Thymic masses of the middle mediastinum: report of 2 cases and review of the literature

Although thymic lesions are relatively common causes of anterior mediastinal masses, they can rarely arise in other mediastinal compartments, as it is well recognized that thymic tissue can lie in ectopic intrathoracic locations. A thymic mass within the middle mediastinum has rarely been reported, with only a single case of a thymic cyst described and no reports of a middle mediastinal thymoma. We report 2 thymic masses (1 thymoma and 1 thymic cyst) found to arise in the middle mediastinum.     

Evidence of male hypogonadism at an early age as a familial risk of type 2 diabetes

Objective

Previous investigations provide evidence of an association of hypogonadism with type 2 diabetes in men, and low testosterone levels have been regarded a risk factor for the disease. Since a strong genetic predisposition to type 2 diabetes has been demonstrated, here we investigate a possible tendency towards hypogonadism in young male offspring of diabetic parents.

Material and methods

The study compares 32 male offspring of diabetic parents with 31 male offspring of nondiabetic parents matched by age. The subjects comprised boys (9–17 years) and young adults (19–25 years). Anthropomorphic measurements were made in all subjects. Fasting blood samples were analyzed for glucose and serum concentrations of testosterone (T), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), insulin and leptin were measured by ELISA. Free testosterone (FT) was calculated using T and SHBG levels.

Results

Serum T, FT and bioavailable T (BAT) levels in offspring of diabetic parents were significantly lower than those of offspring of nondiabetic parents across all age groups. Mean serum LH levels were also lower in offspring of diabetic parents compared to the controls. Although LH levels in young adults with diabetic parents, tended to be lower than those of age-matched controls but the difference was not statistically significant. Serum insulin and leptin, and insulin resistance measured by HOMA-IR were significantly raised in older offspring of diabetic parents but were within the normal range.

Conclusion

Whereas hypogonadism was the only indicator of a possible predisposition to metabolic dysfunction in peripubertal children of diabetic parents, a significant change in other metabolic markers becomes apparent at a more advanced age.     

Temperature changes during and after eccentric contractions and its effect on force and desmin loss in rat

The typical features of eccentric exercise-induced muscle damage is prolonged loss of muscle strength and the most rapid structural change in the fibers is loss of immunostaining for the intermediate filament protein, desmin. In this study isolated perfused rat muscle was used to examine the direct effect of temperature changes on the eccentric contraction-induced force and desmin loss. The left medial gastrocnemius muscle was separated and the entire lower limb was transferred into a prewarmed (35°C) organ bath. Temperature was adjusted to 31 or 39°C during and after eccentric contractions. Maximal isometric force and desmin loss were measured after 15 isometric or eccentric contractions. According to our data, organ bath temperature changes during or after eccentric contractions had no significant effect on force loss. However, a strong correlation between desmin loss and temperature changes during (r = 0.886, P< 0.05) and a weak correlation between desmin loss and temperature changes after (r= 0.699, P<0.05) eccentric contractions was observed. Our results suggest that cooling during eccentric contractions may decrease desmin loss but temperature changes after eccentric contractions have no effect on desmin loss.     

TIGIT regulates apoptosis of risky memory T cell subsets implicated in belatacept-resistant rejection

Belatacept confers increased patient and graft survival in renal transplant recipients relative to calcineurin inhibitors, but is associated with an increased rate of acute rejection. Recent immunophenotypic studies comparing pretransplant T cell phenotypes of patients who reject versus those who remain stable on belatacept identified three potential “risky” memory T cell subsets that potentially underlie belatacept-resistant rejection: CD4⁺ CD28⁺ T_EM, CD8⁺ CD28^null, and CD4⁺ CD57⁺ PD1⁻ subsets. Here, we compared key phenotypic and functional aspects of these human memory T cell subsets, with the goal of identifying additional potential targets to modulate them. Results demonstrate that TIGIT, an increasingly well-appreciated immune checkpoint receptor, was expressed on all three risky memory T cell subsets in vitro and in vivo in the presence of belatacept. Coculture of human memory CD4⁺ and CD8⁺ T cells with an agonistic anti-TIGIT mAb significantly increased apoptotic cell death of all three risky memory T cell subsets. Mechanistically, TIGIT-mediated apoptosis of risky memory T cells was dependent on FOXP3⁺ Treg, suggesting that agonism of the TIGIT pathway increases FOXP3⁺ Treg suppression of human memory T cell populations. Overall, these data suggest that TIGIT agonism could represent a new therapeutic target to inhibit belatacept-resistant rejection during transplantation.     

Obtaining EQ-5D-5L utilities from the disease specific quality of life Alzheimer’s disease scale: development and results from a mapping study

Quality of Life Research - The Quality of Life Alzheimer’s Disease Scale (QoL-AD) is commonly used to assess disease specific health-related quality of life (HRQoL) as rated by patients and...     

