Electrical Conductances and association constants in dilute aqueous NdCl\textsubscript{3} solutions from 298 to 523 K along an isobar of 25 MPa

Electrical measurements were performed in dilute aqueous NdCl3 solutions from 298 to 523 K along the 25 MPa isobar to obtain limiting conductances and association constants. The specific conductance data were estimated using a continuous flow cell and a Markov Chain Monte Carlo (MCMC) correction algorithm. The limiting conductances for the salts in water were derived by regressing the mean spherical approximation (MSA) conductance model and speciation analyses based on the MCMC algorithm and the Deep Earth Water (DEW) model. The limiting conductances derived from the experimental data agree well with a predictive correlation proposed by Smolyakov, Anderko, and Lencka. Only the first association constant between neodymium and chloride could be derived at low temperatures (< 373 K) due to the apparent large statistical uncertainty of the second association constant. Above 373 K, both association constants could be derived and show a reasonable agreement with Migdisov and Williams-Jones and Gammons et al.Comment: 34 pages, 8 figures, to be submitted as an articl

Iatrogenic Spinal Cord Injury Resulting From Cervical Spine Surgery.

STUDY DESIGN: Retrospective cohort study of prospectively collected data. OBJECTIVE: To examine the incidence of iatrogenic spinal cord injury following elective cervical spine surgery. METHODS: A retrospective multicenter case series study involving 21 high-volume surgical centers from the AOSpine North America Clinical Research Network was conducted. Medical records for 17 625 patients who received cervical spine surgery (levels from C2 to C7) between January 1, 2005, and December 31, 2011, were reviewed to identify occurrence of iatrogenic spinal cord injury. RESULTS: In total, 3 cases of iatrogenic spinal cord injury following cervical spine surgery were identified. Institutional incidence rates ranged from 0.0% to 0.24%. Of the 3 patients with quadriplegia, one underwent anterior-only surgery with 2-level cervical corpectomy, one underwent anterior surgery with corpectomy in addition to posterior surgery, and one underwent posterior decompression and fusion surgery alone. One patient had complete neurologic recovery, one partially recovered, and one did not recover motor function. CONCLUSION: Iatrogenic spinal cord injury following cervical spine surgery is a rare and devastating adverse event. No standard protocol exists that can guarantee prevention of this complication, and there is a lack of consensus regarding evaluation and treatment when it does occur. Emergent imaging with magnetic resonance imaging or computed tomography myelography to evaluate for compressive etiology or malpositioned instrumentation and avoidance of hypotension should be performed in cases of intraoperative and postoperative spinal cord injury

A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness

Objective: This article compares the effects of initiating three contemporary antiretroviral therapy (ART) regimens on progression of carotid artery intima-media thickness (IMT) over 3 years. Design: Randomized clinical trial. Setting: Multicenter (26 institutions). Patients: ART-naive HIV-infected individuals (n ¼ 328) without known cardiovascular disease or diabetes mellitus. Intervention: Random assignment to tenofovir/emtricitabine along with atazanavir/ ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL). Main outcome measures: Right-sided carotid IMT was evaluated by B-mode ultrasonography before ART initiation, and then after 48, 96, and 144 weeks. Comparisons of yearly rates of change in carotid IMT used mixed-effects linear regression models that permitted not only evaluation of the effects of ART on carotid IMT progression but also how ART-associated changes in traditional risk factors, bilirubin, and markers of HIV infection were associated carotid IMT progression. Results: HIV-1 RNA suppression rates were high in all arms (&gt;85%) over 144 weeks. Modest increases in triglycerides and non-high-density lipoprotein cholesterol levels were observed in the protease inhibitor-containing arms compared with decreases with RAL. In contrast, carotid IMT progressed more slowly on ATV/r [8.2, 95% confidence interval (5.6, 10.8) mm/year] than DRV/r [12.9 (10.3, 15.5) mm/year, P ¼ 0.013]; changes with RAL were intermediate [10.7 (9.2, 12.2) mm/year, P ¼ 0.15 vs. ATV/r; P ¼ 0.31 vs. DRV/r]. Bilirubin and non-high-density lipoprotein cholesterol levels appeared to influence carotid IMT progression rates. Conclusion: In ART-naive HIV-infected individuals at low cardiovascular disease risk, carotid IMT progressed more slowly in participants initiating ATV/r than those initiating DRV/r, with intermediate changes associated with RAL. This effect may be due, in part, to hyperbilirubinemia

The Frequency of Malaria Is Similar among Women Receiving either Lopinavir/Ritonavir or Nevirapine-based Antiretroviral Treatment

HIV protease inhibitors (PIs) show antimalarial activity in vitro and in animals. Whether this translates into a clinical benefit in HIV-infected patients residing in malaria-endemic regions is unknown. We studied the incidence of malaria, as defined by blood smear positivity or a positive Plasmodium falciparum histidine-rich protein 2 antigen test, among 444 HIV-infected women initiating antiretroviral treatment (ART) in the OCTANE trial (A5208; ClinicalTrials.gov: NCT00089505). Participants were randomized to treatment with PI-containing vs. PI-sparing ART, and were followed prospectively for ≥48 weeks; 73% also received cotrimoxazole prophylaxis. PI-containing treatment was not associated with protection against malaria in this study population

Nevirapine and Efavirenz Elicit Different Changes in Lipid Profiles in Antiretroviral- Therapy-Naive Patients Infected with HIV-1

