External validation of the post-varicocele repair semen analysis nomogram to predict total motile sperm count: A multicenter study

Total motile sperm count is an important parameter for predicting the probability of natural pregnancy. We have externally validated the Samplaski's post-varicocele repair semen analysis nomogram to confirm the predictive accuracy of total motile sperm count. A total of 300 patients who had undergone varicocelectomy between July 2016 and July 2019 from 4 treatment centres were included in this validation cohort study. The predictive performance of the externally validated nomogram was revealed by applying the Pearson correlation coefficient (R = 0.328; 95% confidence interval (CI) 0.220–0.435; p < .001). Compared to Samplaski's nomogram result (R = 0.581; 95% CI 0.186–0.729), our study also revealed a statistically significant rate. However, it had a relatively lower correlation coefficient rate. Notably, the predicted total motile sperm count was lower than the observed post-varicocelectomy total motile sperm count. The calibration plot revealed that the discrepancy between the predicted and observed total motile sperm count was plausible. However, it had low explanatory power in this nomogram model. This validation study demonstrates that the post-varicocele repair Samplaski's nomogram predicts a relatively lower total motile sperm count than the observed count.     

The Recency Period for Estimation of Human Immunodeficiency Virus Incidence by the AxSYM Avidity Assay and BED-Capture Enzyme Immunoassay in the Republic of Korea

Objectives

Measurement of the incidence of the human immunodeficiency virus (HIV) is very important for epidemiological studies. Here, we determined the recency period with the AxSYM avidity assay and the BED-capture enzyme immunoassay (BED-CEIA) in Korean seroconverters.

Methods

Two hundred longitudinal specimens from 81 seroconverters with incident HIV infections that had been collected at the Korea National Institute of Health were subjected to the AxSYM avidity assay (cutoff = 0.8) and BED-CEIA (cutoff = 0.8). The statistical method used to estimate the recency period in recent HIV infections was nonparametric survival analyses. Sensitivity and specificity were calculated for 10-day increments from 120 days to 230 days to determine the recency period.

Results

The mean recency period of the avidity assay and BED-CEIA using a survival method was 158 days [95% confidence interval (CI), 135–181 days] and 189 days (95% CI, 170–208 days), respectively. Based on the use of sensitivity and specificity, the mean recency period for the avidity assay and BED-CEIA was 150 days and 200 days, respectively.

Conclusion

We determined the recency period to estimate HIV incidence in Korea. These data showed that the nonparametric survival analysis often led to shorter recency periods than analysis of sensitivity and specificity as a new method. These findings suggest that more data from seroconverters and other methodologies are needed to determine the recency period for estimating HIV incidence.     

Anti-arthritis effects of (E)-2,4-bis(p-hydroxyphenyl)- 2-butenal are mediated by inhibition of the STAT3 pathway

Background and Purpose

Products of Maillard reactions between aminoacids and reducing sugars are known to have anti-inflammatory properties. Here we have assessed the anti-arthritis effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal and its possible mechanisms of action.

Experimental Approach

We used cultures of LPS-activated macrophages (RAW264.7 cells) and human synoviocytes from patients with rheumatoid arthritis for in vitro assays and the collagen-induced arthritis model in mice. NO generation, iNOS and COX2 expression, and NF-κB/IKK and STAT3 activities were measured in vitro and in joint tissues of arthritic mice, along with clinical scores and histopathological assessments. Binding of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal to STAT3 was evaluated by a pull-down assay and its binding site was predicted using molecular docking studies with Autodock VINA.

Key Results

(E)-2,4-bis(p-hydroxyphenyl)-2-butenal (2.5–10 μg·mL⁻¹) inhibited LPS-inducedNO generation, iNOS and COX2 expression, and NF-κB/IKK and STAT3 activities in macrophage and human synoviocytes. This compound also suppressedcollagen-induced arthritic responses in mice by inhibiting expression of iNOS and COX2, and NF-κB/IKK and STAT3 activities; it also reduced bone destruction and fibrosis in joint tissues. A pull-down assay showed that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal interfered with binding of ATP to STAT3. Docking studies suggested that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal bound to the DNA-binding interface of STAT3 possibly inhibiting ATP binding to STAT3 in an allosteric manner.

Conclusions and Implications

(E)-2,4-bis(p-hydroxyphenyl)-2-butenal exerted anti-inflammatory and anti-arthritic effects through inhibition of the NF-κB/STAT3 pathway by direct binding to STAT3. This compound could be a useful agent for the treatment of arthritic disease.     

Chitosan-Based Hybrid Nanocomplex for siRNA Delivery and Its Application for Cancer Therapy

Purpose

Chitosan, a natural and biocompatible cationic polymer, is an attractive carrier for small interfering RNA (siRNA) delivery. The purpose of this study was to develop a chitosan-based hybrid nanocomplex that exhibits enhanced physical stability in the bloodstream compared with conventional chitosan complexes. Hybrid nanocomplexes composed of chitosan, protamine, lecithin, and thiamine pyrophosphate were prepared for systemic delivery of survivin (SVN) siRNA.

