Improvements in Depression and Changes in Fatigue: Results from the SLAM DUNC Depression Treatment Trial

Fatigue and depression are common co-morbid conditions among people with HIV infection. We analyzed a population of HIV-infected adults with depression, who were enrolled in a depression treatment trial, to examine the extent to which improvements in depression over time were associated with improvements in HIV-related fatigue. Data for this analysis come from a randomized controlled trial to evaluate the effectiveness of improved depression treatment on antiretroviral adherence. Fatigue was measured using the HIV-Related Fatigue Scale, and depressive symptoms were measured with the Hamilton Depression Rating Scale. Participants (n = 234) were on average nearly 44 years of age and predominantly male, black or African American, and unemployed. Individuals who experienced stronger depression response (i.e., greater improvement in depression score) had larger decreases in fatigue. However, even among those who demonstrated a full depression response, nearly three-quarters continued to have either moderate or severe fatigue at 6 and 12 months

The effect of antidepressant treatment on HIV and depression outcomes: results from a randomized trial

Depression is a major barrier to HIV treatment outcomes

Modeling Within-Host Dynamics of Influenza Virus Infection Including Immune Responses

Influenza virus infection remains a public health problem worldwide. The mechanisms underlying viral control during an uncomplicated influenza virus infection are not fully understood. Here, we developed a mathematical model including both innate and adaptive immune responses to study the within-host dynamics of equine influenza virus infection in horses. By comparing modeling predictions with both interferon and viral kinetic data, we examined the relative roles of target cell availability, and innate and adaptive immune responses in controlling the virus. Our results show that the rapid and substantial viral decline (about 2 to 4 logs within 1 day) after the peak can be explained by the killing of infected cells mediated by interferon activated cells, such as natural killer cells, during the innate immune response. After the viral load declines to a lower level, the loss of interferon-induced antiviral effect and an increased availability of target cells due to loss of the antiviral state can explain the observed short phase of viral plateau in which the viral level remains unchanged or even experiences a minor second peak in some animals. An adaptive immune response is needed in our model to explain the eventual viral clearance. This study provides a quantitative understanding of the biological factors that can explain the viral and interferon kinetics during a typical influenza virus infection

Safety and efficacy of exercise training in adults with Pompe disease: evalution of endurance, muscle strength and core stability before and after a 12 week training program

BACKGROUND: Pompe disease is a proximal myopathy. We investigated whether exercise training is a safe and useful adjuvant therapy for adult Pompe patients, receiving enzyme replacement therapy. METHODS: Training comprised 36 sessions of standardized aerobic, resistance and core stability exercises over 12 weeks. Before and after, the primary outcome measures safety, endurance (aerobic exercise capacity and distance walked on the 6 min walk test) and muscle strength, and secondary outcome measures core stability, muscle function and body composition, were evaluated. RESULTS: Of 25 patients enrolled, 23 successfully completed the training. Improvements in endurance were shown by increases in maximum workload capacity (110 W before to 122 W after training, [95 % CI of the difference 6 · 0 to 19 · 7]), maximal oxygen uptake capacity (69 · 4 % and 75 · 9 % of normal, [2 · 5 to 10 · 4]), and maximum walking distance (6 min walk test: 492 meters and 508, [−4 · 4 to 27 · 7] ). There were increases in muscle strength of the hip flexors (156 · 4 N to 180 · 7 N [1 · 6 to 13 · 6) and shoulder abductors (143 · 1 N to 150 · 7 N [13 · 2 to 35 · 2]). As an important finding in secondary outcome measures the number of patients who were able to perform the core stability exercises rose, as did the core stability balancing time (p < 0.05, for all four exercises). Functional tests showed small reductions in the time needed to climb four steps (2 · 4 sec to 2 · 1, [− 0 · 54 to −0 · 04 ]) and rise to standing position (5 · 8 sec to 4 · 8, [−2 · 0 to 0 · 0]), while time to run, the quick motor function test results and body composition remained unchanged. CONCLUSIONS: Our study shows that a combination of aerobic, strength and core stability exercises is feasible, safe and beneficial to adults with Pompe disease

