Peripheral inflammation and depressed mood independently predict neurocognitive worsening over 12 years.

Background: Neurocognitive (NC) impairment in people with HIV (PWH) is associated with important adverse outcomes, but no markers exist to predict long-term NC decline. We evaluated depressed mood and markers of persistent inflammation, oxidative stress and altered amyloid processing (all common in PWH) as predictors of NC worsening over 12 years. Methods: PWH were enrolled and followed longitudinally in the CNS HIV Antiretroviral Effects Research (CHARTER) study at six US sites. At entry we quantified biomarkers in blood of inflammation: (interleukin-6 [IL-6], C-reactive protein [CRP], monocyte chemoattractant protein type 1 [MCP-1], D-dimer, soluble sCD14 (sCD14), soluble tumor necrosis factor receptor - type II [sTNFR-II], neopterin, and soluble CD40 ligand [sCD40L], oxidative stress (protein carbonyls, 8-oxo-2'-deoxyguanosine [8-oxo-dG]) and altered amyloid processing [amyloid beta (Aß)-42, soluble amyloid precursor protein-α (sAPPα)] using commercial immunoassays. The Beck Depression Inventory-II (BDI-II) assessed depressed mood at entry. NC decline over 12 years was evaluated using the published and validated summary (global) regression-based change score (sRBCS). A factor analysis reduced dimensionality of the biomarkers. Univariable and multiple regression models tested the relationship between baseline predictors and the outcome of neurocognitive decline. Results: Participants were 191 PWH, 37 (19.4%) women, 46.6% African American, 43.5% non-Hispanic white, 8.83% Hispanic, 15.7% white, 1.6% other; at study entry mean (SD) age 43.6 (8.06) years, estimated duration of HIV infection (median, IQR) 9.82 [4.44, 14.5] years, nadir CD4 104/µL (19,205), current CD4 568/µL (356, 817), and 80.1% had plasma HIV RNA <50 c/mL. Participants were enrolled between 2003 and 2007; median (IQR) duration of follow-up 12.4 [9.69, 16.2] years. Three biomarker factors were identified: Factor (F)1 (IL-6, CRP), F2 (sTNFR-II, neopterin) and F3 (sCD40L, sAPPα). Participants with higher F1, reflecting worse systemic inflammation at baseline, and higher F3, had greater decline in global neurocognition (r â€‹= â€‹-0.168, p â€‹= â€‹0.0205 and r â€‹= â€‹-0.156, p â€‹= â€‹0.0309, respectively). Of the F1 components, higher CRP levels were associated with worse decline (r â€‹= â€‹-0.154, p â€‹= â€‹0.0332), while IL-6 did not (r â€‹= â€‹-0.109, p â€‹= â€‹0.135). NC change was not significantly related to F2, nor to demographics, nadir and current CD4, viral suppression or baseline NC comorbidity ratings. Individuals with worse depressed mood at entry also experienced more NC decline (r â€‹= â€‹-0.1734, p â€‹= â€‹0.0006). Together BDI-II (p â€‹= â€‹0.0290), F1 (p â€‹= â€‹0.0484) and F3 (p â€‹= â€‹0.0309) contributed independently to NC decline (p â€‹= â€‹0.0028); their interactions were not significant. Neither CRP nor IL-6 correlated significantly with depression. Conclusions: PWH with greater systemic inflammation and more depression at entry had greater NC decline over 12 years. Understanding the basis of this inflammatory state might be particularly important. These findings raise the possibility that targeted anti-inflammatory or antidepressant therapies may help prevent NC worsening in PWH with depression and inflammation.

Cerebrospinal Fluid Ceruloplasmin, Haptoglobin, and Vascular Endothelial Growth Factor Are Associated with Neurocognitive Impairment in Adults with HIV Infection.