Methods

Physicochemical properties of the nanoparticles including mean diameters and zeta potentials were characterized, and target gene silencing and cellular uptake efficiencies of the siRNA nanocomplexes in prostate cancer cells (PC-3 cells) were measured. In vivo tumor targetability and anti-tumor efficacy by systemic administration were assessed in a PC-3 tumor xenograft mouse model by near-infrared fluorescence (NIRF) imaging and tumor growth monitoring, respectively.

Results

Mean diameters of the SVN siRNA-loaded hybrid nanocomplex (GP-L-CT) were less than 200 nm with a positive zeta potential value in water and were maintained without aggregation in culture media and 50% fetal bovine serum. SVN expression in PC-3 cells was reduced to 21.9% after treating with GP-L-CT. The tumor targetability and growth inhibitory efficacies of GP-L-CT supported the use of this novel hybrid nanocomplex as a cancer therapeutic and as a theranostic system for systemic administration.

Conclusions

A chitosan-based hybrid nanocomplex was successfully developed for the systemic delivery of SVN siRNA, which could serve as an alternative to cationic polymeric nanoparticles that are unstable in serum.     

Expression of hedgehog proteins in periampullary cancer]

BACKGROUND/AIMS: Hedgehog protein is an essential molecule for gastrointestinal tract development, and disruption of hedgehog signaling pathway is linked to some gastrointestinal tumorigenesis. Here, we performed hedgehog immunostaining in periampullary cancer to evaluate the differences according to the location type of cancer and the differentiation of adenocarcinoma. METHODS: We retrieved surgical specimens from 43 periampullary cancer patients (15 ampulla of Vater cancer, 12 distal common bile duct cancer, 13 pancreatic head cancer, and 3 combined ampulla of Vater/bile duct cancer). Immunohistochemical stain was performed in both normal and cancerous tissue portions of each case using Sonic hedgehog (H-160) rabbit polyclonal antibody. Immunohistochemical stain results were grouped into three groups according to the percentage of positive cytoplasmic stain in tumor volume (unstained: <5%, weakly stained: 5-50%, and strongly stained: >50%). RESULTS: All of the normal tissue revealed negative immunohistochemical stain while cancerous tissue revealed positivity in 95.3% (41/43 cases). Strongly stained cases were more frequently seen in ampulla of Vater cancers (13/15) and in combined ampulla of Vater/bile duct cancers (3/3) than in distal common bile duct cancers (4/12) and in pancreatic head cancers (3/13) (p=0.002). In addition, strongly stained cases were more frequently seen in well-differentiated adenocarcinoma than the others (p<0.001). CONCLUSIONS: Most of the periampullary cancers show hedgehog protein expression. In addition, hedgehog protein immunostainings shows stronger expression in ampulla of Vater cancers and in well-differentiated adenocarcinoma.     

Acute Lower Respiratory Tract Infections in Soldiers,South Korea,April 2011–March 2012

During April 2011–March 2012, we retrospectively reviewed medical records for South Korea soldiers to assess the etiology and epidemiology of acute viral lower respiratory tract infections. Adenovirus was the most commonly identified virus (63.2%) and the most common cause of pneumonia (79.3%) and hospitalization (76.6%); 3 soldiers died of adenovirus-related illness.     

Preoperative Weakness and Demyelination of the Corticospinal Tract in Meningioma Patients : Changes in Diffusion Parameters Using Diffusion Tensor Imaging

Objective

Differentiation of demyelination in white matter from axonal damage can be determined using diffusion tensor imaging (DTI). In this study using meningioma patients an attempt was made to evaluate the relationship between preoperative weakness and the changes of diffusion parameters in the corticospinal tract (CST) using DTI.

Methods

Twenty-six patients with meningioma were enrolled in this study. Eleven of them suffered from objective motor weakness and were classified as Group 1. The remaining 15 patients did not present motor weakness and were classified as Group 2. Fiber tractography and CST diffusion parameters were obtained using DTIStudio. The ratios (lesion side mean value/contralateral side mean value) of CST diffusion parameters were compared with 1.0 as a test value using a one-sample t-test.

Results

In Group 1, fractional anisotropy (FA), tensor trace (TT), and radial diffusivity (RD, λ2 and λ3) of the CST were significantly different between two hemispheres, but axial diffusivity (AD, λ1) of the CST was not significantly different between two hemispheres. In Group 2, FA and λ3 of CST did not differ significantly between the hemispheres. In Group 2, TT, λ1, and λ2 of CST in the ipsilateral hemisphere were significantly higher than those of the unaffected hemisphere. However, the differences were small.

Conclusion

Motor weakness was related to a low FA and high TT resulting from increased RD of the CST fibers. CST diffusion changes in patients with weakness are similar to those for demyelination.