Limitations in Access to Dental and Medical Specialty Care for Publicly Insured Children

Medicaid and the state-run Children’s Health Insurance Program (CHIP) cover about 42 million children, many of whom would not have access to care without public insurance. Federal law requires that this access be equivalent to that of privately insured children for covered services, and many states have implemented policies to improve longstanding disparities in primary and preventive care. Reimbursement rates are up, but significant disparities remain, especially for dental and specialty services. It is important to understand the distinct effect of provider-related barriers, because they are potentially more modifiable through health policy than patient-related ones. This Issue Brief summarizes research that directly measures the willingness of dental and medical providers to see publicly-insured children, using research assistants posing as mothers calling for an urgent appointment for their child

Characterizing Emergency Department Discussions about Depression

Background: The reality of emergency health care in the United States today requires new approaches to mental health in the emergency department (ED). Major depression is a disabling condition that disproportionately affects women. Objectives: To characterize ED provider–patient discussions about depression. Methods: This was a secondary analysis of a database of audiotaped ED visits with women patients collected during a clinical trial of computer screening for domestic violence and other psychosocial risks. Nonemergent female patients, ages 18–65 years, were enrolled from two socioeconomically diverse academic EDs. All audio files with two or more relevant comments were identified as significant depression discussions and independently coded using a structured coding form. Results: Of 871 audiorecorded ED visits, 70 (8%) included discussions containing any reference to depression and 20 (2%) constituted significant depression discussions. Qualitative analysis of the 20 significant discussions found that 16 (80%) required less than 90 seconds to complete. Ten included less than optimal provider communication characteristics. Despite the brevity or quality of the communication, 15 of the 20 yielded high patient satisfaction with their ED treatment. Conclusions: ED providers rarely addressed depression. Qualitative analysis of significant patient– provider interactions regarding depression found that screening for depression in the ED can be accomplished with minimal expenditure of provider time and effort. Attention to psychosocial risk factors has the potential to improve the quality of ED care and patient satisfaction

Dose-Related Effects of Repeated ETC-216 (Recombinant Apolipoprotein A-IMilano/1-Palmitoyl-2-Oleoyl Phosphatidylcholine Complexes) Administrations on Rabbit Lipid-Rich Soft Plaques In Vivo Assessment by Intravascular Ultrasound and Magnetic Resonance Imaging

ObjectivesThis study sought to evaluate in vivo the minimal dose of apolipoprotein (apo) A-IMilano phospholipid complex (recombinant apoA-IMilano and 1-palmitoyl-2-oleoyl phosphatidylcholine complexes [ETC-216]) able to induce atherosclerosis regression in a rabbit model of lipid-rich plaques.BackgroundA single high dose of recombinant apoA-IMilano has promoted atherosclerosis regression in animal models. More recently, regression of atherosclerosis was achieved in coronary patients by repeated infusions of ETC-216.MethodsThirty-six rabbits underwent perivascular injury at both carotid arteries, followed by a 1.5% cholesterol diet. After 90 days, rabbits were randomly divided into 6 groups and treated 5 times with vehicle or ETC-216 at 5, 10, 20, 40, or 150 mg/kg dose every 4 days. Carotid plaque changes were evaluated in vivo by intravascular ultrasound (IVUS) and magnetic resonance imaging (MRI), performed before and at the end of treatments. Magnetic resonance imaging scans were also recorded after administration of the second dose for rabbits infused with vehicle 40 or 150 mg/kg.ResultsAtheroma volume in vehicle-treated rabbits increased dramatically between the first and the second IVUS analyses (+26.53%), whereas in ETC-216–treated animals, a reduced progression at the lower doses and a significant regression at the higher doses, up to −6.83%, was detected. Results obtained by MRI analysis correlated significantly with those at IVUS (r = 0.706; p < 0.0001). The MRI evaluations after the second infusion established that a significant regression was achieved with only 2 administrations of the highest dose.ConclusionsThese results confirm the efficacy of ETC-216 for atherosclerosis treatment and provide guidance for dose selection and frequency to obtain a significant reduction of plaque volume

Ionizable Amphiphilic Dendrimer-Based Nanomaterials with Alkyl-Chain-Substituted Amines for Tunable siRNA Delivery to the Liver Endothelium In Vivo

A library of dendrimers was synthesized and optimized for targeted small interfering RNA (siRNA) delivery to different cell subpopulations within the liver. Using a combinatorial approach, a library of these nanoparticle-forming materials was produced wherein the free amines on multigenerational poly(amido amine) and poly(propylenimine) dendrimers were substituted with alkyl chains of increasing length, and evaluated for their ability to deliver siRNA to liver cell subpopulations. Interestingly, two lead delivery materials could be formulated in a manner to alter their tissue tropism within the liver—with formulations from the same material capable of preferentially delivering siRNA to 1) endothelial cells, 2) endothelial cells and hepatocytes, or 3) endothelial cells, hepatocytes, and tumor cells in vivo. The ability to broaden or narrow the cellular destination of siRNA within the liver may provide a useful tool to address a range of liver diseases.National Institutes of Health (U.S.) Centers of Cancer and Nanotechnology Excellence (Grant U54 CA151884)Armed Forces Institute of Regenerative Medicine (Grant W81XWH-08-2-0034)Alnylam Pharmaceuticals (Firm

