An mRNA-encoded dominant-negative inhibitor of transcription factor RUNX1 suppresses vitreoretinal disease in experimental models.

Messenger RNA (mRNA)-based therapies are a promising approach to medical treatment. Except for infectious diseases, no other disease has mRNA-based therapies available. The eye is an ideal model for mRNA therapeutic development because it requires limited dosing.

Loss of the Endothelial Glycocalyx Component EMCN Leads to Glomerular Impairment.

Background: EMCN (endomucin), an endothelial-specific glycocalyx component, was found to be highly expressed by the endothelium of the renal glomerulus. We reported an anti-inflammatory role of EMCN and its involvement in the regulation of VEGF (vascular endothelial growth factor) activity through modulating VEGFR2 (VEGF receptor 2) endocytosis. The goal of this study is to investigate the phenotypic and functional effects of EMCN deficiency using the first global EMCN knockout mouse model.

Deletion of the endothelial glycocalyx component endomucin leads to impaired glomerular structure and function.

Background: Endomucin (EMCN), an endothelial-specific glycocalyx component, was found to be highly expressed by the endothelium of the renal glomerulus. We reported an anti-inflammatory role of EMCN and its involvement in the regulation of vascular endothelial growth factor (VEGF) activity through modulating VEGF receptor 2 (VEGFR2) endocytosis. The goal of this study is to investigate the phenotypic and functional effects of EMCN deficiency using the first global EMCN knockout mouse model.

APOE Christchurch-mimetic therapeutic antibody reduces APOE-mediated toxicity and tau phosphorylation.

Introduction: We discovered that the APOE3 Christchurch (APOE3Ch) variant may provide resistance to Alzheimer's disease (AD). This resistance may be due to reduced pathological interactions between ApoE3Ch and heparan sulfate proteoglycans (HSPGs).

Methods: We developed and characterized the binding, structure, and preclinical efficacy of novel antibodies targeting human ApoE-HSPG interactions.

Resilience to autosomal dominant Alzheimer's disease in a Reelin-COLBOS heterozygous man.

We characterized the world's second case with ascertained extreme resilience to autosomal dominant Alzheimer's disease (ADAD). Side-by-side comparisons of this male case and the previously reported female case with ADAD homozygote for the APOE3 Christchurch (APOECh) variant allowed us to discern common features. The male remained cognitively intact until 67 years of age despite carrying a PSEN1-E280A mutation.

Stigma as a Source of Stress for Adolescent Mothers and Their Babies.

Adolescent pregnancy and the babies of teen mothers have been a focus of attention and concern for many years. The literature on the health of pregnant and parenting teens, however, is largely silent about the impact of stigma on them and their children. Stigma is a pervasive cultural attitude, which leads us to overlook potentially good outcomes for this vulnerable population and contributes to poor outcomes for these mothers and babies.

Toward Evaluation in Public Services: Getting Past the Barriers.

Evaluation of public programs in mental health and in other fields is often blocked when "reasons not to" are cited. These include "HIPAA," "IRB," "not my job," "it's already evidence based," "we know what's right," "we don't know enough," "we don't have baseline data," and "there's too much to do." Examining these reasons, the values thought to justify them, and possible ways to respond will facilitate evaluation research.

Being with the patient: the use of "clinical evidence," reconsidered.

Our objective was to review the use in psychiatry of data arising from interaction with the patient, here called "clinical evidence." We conducted a clinical and historical review. Data from interactions with patients are increasingly marginalized in psychiatry, even as interactional data have an increasing role elsewhere in healthcare.

Child and adolescent mental health policy: promise to provision.

Mental health policy enables the translation of the knowledge base of 'how' to help children and families into the actual 'provision' of help. Amid competing pressures to leave the allocation of services to the market, policy is required to define needs, select priorities, match resources with need, and to measure what has been accomplished. Crafting policy requires balancing contrasting goals and approaches, here spelled out.

Case study: the internet as a developmental tool in an adolescent boy with psychosis.

The Internet has become an increasingly important part of teen culture; however, there still remains little in the medical/psychiatric literature pertaining to the impact of the Internet on adolescent development. Despite the potential problems associated with communication online, the Internet offers a variety of positive opportunities for teens. In this report, we present a case study that illustrates the Internet as a helpful tool in a 15-year-old adolescent boy with a history of chronic neurological illness accompanied by refractory psychosis.

Child and adolescent inpatient restraint reduction: a state initiative to promote strength-based care.

Objective: To reduce the use of restraint and seclusion with children and adolescents in psychiatric inpatient units by promoting a preventive, strength-based model of care.

Method: The State Mental Health Authority used data analysis, quality improvement strategies, regulatory oversight, and technical assistance to develop and implement system change over a 22-month period. No changes in regulation or policy were undertaken.

Alliance formation with parents: limit-setting and the effect of mandated reporting.

The ability of parents to cooperate in their children's treatment is not fixed, but is a potential that evolves in a clinical relationship. Such clinical work includes a hierarchy of limit-setting, ranging from education to legal intervention. The experience of an inpatient child psychosomatic service indicates that such limit-setting was relevant in more than 50% of cases, and served to enhance the alliance with parents and children.