Dysregulated iron transport and a compromised blood-brain barrier are implicated in HIV-associated neurocognitive disorders (HAND). We quantified the levels of proteins involved in iron transport and/or angiogenesis-ceruloplasmin, haptoglobin, and vascular endothelial growth factor (VEGF)-as well as biomarkers of neuroinflammation, in cerebrospinal fluid (CSF) from 405 individuals with HIV infection and comprehensive neuropsychiatric assessments. Associations with HAND [defined by a Global Deficit Score (GDS) ≥ 0.5, GDS as a continuous measure (cGDS), or by Frascati criteria] were evaluated for the highest versus lowest tertile of each biomarker, adjusting for potential confounders. Higher CSF VEGF was associated with GDS-defined impairment [odds ratio (OR) 2.17, p = 0.006] and cGDS in unadjusted analyses and remained associated with GDS impairment after adjustment (p = 0.018). GDS impairment was also associated with higher CSF ceruloplasmin (p = 0.047) and with higher ceruloplasmin and haptoglobin in persons with minimal comorbidities (ORs 2.37 and 2.13, respectively; both p = 0.043). In persons with minimal comorbidities, higher ceruloplasmin and haptoglobin were associated with HAND by Frascati criteria (both p < 0.05), and higher ceruloplasmin predicted worse impairment (higher cGDS values, p < 0.01). In the subgroup with undetectable viral load and minimal comorbidity, CSF ceruloplasmin and haptoglobin were strongly associated with GDS impairment (ORs 5.57 and 2.96, respectively; both p < 0.01) and HAND (both p < 0.01). Concurrently measured CSF IL-6 and TNF-α were only weakly correlated to these three biomarkers. Higher CSF ceruloplasmin, haptoglobin, and VEGF are associated with a significantly greater likelihood of HAND, suggesting that interventions aimed at disordered iron transport and angiogenesis may be beneficial in this disorder.

The role of nano-roughness in antifouling.

Nano-engineered superhydrophobic surfaces have been investigated for potential fouling resistance properties. Integrating hydrophobic materials with nanoscale roughness generates surfaces with superhydrophobicity that have water contact angles (theta) >150 degrees and concomitant low hysteresis (<10 degrees ). Three superhydrophobic coatings (SHCs) differing in their chemical composition and architecture were tested against major fouling species (Amphora sp., Ulva rigida, Polysiphonia sphaerocarpa, Bugula neritina, Amphibalanus amphitrite) in settlement assays. The SHC which had nanoscale roughness alone (SHC 3) deterred the settlement of all the tested fouling organisms, compared to selective settlement on the SHCs with nano- and micro-scale architectures. The presence of air incursions or nanobubbles at the interface of the SHCs when immersed was characterized using small angle X-ray scattering, a technique sensitive to local changes in electron density contrast resulting from partial or complete wetting of a rough interface. The coating with broad spectrum antifouling properties (SHC 3) had a noticeably larger amount of unwetted interface when immersed, likely due to the comparatively high work of adhesion (60.77 mJ m(-2) for SHC 3 compared to 5.78 mJ m(-2) for the other two SHCs) required for creating solid/liquid interface from the solid/vapour interface. This is the first example of a non-toxic, fouling resistant surface against a broad spectrum of fouling organisms ranging from plant cells and non-motile spores, to complex invertebrate larvae with highly selective sensory mechanisms. The only physical property differentiating the immersed surfaces is the nano-architectured roughness which supports longer standing air incursions providing a novel non-toxic broad spectrum mechanism for the prevention of biofouling.

Fine structure in swift heavy ion tracks in amorphous SiO2.

We report on the observation of a fine structure in ion tracks in amorphous SiO2 using small angle x-ray scattering measurements. Tracks were generated by high energy ion irradiation with Au and Xe between 27 MeV and 1.43 GeV. In agreement with molecular dynamics simulations, the tracks consist of a core characterized by a significant density deficit compared to unirradiated material, surrounded by a high density shell. The structure is consistent with a frozen-in pressure wave originating from the center of the ion track as a result of a thermal spike.

The influence of a nurse practitioner on out of hours work intensity for surgical house officers.