Enucleation and evisceration: an analysis of indications,histopathological findings,and surgical trends over 23 years at a tertiary care hospital in western Canada

Objective

To report indications for eye removal, histopathological diagnosis, and surgical trends in enucleation versus evisceration over a 23-year period.

Helically-driven granular mobility and gravity-variant scaling relations

This study discusses the role and function of helical design as it relates to slippage during translation of a vehicle in glass bead media. We show discrete element method (DEM) and multi-body dynamics (MBD) simulations and experiments of a double-helix Archimedes screw propelled vehicle traveling in a bed of soda-lime glass beads. Utilizing granular parameters from the literature and a reduced Young''s modulus, we validate the set of granular parameters against experiments. The results suggest that MBD-DEM provides reliable dynamic velocity estimates. We provide the glass, ABS, and glass–ABS simulation parameters used to obtain these results. We also examine recently developed granular scaling laws for wheels applied to these shear-driven vehicles under three different simulated gravities. The results indicate that the system obeys gravity granular scaling laws for constant slip conditions but is limited in each gravity regime when slip begins to increase.

This study discusses the role and function of helical design as it relates to slippage during translation of a vehicle in glass bead media.     

Development of a composite degradable/nondegradable tissue-engineered vascular graft

The present study aimed to determine the feasibility of constructing a reinforced autologous vascular graft by combining the advantages of fibrin gel as an autologous cell carrier material with the inherent mechanical strength of an integrated mesh structure. It was hypothesized that the mesh and dynamic culture conditions could be combined to generate mechanically stable and implantable vascular grafts within a shorter cultivation period than traditional methods. A two-step moulding technique was developed to integrate a polyvinylidene fluoride (PVDF) mesh (pore size: 1-2 mm) in the wall of a fibrin-based vascular graft (I.D. 5 mm) seeded with carotid myofibroblasts. The graft was cultured under increasing physiological flow conditions for 2 weeks. Histology, burst strength, and suture retention strength were evaluated. Cell growth and tissue development was excellent within the fibrin gel matrix surrounding the PVDF fibers, and tissue structure demonstrated remarkable similarity to native tissue. The grafts were successfully subjected to physiological flow rates and pressure gradients from the outset, and mechanical properties were enhanced by the mesh structure. Mean suture retention strength of the graft tissue was 6.3 N and the burst strength was 236 mm Hg. Using the vascular composite graft technique, the production of tissue engineered, small-caliber vascular grafts with good mechanical properties within a conditioning period of 14 days is feasible.     

Predicting seizure-free status for temporal lobe epilepsy patients undergoing surgery: prognostic value of quantifying maximal metabolic asymmetry extending over a specified proportion of the temporal lobe.

Conventional visual analysis of brain (18)F-FDG PET scans is useful for predicting postsurgical improvement for temporal lobe epilepsy (TLE) patients, but prognostic value for identifying patients who will achieve seizure-free status is considerably lower. We aimed to develop an approach with which to quantitatively assess prognostically pertinent aspects of metabolic asymmetry in presurgical PET scans for forecasting postsurgical seizure-free clinical outcomes. METHODS: Presurgical brain PET scans of 75 TLE patients were examined using a display/analysis tool that quantified maximal metabolic asymmetry in a specified proportion (x%) of the temporal lobe pixels in the most asymmetric plane, generating a temporal lobe asymmetry index (T-AI(x)). Results of this analysis were compared with patients' actual postsurgical outcomes after an average of approximately 4 y of clinical follow-up. The investigation was divided into 2 main steps: The PET scans examined in the first step, selected by chronological order of scan acquisition dates, comprised just less than two thirds of the patient group studied (n=47) and were used to look for parameters predicting seizure-free postsurgical outcome; in the second step, the predictive value of the parameters suggested by the analysis in the first step was independently examined using the set of remaining PET scans (n=28) to check for wider applicability of the approach. RESULTS: Of the 75 patients studied, 42 became seizure free after surgery, whereas 33 continued to seize beyond the immediate postoperative period, during a mean 3.8-y follow-up interval. The specified proportion of temporal pixels with which to assess maximal asymmetry that provided the highest prognostic value with respect to achieving seizure-free status was 20%. Across the study population, those patients with scans having lower T-AI(20) values (corresponding to <40% difference in pixel intensities between left and right temporal lobes, among the 20% most asymmetric left-right pixel pairs measured in the most asymmetric plane) were only half as likely to continue to have seizures postsurgically as those with scans having higher T-AI(20) values (positive likelihood ratio for achieving seizure-free outcome, 1.98; 95% confidence interval, 1.07-3.67). Overall, those patients with greater maximal asymmetry, as indexed by higher T-AI(20) values, had a significantly decreased chance of achieving seizure-free status after surgery than those with lower degrees of asymmetry (P=0.017), and this same tendency was observed for both the first and second series of PET scans examined. CONCLUSION: A quantifying approach to assessing maximal temporal asymmetry over a specified proportion of the temporal lobe may help to predict whether patients will likely be free of seizures during the years after neurosurgical resection of epileptogenic tissue.