Preservation of All Chordae Tendineae and Papillary Muscle During Mitral Valve Replacement with a Tilting Disc Valve

Mitral valve replacement was performed in 21 patients using a surgical technique that preserves the entire papillary muscle and chordal apparatus. With this technique, the anterior mitral leaflet is split from the center of the free edge toward the annulus. Bilateral incisions are made from the proximal end of this split to the two mitral commissures, detaching the anterior leaflet from the annulus. These two halves of the leaflet, with all chordae intact (corresponding to the anterolateral and posteromedial papillary muscles), are judiciously trimmed to remove areas of leaflet untethered by chordae tendineae and (when necessary) fibrous thickening; then swung posteriorly and sutured to the posterior mitral annulus using mattress sutures with pledgets. This surgical technique is expected to favor the preservation of left ventricular function and avoid occurrence of irreversible left ventricular dilation/dysfunction, and has been used successfully for calcific and degenerative etiologies, using both tilting disc valves and porcine bioprostheses. It is especially useful in the implantation of tilting disc and bileaflet mechanical prostheses because anterior subvalvular chordae tissue may interfere with the disc excursion and relocated to the posterior leaflet annulus.     

Legal Protections in Public Accommodations Settings: A Critical Public Health Issue for Transgender and Gender‐Nonconforming People

Context

Gender minority people who are transgender or gender nonconforming experience widespread discrimination and health inequities. Since 2012, Massachusetts law has provided protections against discrimination on the basis of gender identity in employment, housing, credit, public education, and hate crimes. The law does not, however, protect against discrimination in public accommodations (eg, hospitals, health centers, transportation, nursing homes, supermarkets, retail establishments). For this article, we examined the frequency and health correlates of public accommodations discrimination among gender minority adults in Massachusetts, with attention to discrimination in health care settings.

Methods

In 2013, we recruited a community-based sample (n = 452) both online and in person. The respondents completed a 1-time, electronic survey assessing demographics, health, health care utilization, and discrimination in public accommodations venues in the past 12 months. Using adjusted multivariable logistic regression models, we examined whether experiencing public accommodations discrimination in health care was independently associated with adverse self-reported health, adjusting for discrimination in other public accommodations settings.

Findings

Overall, 65% of respondents reported public accommodations discrimination in the past 12 months. The 5 most prevalent discrimination settings were transportation (36%), retail (28%), restaurants (26%), public gatherings (25%), and health care (24%). Public accommodations discrimination in the past 12 months in health care settings was independently associated with a 31% to 81% increased risk of adverse emotional and physical symptoms and a 2-fold to 3-fold increased risk of postponement of needed care when sick or injured and of preventive or routine health care, adjusting for discrimination in other public accommodations settings (which also conferred an additional 20% to 77% risk per discrimination setting endorsed).

Conclusions

Discrimination in public accommodations is common and is associated with adverse health outcomes among transgender and gender-nonconforming adults in Massachusetts. Discrimination in health care settings creates a unique health risk for gender minority people. The passage and enforcement of transgender rights laws that include protections against discrimination in public accommodations—inclusive of health care—are a public health policy approach critically needed to address transgender health inequities.     

Preparation and properties of Nα-Bpoc-amino acid pentafluorophenyl esters

The preparation and properties are reported of several N^x-Bpoc -amino acid pentafluorophenyl esters, including those bearing tert-butyl-, allyl- and trityl-based protecting groups. These derivatives have been used in the solid-phase peptide synthesis of sevral short peptides.     

A DNA vaccine protects mice against the rickettsial agent Cowdria ruminantium

A DNA vaccine (VCL1010/MAP1) containing the major antigenic protein 1 (MAP1) gene of Cowdria ruminantium , driven by the human cytomegalovirus (HCMV) enhancer-promoter, was injected intramuscularly into 8–10 week-old female DBA/2 mice after treating them with 50 μl/muscle of 0.5% bupivacaine three days previously. Up to 75% of the immunized mice seroconverted and reacted with C. ruminantium antigen blots. Splenocytes from immunized mice, but not from control mice, proliferated in response to the recombinant MAP1 and to C. ruminantium antigens in in vitro lymphocyte proliferation tests. These proliferating cells secreted IFN-gamma and IL-2 at concentrations ranging from 610 pg/ml to 1290 pg/ml and from 152 pg/ml to 310 pg/ml, respectively. Only up to 45 pg/ml and 42 pg/ml of IFN-gamma and IL-2, respectively, were detected in supernatants of splenocytes from control mice. In experiments testing different VCL1010/MAP1 DNA vaccine dose regimens (25–100 μg/dose, two or four immunizations), survival rates of 23% to 88% (35/92 survivors/total in all VCL1010/MAP1 immunized groups) were observed on challenge with a lethal dose of cell culture-derived C. ruminantium organisms. In contrast, survival rates of 0% to 3% (1/144 survivors/total in all control groups) were recorded for control mice. This study demonstrates that MAP1 is a protective antigen and validates the concept of DNA vaccines against heartwater .     

Subacute Toxicity of a Novel Inhibitor of Acyl-CoA: Cholesterol Acyltransferase in Beagle Dogs

PD 132301–2 is a substituted urea hypolipidemic and antiatheroscleroticagent that is a potent inhibitor of acyl-CoA:cholesterol acyltransferase(ACAT). To determine its subacute toxicity, PD 132301–2was administered orally to beagle dogs at 0, 6, 12, 25, 50,200, 400, or 800 mg/kg/day for 2 weeks. Clinicopathologic evaluationswere completed on all dogs. Liver and adrenal total and esterifiedcholesterol concentrations, adrenocorticotrophic hormone (ACTH)responsiveness, and adrenal ultrastructure were determined at0, 6, 12, and 25 mg/kg. At 12 mg/kg or greater, salivation,epiphora, conjunctivitis, emesis, anorexia or decreased foodconsumption, and soft to mucoid feces and/or diarrhea were noted.Suppression of ACTH response occurred by Day 6 at all doses.Adrenocortical degeneration and/or necrosis in zona fasciculataand reticularis was seen at all doses; adrenal free and esterifiedcholesterol were normal at 6 mg/kg and decreased at 12 and 25mg/kg. Increases in serum alanine aminotransferase (2- to 15-fold),aspartate aminotransferase (2- to 12-fold), and alkaline phosphatase(2- to 7-fold) were noted at 50 mg/kg or greater. Periportalhepatocellular hypertrophy and hypereosinophilia occurred at50 mg/kg or greater; hepatic cholesterol values were not significantlyaffected by treatment. Dose-dependent ultrastructural alterationsin adrenocortical cells included decreased numbers of mitochondriaand smooth endoplasmic reticulum profiles, qualitative and quantitativechanges in lipid globules, and increased numbers of autolysosomes.PD 132301-2 or one of its metabolites has potent adrenocorticolyticproperties and limited hepatotoxic properties by mechanism(s)that are likely independent of systemic ACAT inhibition.