Plasma Leptin Levels and Incidence of Heart Failure, Cardiovascular Disease, and Total Mortality in Elderly Individuals

OBJECTIVE: Obesity predisposes individuals to congestive heart failure (CHF) and cardiovascular disease (CVD). Leptin regulates energy homeostasis, is elevated in obesity, and influences ventricular and vascular remodeling. We tested the hypothesis that leptin levels are associated with greater risk of CHF, CVD, and mortality in elderly individuals. RESEARCH DESIGN AND METHODS: We evaluated 818 elderly (mean age 79 years, 62% women) Framingham Study participants attending a routine examination at which plasma leptin was assayed. RESULTS: Leptin levels were higher in women and strongly correlated with BMI (P < 0.0001). On follow-up (mean 8.0 years), 129 (of 775 free of CHF) participants developed CHF, 187 (of 532 free of CVD) experienced a first CVD event, and 391 individuals died. In multivariable Cox regression models adjusting for established risk factors, log-leptin was positively associated with incidence of CHF and CVD (hazard ratio [HR] per SD increment 1.26 [95% CI 1.03–1.55] and 1.28 [1.09–1.50], respectively). Additional adjustment for BMI nullified the association with CHF (0.97 [0.75–1.24]) but only modestly attenuated the relation to CVD incidence (1.23 [1.00–1.51], P = 0.052). We observed a nonlinear, U-shaped relation between log-leptin and mortality (P = 0.005 for quadratic term) with greater risk of death evident at both low and high leptin levels. CONCLUSIONS: In our moderate-sized community-based elderly sample, higher circulating leptin levels were associated with a greater risk of CHF and CVD, but leptin did not provide incremental prognostic information beyond BMI. Additional investigations are warranted to elucidate the U-shaped relation of leptin to mortality.National Institutes of Health's National Heart, Lung, and Blood Institute (N01-HC25195, N01-HV28178, K24-HL04334, R01-DK080739

Moving Past Assumptions: Recognizing Parents as Allies in Promoting the Sexual Literacies of Adolescents through a University-Community Collaboration

This article recounts how a university-community collaborative challenged prevailing assumptions about parents as barriers to the provision of gender and sexuality information to their children, allowing for the recognition of parents as critical stakeholders and partners in sexual literacy work with youth. We provide evidence that parents’ support for inclusive sexuality education uniquely situates them to educate and advocate for young people around these issues, and in so doing we hope to disrupt the rhetoric that casts parents in the United States as solely gatekeepers when it comes to young people’s access to information about the broad spectrum of human sexuality

Factor VIII:C concentrate purified from plasma using monoclonal antibodies: human studies

Conventional clotting factor concentrates have, until recently, been of intermediate purity, containing less than 1% of the coagulation factor, and greater than 99% extraneous plasma proteins such as fibrinogen, fibronectin, gamma globulins, and traces of many others. We report here the results of a new factor VIII concentrate that is purified from human plasma using a mouse monoclonal antibody to factor VIII:vWF in an affinity chromatography system. The resultant concentrate has an activity of between 3,000 and 5,000 U/mg protein before albumin is added as a stabilizer. Seven patients with severe hemophilia A and no inhibitor who were positive for antibody to human immunodeficiency virus (HIV) have been treated solely with this concentrate for over 24 months. Factor usage in these patients has ranged from 611 U/kg/yr to 2,022 U/kg/yr. These patients have infused approximately once per week on the average, most often for joint hemorrhages. The efficacy of the concentrate is excellent. No allergic reactions have occurred and no factor VIII antibodies have developed. In these seven patients mean CD4 counts stabilized (856 +/- 619 at screen v 778 +/- 686 at 24 months) and there was reversal of skin test anergy. In a comparison group on conventional intermediate purity concentrate chosen retrospectively decreases in mean CD4 cell counts similarly did not occur. However, the number of the comparison patients who were anergic increased over the course of the study. These observations indicate the possibility that more highly purified concentrates may stabilize immune function in HIV seropositive patients