Real-Time Reverse Transcription PCR for Detection and Quantitative Analysis of Equine Influenza Virus

Equine influenza is a cause of epizootic respiratory disease of the equine. The detection of equine influenza virus using real-time Light Cycler reverse transcription (RT)-PCR technology was evaluated over two influenza seasons with the analysis of 171 samples submitted for viral respiratory disease. Increased sensitivity was found in overall viral detection with this system compared to Directigen Flu A and virus isolation, which were 40% and 23%, respectively, that of the RT-PCR. The assay was also evaluated as a viable replacement for the more traditional methods of quantifying equine influenza virus, 50% egg infectious dose and 50% tissue culture infectious dose. There was a significant positive correlation (P < 0.05) between the quantitative RT-PCR and both of these assays

Attenuation of Equine Influenza Viruses through Truncations of the NS1 Protein

Equine influenza is a common disease of the horse, causing significant morbidity worldwide. Here we describe the establishment of a plasmid-based reverse genetics system for equine influenza virus. Utilizing this system, we generated three mutant viruses encoding carboxy-terminally truncated NS1 proteins. We have previously shown that a recombinant human influenza virus lacking the NS1 gene (delNS1) could only replicate in interferon (IFN)-incompetent systems, suggesting that the NS1 protein is responsible for IFN antagonist activity. Contrary to previous findings with human influenza virus, we found that in the case of equine influenza virus, the length of the NS1 protein did not correlate with the level of attenuation of that virus. With equine influenza virus, the mutant virus with the shortest NS1 protein turned out to be the least attenuated. We speculate that the basis for attenuation of the equine NS1 mutant viruses generated is related to their level of NS1 protein expression. Our findings show that the recombinant mutant viruses are impaired in their ability to inhibit IFN production in vitro and they do not replicate as efficiently as the parental recombinant strain in embryonated hen eggs, in MDCK cells, or in vivo in a mouse model. Therefore, these attenuated mutant NS1 viruses may have potential as candidates for a live equine influenza vaccine

Zerovalent Nickel Compounds Supported by 1,2-Bis(diphenylphosphino)benzene: Synthesis, Structures, and Catalytic Properties

Zerovalent nickel compounds which feature 1,2-bis­(diphenylphosphino)­benzene (dppbz) were obtained via the reactivity of dppbz towards Ni­(PMe₃)₄, which affords sequentially (dppbz)­Ni­(PMe₃)₂ and Ni­(dppbz)₂. Furthermore, the carbonyl derivatives (dppbz)­Ni­(PMe₃)­(CO) and (dppbz)­Ni­(CO)₂ may be obtained via the reaction of CO with (dppbz)­Ni­(PMe₃)₂. Other methods for the synthesis of these carbonyl compounds include (i) the formation of (dppbz)­Ni­(CO)₂ by the reaction of Ni­(PPh₃)₂(CO)₂ with dppbz and (ii) the formation of (dppbz)­Ni­(PMe₃)­(CO) by the reaction of (dppbz)­Ni­(CO)₂ with PMe₃. Comparison of the ν­(CO) IR spectroscopic data for (dppbz)­Ni­(CO)₂ with other (diphosphine)­Ni­(CO)₂ compounds provides a means to evaluate the electronic nature of dppbz. Specifically, comparison with (dppe)­Ni­(CO)₂ indicates that the <i>o</i>-phenylene linker creates a slightly less electron donating ligand than does an ethylene linker. The steric impact of the dppbz ligand in relation to other diphosphine ligands has also been evaluated in terms of its buried volume (%<i>V</i>_bur) and steric maps. The nickel center of (dppbz)­Ni­(PMe₃)₂ may be protonated by formic acid at room temperature to afford [(dppbz)­Ni­(PMe₃)₂H]⁺, but at elevated temperatures, effects catalytic release of H₂ from formic acid. Analogous studies with Ni­(dppbz)₂ and Ni­(PMe₃)₄ indicate that the ability to protonate the nickel centers in these compounds increases in the sequence Ni­(dppbz)₂ < (dppbz)­Ni­(PMe₃)₂ < Ni­(PMe₃)₄; correspondingly, the p<i>K</i>_a values of the protonated derivatives increase in the sequence [Ni­(dppbz)₂H]⁺ < [(dppbz)­Ni­(PMe₃)₂H]⁺ < [Ni­(PMe₃)₄H]⁺. (dppbz)­Ni­(PMe₃)₂ and Ni­(PMe₃)₄ also serve as catalysts for the formation of alkoxysilanes by (i) hydrosilylation of PhCHO by PhSiH₃ and Ph₂SiH₂ and (ii) dehydrocoupling of PhCH₂OH with PhSiH₃ and Ph₂SiH₂

