Nervous wreck (Nwk), a protein that is present at Type 1 glutamatergic synapses that contains an SH3 domain and an FCH motif, is a Drosophila homolog of the human srGAP3/MEGAP protein, which is associated with mental retardation. Confocal microscopy revealed that circles in Nwk reticulum enclosed T-shaped active zones (T-AZs) and partially colocalized with synaptic vesicle (SV) markers and both exocytosis and endocytosis components. Results from an electron microscopic (EM) analysis showed that Nwk proteins localized at synaptic edges and in SV pools. Both the synaptic areas and the number of SVs in the readily releasable (RRPs) and reserve (RPs) SV pools in nwk2 were significantly reduced. Synergistic, morphological phenotypes observed from eag¹;nwk² neuromuscular junctions suggested that Nwk may regulate synaptic plasticity differently from activity-dependent Hebbian plasticity. Although the synaptic areas in eag¹;nwk² boutons were not significantly different from those of nwk², the number of SVs in the RRPs was similar to those of Canton-S. In addition, three-dimensional, high-voltage EM tomographic analysis demonstrated that significantly fewer enlarged SVs were present in nwk² RRPs. Furthermore, Nwk formed protein complexes with Drosophila Synapsin and Synaptotagmin 1 (DSypt1). Taken together, these findings suggest that Nwk is able to maintain synaptic architecture and both SV size and distribution at T-AZs by interacting with Synapsin and DSypt1.

OBJECTIVE: The aim of this study was to evaluate the association between the components of the metabolic syndrome (MS) and bone mineral density (BMD). METHODS: We conducted a retrospective cross-sectional analysis for 128 men (mean age 50.4 +/- 8.3 years) and 391 women (mean age 46.9 +/- 11.6 years) in Korea University Guro Hospital, Korea. Height (cm), weight (kg), waist circumference (cm), and blood pressure (mmHg) were measured. Fasting plasma glucose (FPG), high-density lipoprotein cholesterol (HDL-C), and triglycerides were measured. BMD at the total hip and lumbar spine was measured by dual X-ray densitometry. All participants completed a standardized questionnaire including medical history, smoking history, alcohol consumption, physical activity and menopausal status. RESULTS: Women with MS had lower BMD at lumbar and total hip sites (0.937 +/- 0.136 g/cm2, P-value 0.010; 0.875 +/- 0.113 g/cm2, P-value 0.045, respectively) than did women without MS. These differences at the spine and femoral neck were persisted after adjusting for age, body mass index, menopause status, alcohol consumption, smoking and physical activity. However, no significant differences in BMD were found in men between those with and without MS. In linear regression analyses, waist circumferences were highly associated with BMD at lumbar and total hip sites in women (beta -0.003, P-value < 0.001; beta -0.001, P-value 0.001, respectively). However, no significant differences were found in men between BMD and components of the MS. CONCLUSION: Among components of MS, waist circumference was associated with BMD in women. But no association was found in men. Women with MS had lower BMD than did women without MS.
Absorptiometry, Photon ; Alcohol Drinking ; Blood Pressure ; Body Mass Index ; Bone Density ; Cholesterol ; Cross-Sectional Studies ; Fasting ; Female ; Femur Neck ; Glucose ; Hip ; Humans ; Korea ; Linear Models ; Lipoproteins ; Male ; Menopause ; Motor Activity ; Osteoporosis ; Plasma ; Retrospective Studies ; Smoke ; Smoking ; Spine ; Triglycerides ; Waist Circumference ; Surveys and Questionnaires

Background/Aims: Transarterial radioembolization (TARE) has shown promising results in treating advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). However, whether TARE can provide superior or comparable outcomes to tyrosine kinase inhibitor (TKI) in patients with HCC and PVTT remains unclear. We compared the outcomes of TARE and TKI therapy in treatment-naïve patients with locally advanced HCC and segmental or lobar PVTT. Methods: This multicenter study included 216 patients initially treated with TARE (n=124) or TKI (sorafenib or lenvatinib; n=92) between 2011 and 2021. Baseline characteristics were balanced using propensity score matching (PSM) or inverse probability of treatment weighting (IPTW). The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS) and objective response rate (ORR). Results: In the unmatched cohort, the median OS of the TARE and TKI groups were 28.2 and 7.2 months, respectively (p<0.001), and the TARE group experienced significantly and independently longer OS compared to the TKI group (adjusted hazard ratio=0.41, 95% confidence interval=0.28–0.60, p<0.001). Similar results were observed in the study cohorts balanced with IPTW (p=0.003) or PSM (p=0.004). Although PFS was comparable between the two groups, the TARE group showed a trend of prolonged PFS in a subpopulation of patients with Vp1 or Vp2 PVTT (p=0.052). In the matched cohorts, the ORR of the TARE group was 53.0–56.7%, whereas that of the TKI group was 12.3–15.0%. Conclusions For patients with advanced HCC with segmental or lobar PVTT and well-preserved liver function, TARE may provide superior OS compared to sorafenib or lenvatinib.

Coronavirus disease 2019 (COVID-19) vaccination may non-specifically alter the host immune system. This study aimed to evaluate the effect of COVID-19 vaccination on hepatitis B surface Ag (HBsAg) titer and host immunity in chronic hepatitis B (CHB) patients. Consecutive 2,797 CHB patients who had serial HBsAg measurements during antiviral treatment were included in this study. Changes in the HBsAg levels after COVID-19 vaccination were analyzed. The dynamics of NK cells following COVID-19 vaccination were also examined using serial blood samples collected prospectively from 25 healthy volunteers. Vaccinated CHB patients (n=2,329) had significantly lower HBsAg levels 1–30 days post-vaccination compared to baseline (median, −21.4 IU/ml from baseline), but the levels reverted to baseline by 91–180 days (median, −3.8 IU/ml). The velocity of the HBsAg decline was transiently accelerated within 30 days after vaccination (median velocity: −0.06, −0.39, and −0.04 log 10 IU/ml/year in pre-vaccination period, days 1–30, and days 31–90, respectively). In contrast, unvaccinated patients (n=468) had no change in HBsAg levels. Flow cytometric analysis showed that the frequency of NK cells expressing NKG2A, an NK inhibitory receptor, significantly decreased within 7 days after the first dose of COVID-19 vaccine (median, −13.1% from baseline; p<0.001). The decrease in the frequency of NKG2A + NK cells was observed in the CD56dimCD16+ NK cell population regardless of type of COVID-19 vaccine. COVID-19 vaccination leads to a rapid, transient decline in HBsAg titer and a decrease in the frequency of NKG2A + NK cells.