Prevalence and predictors of airflow obstruction in an HIV tertiary care clinic in Montreal, Canada: a cross-sectional study.

OBJECTIVES: The reported prevalence of chronic obstructive pulmonary disease (COPD) in people living with HIV (PLWHIV) varies widely. Our objective was to estimate the prevalence of airflow obstruction and COPD in unselected PLWHIV and identify characteristics that increase the risk of nonreversible airflow obstruction in order to guide case finding strategies for COPD. METHODS: All adults attending the Chronic Viral Illness Service were invited to participate in the study, regardless of smoking status or history of known COPD/asthma. Individuals underwent spirometric testing both before and after use of a salbutamol bronchodilator. Airflow obstruction was defined as forced expiratory volume in 1 s (FEV1 )/forced vital capacity (FVC) < 0.7 post-bronchodilation, whereas COPD was defined as FEV1 /FVC < 0.7 post-bronchodilation and Medical Research Council (MRC) score > 2. Multivariate logistic regression was used to evaluate risk factors associated with airflow obstruction, reported as adjusted odds ratios (aORs). RESULTS: Five hundred and three participants successfully completed spirometry testing. The median (Q1; Q3) age was 52 (44; 58) years. The median (Q1; Q3) CD4 count was 598 (438; 784) cells/µL and the median (Q1; Q3) nadir CD4 count was 224 (121; 351) cells/µL. There were 119 (24%) current smokers and 145 (29%) former smokers. Among those screened, 54 (11%) had airflow obstruction whereas three (1%) of the participants had COPD. Factors that were associated with airflow obstruction included a history of smoking [aOR 2.2; 95% confidence interval (CI) 1.1; 4.7], older age (aOR 1.6; 95% CI 1.2; 2.2), and lower CD4 count (aOR 0.8; 95% CI 0.7; 1.0). CONCLUSIONS: Airflow obstruction was relatively uncommon. Our findings suggest that PLWHIV who are ≥50 years old, smokers and those with nadir CD4 counts ≤ 200 cells/µL could be targeted to undergo spirometry to diagnose chronic airflow obstruction.

Low SAR 31 P (multi-echo) spectroscopic imaging using an integrated whole-body transmit coil at 7T.

Phosphorus (31 P) MRSI provides opportunities to monitor potential biomarkers. However, current applications of 31 P MRS are generally restricted to relatively small volumes as small coils are used. Conventional surface coils require high energy adiabatic RF pulses to achieve flip angle homogeneity, leading to high specific absorption rates (SARs), and occupy space within the MRI bore. A birdcage coil behind the bore cover can potentially reduce the SAR constraints massively by use of conventional amplitude modulated pulses without sacrificing patient space. Here, we demonstrate that the integrated 31 P birdcage coil setup with a high power RF amplifier at 7 T allows for low flip angle excitations with short repetition time (TR ) for fast 3D chemical shift imaging (CSI) and 3D T1 -weighted CSI as well as high flip angle multi-refocusing pulses, enabling multi-echo CSI that can measure metabolite T2 , over a large field of view in the body. B1+ calibration showed a variation of only 30% in maximum B1 in four volunteers. High signal-to-noise ratio (SNR) MRSI was obtained in the gluteal muscle using two fast in vivo 3D spectroscopic imaging protocols, with low and high flip angles, and with multi-echo MRSI without exceeding SAR levels. In addition, full liver MRSI was achieved within SAR constraints. The integrated 31 P body coil allowed for fast spectroscopic imaging and successful implementation of the multi-echo method in the body at 7 T. Moreover, no additional enclosing hardware was needed for 31 P excitation, paving the way to include larger subjects and more space for receiver arrays. The increase in possible number of RF excitations per scan time, due to the improved B1+ homogeneity and low SAR, allows SNR to be exchanged for spatial resolution in CSI and/or T1 weighting by simply manipulating TR and/or flip angle to detect and quantify ratios from different molecular species.

Proton MRS of cervical cancer at 7 T.

