Effect of CD4+ T cell count and antiretroviral treatment on two serological HIV incidence assays

Serological assays are increasingly being used to measure HIV incidence in cross-sectional studies, but their specificity to determine incident infections remains problematic. We estimated the specificity of the BED assay in a cohort of long-term HIV-infected adults before and during antiretroviral treatment (ART) and evaluated an HIV avidity assay to detect BED-based false-recent results. We used the BED assay to test stored specimens from known long-term HIV-1-infected adult Ugandans before and at 3, 12, and 24 months after ART initiation. We evaluated the frequency of false-recent classifications by ART status and CD4(+) T(+) cell count. Specimens classified as BED false-recent were further tested with an avidity assay. In all, 950 blood specimens from 253 adults were tested with the BED assay. Of these, 149 (15.7%) specimens tested false-recent and 64 (24.9%) individuals tested false-recent at least once. Among all specimens tested, the proportion of false-recent rose with increasing CD4(+) cell count (<250 cells/μl: 11.3%, 250-499: 17.8%, ≥500: 21.4%; p for trend=0.002). Of 197 persons with all four BED results available, 75.6% were classified as long-term infected throughout and 8.1% as false-recent throughout; the remainder changed classification once (12.2%) or twice (4.1%). Of 105 false-recent specimens retested with the avidity assay, 101 (96.2%) were correctly classified as "long-term." The BED assay's specificity varied with CD4(+) cell count and use of ART. Knowledge of these parameters for blood samples could improve incidence estimates using the BED assay. The additional use of an avidity assay may help to minimize the proportion of BED false-recent specimens.     

Repeat versus primary slings in patients with intrinsic sphincter deficiency

Introduction and hypothesis

Our goal was to compare outcomes of repeat vs. primary synthetic slings in patients with stress urinary incontinence (SUI) with intrinsic sphincter deficiency (ISD).

Materials and methods

We reviewed patients who underwent a sling for SUI with ISD from 2003 to 2010. The patients were divided into two groups according to whether they underwent primary or repeat sling. Surgical success was defined as no incontinence and no reintervention (i.e., urethral bulking) during follow-up. Statistical analysis included the unpaired t test, Wilcoxon rank sums test, chi-squared/Fisher’s exact tests, and logistic regression to identify risk factors associated with failure.

Results

Six hundred and thirty-seven patients with ISD underwent a sling procedure at our institution; 557 (87 %) a primary sling and 80 (13 %) a repeat sling. Patient demographics were similar. Preoperatively, patients with recurrent SUI reported more subjective bother. Mean follow-up was 66.5 weeks (24–374). Success was achieved in 81 % of primary compared with 55 % of repeat slings (p?<?0.0001). Repeat patients were 3.4 times more likely to fail surgery [odds ratio (OR)?=?3.43, 95 % confidence interval (CI) 2.1–5.6]. Additionally 30 % of the repeat group underwent urethral bulking postoperatively compared with 8.6 % in the primary group (OR?=?4.4, 95 % CI 2.5–7.7). Prior incontinence procedures, a positive supine stress test, and transobturator sling were independent risk factors for failure. Among the types of slings placed (transobturator, retropubic, tensioned pubovaginal), pubovaginal slings were most successful (OR?=?2.7, 95 % CI 1.4–5.2).

Conclusion

In women with ISD, repeat slings are associated with lower success rates compared with primary slings. Pubovaginal slings resulted in the highest success rate compared with both transobturator and retropubic slings.     

ECG changes in patients with acute ethanol intoxication

Objectives. To assess how ethanol in potential lethal serum concentrations affects features of the ECG that may be associated with cardiac arrhythmias. Design. We included 84 patients, who were hospitalised with assumed acute ethanol intoxication. In the emergency room resting ECG was recorded and blood was collected for serum osmolality measurement used as a proxy for ethanol level. Thirty-two also had ECG recorded at discharge. Twenty-seven hospitalised patients without known alcohol ingestion served as controls. ECG segment durations were compared with controls and related to intoxication level. Results. In subjects with moderately elevated to high serum osmolality, the P wave and QTc intervals were prolonged compared with sober subjects. P wave, PR, QRS and QTc intervals were longer when the subjects had high blood ethanol levels (at admission) than at discharge (p-values: 0.0001, 0.0002, 0.010 and < 0.0001 for P wave, PR, QRS and QTc intervals. n = 32). Conclusions. Ethanol at high to very high blood concentration causes several changes in the ECG that might be associated with increased risk of arrhythmias.     

