HIV-1 Nef interferes with T-lymphocyte circulation through confined environments in vivo

HIV-1 negative factor (Nef) elevates virus replication and contributes to immune evasion in vivo. As one of its established in vitro activities, Nef interferes with T-lymphocyte chemotaxis by reducing host cell actin dynamics. To explore Nef’s influence on in vivo recirculation of T lymphocytes, we assessed lymph-node homing of Nef-expressing primary murine lymphocytes and found a drastic impairment in homing to peripheral lymph nodes. Intravital imaging and 3D immunofluorescence reconstruction of lymph nodes revealed that Nef potently impaired T-lymphocyte extravasation through high endothelial venules and reduced subsequent parenchymal motility. Ex vivo analyses of transendothelial migration revealed that Nef disrupted T-lymphocyte polarization and interfered with diapedesis and migration in the narrow subendothelial space. Consistently, Nef specifically affected T-lymphocyte motility modes used in dense environments that pose high physical barriers to migration. Mechanistically, inhibition of lymph node homing, subendothelial migration and cell polarization, but not diapedesis, depended on Nef’s ability to inhibit host cell actin remodeling. Nef-mediated interference with in vivo recirculation of T lymphocytes may compromise T-cell help and thus represents an important mechanism for its function as a HIV pathogenicity factor.     

Solution‐Processable Donor‐Acceptor‐Donor Oligomers with Cross‐Linkable Functionality

Electron‐acceptor units, combined with bithiophene substituted with flexible chains end‐functionalized with cross‐linkable moieties, provide soluble donor‐acceptor‐donor (DAD) π‐conjugated oligomer‐type molecules with cross‐linking ability and broad absorption in the visible spectrum. A study on the cross‐linking conditions of the new oligomers to yield insoluble polymer networks is presented, including conditions for obtaining polymer films over poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate‐covered substrates. The combination of the DAD molecular design and cross‐linking functionality opens prospects for applications in solution‐processed small‐molecule solar cells with morphologically‐stable organic layers.

     

Discordance between ambulatory monitoring and programmed stimulation in assessing efficacy of class IA antiarrhythmic agents in patients with ventricular tachycardia

Concordance between programmed stimulation and 24 hour ambulatory electrocardiographic (Holter) monitoring was studied in 54 patients with sustained ventricular tachycardia during 84 therapeutic trials with class IA antiarrhythmic agents. During baseline studies before treatment, all patients had frequent (greater than or equal to 30/h) ventricular premature complexes on Holter recordings and sustained ventricular tachycardia inducible by one to three extrastimuli. During treatment, programmed stimulation and Holter monitoring were repeated. Efficacy of treatment determined by programmed stimulation (ventricular tachycardia no longer inducible or nonsustained) was compared with three Holter criteria of efficacy: I = 83% or more reduction of ventricular premature complexes and abolition of ventricular tachycardia; II = 50% or more reduction of ventricular premature complexes and 90% or more reduction of couplets and abolition of ventricular tachycardia; III = abolition of ventricular tachycardia in patients with ventricular tachycardia during a baseline Holter recording. Treatments were judged effective by programmed stimulation criteria in only 25% of cases but in 51, 63 and 75% of cases by Holter criterion I, II and III, respectively. Results of programmed stimulation and Holter monitor were discordant (effective by one criterion but ineffective by the other) in 50% of cases using Holter criterion I, in 54% using Holter criterion II and in 61% using Holter criterion III. In the majority of discordant results, treatments appeared efficacious by Holter criteria but ineffective by programmed stimulation criteria, suggesting insensitivity of efficacy by Holter criteria or nonspecificity of induced ventricular tachycardia during treatment, or both.     

The late effect of Kinesio Taping® on handgrip strength

Kinesio Taping^® elastic tape is increasingly used in physiotherapy treatment. However, there is a lack of scientific research regarding the late effects of its use. This study quantified the late effects of applying the Kinesio Taping^® elastic tape by measuring changes in handgrip muscle strength after 24, 48 and 72 h of application. The Kinesio Taping^® elastic tape was applied on the dominant and non-dominant limbs of 36 volunteers randomly assigned to three groups: muscle facilitation, muscle inhibition and control group. The statistical test showed there was a statistically significant difference among all groups of dominant limb and non-dominant limb. However, the analysis on intragroup relationship to periods of application (Initial, 24, 48 and 72 h) and the interaction among repeated measures showed there was no statistically significant difference. This result may contribute to the investigation of the late effects of the Kinesio Taping^® elastic tape on the physical rehabilitation.     

