Recurrence of progressive familial intrahepatic cholestasis (PFIC) type II poses challenges during postoperative liver transplant care. Posttransplant patients with PFIC type II risk developing recurrent cholestasis with normal gamma-glutamyl transferase activity, which mimics the original bile salt export pump (BSEP) protein deficiency and is related to a form of immunoglobulin G antibody (anti-BSEP)-mediated rejection. Bortezomib effectively induces apoptosis of actively antibody-producing plasma cells that may have a role in antibodymediated rejection. In this case, we used bortezomib to treat PFIC type II recurrence after liver transplantation in a child.

Background/Aims: Cardiorespiratory fitness (CRF), as measured by maximal oxygen consumption (VO2max), is an important independent predictive factor of cardiovascular outcomes in patients with heart failure (HF). However, it is unclear whether conventional equations for estimating CRF are applicable to patients with HF with preserved ejection fraction (HFpEF). Methods: This study included 521 patients with HFpEF (EF ≥ 50%) whose CRF was directly measured by cardiopulmonary exercise test using a treadmill. We developed a new equation (Kor-HFpEF) for half of the patients in the HFpEF cohort (group A, n = 253) and validated it for the remaining half (group B, n = 268). The accuracy of the Kor-HFpEF equation was compared to that of the other equations in the validation group. Results: In the total HFpEF cohort, the directly measured VO2max was significantly overestimated by the FRIEND and ACSM equations (p < 0.001) and underestimated by the FRIEND-HF equation (p <0.001) (direct 21.2 ± 5.9 mL/kg/min; FRIEND 29.1 ± 11.8 mL/kg/min; ACSM 32.5 ± 13.4 mL/kg/min; FRIEND-HF 14.1 ± 4.9 mL/kg/min). However, the VO2max estimated by the Kor-HFpEF equation (21.3 ± 4.6 mL/kg/min) was similar to the directly measured VO2max (21.7 ± 5.9 mL/kg/min, p = 0.124), whereas the VO2max estimated by the other three equations was still significantly different from the directly measured VO2max in group B (all p < 0.001). Conclusions Traditional equations used to estimate VO2max were not applicable to patients with HFpEF. We developed and validated a new Kor-HFpEF equation for these patients, which had a high accuracy.

Background: Transient receptor potential canonical (TRPC) channels are non-selective cationic channels with perme‑ ability to ­Ca2+ and ­Na+ . Despite their importance, there are currently few studies on TRPC in the periodontal ligament (PDL) and bone cells in the dental field. To provide biological information regarding TRPC in PDL cells and periodontal tissue, we evaluated TRPC channels expression in the osteoblast differentiation of PDL cells and periodontitis-induced tissue. Human PDL cells were cultured in osteogenic differentiation media for 28 days, and the expression of Runx2, osteocalcin (OCN), and TRPC1, 3, 4, and 6 was evaluated by real-time PCR. In ligature-induced periodontitis mice, the alveolar bone and osteoid areas, the osteoclast number, and the expression of Runx2, OCN, TRPC3, and TRPC6 was evaluated by H&E staining, TRAP staining, and immunohistochemistry, respectively. Results: In the PDL cell differentiation group, TRPC6 expression peaked on day 7 and TRPC3 expression generally increased during differentiation. During the 28 days of periodontitis progression, alveolar bone loss and osteoclast numbers increased compared to the control group during the experimental period and the osteoid area increased from day 14. TRPC6 expression in the periodontitis group increased in the PDL area and in the osteoblasts compared to the control group, whereas TRPC3 expression increased only in the PDL area on days 7 and 28. Conclusions These results indicate changes of TRPC3 and TRPC6 expression in PDL cells that were differentiating into osteoblasts and in periodontitis-induced tissue, suggesting the need for research on the role of TRPC in osteo‑ blast differentiation or periodontitis progression.

Background/Aims: To prevent the perinatal transmission of hepatitis B virus (HBV) from mother to child, administration of an antiviral agent during pregnancy has been attempted in women who are either hepatitis B e antigen positive or have a high viral load. In this systematic review and meta-analysis with randomized controlled trials, we analyzed the efficacy and safety of tenofovir disoproxil fumarate (TDF) in preventing the perinatal transmission of HBV in pregnant women who have high HBV DNA titers. Methods: Multiple comprehensive databases (PubMed, EMBASE, and Cochrane databases) were searched for studies evaluating the efficacy of TDF for the prevention of perinatal transmission of HBV. Results: Two studies (one open label study and one double blind study) were included and analyzed. Intention-to-treat analysis (527 pregnancies) showed that the preventive effect of TDF was not significant (odds ratio [OR], 0.53; 95% confidence interval[CI], 0.13 to 2.17; p = 0.38, I2 = 81%). However, the per-protocol analysis showed that TDF significantly reduced perinatal transmission (OR, 0.10; 95% CI, 0.01 to 0.77; p = 0.03, I2 = 0%). There was no significant difference between the TDF group and the control group with respect to maternal and fetal safety outcomes. Conclusions In pregnant women who have high HBV DNA titers, TDF can reduce the perinatal transmission from mother to child without significant adverse events.