Toward artificial developmental regulators

A polyamide-peptide conjugate is designed which recruits sequence specifically the developmental regulator Exd to a cognate DNA site. In particular, an eight-ring hairpin polyamide (Im-Im-Py(C3H6NHR)-Py-gamma-Im-Py-Py-Py-beta-Dp) with a heptapeptide (R = Ac-Phe-Tyr-Pro-Trp-Met-Lys-Gly-) attached on a central ring was shown to induce cooperative binding of the Drosophila Hox protein cofactor Exd with a Kd of 4.4 nM in vitro, an order of magnitude more efficient than the natural Hox protein partner Ubx. The conjugate joins two sequence specific domains, one for DNA and one for the protein. This small molecule thus serves as a cooperative protein-DNA dimerizer, which mimics the natural Hox family of developmental regulators

Field Demonstration of a High-Efficiency Packaged Rooftop Air Conditioning Unit at Fort Gordon, Augusta, GA

As part of a larger program targeting the market transformation of packaged rooftop air conditioning, five high-efficiency rooftop air conditioning products were selected in 2002 by the U.S. Department of Energy (DOE) under the Unitary Air Conditioner (UAC) Technology Procurement (http://www.pnl.gov/uac). In February 2003, Fort Gordon in Augusta, Georgia was chosen as the demonstration site. With the goal of validating the field performance and operation of one of the awarded products, a 10-ton high-efficiency packaged rooftop unit (RTU) manufactured by Global Energy Group (GEG) was installed at Fort Gordon in October 2003. Following equipment installation, power metering, air- and refrigerant-side instrumentation was installed on the GEG RTU and a 4-year old typical-efficiency 20-ton RTU manufactured by AAON . The GEG and AAON units were instrumented identically and operated May through July, 2005, to observe performance under a range of conditions. Based on the data collected as part of this demonstration, the GEG equipment performed at least 8% better in stage-1 (single compressor running) cooling and at least 16% better in stage-2 (both compressors running) than the baseline AAON equipment. Performance comparisons are based on what we call application EER normalized to equivalent specific fan power. The full-load, specific-fan-power-normalized application EERs at ARI design conditions were 10.48 Btu/Wh for the GEG and 9.00 Btu/Wh for the baseline machine. With a cost premium of nearly 50%, and slightly higher maintenance costs, the life-cycle cost analysis shows that the GEG technology pays for itself--a positive net-present value (NPV)--only in climates and buildings with long cooling seasons. Manufacture of this equipment on a larger scale can be expected to reduce costs to the point where it is more broadly cost-effective. The assumed 10-ton baseline and new-technology unit costs are $3824.00 and$5525.00 respectively. If the new technology cost is assumed to drop as sales increase to $4674.50 for a 10-ton unit (i.e. the original cost difference is halved), the life-cycle costs improve. A grid of first cost, annual maintenance cost and electricity price is enumerated and the results presented in the report show the sensitivity of life cycle cost to these three financial parameters in each of eight different climates

Webometric analysis of departments of librarianship and information science: a follow-up study

This paper reports an analysis of the websites of UK departments of library and information science. Inlink counts of these websites revealed no statistically significant correlation with the quality of the research carried out by these departments, as quantified using departmental grades in the 2001 Research Assessment Exercise and citations in Google Scholar to publications submitted for that Exercise. Reasons for this lack of correlation include: difficulties in disambiguating departmental websites from larger institutional structures; the relatively small amount of research-related material in departmental websites; and limitations in the ways that current Web search engines process linkages to URLs. It is concluded that departmental-level webometric analyses do not at present provide an appropriate technique for evaluating academic research quality, and, more generally, that standards are needed for the formatting of URLs if inlinks are to become firmly established as a tool for website analysis