Myocardial tissue remodeling after orthotopic heart transplantation: a pilot cardiac magnetic resonance study

After orthotopic heart transplantation (OHT), the allograft undergoes characteristic alterations in myocardial structure, including hypertrophy, increased ventricular stiffness, ischemia, and inflammation, all of which may decrease overall graft survival. Methods to quantify these phenotypes may clarify the pathophysiology of progressive graft dysfunction post-OHT. We performed cardiac magnetic resonance (CMR) with T1 mapping in 26 OHT recipients (mean age 47?±?7 years, 30?% female, median follow-up post-OHT 6 months) and 30 age-matched healthy volunteers (mean age 50.5?±?15 years; LVEF 63.5?±?7?%). OHT recipients had a normal left ventricular ejection fraction (LVEF 65.3?±?11?%) with higher LV mass relative to age-matched healthy volunteers (114?±?27 vs. 85.8?±?18 g; p?<?0.001). There was no late gadolinium enhancement in either group. Both myocardial extracellular volume fraction (ECV) and intracellular lifetime of water (τ_ic), a measure of cardiomyocyte hypertrophy, were higher in patients post-OHT (ECV: 0.39?±?0.06 vs. 0.28?±?0.03, p?<?0.0001; τ_ic: 0.12?±?0.08 vs. 0.08?±?0.03, p?<?0.001). ECV was associated with LV mass (r?=?0.74, p?<?0.001). In follow-up, OHT recipients with normal biopsies by pathology (ISHLT grade 0R) in the first year post-OHT exhibited a lower ECV relative to patients with any rejection ≥2R (0.35?±?0.02 for 0R vs. 0.45?±?0, p?<?0.001). Higher ECV but not LVEF was significantly associated with a reduced rejection-free survival. After OHT, markers of tissue remodeling by CMR (ECV and τ_ic) are elevated and associated with myocardial hypertrophy. Interstitial myocardial remodeling (by ECV) is associated with cellular rejection. Further research on the impact of graft preservation and early immunosuppression on tissue-level remodeling of the allograft is necessary to delineate the clinical implications of these findings.     

Pancreatic ductal system obstruction and acute recurrent pancreatitis

Acute recurrent pancreatitis is a clinical entity largely associated with pancreatic ductal obstruction. This latter includes congenital variants, of which pancreas divisum is the most frequent but also controversial, chronic pancreatitis, tumors of the pancreaticobiliary junction and sphincter of Oddi dysfunction. This review summarizes current knowledge about diagnostic work-up and therapy of these conditions.     

Evaluation of Irreversible Compression Ratios for Medical Images Thin Slice CT and Update of Canadian Association of Radiologists (CAR) Guidelines

In June 2008, the Canadian Association of Radiologists published its Standards for Irreversible Compression in Digital Diagnostic Imaging within Radiology (Canadian Association of Radiologists 2012). The study suggested that at low levels of compression there was no difference in diagnostic accuracy between uncompressed JPEG and JPEG 2000. There were two exceptions; CT neurological and CT body images resulted in lower rating of image quality (Koff et al., J Digit Imaging 22(6):569–78, 2009). The slice thicknesses used in the previous study were greater than 5 mm. However, other studies (Ringl et al., Radiology 240:869–87, 2006) suggest that thin CT slices might modify image tolerance to irreversible compression. Therefore, a new clinical evaluation using CT slices less than 3 mm was initiated. We examined CT images in four body regions (chest, body, musculoskeletal, and neurological). Twenty-five radiologists from across Canada participated. Each read a total of 70 CTs in his specialty; 10 at each of seven levels of compression (uncompressed, JPEG and JPEG 2000 at low, medium, and high compression (varying by region)). Each reader diagnosed the case, rated his confidence, and compared the compressed to the uncompressed image and rated the degree of degradation. Data were analyzed for sensitivity, specificity, accuracy, confidence, and degradation at three levels and two types of compression as well as the original image. There were no overall differences in sensitivity, specificity, accuracy, or confidence. JPEG images, at all levels of compression, were rated lower in terms of perceived difference (4.16/5 vs. 4.53/5 for JPEG 2000 and 4.68/5 for uncompressed). However, the rating of perceived difference was not significantly correlated with accuracy. Analysis of individual body regions did not reveal any systematic effects of compression in any region.