Effect of topical application of fluoride gel NaF 2% on enzymatic and non-enzymatic antioxidant parameters of saliva

ObjectiveThe aim of the study was to evaluate the effect of topical fluoride gel NaF 2% application on antioxidant parameters of whole saliva from children.DesignThe saliva mechanically stimulated with parafilm was collected from 25 children (6–12 years) attending the Clinic of Paediatric Dentistry of Universidade Cruzeiro do Sul, São Paulo, Brazil, before (control group) and immediately after application of neutral fluoride gel NaF 2% (fluoride-gel group), according to the Standards for Research Using Human Subjects, Resolution 196/96 of the USA National Health Council of 10/10/1996. Afterwards, pre-post ferric-reducing antioxidant power (FRAP), trolox-equivalent antioxidant capacity (TEAC), uric acid, reduced/oxidised glutathione content (GSH/GSSG) and total peroxidase activity (TPO) were evaluated in whole saliva of both groups.ResultsAll non-enzymatic antioxidant parameters were augmented by fluoride-gel NaF 2% application, whereas a notable reduction (31%) of peroxidase activity was concomitantly observed in the children's saliva (p ≤ 0.05). Nevertheless, the reducing power of saliva was kept unaltered under these circumstances (p ≤ 0.05).ConclusionsDespite the reduced activity of peroxidase (an important antimicrobial and antioxidant enzyme), the topical fluoride gel NaF 2% favourably stimulated the release of non-enzymatic antioxidant components of saliva, sustaining the reducing power of saliva and the natural defences of the oral cavity.     

How does brain activation differ in children with unilateral cerebral palsy compared to typically developing children,during active and passive movements,and tactile stimulation? An fMRI study

The aim of the functional magnetic resonance imaging (fMRI) study was to investigate brain activation associated with active and passive movements, and tactile stimulation in 17 children with right-sided unilateral cerebral palsy (CP), compared to 19 typically developing children (TD). The active movements consisted of repetitive opening and closing of the hand. For passive movements, an MRI-compatible robot moved the finger up and down. Tactile stimulation was provided by manually stroking the dorsal surface of the hand with a sponge cotton cloth. In both groups, contralateral primary sensorimotor cortex activation (SM1) was seen for all tasks, as well as additional contralateral primary somatosensory cortex (S1) activation for passive movements. Ipsilateral cerebellar activity was observed in TD children during all tasks, but only during active movements in CP children. Of interest was additional ipsilateral SM1 recruitment in CP during active movements as well as ipsilateral S1 activation during passive movements and tactile stimulation. Another interesting new finding was the contralateral cerebellum activation in both groups during different tasks, also in cerebellar areas not primarily linked to the sensorimotor network. Active movements elicited significantly more brain activation in CP compared to TD children. In both groups, active movements displayed significantly more brain activation compared to passive movements and tactile stimulation.     

Driving and off‐road impairments underlying failure on road testing in Parkinson's disease

Parkinson's disease (PD) affects driving ability. We aimed to determine the most critical impairments in specific road skills and in clinical characteristics leading to failure on a road test in PD. In this cross‐sectional study, certified driving assessment experts evaluated specific driving skills in 104 active, licensed drivers with PD using a standardized, on‐road checklist and issued a global decision of pass/fail. Participants also completed an off‐road evaluation assessing demographic features, disease characteristics, motor function, vision, and cognition. The most important driving skills and off‐road predictors of the pass/fail outcome were identified using multivariate stepwise regression analyses. Eighty‐six (65%) passed and 36 (35%) failed the on‐road driving evaluation. Persons who failed performed worse on all on‐road items. When adjusted for age and gender, poor performances on lateral positioning at low speed, speed adaptations at high speed, and left turning maneuvers yielded the best model that determined the pass/fail decision (R² = 0.56). The fail group performed poorer on all motor, visual, and cognitive tests. Measures of visual scanning, motor severity, PD subtype, visual acuity, executive functions, and divided attention were independent predictors of pass/fail decisions in the multivariate model (R² = 0.60). Our study demonstrated that failure on a road test in PD is determined by impairments in specific driving skills and associated with deficits in motor, visual, executive, and visuospatial functions. These findings point to specific driving and off‐road impairments that can be targeted in multimodal rehabilitation programs for drivers with PD. © 2013 International Parkinson and Movement Disorder Society     