BACKGROUND: Patients infected with HIV-1 initiating antiretroviral therapy (ART) containing a non-nucleoside reverse transcriptase inhibitor (NNRTI) show presumably fewer atherogenic lipid changes than those initiating most ARTs containing a protease inhibitor. We analysed whether lipid changes differed between the two most commonly used NNRTIs, nevirapine (NVP) and efavirenz (EFV). METHODS AND FINDINGS: Prospective analysis of lipids and lipoproteins was performed in patients enrolled in the NVP and EFV treatment groups of the 2NN study who remained on allocated treatment during 48 wk of follow-up. Patients were allocated to NVP (n = 417), or EFV (n = 289) in combination with stavudine and lamivudine. The primary endpoint was percentage change over 48 wk in high-density lipoprotein cholesterol (HDL-c), total cholesterol (TC), TC:HDL-c ratio, non-HDL-c, low-density lipoprotein cholesterol, and triglycerides. The increase of HDL-c was significantly larger for patients receiving NVP (42.5%) than for patients receiving EFV (33.7%; p = 0.036), while the increase in TC was lower (26.9% and 31.1%, respectively; p = 0.073), resulting in a decrease of the TC:HDL-c ratio for patients receiving NVP (−4.1%) and an increase for patients receiving EFV (+5.9%; p < 0.001). The increase of non-HDL-c was smaller for patients receiving NVP (24.7%) than for patients receiving EFV (33.6%; p = 0.007), as were the increases of triglycerides (20.1% and 49.0%, respectively; p < 0.001) and low-density lipoprotein cholesterol (35.0% and 40.0%, respectively; p = 0.378). These differences remained, or even increased, after adjusting for changes in HIV-1 RNA and CD4+ cell levels, indicating an effect of the drugs on lipids over and above that which may be explained by suppression of HIV-1 infection. The increases in HDL-c were of the same order of magnitude as those seen with the use of the investigational HDL-c-increasing drugs. CONCLUSION: NVP-containing ART shows larger increases in HDL-c and decreases in TC:HDL-c ratio than an EFV-containing regimen. Based on these findings, protease-inhibitor-sparing regimens based on non-nucleoside reverse transcriptase inhibitor, particularly those containing NVP, may be expected to result in a reduced risk of coronary heart disease

The Role of Natural Killer (NK) Cells and NK Cell Receptor Polymorphisms in the Assessment of HIV-1 Neutralization

The importance of innate immune cells in HIV-1 pathogenesis and protection has been highlighted by the role of natural killer (NK) cells in the containment of viral replication. Use of peripheral blood mononuclear cells (PBMC) in immunologic studies provides both HIV-1 target cells (ie. CD4+ T cells), as well as anti-HIV-1 effector cells, such as NK cells. In this study, NK and other immune cell populations were analyzed in HIV-negative donor PBMC for an impact on the anti-HIV activity of polyclonal and monoclonal antibodies. NK cell percentages were significantly higher in donor PBMC that supported lower levels of viral replication. While the percentage of NK cells was not directly associated with neutralization titers, NK cell-depletion significantly diminished the antiviral antibody activity by up to three logs, and polymorphisms in NK killer immunoglobulin receptor (KIR) and FcγRIIIa alleles appear to be associated with this affect. These findings demonstrate that NK cells and NK cell receptor polymorphisms may influence assessment of traditional HIV-1 neutralization in a platform where antibody is continuously present. This format appears to simultaneously assess conventional entry inhibition (neutralization) and non-neutralizing antibody-dependent HIV inhibition, which may provide the opportunity to delineate the dominant antibody function(s) in polyclonal vaccine responses

Safety and Immunogenicity Study of Multiclade HIV-1 Adenoviral Vector Vaccine Alone or as Boost following a Multiclade HIV-1 DNA Vaccine in Africa

We conducted a double-blind, randomized, placebo-controlled Phase I study of a recombinant replication-defective adenovirus type 5 (rAd5) vector expressing HIV-1 Gag and Pol from subtype B and Env from subtypes A, B and C, given alone or as boost following a DNA plasmid vaccine expressing the same HIV-1 proteins plus Nef, in 114 healthy HIV-uninfected African adults.Volunteers were randomized to 4 groups receiving the rAd5 vaccine intramuscularly at dosage levels of 1×10(10) or 1×10(11) particle units (PU) either alone or as boost following 3 injections of the DNA vaccine given at 4 mg/dose intramuscularly by needle-free injection using Biojector® 2000. Safety and immunogenicity were evaluated for 12 months. Both vaccines were well-tolerated. Overall, 62% and 86% of vaccine recipients in the rAd5 alone and DNA prime - rAd5 boost groups, respectively, responded to the HIV-1 proteins by an interferon-gamma (IFN-γ) ELISPOT. The frequency of immune responses was independent of rAd5 dosage levels. The highest frequency of responses after rAd5 alone was detected at 6 weeks; after DNA prime - rAd5 boost, at 6 months (end of study). At baseline, neutralizing antibodies against Ad5 were present in 81% of volunteers; the distribution was similar across the 4 groups. Pre-existing immunity to Ad5 did not appear to have a significant impact on reactogenicity or immune response rates to HIV antigens by IFN-γ ELISPOT. Binding antibodies against Env were detected in up to 100% recipients of DNA prime - rAd5 boost. One volunteer acquired HIV infection after the study ended, two years after receipt of rAd5 alone.The HIV-1 rAd5 vaccine, either alone or as a boost following HIV-1 DNA vaccine, was well-tolerated and immunogenic in African adults. DNA priming increased the frequency and magnitude of cellular and humoral immune responses, but there was no effect of rAd5 dosage on immunogenicity endpoints.ClinicalTrials.gov NCT00124007