Comparison of Sensitivities of Virus Isolation, Antigen Detection, and Nucleic Acid Amplification for Detection of Equine Influenza Virus

Four seronegative foals aged 6 to 7 months were exposed to an aerosol of influenza strain A/Equi/2/Kildare/89 at 10(6) 50% egg infective doses (EID(50))/ml. Nasopharyngeal swabs were collected for 10 consecutive days after challenge. Virus isolation was performed in embryonated eggs, and the EID(50) was determined for all positive samples. The 50% tissue culture infective dose was determined using Madin-Darby canine kidney (MDCK) cells. Samples were also tested by an in vitro enzyme immunoassay test, Directigen Flu A, and by reverse transcription-PCR (RT-PCR) using nested primers from the nucleoprotein gene and a single set of primers from the matrix gene. RT-PCR using the matrix primers and virus isolation in embryonated eggs proved to be the most sensitive methods for the detection of virus. The Directigen Flu A test was the least sensitive method. The inclusion of 2% fetal calf serum in the viral transport medium inhibited the growth of virus from undiluted samples in MDCK cells but was essential for the maintenance of the virus titer in samples subjected to repeated freeze-thaw cycles

Reaction of Cp*₂Zr(2,3-dimethylbutadiene) with Isonitriles and CO

We have investigated the reaction of isonitriles with a permethylzirconocene complex of 2,3-dimethylbutadiene. Cp*₂Zr­(2,3-dimethylbutadiene) (<b>1</b>) reacts with <i>tert</i>-alkyl isonitriles to give η²-iminoacyl complexes Cp*₂Zr­[CH₂C­(CH₃)­C­(CH₃)­CH₂C­(NR)] <b>2</b> (R = ^<i>t</i>Bu) and <b>3</b> (R = 1-adamantyl). Treatment of <b>2</b> with excess isopropyl isonitrile gives the η¹,η²-bis­(iminoacyl) complex Cp*₂Zr­[C­(N^<i>i</i>Pr)­CH₂C­(CH₃)­C­(CH₃)­CH₂C­(­(N^<i>i</i>Pr)] (<b>4</b>) and free <i>tert</i>-butyl isonitrile. The reaction of <b>1</b> with 2 equiv of isopropyl isonitrile also affords <b>4</b>, through the intermediate Cp*₂Zr­[CH₂C­(CH₃)­C­(CH₃)­CH₂C­(N^<i>i</i>Pr)] (<b>5</b>). Carbonylation of <b>2</b> affords the Zr formimidoyl cyclopentadienolate <b>6</b>. Treatment of a Zr hydride cyclopentadienolate (<b>7</b>), obtained from the carbonylation of <b>1</b>, with <i>tert</i>-butyl isonitrile also affords <b>6</b>. Isotopic labeling shows that the insertion of <i>tert</i>-butyl isonitrile into <b>1</b> and <b>7</b> is reversible. All complexes were characterized by spectroscopic and crystallographic methods