlled trials (RCTs) and observational studies of telehealth strategies for women's reproductive health and IPV versus usual care.