The differentiation grade of cervical cancer is histologically assessed by examining biopsies or surgical specimens. MRS is a highly sensitive technique that images tissue metabolism and can be used to increase the specificity of tissue characterization in a non-invasive manner. We aim to explore the feasibility of using in vivo 1 H-MRS at 7 T in women with cervical cancer to study tissue fatty acid composition. 10 women with histologically proven Stage IB1-IIB cervical cancer were scanned with a whole-body 7 T MR system with a multi-transmit system and an internal receive only monopole antenna. A STEAM sequence was used to obtain 1 H-MRS data. Fatty acid resonances were fitted with Lorentzian curves and the 2.1 ppm/1.3 ppm ratios were calculated. 1 H-MRS data showed fatty acid signals resonating at 2.1 ppm, 1.9 ppm, 1.5 ppm, 1.3 ppm and 0.9 ppm. Mean 2.1/1.3 ppm ratios were 0.019 ± 0.01, 0.021 ± 0.006, 0.12 ± 0.089 and 0.39 ± 0.27 for normal, Grade I, Grade II and Grade III groups respectively. Poorly differentiated tumor tissue (Grade III) showed elevated fatty acid ratios when compared with the well differentiated tumor (Grade I) or normal tissue. 1 H-MRS in cervical cancer at 7 T is feasible and individual fatty acid signals were detected. In addition, poorly differentiated tumors show more fatty acid unsaturation. The 2.1 ppm/1.3 ppm ratio has potential for tumor characterization in a non-invasive manner for uterine cervical cancer.

IL17RA gene variants and anti-TNF response among psoriasis patients.

Polymorphisms at genes encoding proteins involved in the pathogenesis of psoriasis (Psor) or in the mechanism of action of biological drugs could influence the treatment response. Because the interleukin (IL)-17 family has a central role in the pathogenesis of Psor, we hypothesized that IL17RA variants could influence the response to anti-TNF drugs among Psor patients. To address this issue we performed a cross-sectional study of Psor patients who received the biological treatments for the first time, with a follow-up of at least 6 months. All of the patients were Caucasian, older than 18 years old, with chronic plaque Psor, and had completed at least 24 weeks of anti-TNF therapy (adalimumab, etanercept or infliximab). The treatment response to anti-TNF agents was evaluated according to the achievement of PASI50 and PASI75 at weeks 12 and 24. Those who achieved PASI75 at week 24 were considered good responders. All patients were genotyped for the selected single-nucleotide polymorphisms (SNPs) at IL17RA gene. A total of 238 patients were included (57% male, mean age 46 years). One hundred and five patients received adalimumab, 91 patients etanercept and 42 infliximab. The rs4819554 promoter SNP allele A was significantly more common among responders at weeks 12 (P=0.01) and 24 (P=0.04). We found a higher frequency of AA versus AG+GG among responders, but the difference was only significant at week 12 (P=0.03, odd ratio=1.86, 95% confidence of interval=1.05-3.27). Thus, in the study population, the SNP rs4819554 in the promoter region of IL17RA significantly influences the response to anti-TNF drugs at week 12.

Argon plasma coagulation treatment of anal high-grade squamous intraepithelial lesions in men who have sex with men living with HIV: results of a 2-year prospective pilot study.

OBJECTIVES: Men who have sex with men (MSM) living with HIV are at high risk for anal high-grade squamous intraepithelial lesions (HSILs) and cancer. The best management of anal HSIL remains unclear. Our objective was to assess whether argon plasma coagulation (APC) could be safe, well tolerated and efficient to treat anal HSILs in MSM living with HIV. METHODS: A prospective phase II, open-label, pilot study was conducted to evaluate APC to treat anal HSILs in 20 HIV-positive MSM. Participants were followed for 2 years after their first treatment. RESULTS: Twenty men with persistent HSILs completed the 2-year study. Their baseline median CD4 count was 490 cells/µL and 85% had undetectable HIV viral loads. Overall, 65% (13/20) of participants were clear of HSILs at their 24-month visit. The initial response rates after the first, second and third APC treatments were 45%, 44% and 67%, respectively, but recurrences were common. The main side effect was pain during and within 1 week after the treatments. There were no long-term side effects, nor serious adverse events related to the procedure. Cost is a drawback. CONCLUSIONS: APC can be used to treat anal HSILs in HIV-seropositive MSM, and requires repeated treatment because of a high recurrence rate. As successful treatment of human papillomavirus (HPV) infection or eradication of the anal transitional zone remains impossible, HSIL treatment is challenging and requires long-term follow-up.

