Slower Skeletal Muscle Oxygenation Kinetics in Adults With Complex Congenital Heart Disease

BackgroundAdults with complex congenital heart disease (CHD) show reduced aerobic exercise capacity and impaired skeletal muscle function compared with healthy peers. Peripheral muscle factors are presumed to be important contributors to the aerobic capacity, but the mechanisms are poorly understood. The aim of the present study was to investigate differences between adults with CHD and controls in muscle oxygenation kinetics at rest, and during and after exercise.MethodsSeventy-four patients with complex CHD (mean age 35.6 ± 14.3 years, female n = 22) were recruited. Seventy-four age- and sex-matched subjects were recruited as controls. Muscle oxygenation was successfully determined on the anterior portion of the deltoid muscle using near-infrared spectroscopy in 65 patients and 71 controls. Measurements were made at rest, during isotonic shoulder flexions (0-90°) to exhaustion, and during recovery.ResultsThe patients with CHD performed fewer shoulder flexions (40 ± 17 vs 69 ± 40; P < 0.001), had lower muscle oxygen saturation (StO₂) at rest (58 ± 18% vs 69 ± 18%; P < 0.001), slower desaturation rate at exercise onset (?9.7 ± 5.9 vs ?15.1 ± 6.5% StO₂ × 3.5 s^?1, P <0.001), and slower resaturation rate post exercise (4.0 ± 2.7 vs 5.4 ± 3.6% StO₂ × 3.5 s^?1; P = 0.009) compared with the controls.ConclusionsIn comparison with age- and sex-matched controls, adults with complex CHD had slower oxygenation kinetics. This altered skeletal muscle metabolism might contribute to the impaired skeletal muscle endurance capacity shown and thereby also to the reduced aerobic capacity in this population.     

Parent–youth conflict as a predictor of depression in adulthood: a 15-year follow-up of a community-based cohort

Experiencing conflictual relations with one’s parents while growing up has been linked to onset, recurrence, and worse treatment outcome of adolescent depression. While this suggests that significant problems in the parent–youth relationship make depressive disorders more relentless, it is not clear whether this effect lasts into adulthood. Our aim was to examine if major and minor conflict with parents while growing up predicts depression in adulthood in youth with and without a history of depression. We utilized data from the Uppsala Longitudinal Adolescent Depression Study. This community-based cohort was assessed with structured diagnostic interviews both at age 16–17 and at follow-up 15 years later. The analyses included 382 individuals (227 with a history of child or adolescent depression; 155 peers without such a history). Binary logistic regression was used, adjusting for sex, disruptive behavior disorders, and additional family-related adversities. Among individuals with adolescent depression, major conflict with parents was strongly associated with adult depression (adjusted OR 2.28, 95% CI 1.07–4.87). While major conflict with parents was rare among non-depressed controls, a non-significant association of similar magnitude was still observed. Minor conflict, on the other hand, was not significantly associated with adult depression. Overall, conflict with parents did not predict adult anxiety disorders, substance use, suicidal behavior, somatoform disorders, or psychotic disorders. In conclusion, major parent–youth conflict during upbringing seems to be linked with an increased risk of depression in adulthood. These findings underscore the need to consider contextual/familial factors in the prevention and clinical management of early-life depression.     

Deep complex convolutional network for fast reconstruction of 3D late gadolinium enhancement cardiac MRI