A Modified Surface on Titanium Deposited by a Blasting Process

Abstract : Hydroxyapatite (HA) coating of hard tissue implants is widely employed for its biocompatible and osteoconductive properties as well as its improved mechanical properties. Plasma technology is the principal deposition process for coating HA on bioactive metals for this application. However, thermal decomposition of HA can occur during the plasma deposition process, resulting in coating variability in terms of purity, uniformity and crystallinity, which can lead to implant failure caused by aseptic loosening. In this study, CoBlast™, a novel blasting process has been used to successfully modify a titanium (V) substrate with a HA treatment using a dopant/abrasive regime. The impact of a series of apatitic abrasives under the trade name MCD, was investigated to determine the effect of abrasive particle size on the surface properties of both microblast (abrasive only) and CoBlast (HA/abrasive) treatments. The resultant HA treated substrates were compared to substrates treated with abrasive only (microblasted) and an untreated Ti. The HA powder, apatitic abrasives and the treated substrates were characterized for chemical composition, coating coverage, crystallinity and topography including surface roughness. The results show that the surface roughness of the HA blasted modification was affected by the particle size of the apatitic abrasives used. The CoBlast process did not alter the chemistry of the crystalline HA during deposition. Cell proliferation on the HA surface was also assessed, which demonstrated enhanced osteo-viability compared to the microblast and blank Ti. This study demonstrates the ability of the CoBlast process to deposit HA coatings with a range of surface properties onto Ti substrates. The ability of the CoBlast technology to offer diversity in modifying surface topography offers exciting new prospects in tailoring the properties of medical devices for applications ranging from dental to orthopedic settings

Atp2c2 Is Transcribed From a Unique Transcriptional Start Site in Mouse Pancreatic Acinar Cells

Proper regulation of cytosolic Ca2+ is critical for pancreatic acinar cell function. Disruptions in normal Ca2+ concentrations affect numerous cellular functions and are associated with pancreatitis. Membrane pumps and channels regulate cytosolic Ca2+ homeostasis by promoting rapid Ca2+ movement. Determining how expression of Ca2+ modulators is regulated and the cellular alterations that occur upon changes in expression can provide insight into initiating events of pancreatitis. The goal of this study was to delineate the gene structure and regulation of a novel pancreas-specific isoform for Secretory Pathway Ca2+ ATPase 2 (termed SPCA2C), which is encoded from the Atp2c2 gene. Using Next Generation Sequencing of RNA (RNA-seq), chromatin immunoprecipitation for epigenetic modifications and promoter-reporter assays, a novel transcriptional start site was identified that promotes expression of a transcript containing the last four exons of the Atp2c2 gene (Atp2c2c). This region was enriched for epigenetic marks and pancreatic transcription factors that promote gene activation. Promoter activity for regions upstream of the ATG codon in Atp2c2’s 24th exon was observed in vitro but not in in vivo. Translation from this ATG encodes a protein aligned with the carboxy terminal of SPCA2. Functional analysis in HEK 293A cells indicates a unique role for SPCA2C in increasing cytosolic Ca2+. RNA analysis indicates that the decreased Atp2c2c expression observed early in experimental pancreatitis reflects a global molecular response of acinar cells to reduce cytosolic Ca2+ levels. Combined, these results suggest SPCA2C affects Ca2+ homeostasis in pancreatic acinar cells in a unique fashion relative to other Ca2+ ATPases. J. Cell. Physiol. 231: 2768–2778, 2016. © 2016 Wiley Periodicals, Inc

Detection of major histocompatibility complex class I-restricted, HIV-specific cytotoxic T lymphocytes in the blood of infected hemophiliacs

Major histocompatibility (MHC)-restricted, human immunodeficiency virus type one (HIV-1)-specific, cytotoxic T lymphocytes (CTLs) were detected in the peripheral blood mononuclear cells (PBMCs) of HIV-1-infected individuals. Using a system of autologous B and T lymphoblastoid cell lines infected with recombinant vaccinia vectors (VVs) expressing HIV-1 gene products, we were able to detect HIV-1-specific cytolytic responses in the PBMCs of 88% of HIV-1-seropositive hemophiliac patients in the absence of in vitro stimulation. These cytolytic responses were directed against both HIV-1 envelope and gag gene products. The responses were resistant to natural killer (NK) cell depletion and were inhibited by monoclonal antibodies (MoAbs) to the T cell receptor, CD8 surface antigens, and MHC class I antigens, suggesting a classical MHC class I restricted, virus-specific CTL response