Boosting the SNR by adding a receive-only endorectal monopole to an external antenna array for high-resolution, T2 -weighted imaging of early-stage cervical cancer with 7-T MRI.

The aim of this study was to investigate the signal-to-noise ratio (SNR) gain in early-stage cervical cancer at ultrahigh-field MRI (e.g. 7 T) using a combination of multiple external antennas and a single endorectal antenna. In particular, we used an endorectal monopole antenna to increase the SNR in cervical magnetic resonance imaging (MRI). This should allow high-resolution, T2 -weighted imaging and magnetic resonance spectroscopy (MRS) for metabolic staging, which could facilitate the local tumor status assessment. In a prospective feasibility study, five healthy female volunteers and six patients with histologically proven stage IB1-IIB cervical cancer were scanned at 7 T. We used seven external fractionated dipole antennas for transmit-receive (transceive) and an endorectally placed monopole antenna for reception only. A region of interest, containing both normal cervix and tumor tissue, was selected for the SNR measurement. Separated signal and noise measurements were obtained in the region of the cervix for each element and in the near field of the monopole antenna (radius < 30 mm) to calculate the SNR gain of the endorectal antenna in each patient. We obtained high-resolution, T2 -weighted images with a voxel size of 0.7 × 0.8 × 3.0 mm3 . In four cases with optimal placement of the endorectal antenna (verified on the T2 -weighted images), a mean gain of 2.2 in SNR was obtained at the overall cervix and tumor tissue area. Within a radius of 30 mm from the monopole antenna, a mean SNR gain of 3.7 was achieved in the four optimal cases. Overlap between the two different regions of the SNR calculations was around 24%. We have demonstrated that the use of an endorectal monopole antenna substantially increases the SNR of 7-T MRI at the cervical anatomy. Combined with the intrinsically high SNR of ultrahigh-field MRI, this gain may be employed to obtain metabolic information using MRS and to enhance spatial resolutions to assess tumor invasion.

Lactococcus lactis carrying a DNA vaccine coding for the ESAT-6 antigen increases IL-17 cytokine secretion and boosts the BCG vaccine immune response.

AIMS: A regimen utilizing Bacille Calmette-Guerin (BCG) and another vaccine system as a booster may represent a promising strategy for the development of an efficient tuberculosis vaccine for adults. In a previous work, we confirmed the ability of Lactococcus lactis fibronectin-binding protein A (FnBPA+) (pValac:ESAT-6), a live mucosal DNA vaccine, to produce a specific immune response in mice after oral immunization. In this study, we examined the immunogenicity of this strain as a booster for the BCG vaccine in mice. METHODS AND RESULTS: After immunization, cytokine and immunoglobulin profiles were measured. The BCG prime L. lactis FnBPA+ (pValac:ESAT-6) boost group was the most responsive group, with a significant increase in splenic pro-inflammatory cytokines IL-17, IFN-γ, IL-6 and TNF-α compared with the negative control. CONCLUSIONS: Based on the results obtained here, we demonstrated that L. lactis FnBPA+ (pValac:ESAT-6) was able to increase the BCG vaccine general immune response. SIGNIFICANCE AND IMPACT OF THE STUDY: This work is of great scientific and social importance because it represents the first step towards the development of a booster to the BCG vaccine using L. lactis as a DNA delivery system.

Temporal B0 field variation effects on MRSI of the human prostate at 7 T and feasibility of correction using an internal field probe.