We have prospectively studied the influence of a nurse practitioner service on out of hours work intensity of surgical house officers. Data collection was achieved by prospective audit. The study was set in the surgical wards in a large teaching hospital. The main outcome measures were; 1) the nature and frequency of overnight calls to the nurse practitioner, and 2) the outcome of these calls (doctor not bleeped, telephone advice given by doctor or doctor attended ward). A total of 645 calls were made over the 75 night study period (8.6 calls/night). Two hundred and ninety-six calls were managed by the nurse practitioner alone. This represents a 46% reduction in work intensity for the surgical house officer. This study illustrates the benefits of a nurse practitioner service and also identifies important areas for undergraduate education in preparing medical students for the common problems encountered during the surgical on-call period.

An eight-position capillary sample spinning stage for the diffractometer at BL20B at the Photon Factory.

An eight-position capillary sample spinning stage has been developed for use in conjunction with the versatile vacuum diffractometer (BIGDIFF) at BL20B at the Photon Factory. BIGDIFF is often used in its powder diffraction mode using powders mounted in capillaries and up to eight imaging plates to record the diffraction pattern from the sample. Using the multiple spinning stage a number of diffraction patterns can be recorded on the imaging plates if the imaging-plate cassette is moved behind the Weissenberg screen to a new position after exposure of the sample to the beam. Not only is this system more efficient in terms of time saved in the pumping-down process, but also it has the advantage of allowing the diffraction patterns of standards to be recorded, thereby calibrating both the angle scale of the diffractometer and the intensity scales of the imaging plates absolutely.

Multiple-wavelength powder diffraction using imaging plates at the Australian National Beamline.

The Australian powder diffractometer at the Photon Factory is capable of recording multiple powder-diffraction scans in less than 5 min per pattern using imaging plates in Debye-Scherrer geometry. This, coupled with incrementing the X-ray beam energy in suitably small steps (down to approximately 2 eV) between exposures, allows fast collection of anomalous diffraction data. Data collected from a copper oxide-based superconductor at energies near the Cu K-absorption edge are presented, along with an account of the technique used to extract multiple-exposure powder-diffraction data from imaging plates.

Calculation of absolute intensities from X-ray imaging plates.

A numerical technique for deriving a conversion factor between the output pixel values from a scanned imaging plate and the actual incident X-ray photon flux is proposed. The technique requires no external calibration by independent detectors, but uses the statistical information inherent in the image. As a test case, this technique was applied to a Fuji BAS2000 imaging-plate scanner. The calculation showed that, at 1.2 A, 163 (8) photons pixel(-1) were required to give one output unit of pixel intensity on an image scanned 20 min after exposure. This conversion factor compared favourably with the independently measured conversion factor of 171.1 (5) photons pixel(-1) (output unit)(-1) obtained from a high-quantum-efficiency Ge detector.

Common overuse running injuries: diagnosis and management.

Running injuries are primarily caused by overuse due to training errors (i.e., running too far, too fast, too soon). A stress fracture should always be considered in a runner with pain, because long-term morbidity may occur if this injury is not recognized. The history and physical examination are usually sufficient to diagnose an overuse injury. Runners should be instructed to increase their mileage gradually in increments of 10 percent or less each week, to wear proper running shoes and to perform stretching and strengthening exercises for the lower extremities on a regular basis. In addition, they should not attempt to "run through pain." Treatment of overuse running injuries includes relative rest, nonsteroidal anti-inflammatory drugs, cross-training and stretching exercises, with a return to running as tolerated. Correction of biomechanical problems with the use of orthotics may be an adjunctive treatment measure.

Postdischarge follow-up of psychiatric inpatients and readmission in an HMO setting.

This study examined the relationship between follow-up and rehospitalization of inpatients discharged from treatment in two divisions of a health maintenance organization (HMO). Among 580 patients discharged, two-thirds made a follow-up visit within 30 days. Slightly less than a third were readmitted within six months. Readmission was less likely for patients who made a follow-up visit and for men. Patients who had a preadmission relationship with a mental health practitioner were more likely to make a follow-up visit and were more likely to be readmitted. Follow-up was also associated with diagnoses of adjustment and affective disorders.

