Sonographic assessment of subacromial bursa distension during arm abduction: establishing a threshold value in the diagnosis of subacromial impingement syndrome

Purpose

In this study, we aimed to establish a quantitative threshold value in the diagnosis of subacromial impingement syndrome by measuring the thickness of the subacromial bursa during abduction and adduction.

Materials and methods

Forty-five patients with subacromial impingement syndrome and 54 healthy individuals underwent dynamic shoulder ultrasonography. The subacromial bursa, between the supraspinatus tendon margin and peribursal adipose tissue, was measured between the acromion and humeral head at its widest part. The subacromial impingement ratio was calculated by dividing the subacromial bursa thickness during abduction to the subacromial bursa thickness during adduction. Shapiro–Wilk test was used in the assessment of normal distribution of parameters.

Results

The mean subacromial bursa thickness in the abduction position was 1.8 ± 1.1 mm in the study group and 0.9 ± 0.3 mm in the control group. The mean subacromial bursa thickness in the adduction position was 0.9 ± 0.5 mm in the study group and 0.8 ± 0.3 mm in the control group. The subacromial impingement ratio showed a statistically significant difference between groups (p < 0.0001), and the ratio being 2.0 ± 0.5 in the study group and 1.2 ± 0.1 in the control group. For measurements performed in the abduction position, the best cut-off value was calculated as 1.3 mm, and sensitivity and specificity were 70.6 and 85.2%, respectively. The best cut-off value was 1.4 for the subacromial impingement ratio, and sensitivity and specificity were 88.2 and 96.3%, respectively.

Conclusion

Subacromial impingement ratio is a very practical and reliable method in subacromial impingement syndrome diagnosis.

     

Epitope mapping of human thyrotropin

Epitope mapping of hTSH was carried out using 19 monoclonal antibodies prepared with hTSH or its beta-subunit as antigen. The affinity constants of the monoclonal antibodies ranged from 9.6 X 10(7) to 5.7 X 10(9) mol/l for hTSH. The binding activities of monoclonal antibodies were maintained or in some cases rather enhanced after removal of the sugar moiety of the subunits of hTSH, and completely diminished after reduction of intramolecular S-S bonds in the subunits of hTSH. Ten monoclonal antibodies recognized the epitopes on hTSH (alpha:beta subunit combined form) and on free alpha-subunit form. Eight other antibodies recognized the epitopes on free/or combined form of beta-subunit, all of which did not recognize any other human glycoprotein hormones. The monoclonal antibodies directed against the alpha-subunit could bind also other human glycoprotein hormones to a varying extent. On the basis of results from competitive binding studies, the antibodies directed against alpha-subunit and those against beta-subunit were each classified into five subgroups recognizing different antigenic determinants. The remaining one antibody recognized an epitope expressed only by hTSH and not by the free subunits. In addition, a positive cooperativity on the binding of hTSH was observed between monoclonal antibodies directed towards a particular epitope on the alpha-subunit and those towards a epitope on the beta-subunit. From these data, two-dimensional map of epitopes on hTSH was constructed. The epitopes on each subunit were found to form a cluster with complicated overlapping, suggesting a highly conformational structure.     

Extended Use of the Control-IQ Closed-Loop Control System in Children With Type 1 Diabetes

OBJECTIVETo further evaluate the safety and efficacy of the Control-IQ closed-loop control (CLC) system in children with type 1 diabetes.RESEARCH DESIGN AND METHODSAfter a 16-week randomized clinical trial (RCT) comparing CLC with sensor-augmented pump (SAP) therapy in 101 children 6–13 years old with type 1 diabetes, 22 participants in the SAP group initiated use of the CLC system (referred to as SAP-CLC cohort), and 78 participants in the CLC group continued use of CLC (CLC-CLC cohort) for 12 weeks.RESULTSIn the SAP-CLC cohort, mean percentage of time in range 70–180 mg/dL (TIR) increased from 55 ± 13% using SAP during the RCT to 65 ± 10% using CLC (P < 0.001), with 36% of the cohort achieving TIR >70% plus time <54 mg/dL <1% compared with 14% when using SAP (P = 0.03). Substantial improvement in TIR was seen after the 1st day of CLC. Time <70 mg/dL decreased from 1.80% to 1.34% (P < 0.001). In the CLC-CLC cohort, mean TIR increased from 53 ± 17% prerandomization to 67 ± 10% during the RCT and remained reasonably stable at 66 ± 10% through the 12 weeks post-RCT. No episodes of diabetic ketoacidosis or severe hypoglycemia occurred in either cohort.CONCLUSIONSThis further evaluation of the Control-IQ CLC system supports the findings of the preceding RCT that use of a closed-loop system can safely improve glycemic control in children 6–13 years old with type 1 diabetes from the 1st day of use and demonstrates that these improvements can be sustained through 28 weeks of use.     

Postprandial thermogenesis at rest and postexercise before and after physical training in lean, obese, and mildly diabetic men.