Spectral degradations as a result of temporal field variations are observed in MRSI of the human prostate. Moving organs generate substantial temporal and spatial field fluctuations as a result of susceptibility mismatch with the surrounding tissue (i.e. periodic breathing, cardiac motion or random bowel motion). Nine patients with prostate cancer were scanned with an endorectal coil (ERC) on a 7-T MR scanner. Temporal B0 field variations were observed with fast dynamic B0 mapping in these patients. Simulations of dynamic B0 corrections were performed using zero- to second-order shim terms. In addition, the temporal B0 variations were applied to simulated MR spectra causing, on average, 15% underestimation of the choline/citrate ratio. Linewidth distortions and frequency shifts (up to 30 and 8 Hz, respectively) were observed. To demonstrate the concept of observing local field fluctuations in real time during MRSI data acquisition, a field probe (FP) tuned and matched for the (19) F frequency was incorporated into the housing of the ERC. The data acquired with the FP were compared with the B0 field map data and used to correct the MRSI datasets retrospectively. The dynamic B0 mapping data showed variations of up to 30 Hz (0.1 ppm) over 72 s at 7 T. The simulated zero-order corrections, calculated as the root mean square, reduced the standard deviation (SD) of the dynamic variations by an average of 41%. When using second-order corrections, the reduction in the SD was, on average, 56%. The FP data showed the same variation range as the dynamic B0 data and the variation patterns corresponded. After retrospective correction, the MRSI data showed artifact reduction and improved spectral resolution. B0 variations can degrade the MRSI substantially. The simple incorporation of an FP into an ERC can improve prostate cancer MRSI without prior knowledge of the origin of the dynamic field distortions.

High sodium intake during postnatal phases induces an increase in arterial blood pressure in adult rats.

Epigenetic studies suggest that diseases that develop in adulthood are related to certain conditions to which the individual is exposed during the initial stages of life. Experimental evidence has demonstrated that offspring born to mothers maintained on high-Na diets during pregnancy have higher mean arterial pressure (MAP) in adulthood. Although these studies have demonstrated the importance of prenatal phases to hypertension development, no evidence regarding the role of high Na intake during postnatal phases in the development of this pathology has been reported. Therefore, in the present study, the effects of Na overload during childhood on induced water and Na intakes and on cardiovascular parameters in adulthood were evaluated. Experiments were carried out in two groups of 21-d-old rats: experimental group, maintained on hypertonic saline (0.3 m-NaCl) solution and food for 60 d, and control group, maintained on tap water and food. Later, both groups were given water and food for 15 d (recovery period). After the recovery period, chronic cannulation of the right femoral artery was performed in unanaesthetised rats to record baseline MAP and heart rate (HR). The experimental group was found to have increased basal MAP (98.6 (sem 2.6) v. 118.3 (sem 2.7) mmHg, P< 0.05) and HR (365.4 (sem 12.2) v. 398.2 (sem 7.5) beats per min, P< 0.05). There was a decrease in the baroreflex index in the experimental group when compared with that in the control group. A water and Na intake test was performed using furosemide. Na depletion was found to induce an increase in Na intake in both the control and experimental groups (12.1 (sem 0.6) ml and 7.8 (sem 1.1), respectively, P< 0.05); however, this increase was of lower magnitude in the experimental group. These results demonstrate that postnatal Na overload alters behavioural and cardiovascular regulation in adulthood.

Composite slice-selective adiabatic excitation for prostate MRSI.

