Recombinant bactericidal/permeability-increasing protein rBPI21 protects against pneumococcal disease

Bactericidal/permeability-increasing (BPI) protein has been shown to play an important role in innate immunity to gram-negative bacteria, by direct microbicidal as well as endotoxin-neutralizing action. Here we examined potential interactions between a recombinant 21-kDa bioactive fragment of BPI, rBPI21, and the gram-positive pathogen Streptococcus pneumoniae. rBPI21 bound to pneumococci and pneumolysin (Ply) in a direct and specific fashion. We observed an enhanced inflammatory response in mouse macrophages when rBPI21 was combined with killed pneumococci or supernatant from overnight growth of pneumococci. In addition, rBPI21 augmented the proapoptotic activity of Ply+ (but not Ply-) pneumococci in TLR4-defective murine macrophages (known to be defective also in their apoptotic response to pneumolysin) in a tumor necrosis factor alpha-dependent manner. rBPI21 also enhanced the association of pneumococci with murine macrophages. In a model of invasive pneumococcal disease in TLR4-defective mice, the intranasal administration of rBPI21 following intranasal inoculation of Ply+ pneumococci both enhanced upper respiratory tract cell apoptosis and prolonged survival. We have thus discovered a novel interaction between pneumococcus and rBPI21, a potent antimicrobial peptide previously considered to target only gram-negative bacteria.     

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     

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.