To determine the independent impact of physical training on postprandial thermogenesis at rest and after 1 hour of cycling at 100 W, 10 lean (15% +/- 1% body fat), 10 obese (33% +/- 2% fat), and six obese diet-controlled, type II diabetic men (34% +/- 4% fat) underwent 12 weeks of vigorous cycle ergometer training (4 h/wk at approximately 70% of maximum oxygen consumption [VO2max]) while maintaining body weight and composition. Body weight was held constant by refeeding the energy expended in each training session. Cardiorespiratory fitness increased by approximately 27%, but body weight and fat did not change. Before and at least 4 days after the last exercise session, energy expenditure was measured for 3 hours under four conditions: (1) rest, no meal; (2) rest, after a 720-kcal mixed meal; (3) postexercise after 1 hour cycling, no meal; and (4) postexercise, meal after exercise. The thermic effect of food was calculated as postprandial minus postabsorptive energy expenditure at rest and postexercise (kcal/3 h). Before and after training, the thermic effect of food during rest was lower in obese than in lean men, and lower in diabetic than in obese men (P less than .05). Thermogenesis was improved after short-term exercise in obese and diabetic men compared with that at rest, but was not normalized (P less than .05 for lean v obese, diabetic men). A significant effect of training on thermogenesis was due to a small but significant increase after training for diabetic men under the postexercise condition. Thus, while short-term exercise enhances but does not normalize thermogenesis in obese and diabetic men, long-term exercise training leading to increased cardiorespiratory fitness, in the absence of changes in body composition, leads to a small increase in thermogenesis in diabetic men, which manifests only after a short period of exercise.     

Semaphorin 6D regulates the late phase of CD4+ T cell primary immune responses

The semaphorin and plexin family of ligand and receptor proteins provides important axon guidance cues required for development. Recent studies have expanded the role of semaphorins and plexins in the regulation of cardiac, circulatory and immune system function. Within the immune system, semaphorins and plexins regulate cell–cell interactions through a complex network of receptor and ligand pairs. Immune cells at different stages of development often express multiple semaphorins and plexins, leading to multivariate interactions, involving more than one ligand and receptor within each functional group. Because of this complexity, the significance of semaphorin and plexin regulation on individual immune cell types has yet to be fully appreciated. In this work, we examined the regulation of T cells by semaphorin 6D. Both in vitro and in vivo T cell stimulation enhanced semaphorin 6D expression. However, semaphorin 6D was only expressed by a majority of T cells during the late phases of activation. Consequently, the targeted disruption of semaphorin 6D receptor–ligand interactions inhibited T cell proliferation at late but not early phases of activation. This proliferation defect was associated with reduced linker of activated T cells protein phosphorylation, which may reflect semaphorin 6D regulation of c-Abl kinase activity. Semaphorin 6D disruption also inhibited expression of CD127, which is required during the multiphase antigen-presenting cell and T cell interactions leading to selection of long-lived lymphocytes. This work reveals a role for semaphorin 6D as a regulator of the late phase of primary immune responses.     

Activity performance problems of patients with cardiac diseases and their impact on quality of life

[Purpose] To describe the functional consequences of patients with cardiac diseases and analyze associations between activity limitations and quality of life. [Subjects and Methods] Seventy subjects (mean age: 60.1±12.0 years) were being treated by Physical Medicine and Rehabilitation and Cardiology Departments were included in the study. Activity limitations and participation restrictions as perceived by the individual were measured by the Canadian Occupational Performance Measure (COPM). The Nottingham Extended Activities of Daily Living (NEADL) Scale was used to describe limitations in daily living activities. To detect the impact of activity limitations on quality of life the Nottingham Health Profile (NHP) was used. [Results] The subjects described 46 different types of problematic activities. The five most identified problems were walking (45.7%), climbing up the stairs (41.4%), bathing (30%), dressing (28.6%) and outings (27.1%). The associations between COPM performance score with all subgroups of NEADL and NHP; total, energy, physical abilities subgroups, were statistically significant. [Conclusion] Our results showed that patients with cardiac diseases reported problems with a wide range of activities, and that also quality of life may be affected by activities of daily living. COPM can be provided as a patient-focused outcome measure, and it may be a useful tool for identifying those problems.Key words: Activity limitation, Cardiac diseases, Quality of life     

Ricolinostat (ACY‐1215) induced inhibition of aggresome formation accelerates carfilzomib‐induced multiple myeloma cell death

Proteasome inhibition induces the accumulation of aggregated misfolded/ubiquitinated proteins in the aggresome; conversely, histone deacetylase 6 (HDAC6) inhibition blocks aggresome formation. Although this rationale has been the basis of proteasome inhibitor (PI) and HDAC6 inhibitor combination studies, the role of disruption of aggresome formation by HDAC6 inhibition has not yet been studied in multiple myeloma (MM). The present study aimed to evaluate the impact of carfilzomib (CFZ) in combination with a selective HDAC6 inhibitor (ricolinostat) in MM cells with respect to the aggresome‐proteolysis pathway. We observed that combination treatment of CFZ with ricolinostat triggered synergistic anti‐MM effects, even in bortezomib‐resistant cells. Immunofluorescent staining showed that CFZ increased the accumulation of ubiquitinated proteins and protein aggregates in the cytoplasm, as well as the engulfment of aggregated ubiquitinated proteins by autophagosomes, which was blocked by ricolinostat. Electron microscopy imaging showed increased autophagy triggered by CFZ, which was inhibited by the addition of ACY‐1215. Finally, an in vivo mouse xenograft study confirmed a decrease in tumour volume, associated with apoptosis, following treatment with CFZ in combination with ricolinostat. Our results suggest that ricolinostat inhibits aggresome formation, caused by CFZ‐induced inhibition of the proteasome pathway, resulting in enhanced apoptosis in MM cells.