Higher magnetic field strengths, such as 7 T, offer increased spectral resolution and higher signal-to-noise ratio. These properties can be very advantageous for MRSI. In particular, signals that generally overlap at lower fields, such as choline, polyamines and creatine, can be resolved at 7 T. However, higher magnetic field strengths suffer from strong radiofrequency (RF) field nonuniformities. These nonuniformities become even stronger when using surface transceivers, such as an endorectal coil for prostate imaging. In order to obtain uniform excitations for accurate MRSI measurements, adiabatic sequences are therefore recommended. Conventional adiabatic MRS sequences (i.e. localization by adiabatic selective refocusing, LASER) have relatively long TEs, especially when optimized to measure the strongly coupled spins of citrate in the prostate. The semi-LASER (sLASER) sequence has a significantly shorter TE, although it does not provide adiabatic excitation. Therefore, we propose an adiabatic sLASER sequence that either has a composite adiabatic slice-selective excitation (cLASER) or a non-slice-selective adiabatic excitation (nsLASER), allowing for shorter TEs, whilst maintaining the adiabatic spin excitation. Furthermore, the spatial properties of the composite adiabatic excitation allow for a high slice excitation bandwidth, resulting in negligible chemical shift displacement artifacts. Exclusion of the slice selection can be considered once the field of view extends beyond the transmit field of the RF coil. The use of a transceiver at high magnetic field strengths has shown that the cLASER and nsLASER sequences are suitable for MRSI of the prostate in both phantom and in vivo validations.

Improved efficiency on editing MRS of lactate and γ-aminobutyric acid by inclusion of frequency offset corrected inversion pulses at high fields.

γ-Aminobutyric acid (GABA) and lactate are metabolites which are present in the brain. These metabolites can be indicators of psychiatric disorders or tumor hypoxia, respectively. The measurement of these weakly coupled spin systems can be performed using MRS editing techniques; however, at high field strength, this can be challenging. This is due to the low available B1 (+) field at high fields, which results in narrow-bandwidth refocusing pulses and, consequently, in large chemical shift displacement artifacts. In addition, as a result of the increased chemical shift displacement artifacts and chemical shift dispersion, the efficiency of the MRS method is reduced, even when using adiabatic refocusing pulses. To overcome this limitation, frequency offset corrected inversion (FOCI) pulses have been suggested as a mean to substantially increase the bandwidth of adiabatic pulses. In this study, a Mescher-Garwood semi-localization by adiabatic selection and refocusing (MEGA-sLASER) editing sequence with refocusing FOCI pulses is presented for the measurement of GABA and lactate in the human brain. Metabolite detection efficiencies were improved by 20% and 75% for GABA and lactate, respectively, when compared with editing techniques that employ adiabatic radiofrequency refocusing pulses. The highly efficient MEGA-sLASER sequence with refocusing FOCI pulses is an ideal and robust MRS editing technique for the measurement of weakly coupled metabolites at high field strengths.

Improving SNR and B1 transmit field for an endorectal coil in 7 T MRI and MRS of prostate cancer.

Higher magnetic field strengths like 7 T and above are desirable for MR spectroscopy given the increased spectral resolution and signal to noise ratio. At these field strengths, substantial nonuniformities in B(1)(+/-) and radiofrequency power deposition become apparent. In this investigation, we propose an improvement on a conventionally used endorectal coil, through the addition of a second element (stripline). Both elements are used as transceivers. In the center of the prostate, approximately 40% signal to noise ratio increase is achieved. In fact, the signal to noise ratio gain obtained with the quadrature configuration locally can be even greater than 40% when compared to the single loop configuration. This is due to the natural asymmetry of the B(1)(+/-) fields at high frequencies, which causes destructive and constructive interference patterns. Global specific absorption rate is reduced by almost a factor of 2 as expected. Furthermore, approximately a 4-fold decrease in local specific absorption rate is observed when normalized to the B(1) values in the center of the prostate. Because of the 4-fold local specific absorption rate decrease obtained with the dual channel setup for the same reference B(1) value (20 µT at 3.5 cm depth into the prostate) as compared to the single loop, the transmission power B(1) duty cycle can be increased by a factor 4. Consequently, when using the two-element endorectal coil, the radiofrequency power deposition is significantly reduced and radiofrequency intense sequences with adiabatic pulses can be safely applied at 7 T for (1)H magnetic resonance spectroscopy and MRI in the prostate. Altogether, in vivo (1)H magnetic resonance spectroscopic imaging of prostate cancer with a fully adiabatic sequence operated at a minimum B(1)(+) of 20 µT shows insensitivity to the nonuniform transmit field, while remaining within local specific absorption rate guidelines of 10 W/kg.

Spreading characteristics of nanofluid droplets impacting onto a solid surface.

