The Total Synthesis of Glycolipids from Streptococcus pneumoniae and a Re-evaluation of Their Immunological Activity.

Invariant natural killer (iNK) T cells, Type I iNKTs, are responsible for the production of pro-inflammatory cytokines which induce a systemic immune response. They are distinctive in possessing an semi-invariant T-cell receptor that recognizes glycolipid antigens presented by CD1d, a protein closely related to the class I major histocompatibility complex, conserved across multiple mammalian species in a class of proteins well-renowned for their high degree of polymorphism. This receptor's first potent identified antigen is the α-galactosylceramide, KRN7000, a synthetic glycosphingolipid closely related to those isolated from bacteria that were found on a Japanese marine sponge. A corresponding terrestrial antigen remained unidentified until two specific diacylglycerol-containing glycolipids, reported to activate iNKT cells, were isolated from Streptococcus pneumoniae. We report the total synthesis and immunological re-evaluation of these two glycolipids. The compounds are unable to meaningfully activate iNKT cells. Computational modelling shows that these ligands, while being capable of interacting with the CD1d receptor, create a different surface for the binary complex that makes formation of the ternary complex with the iNKT T-cell receptor difficult. Together these results suggest that the reported activity might have been due to an impurity in the original isolated sample and highlights the importance of taking care when reporting biological activity from isolated natural products.

A Comparison of the Effects of Stochastic Resonance Therapy, Whole-Body Vibration, and Balance Training on Pain Perception and Sensorimotor Function in Patients With Chronic Nonspecific Neck Pain: Protocol for a Randomized Controlled Trial.

BACKGROUND: Neck pain is a prevalent pathological condition, and together with low back pain, it presents as the leading cause of years lived with disability worldwide in 2015 and continues to contribute substantially to the global burden of disease. OBJECTIVE: This study will investigate and compare the effects of stochastic resonance therapy (SRT), whole-body vibration (WBV), and balance training (BLT) in the management of chronic nonspecific neck pain. METHODS: In total, 45 participants with chronic neck pain will be randomly allocated into SRT, WBV, and BLT groups. Pain intensity, pressure pain threshold, neck disability, and cervical joint position sense will be measured before, immediately after, and 15 minutes after the first intervention session and after 4 weeks of intervention. A follow-up postintervention measurement would be taken after 4 weeks. The SRT group will train on an SRT device (SRT Zeptor Medical plus noise, Zeptoring). The WBV group will train on a Galileo vibration device (Novotec Medical), while the BLT group will perform balance exercises. All participants shall train 3 times a week for a period of 4 weeks. Mixed ANOVA will be used to determine the main and effects of interactions within (before intervention, post intervention 1, post intervention 2, post intervention 3, and follow-up) and between (SRT, WBV, and BLT) factors on the study outcome variables. RESULTS: Recruitment of participants started in May 2021, and as of May 2022, a total of 20 patients have been enrolled in the study. All participants are expected to have completed the trial by the end of 2022, and data analysis will commence thereafter. CONCLUSIONS: The outcome of this study will shed closer light on the effects of SRT, WBV, and BLT on pain and function in patients with chronic neck pain. TRIAL REGISTRATION: German Clinical Trials Register DRKS00023881; https://tinyurl.com/ycxuhj37. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34430.

Management Options and Outcomes for Patients with Femoral Fractures with Post-Polio Syndrome of the Lower Extremity: A Critical Analysis Review.

Post-polio syndrome is characterized by a late functional deterioration (usually after >=15 years from the initial infection) in patients with a history of paralytic poliomyelitis infection, and it is defined by the March of Dimes criteria. Patients with post-polio syndrome are at increased risk for falls and associated hip and femoral fractures as a result of lower bone mineral density, decreased lean muscle mass, and musculoskeletal deformities. Current evidence suggests that treatment modalities for femoral fractures should emphasize fixation that allows early progressive weight-bearing and ambulation to optimize functional outcomes. Good results after hip arthroplasty have been described with both cemented and uncemented implants in patients who have been treated for osteoarthritis, but there has been little evidence guiding hip fracture management. Anatomic challenges that are encountered are osteoporotic bone, a valgus neck-shaft angle, increased femoral anteversion, and a small femoral canal diameter. Intramedullary nailing of hip and femoral fractures can be challenging due to the small femoral canal diameter that frequently is encountered. Alternative methods of fixation have shown promising results. These include the use of sliding hip screws for hip fracture management and fixed-angle locking plates for hip and femoral fracture management.