TAFRO syndrome is a systemic inflammatory disorder characterized by thrombocytopenia, anasarca including pleural effusion and ascites, fever, renal insufficiency, and organomegaly including hepatosplenomegaly and lymphadenopathy. Its onset may be acute or sub-acute, but its etiology is undetermined. Although several clinical and pathological characteristics of TAFRO syndrome resemble those of multicentric Castleman disease (MCD), other specific features can differentiate between them. Some TAFRO syndrome patients have been successfully treated with glucocorticoids and/or immunosuppressants, including cyclosporin A, tocilizumab and rituximab, whereas others are refractory to treatment, and eventually succumb to the disease. Early and reliable diagnoses and early treatments with appropriate agents are essential to enhancing patient survival. The present article reports the 2015 updated diagnostic criteria, disease severity classification and treatment strategy for TAFRO syndrome, as formulated by Japanese research teams. These criteria and classification have been applied and retrospectively validated on clinicopathologic data of 28 patients with this and similar conditions (e.g. MCD with serositis and thrombocytopenia).

Accumulation of Aβ peptides is a hallmark of Alzheimer's disease (AD) and is considered a causal factor in the pathogenesis of AD. β-Secretase (BACE1) is a key enzyme responsible for producing Aβ peptides, and thus agents that inhibit BACE1 should be beneficial for disease-modifying treatment of AD. Here we describe the discovery and optimization of novel oxazine-based BACE1 inhibitors by lowering amidine basicity with the incorporation of a double bond to improve brain penetration. Starting from a 1,3-dihydrooxazine lead 6 identified by a hit-to-lead SAR following HTS, we adopted a p K lowering strategy to reduce the P-gp efflux and the high hERG potential leading to the discovery of 15 that produced significant Aβ reduction with long duration in pharmacodynamic models and exhibited wide safety margins in cardiovascular safety models. This compound improved the brain-to-plasma ratio relative to 6 by reducing P-gp recognition, which was demonstrated by a P-gp knockout mouse model.

Basketball is a major sport worldwide among different age groups that leads to a high frequency of injuries at multiple body sites. Upper and lower extremities and lower back are common pain sites in basketball players; however, there is little information about the relationship between upper or lower extremity pain and lower back pain. This study elucidated the associations between upper extremity (shoulder and elbow) pain and lower back pain (LBP) among young basketball players. We conducted a cross-sectional study using self-reported questionnaires mailed to 25,669 young athletes; the final study population comprised 590 basketball players, and their median age was 13 years (range: 6-15 years). The point prevalence rates of lower back, shoulder, elbow, and upper extremity pain among young basketball players were 12.9% (76/590), 4.6% (27/590), 2.7% (16/590), and 7.1% (42/590), respectively. Multivariate logistic regression analyses revealed that upper extremity pain was significantly associated with LBP (adjusted odds ratio [OR]: 7.86; 95% confidential interval [CI], 3.93-15.72). Shoulder pain was significantly associated with training per week (> 4 days) (adjusted OR: 4.15; 95% CI: 1.29-13.40) and LBP (adjusted OR: 13.77; 95% CI: 5.70-33.24). This study indicates that upper extremity and shoulder pain is associated with LBP among young basketball players. Assessing for lower back pain, as well as elbow and/or shoulder pain, may help prevent severe injuries in young basketball players. In conclusion, parents and coaches should be properly re-educated to help improve lower back, upper extremity, and shoulder pain among young basketball players.

Muscle pain is a common condition that relates to various pathologies. Muscle overuse induces muscle pain, and neutrophils are key players in pain production. Neutrophils also play a central role in chronic pain by secreting interleukin (IL)-18. The aim of this study was to investigate the involvement of neutrophils and IL-18 in a mouse model of muscle pain. The right hind leg muscles of BALB/c mice were stimulated electrically to induce excessive muscle contraction. The left hind leg muscles were not stimulated. The pressure pain threshold, number of neutrophils, and IL-18 levels were investigated. Furthermore, the effects of the IL-18-binding protein and Brilliant Blue G on pain were investigated. In stimulated muscles, pressure pain thresholds decreased, and neutrophil and IL-18 levels increased compared with that in non-stimulated muscles. The administration of IL-18-binding protein and Brilliant Blue G attenuated hyperalgesia caused by excessive muscle contraction. These results suggest that increased IL-18 secretion from larger numbers of neutrophils elicits mechanical hyperalgesia.