No abstract

Tuberculosis is a global health problem and at least one-third of the world’s population is infected with Mycobacterium tuberculosis (MTB). MTB is a successful pathogen that enhances its own intracellular survival by inhibiting inflammation and arresting phago-lysosomal fusion. We previously demonstrated that Toxoplasma gondii (T. gondii) dense granule antigen (GRA) 7 interacts with TNF receptor-associated factor 6 via Myeloid differentiation primary response gene 88, enabling innate immune responses in macrophages. To extend these studies, we found that GRA7 interacts with host proteins involved in antimicrobial host defense mechanisms as a therapeutic strategy for tuberculosis. Here, we show that protein kinase C (PKC)α-mediated phosphorylation of T. gondii GRA7-I (Ser52) regulates the interaction of GRA7 with PYD domain of apoptosis-associated speck-like protein containing a carboxy-terminal CARD, which is capable of oligomerization and inflammasome activation can lead to antimicrobial defense against MTB. Furthermore, GRA7-III interacted with the PX domain of phospholipase D1, facilitating its enzyme activity, phago-lysosomal maturation, and subsequent antimicrobial activity in a GRA7-III (Ser135) phosphorylation-dependent manner via PKCα. Taken together, these results underscore a previously unrecognized role of GRA7 in modulating antimicrobial host defense mechanism during mycobacterial infection.

No abstract

Inadequate pain management after total knee arthroplasty (TKA) impedes recovery, increases the risk of postoperative complications, and results in patient dissatisfaction. Although the preemptive use of multimodal measures is currently considered the principle of pain management after TKA, no gold standard pain management protocol has been established. Peripheral nerve blocks have been used as part of a contemporary multimodal approach to pain control after TKA. Femoral nerve block (FNB) has excellent postoperative analgesia and is now a commonly used analgesic modality for TKA pain control. However, FNB leads to quadriceps muscle weakness, which impairs early mobilization and increases the risk of postoperative falls. In this context, emerging evidence suggests that adductor canal block (ACB) facilitates postoperative rehabilitation compared with FNB because it primarily provides a sensory nerve block with sparing of quadriceps strength. However, whether ACB is more appropriate for contemporary pain management after TKA remains controversial. The objective of this study was to review and summarize recent studies regarding practical issues for ACB and comparisons of analgesic efficacy and functional recovery between ACB and FNB in patients who have undergone TKA.