Several deep‐learning models have been proposed to shorten MRI scan time. Prior deep‐learning models that utilize real‐valued kernels have limited capability to learn rich representations of complex MRI data. In this work, we utilize a complex‐valued convolutional network (?Net ) for fast reconstruction of highly under‐sampled MRI data and evaluate its ability to rapidly reconstruct 3D late gadolinium enhancement (LGE) data. ?Net preserves the complex nature and optimal combination of real and imaginary components of MRI data throughout the reconstruction process by utilizing complex‐valued convolution, novel radial batch normalization, and complex activation function layers in a U‐Net architecture. A prospectively under‐sampled 3D LGE cardiac MRI dataset of 219 patients (17 003 images) at acceleration rates R = 3 through R = 5 was used to evaluate ?Net . The dataset was further retrospectively under‐sampled to a maximum of R = 8 to simulate higher acceleration rates. We created three reconstructions of the 3D LGE dataset using (1) ?Net , (2) a compressed‐sensing‐based low‐dimensional‐structure self‐learning and thresholding algorithm (LOST), and (3) a real‐valued U‐Net (realNet) with the same number of parameters as ?Net . LOST‐reconstructed data were considered the reference for training and evaluation of all models. The reconstructed images were quantitatively evaluated using mean‐squared error (MSE) and the structural similarity index measure (SSIM), and subjectively evaluated by three independent readers. Quantitatively, ?Net ‐reconstructed images had significantly improved MSE and SSIM values compared with realNet (MSE, 0.077 versus 0.091; SSIM, 0.876 versus 0.733, respectively; p < 0.01). Subjective quality assessment showed that ?Net ‐reconstructed image quality was similar to that of compressed sensing and significantly better than that of realNet. ?Net reconstruction was also more than 300 times faster than compressed sensing. Retrospective under‐sampled images demonstrate the potential of ?Net at higher acceleration rates. ?Net enables fast reconstruction of highly accelerated 3D MRI with superior performance to real‐valued networks, and achieves faster reconstruction than compressed sensing.     

Extracellular HMGB1 as a therapeutic target in inflammatory diseases

Introduction: High-mobility group box 1 (HMGB1) is a ubiquitous nuclear protein that promotes inflammation when released extracellularly after cellular activation, stress, damage or death. HMGB1 operates as one of the most intriguing molecules in inflammatory disorders via recently elucidated signal and molecular transport mechanisms. Treatments based on antagonists specifically targeting extracellular HMGB1 have generated encouraging results in a wide number of experimental models of infectious and sterile inflammation. Clinical studies are still to come.

Areas covered: We here summarize recent advances regarding pathways for extracellular HMGB1 release, receptor usage, and functional consequences of post-translational modifications. The review also addresses results of preclinical HMGB1-targeted therapy studies in multiple inflammatory conditions and outlines the current status of emerging clinical HMGB1-specific antagonists.

Expert opinion: Blocking excessive amounts of extracellular HMGB1, particularly the disulfide isoform, offers an attractive clinical opportunity to ameliorate systemic inflammatory diseases. Therapeutic interventions to regulate intracellular HMGB1 biology must still await a deeper understanding of intracellular HMGB1 functions. Future work is needed to create more robust assays to evaluate functional bioactivity of HMGB1 antagonists. Forthcoming clinical studies would also greatly benefit from a development of antibody-based assays to quantify HMGB1 redox isoforms, presently assessed by mass spectrometry methods.     

Screw vs cement-implant-retained restorations: an experimental study in the beagle. Part 2. Immunohistochemical evaluation of the peri-implant tissues

Crestal bone loss has been reported to occur around dental implants. Even if the causes of this bone loss are not completely understood, the presence of a microgap between implant and abutment with a possible contamination of the internal portion of the implants has been suggested. The aim of this study was to see if there were differences in the vascular endothelial growth factor (VEGF) expression, microvessel density (MVD), proliferative activity (MIB-1), and inflammatory infiltrate in the soft tissues around implants with screwed and cemented abutments. Sandblasted and acid-etched implants were inserted in the mandibles of 6 Beagle dogs. Ten 3.5- x 10-mm root-form implants were inserted in each mandible. A total of 60 implants (30 with screwed abutments and 30 with cemented abutments) were used. After 12 months, all the bridges were removed and all abutments were checked for mobility. A total of 8 loosened screws (27%) were found in the screwed abutments, whereas no loosening was observed in cemented abutments. A gingival biopsy was performed in 8 implants with cemented abutments, in 8 implants with screwed abutments, and in 8 implants with unscrewed abutments. No statistically significant differences were found in the inflammatory infiltrate and in the MIB-1 among the different groups. No statistically significant difference was found in the MVD between screwed and cemented abutments (P = .2111), whereas there was a statistically significant difference in MVD between screwed and unscrewed abutments (P = .0277) and between cemented and unscrewed abutments (P = .0431). A low intensity of VEGF was prevalent in screwed and in cemented abutments, whereas a high intensity of VEGF was prevalent in unscrewed abutments. These facts could be explained by the effects induced, in the abutments that underwent a screw loosening, by the presence of bacteria inside the hollow portion of the implants or by enhanced reparative processes.