Histomorphology of the subregions of the scapholunate ligament and its enthesis

Background  The scapholunate interosseous ligament (SLIL) has three subregions: dorsal, proximal, and volar. The SLIL enthesis has not previously been studied despite its important mechanical function in wrist joint biomechanics. Questions/Purposes  This study aims to compare the histomorphological differences between the SLIL subregions, including at their entheses. Three questions are explored: Do the gross dimensions differ between SLIL subregions? Does the enthesis qualitatively, and its calcified fibrocartilage (CF) quantitatively, differ between (a) SLIL subregions and (b) scaphoid and lunate attachments? Methods  Twelve fresh-frozen human cadaveric wrists were dissected and the gross dimensions of the SLIL subregions measured. Subregions were histologically processed for morphological and compositional analyses, including quantification of enthesis CF area. Results  The dorsal subregion was the thickest. The dorsal and volar subregions had fibrocartilaginous entheses, while the proximal subregion was attached to articular cartilage. The dorsal subregion had significantly more CF than the volar subregion. There was no significant difference in the enthesis CF between scaphoid and lunate attachments in the three subregions. Conclusions  There are significant morphological differences between the SLIL subregions. The dorsal subregion has the largest amount of CF, which is consistent with the greater biomechanical force subjected to this subregion. The similar histomorphology of the ligament at the scaphoid and lunate entheses suggests that similar biomechanical forces are applied to both attachments. Clinical Relevance  The histomorphological results confirm that the dorsal subregion is the strongest of the three subregions. The results from the entheseal region may have important implications in the study of graft incorporation during SLIL reconstruction

TLR7 and TLR8 Gene Variations and Susceptibility to Hepatitis C Virus Infection

Toll-like receptors (TLRs) play pivotal roles in the innate immune system and control inflammatory responses and adaptive immunity. We previously evaluated associations between TLR7 and TLR8 gene SNPs and susceptibility to hepatitis C virus (HCV) infection. Our results suggested that TLR7IVS2-151G and TLR8-129G alleles were present at higher frequency in males of an HCV-infected group as compared to a control group (24.1% vs. 14.4%, p = 0.028; 17.6% vs. 6.8%, p = 0.004, respectively). Based upon their recognition of single stranded viral RNA, this suggested that TLR7 and TLR8 played a significant role in anti-HCV immune responses. Here, we studied the functional effects of these polymorphisms by analyzing the mRNA expressions of TLR7 and TLR8 and cytokine production induced ex vivo by TLR7- and TLR8-specific agonists using whole blood of subjects with different genotypes. The percentage of CD14+ cells from those with an AG haplotype that expressed TLR7 and TLR8 was significantly lower, but higher in intensity compared to cells from those with GG and AC haplotypes. Cells from those with an AG haplotype produced more IFN-α and less amounts of pro-inflammatory cytokines upon stimulation. This suggests that variations in TLR7 and TLR8 genes might impair immune responses during HCV infection

Examining the generalizability of research findings from archival data

This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability—for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples

The Immunobiology of Nipah Virus

Nipah virus (NiV) is a highly lethal zoonotic paramyxovirus that emerged in Malaysia in 1998. It is a human pathogen capable of causing severe respiratory infection and encephalitis. The natural reservoir of NiV, Pteropus fruit bats, remains a continuous virus source for future outbreaks, although infection in the bats is largely asymptomatic. NiV provokes serious disease in various mammalian species. In the recent human NiV outbreaks in Bangladesh and India, both bats-to-human and human-to-human transmissions have been observed. NiV has been demonstrated to interfere with the innate immune response via interferon type I signaling, promoting viral dissemination and preventing antiviral response. Studies of humoral immunity in infected NiV patients and animal models have shown that NiV-specific antibodies were produced upon infection and were protective. Studies on cellular immunity response to NiV infection in human and animal models also found that the adaptive immune response, specifically CD4+ and CD8+ T cells, was stimulated upon NiV infection. The experimental vaccines and therapeutic strategies developed have provided insights into the immunological requirements for the development of successful medical countermeasures against NiV. This review summarizes the current understanding of NiV pathogenesis and innate and adaptive immune responses induced upon infection