Increases of neutrophils and osteoclasts are pathological changes of periodontitis. RANKL is an osteoclast differentiation factor. The effect of periodontopathogen LPS on RANKL-expressing neutrophils has not been clarified yet. We evaluated numerical changes of RANKL-expressing neutrophils in air pouches of mice injected with LPSs of Fusobacterium nucleatum and Porphyromonas gingivalis. Mice with air pouches were assigned into saline (C)-, E. coli LPS- (Ec LPS)-, F. nucleatum LPS (Fn LPS)-, P. gingivalis LPS (Pg LPS)-, and Fn LPS and Pg LPS (Fn + Pg LPS)-injected groups. CD11b +Ly6G + neutrophils and CD11b +Ly6G+RANKL + neutrophils in blood and air pouch exudates were determined by flow cytometry. In blood, compared to the C group, the Fn LPS group showed increases of CD11b +Ly6G + neutrophils and CD11b +Ly6G +RANKL + neutrophils whereas the Pg LPS group showed no significant differences. These increases in the Fn LPS group were not different to those in the Ec LPS group. In exudates, Fn LPS and Pg LPS groups showed increases of CD11b +Ly6G + neutrophils and CD11b +Ly6G +RANKL + neutrophils compared to the C group. Increased levels in the Fn LPS group were not different to those in the Ec LPS group, but Pg LPS group was lower than those in the Ec LPS group. In blood and exudates, the Fn+ Pg LPS group showed no difference in levels of these neutrophils compared to the Ec LPS group. LPSs of F. nucleatum and P. gingivalis increased RANKL-expressing neutrophils although the degrees of increases were different. These suggest that periodontopathogen LPS can act as a stimulant to increase RANKL-expressing neutrophils.

Increases of neutrophils and osteoclasts are pathological changes of periodontitis. RANKL is an osteoclast differentiation factor. The effect of periodontopathogen LPS on RANKL-expressing neutrophils has not been clarified yet. We evaluated numerical changes of RANKL-expressing neutrophils in air pouches of mice injected with LPSs of Fusobacterium nucleatum and Porphyromonas gingivalis. Mice with air pouches were assigned into saline (C)-, E. coli LPS- (Ec LPS)-, F. nucleatum LPS (Fn LPS)-, P. gingivalis LPS (Pg LPS)-, and Fn LPS and Pg LPS (Fn + Pg LPS)-injected groups. CD11b +Ly6G + neutrophils and CD11b +Ly6G+RANKL + neutrophils in blood and air pouch exudates were determined by flow cytometry. In blood, compared to the C group, the Fn LPS group showed increases of CD11b +Ly6G + neutrophils and CD11b +Ly6G +RANKL + neutrophils whereas the Pg LPS group showed no significant differences. These increases in the Fn LPS group were not different to those in the Ec LPS group. In exudates, Fn LPS and Pg LPS groups showed increases of CD11b +Ly6G + neutrophils and CD11b +Ly6G +RANKL + neutrophils compared to the C group. Increased levels in the Fn LPS group were not different to those in the Ec LPS group, but Pg LPS group was lower than those in the Ec LPS group. In blood and exudates, the Fn+ Pg LPS group showed no difference in levels of these neutrophils compared to the Ec LPS group. LPSs of F. nucleatum and P. gingivalis increased RANKL-expressing neutrophils although the degrees of increases were different. These suggest that periodontopathogen LPS can act as a stimulant to increase RANKL-expressing neutrophils.

Periodontitis is a bacteria-induced inflammatory disease associated with alveolar bone loss. Osteoclast is a macrophage-lineage cell that exhibits phagocytic activity; however, osteoclast phagocytic activity has not been demonstrated under pathological conditions. Diabetes is a pathological condition that exacerbates alveolar bone loss via periodontitis; therefore, we examined phagocytic osteoclasts in diabetic rats that had periodontitis. The rats were divided into the control (C), periodontitis (P), and diabetes with periodontitis (DP) groups. Diabetes and periodontitis were induced by streptozotocin injection and ligature of the mandibular first molars, respectively. On days 3 and 20 after the ligature, the rats were sacrificed, and osteoclasts containing inclusions were quantified by tartrate-resistant acid phosphatase staining. On day 3, there were more osteoclasts containing inclusions in the DP group than in the C group. Among inclusions, osteocyte-like cells and dense bodies were more frequently observed in the DP group than in the C group. Cytoplasm-like structures were elevated more in the DP group than in the C and P groups. However, no differences were observed on day 20. Interestingly, some osteoclasts were in contact with the osteocytes within the exposed lacunae and contained several inclusions within a large vacuole. Thus, the elevation of phagocytic osteoclasts in rats with diabetes and periodontitis provides insight into the role of osteoclast phagocytic activity under pathological conditions.