Neisserial outer membrane vesicles bind the coinhibitory receptor carcinoembryonic antigen-related cellular adhesion molecule 1 and suppress CD4+ T lymphocyte function

Pathogenic Neisseria bacteria naturally liberate outer membrane "blebs," which are presumed to contribute to pathology, and the detergent-extracted outer membrane vesicles (OMVs) from Neisseria meningitidis are currently employed as meningococcal vaccines in humans. While the composition of these vesicles reflects the bacteria from which they are derived, the functions of many of their constituent proteins remain unexplored. The neisserial colony opacity-associated Opa proteins function as adhesins, the majority of which mediate bacterial attachment to human carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs). Herein, we demonstrate that the Opa proteins within OMV preparations retain the capacity to bind the immunoreceptor tyrosine-based inhibitory motif-containing coinhibitory receptor CEACAM1. When CD4(+) T lymphocytes were exposed to OMVs from Opa-expressing bacteria, their activation and proliferation in response to a variety of stimuli were effectively halted. This potent immunosuppressive effect suggests that localized infection will generate a "zone of inhibition" resulting from the diffusion of membrane blebs into the surrounding tissues. Moreover, it demonstrates that OMV-based vaccines must be developed from strains that lack CEACAM1-binding Opa variants.     

Identification and dynamics of spontaneous burst initiation zones in unidimensional neuronal cultures

Spontaneous activity is typical of in vitro neural networks, often in the form of large population bursts. The origins of this activity are attributed to intrinsically bursting neurons and to noisy backgrounds as well as to recurrent network connections. Spontaneous activity is often observed to emanate from localized sources or initiation zones, propagating from there to excite large populations of neurons. In this study, we use unidimensional cultures to overcome experimental difficulties in identifying initiation zones in vivo and in dissociated two-dimensional cultures. We found that spontaneous activity in these cultures is initiated exclusively in localized zones that are characterized by high neuronal density but also by recurrent and inhibitory network connections. We demonstrate that initiation zones compete in driving network activity in a winner-takes-most scenario.     

The influence of preoperative teres minor muscle fatty degeneration on active external rotation following reverse total shoulder arthroplasty

BackgroundReverse total shoulder arthroplasty (rTSA) improves shoulder elevation in patients treated for cuff tear arthropathy (CTA) or irreparable massive cuff tears. Patient satisfaction can be limited by reduced active external rotation (AER). Rotator cuff muscles that externally rotate the shoulder are infraspinatus and teres minor (TM).AimThe purpose of this study was to assess the correlation between preoperative TM fatty degeneration and postoperative AER after rTSA performed for CTA or irreparable cuff tears.MethodsConstant scores and active range of motion were consecutively collected for 109 shoulders in 97 patients (mean: 75.73 ± 8.94 years; 31 male, 66 female) over a 10-year period. AER was evaluated with the humerus in adduction (AER1) and in abduction. TM muscle atrophy was scored according to Goutallier's classification, assessed on preoperative computed tomography scans.ResultsMultivariate analysis showed that TM fatty infiltration was a predictor of AER1. AER1 decreased by 4.9 degrees preoperatively and by 6.4 degrees at the final follow-up, for each increment in Goutallier grade (P = .02). Postoperatively, AER evaluated with humerus in abduction improved significantly (P < .001), but did not correlate with TM Goutallier grade. At a mean follow-up of 38 months (range: 24 to 96), mean Constant score improved from 20.5 ± 11.1 to 68.4 ± 14.9 (P < .001), as did shoulder active range of motion in all planes including AER1 (P < .001).ConclusionThis is the first study to quantify the inverse correlation between AER and TM Goutallier grade, both preoperatively and after rTSA; this information guides prognosis for patients with TM degeneration undergoing rTSA. Further studies are necessary to have a better understanding and find reliable solutions.Level of evidenceLevel III; Case Series     

REPIMPACT - a prospective longitudinal multisite study on the effects of repetitive head impacts in youth soccer

Brain Imaging and Behavior - Repetitive head impacts (RHI) are common in youth athletes participating in contact sports. RHI differ from concussions; they are considered hits to the head that...     

Predictors of improvement in diastolic function after transcatheter aortic valve implantation

Background

Aortic stenosis is associated with concentric left ventricle (LV) hypertrophy or remodeling resulting in impaired diastolic function and elevated left-sided filling pressure. We investigated the changes in LV geometry and LV filling hemodynamics, giving emphasis to parameters associated with changes in diastolic function after transcatheter aortic valve implantation (TAVI).

Methods

Comprehensive diastolic assessment was performed before and six months after TAVI in 70 patients with severe aortic stenosis. Patients with any degree of mitral stenosis or >mild left-sided valvular regurgitation were excluded.

Results

In the entire cohort six months after TAVI, LV end-diastolic diameter increased (44.1 ± 6 versus 45 ± 6 mm, P = 0.02), whereas LV mass and relative wall thickness (RWT) decreased (270.1 ± 76 versus 245.1 ± 75 g and 0.53 ± 0.15 versus 0.46 ± 0.1, respectively; P < 0.0001 for both). Lateral e′ increased (5.8 ± 2 versus 6.6 ± 3 cm/s, P = 0.03) and left atrium (LA) volume, E/e′ ratio, and systolic pulmonary pressure decreased (88.1 ± 30 versus 80 ± 28 cc, 18 ± 7.8 versus 16.3 ± 5.5, and 42.7 ± 14.9 versus 38.7 ± 12 mmHg, respectively; P < 0.05 for all), suggesting reduction in LA pressure. The improvement in LA volume and E/e′ was almost exclusively seen in patients with LV hypertrophy before TAVI (P < 0.05 both), as opposed to patients with concentric remodeling.

Conclusions

In our preliminary study, TAVI resulted in LV and LA reverse remodeling, and improved LV relaxation and LA filling pressure in patients with severe aortic stenosis and concentric hypertrophy. Patients with concentric remodeling at baseline seem to have limited improvement in LV diastolic function and filling pressure following TAVI, but larger clinical trials would be required to conclude if they have no improvement at all.     

The Use of Dietary Supplements to Alleviate Androgen Deprivation Therapy Side Effects during Prostate Cancer Treatment

Prostate cancer (PCa), the most commonly diagnosed cancer and second leading cause of male cancer death in Western societies, is typically androgen-dependent, a characteristic that underlies the rationale of androgen deprivation therapy (ADT). Approximately 90% of patients initially respond to ADT strategies, however many experience side effects including hot flashes, cardiotoxicity, metabolic and musculoskeletal alterations. This review summarizes pre-clinical and clinical studies investigating the ability of dietary supplements to alleviate adverse effects arising from ADT. In particular, we focus on herbal compounds, phytoestrogens, selenium (Se), fatty acids (FA), calcium, and Vitamins D and E. Indeed, there is some evidence that calcium and Vitamin D can prevent the development of osteoporosis during ADT. On the other hand, caution should be taken with the antioxidants Se and Vitamin E until the basis underlying their respective association with type 2 diabetes mellitus and PCa tumor development has been clarified. However, many other promising supplements have not yet been subjected large-scale clinical trials making it difficult to assess their efficacy. Given the demographic trend of increased PCa diagnoses and dependence on ADT as a major therapeutic strategy, further studies are required to objectively evaluate these supplements as adjuvant for PCa patients receiving ADT.