Comparison Between Pre-Exhaustion and Traditional Exercise Order on Muscle Activation and Performance in Trained Men

The purpose of this study was to measure the acute effects of pre-exhaustion vs. traditional exercise order on neuromuscular performance and sEMG in trained men. Fourteen young, healthy, resistance trained men (age: 25.5 ± 4.0 years, height: 174.9 ± 4.1 cm, and total body mass: 80.0 ± 11.1 kg) took part of this study. All tests were randomized and counterbalanced for all subjects and experimental conditions. Volunteers attended one session in the laboratory. First, they performed ten repetition maximum (10RM) tests for each exercise (bench press and triceps pushdown) separately. Secondly, they performed all three conditions at 10RM: pre-test (bench press and triceps pushdown, separately), pre-exhaustion (triceps pushdown+bench press, PE) and traditional (bench press+triceps pushdown, TR), and rested 30 minutes between conditions. Results showed that pre-test was significantly greater than PE (p = 0.031) but not different than TR, for total volume load lifted. There was a significant difference between the pre-test and the time-course of lactate measures (p = 0.07). For bench press muscle activity of the pectoralis major, the last repetition was significantly greater than the first repetition (pre-test: p = 0.006, PE: p = 0.016, and TR: p = 0.005). Also, for muscle activity of the triceps brachii, the last repetition was significantly greater than the first repetition (pre-test: p = 0.001, PE: p = 0.005, and TR: p = 0.006). For triceps pushdown, muscle activity of the triceps brachii, the last repetition was significantly greater than the first repetition (pre-test: p = 0.006, PE: p = 0.016, and TR: p = 0.005). For RPE, there were no significant differences between PE and TR (p = 0.15). Our results suggest that exercise order decreases repetitions performed, however, neuromuscular fatigue, lactate, and RPE are not impacted. The lack of difference in total volume load lifted between PE and TR might explain, at least in part, the similar metabolic and perceptual responses.

Key points

• The effects of different exercise order schemes (e.g. PE and TR) on muscle activity and strength performance indicated that similar responses were observed when comparing these schemes.
• Strength and conditioning coaches should consider these results when prescribing resistance training programs.
• The primary target (e.g. muscle group) of the training session should trained first, when fatigue level low, in order to maximize training outcomes.

Key words: Exercise performance, resistance training, biomechanics     

Disease-directed design of biodegradable polymers: Reactive oxygen species and pH-responsive micellar nanoparticles for anticancer drug delivery

Herein, we report reactive oxygen species (ROS)- and pH-responsive biodegradable polyethylene glycol (PEG)-block-polycarbonate by installing thioether groups onto the polycarbonate and its self-assembled core/shell structured micelles for anticancer drug delivery. Oxidation of thioethers to sulfoxide and subsequently sulfone induces an increase in hydrophilicity, resulting in more hydrophilic micellar core. This phase-change caused the micelles to swell and enhance cargo release. Carboxylic acid groups have also been installed onto thioether-containing polycarbonate to promote loading of amine-containing anticancer doxorubicin through electrostatic interaction. Urea-functionalized thioether-containing PEG-block-polycarbonates were synthesized to mix with the acid-functionalized PEG-block-polycarbonate for stabilizing micelle structure through hydrogen-bonding interaction. The mixed micelles were 50?nm in diameter and had a 25?wt% loading capacity for doxorubicin. Enhanced drug release from the micelles was triggered by low pH and high content of ROS. Drug-encapsulated micelles accumulated in tumors through leaky tumor vasculature in PC-3 human prostate cancer xenograft mouse model.