DNAJA1 controls the fate of misfolded mutant p53 through the mevalonate pathway

Stabilization of mutant p53 (mutp53) in tumours greatly contributes to malignant progression. However, little is known about the underlying mechanisms and therapeutic approaches to destabilize mutp53. Here, through high-throughput screening we identify statins, cholesterol-lowering drugs, as degradation inducers for conformational or misfolded p53 mutants with minimal effects on wild-type p53 (wtp53) and DNA contact mutants. Statins preferentially suppress mutp53-expressing cancer cell growth. Specific reduction of mevalonate-5-phosphate by statins or mevalonate kinase knockdown induces CHIP ubiquitin ligase-mediated nuclear export, ubiquitylation, and degradation of mutp53 by impairing interaction of mutp53 with DNAJA1, a Hsp40 family member. Knockdown of DNAJA1 also induces CHIP-mediated mutp53 degradation, while its overexpression antagonizes statin-induced mutp53 degradation. Our study reveals that DNAJA1 controls the fate of misfolded mutp53, provides insights into potential strategies to deplete mutp53 through the mevalonate pathway–DNAJA1 axis, and highlights the significance of p53 status in impacting statins’ efficacy on cancer therapy

Omega-3 PUFA metabolism and brain modifications during aging

In Canada, 5.5 million (16% of Canadians) adults are >65 years old and projections suggest this number will be approximately 20% of Canadians by 2024. A major concern regarding old age is a decline in health, especially if this entails a loss of self-sufficiency and independence caused by a decline in cognition. The brain contains 60% of fat and is one of the most concentrated organs in long chain omega-3 fatty acids such as docosahexaenoic acid (DHA). During aging, there are physiological modifications in the metabolism of lipids that could also have consequences on brain structure and levels of DHA. This review will hence discuss the physiological modifications in the metabolism of lipids during aging with a focus on long chain omega-3 and omega-6 fatty acids and also outline the structural and functional modifications of the brain during aging including brain lipid modifications and its relation to higher levels of DHA and cognition. Therefore, in this review, we outline the importance of collecting more data on the biology of aging since it might highly improve our understanding about what are «normal» modifications occurring during aging and what can become pathological

Plasma Cholesteryl Ester Transfer Protein (CETP) in Relation to Human Pathophysiology

Plasma CETP was initially isolated as a highly purified 74 kD protein. The human CETP gene is located at chromosome 16q13, near the locus of the lecithin cholesterol acyltransferase (LCAT) gene. The CETP gene consists of 16 exons, spanning 25 kb. The CETP mRNA encodes 476 amino acids. The mature CETP contains four N-linked sugars with a variable glycosylation site of 341Asn. CETP mRNA is expressed in various tissues, but liver cells, adipocytes, and macrophages are abundant sources. One of the determinants of high density lipoprotein (HDL) neutral lipid composition is plasma CETP. In incubated human plasma, transfer and equilibration of (LCAT)-generated cholesteryl ester (CE) is found. Humans, hamsters, guinea pigs, and chickens belong to a group with intermediate CETP activity. Plasma CETP binds neutral lipids CE or triglyceride (TG), and phospholipid (PL) on HDL3, but CETP selectively promotes an exchange of CE and TG among lipoproteins. On the one hand, HDL-TG can be hydrolyzed by hepatic lipase, and on the other hand, plasma CETP decreases HDL particle size via CE/TG exchange between chylomicron/VLDL and HDL. Thus, CETP thereby accelerates the catabolic rate of HDL apolipoproteins. CETP enhances HDL remodeling from large HDL to small subclasses including pre-HDL. However, CETP deficiency would decrease cholesterol esterification rate, thereby inhibiting maturation of preb-HDL to α-migrating spherical HDL. Therefore, in CETP deficiency, large-to-small HDL remodeling is decreased and preb-HDL catabolism is also decreased. © 2010 Elsevier Inc. All rights reserved.[Book Chapter

Navigating Rough Seas: Women on Waves’ Legal Options for Overcoming Resistant States

Women on Waves is a Dutch nonprofit that seeks to provide women with safe abortion services and health information, as well as to raise public awareness of countries with restrictive abortion laws. One of the means through which the group achieves these goals is its ship campaigns, in which Women on Waves sails a ship to the harbor of a country with restrictive laws, and then brings local women out to international waters to give them medical abortion pills. In 2017, Guatemala expelled the group’s ship from its dock before it had the chance to fulfill its mission, claiming that Women on Waves represented a threat to public order and security. This Comment examines possible legal actions that Women on Waves and/or Guatemalan women could pursue against Guatemala following this incident, including claims based on violations of the International Covenant on Civil and Political Rights and/or the American Convention on Human Rights, as well as the right to innocent passage in the law of the sea