This paper reports an experimental investigation on the spreading characteristics of nanofluid droplets impinging on aluminum substrate under the influence of several key factors such as nanoparticle volume fraction, substrate temperature, and the Weber number. Sample nanofluid used is prepared by dispersing several volumetric concentrations (1 to 5%) of titanium dioxide nanoparticles in ethylene glycol. The entire dynamic process of each droplet collision with the substrate surface and the spreading phenomena is captured by using a high speed camera and then the transient spreading diameter and height of droplet are determined. It is found that the higher the concentration of nanoparticles the larger the spreading diameter of nanofluid droplet. As the surface temperature increases, the overall spreading diameter and height of nanofluid droplet significantly decreases and increases, respectively. At larger Weber number, the final spreading of the nanofluid droplet is also found to be larger than that of lower Weber number. Present results demonstrate that spreading characteristics of nanofluid droplets impacting onto solid surface are greatly influenced by each of the aforementioned factors.

Acceptability of anal cancer screening tests for women living with HIV in the EVVA study.

Background: Anal cancer is potentially preventable through screening. For screening to be implemented, the screening procedures must be acceptable to the affected population. The objective of the present study was to measure the acceptability of currently available anal cancer screening tests in a population of women living with hiv who had experienced the tests. Methods: The evva study ("Evaluation of Human Immunodeficiency Virus, Human Papillomavirus, and Anal Intraepithelial Neoplasia in Women") is a prospective cohort study of adult women living with hiv in Montreal, Quebec. Participants were screened with cervical or anal hpv testing and cervical or anal cytology every 6 months for 2 years. High-resolution anoscopy (hra) and digital anal rectal examination (dare) were also performed systematically, with biopsies, at baseline and at 2 years. An acceptability questionnaire was administered at the final visit or at study withdrawal. Results: Of 124 women who completed the acceptability questionnaire, most considered screening "an absolute necessity" in routine care for all women living with hiv [77%; 95% confidence interval (ci): 69% to 84%]. Yearly anal cytology or anal hpv testing was considered very acceptable by 81% (95% ci: 73% to 88%); hra every 2 years was considered very acceptable by 84% (95% ci: 77% to 90%); and yearly dare was considered very acceptable by 87% (95% ci: 79% to 92%). Acceptability increased to more than 95% with a longer proposed time interval. Pain was the main reason for lower acceptability. Conclusions: Most participating women considered anal cancer screening necessary and very acceptable. Longer screening intervals and adequate pain management could further increase the acceptability of repeated screening.

Acute effect of passive cycle-ergometry and functional electrical stimulation on nitrosative stress and inflammatory cytokines in mechanically ventilated critically ill patients: a randomized controlled trial.

Early mobilization is beneficial for critically ill patients because it reduces muscle weakness acquired in intensive care units. The objective of this study was to assess the effect of functional electrical stimulation (FES) and passive cycle ergometry (PCE) on the nitrous stress and inflammatory cytometry in critically ill patients. This was a controlled, randomized, open clinical trial carried out in a 16-bed intensive care unit. The patients were randomized into four groups: Control group (n=10), did not undergo any therapeutic intervention during the study; PCE group (n=9), lower-limb PCE for 30 cycles/min for 20 min; FES group (n=9), electrical stimulation of quadriceps muscle for 20 min; and FES with PCE group (n=7), patients underwent PCE and FES, with their order determined randomly. The serum levels of nitric oxide, tumor necrosis factor alpha, interferon gamma, and interleukins 6 and 10 were analyzed before and after the intervention. There were no differences in clinical or demographic characteristics between the groups. The results revealed reduced nitric oxide concentrations one hour after using PCE (P<0.001) and FES (P<0.05), thereby indicating that these therapies may reduce cellular nitrosative stress when applied separately. Tumor necrosis factor alpha levels were reduced after the PCE intervention (P=0.049). PCE and FES reduced nitric oxide levels, demonstrating beneficial effects on the reduction of nitrosative stress. PCE was the only treatment that reduced the tumor necrosis factor alpha concentration.