Fertility after induced abortion: a prospective follow-up study.

Abortion has been alleged to cause sterility. To address this issue, 1235 postabortal women, 912 women recently delivered, and 939 women from the authors' gynecology clinics were studied for as long as 3.5 years. Cumulative pregnancy rates were similar for abortion group patients, delivery group patients, and the previously pregnant clinic group. When pregnancy rates were examined by different assumptions as to entrance into follow-up, the abortion group differed only in a somewhat lower pregnancy rate after nine months, when the use of contraceptives was greater than that of the other two groups. Pregnancy rates for all three groups were influenced by age of subject, parity, race, marital and Medicaid status, and a history of urinary tract infections. Induced abortion status did not influence pregnancy rates except that women reporting three or more induced abortions had a higher pregnancy rate.

A study of the electron transfer properties of the heme undecapeptide from cytochrome c by 1H nmr spectroscopy.

Nuclear magnetic resonance (nmr) spectroscopy has been used to investigate the heme undecapeptide from cytochrome c. Assignments of resonances to specific residues have been made based on spin decoupling, redox titration, and the pH and temperature dependence of resonance lines. An outline structure is presented based on the assignments, secondary shift data, and the x-ray crystal structure of cytochrome c. An equation is derived to relate the width of an nmr line during a redox titration to the percentage of each oxidation state. Using this equation the self-exchange rate constant for electron transfer for the heme peptide is 1.3 x 10(7) M-1 sec-1 at 330 degrees K. Discussion of the self-exchange rate constants of cytochrome c, cytochrome c3, and cytochrome c551 is related to this constant for the heme undecapeptide.

Cation binding by the rat-incisor-dentine phosphoprotein. A spectroscopic investigation.

Nuclear magnetic resonance and electron paramagnetic resonance spectroscopy have been used to quantify metal binding to the phosphoprotein extractable from demineralized rat incisor dentine. Paramagnetic cation probes enable identification of the metal binding sites. Cations are able to diffuse across the protein surface while forming a relatively long-lived metal-phosphoprotein complex. The ability of the protein to sequester surface-mobile Ca(II) is discussed in terms of its ability to act as a possible nucleation site for the initial localization of Ca(II) within the dentine matrix.

NMR study of the interaction of plastocyanin with chromium(II) analogues of inorganic electron transfer reagents.

High resolution nuclear magnetic resonance spectroscopy has been used to examine the interaction of plastocyanins from French bean (Phaseolus vulgaris) and cucumber (Cucumis sativus) with three complexes--potassium hexacyano-chromate(III), hexamminechromium(III) nitrate and tris(1,10-phenanthroline)-chromium(III) perchlorate--which are analogues of inorganic electron transfer reagents. The results indicate a high degree of specificity in the binding of these complexes and two binding sites on the protein are identified. One binding site is situated close to the copper atom and is clearly suited to outer sphere electron transfer through one of the histidine ligands. The other binding site is more distant from the copper atom and this mechanism cannot be operative. Electron transfer via hydrophobic channels or electron tunneling are possible mechanisms of electron transfer.

Structural homology of cytochromes c.

Cytochromes c from many eukaryotic and diverse prokaryotic organisms have been investigated and compared using high-resolution nuclear magnetic resonance spectroscopy. Resonances have been assigned to a large number of specific groups, mostly in the immediate environment of the heme. This information, together with sequence data, has allowed a comparison of the heme environment and protein conformation for these cytochromes. All mitochondrial cytochromes c are found to be very similar to the cytochromes c2 from Rhodospirillaceae. In the smaller bacterial cytochromes, Pseudomonas aeruginosa cytochrome c551 and Euglena gracilis cytochrome c552, the orientation of groups near the heme is very similar, but the folding of the polypeptide chain is different. The heme environment of these two proteins is similar to that of the larger bacterial and mitochondrial cytochromes. Two low-potential cytochromes, Desulfovibrio vulgaris cytochrome c553 and cytochrome c554 from a halotolerant micrococcus have heme environments which are not very similar to those of the other proteins reported here.