Outcome of Brain Lymphoma in a High Epstein-Barr Virus-Prevalence Country After Kidney Transplantation.

BACKGROUND: The incidence of post-transplant lymphoproliferative disorder (PTLD) in adult kidney transplant (KTx) recipients is less common in Taiwan. In our institute, we observed that brain lymphoma was the most notorious type. METHODS: The study describes the clinical, histologic, and radiological features of primary central nervous lymphoma (PCNSL) and the outcomes and associations with Epstein-Barr virus (EBV) infection in our center. RESULTS: Among 1470 KTx recipients, 5 patients had tissue-proven brain lymphoma (0.34%). The brain pathology disclosed diffuse large B-cell lymphoma in all patients. EBV was detected through in situ hybridization for Epstein-Barr encoding region (EBER) to disclose the EBV inclusion in the nuclei of lymphoma cells. The first treatment step was the reduction of immunosuppressants; 4 patients received whole-brain radiotherapy after complete resection of PCNSL, and 1 received concurrent chemoradiotherapy. Only one patient had poor performance status at the time of diagnosis and had a poor response to treatment with steroids. Four patients survived (mean 36.5 months, range 8.6 to 57.6 months), but one died after rapid neurologic deterioration. CONCLUSION: Epstein-Barr virus inclusion was found in PCNSL in our patients; however, the role of EBV in PCNSL remains to be clarified. Post-transplant lymphoproliferative disorder is a rare malignancy after KTx with a predilection of brain involvement in Taiwan. We report a successful care experience in a patient with primary CNS lymphoma with better survival.

Association between Immunohistochemistry Markers and Tumor Features and Their Diagnostic and Prognostic Values in Intrahepatic Cholangiocarcinoma.

This study investigated the expression of some frequently used immunohistochemistry (IHC) markers. Besides, we evaluated their correlations with the clinical features and outcomes of intrahepatic cholangiocarcinoma (ICC). Patients who underwent surgical removal of the ICC tumors were followed up for 4 years. The paraffin-embedded sections were used to obtain different markers, including CK7, CK19, CK20, CDX2, Glypican3, Hepa1, Ki-67, Villin, and SATB1. Overall survival in relation to IHC marker expression patterns and other clinical characteristics was evaluated by Kaplan-Meier survival curve and log-rank test, followed by the Cox proportional hazard model (to evaluate the relationship between multiple factors and the overall postoperative survival). A total of 122 ICC patients (67 males and 55 females, averagely aged 57.75) were included in this study. There were 44 cases with vascular invasion, 46 cases with lymphatic metastasis, and 13 cases with distant metastasis. CK7 was negatively correlated with lymphatic metastasis; and in distant-metastasis cases, the positive ratio of SATB1 was lower. Interestingly, SATB1 expression indicated a poorer survival, while Villin expression was associated with a better survival. The COX regression analysis showed that female was a protective factor versus male, Villin expression was a strong protective factor, and Ki-67 expression was correlated with a poor survival. Together, IHC markers are associated with tumor features and postoperative survival, especially for SATB1 as a risk factor and Villin as a protective marker, and female ICC patients may have better survival than males.

A Successful Organized Effort to Improve Operating Room First-Case Starts in a Tertiary Academic Medical Center.

BACKGROUND: Operating room (OR) inefficiency drives up cost, decreases revenue, and leads to surgeon, staff, and patient dissatisfaction. Given a low mean first-case start rate in our tertiary academic medical center, we developed a process to improve first-case start rates in an effort to increase OR efficiency. METHODS: A working group of the OR Executive Committee was constituted to develop and implement a multistep operational plan. This plan was predicated on a sensible staggered start framework, coordination of stakeholder responsibilities, a visual preoperative Stop/Go checklist tool, real-time measurement, and feedback. RESULTS: Within 11 days of implementation, 95% of first-start OR cases were tracked to start on time. Throughout the observation period (May 2015-July 2016), the goal of a daily mean 80% on-time start rate was either met or exceeded. CONCLUSIONS: Implementation of an organized collaborative effort led to dramatic improvements in first OR case on-time rates. Such improvement in OR utilization may lead to an increase in staff and patient satisfaction and cost reduction.

Inhibition of 17-beta-estradiol on neuronal excitability via enhancing GIRK1-mediated inwardly rectifying potassium currents and GIRK1 expression.

BACKGROUND: Catamenial epilepsy is a common central nervous system disease in female, which is influenced by the 17-ß-estradiol (estrogen) level during the menstrual cycle. Low level (<0.05ng/ml) of estrogen normally accompanies with the perimenstrual classification of catamenial epilepsy, however, without clear mechanism. In previous studies, estrogen has been demonstrated to possess widely regulatory effects on potassium channels. Here, the effect of 17-ß-estradiol on modulating inwardly rectifying K+ (Kir) currents was investigated in cultured hippocampal neurons. The underlying mechanism was also detected. METHODS: In this research, null-estrogen cultures and spaying animals were used to mimicked the low level estrogen condition in menstrual period. Patch clamp recordings, western blotting and pharmacological experiments were performed to detect the effects of estrogen receptors and the underlying mechanisms. RESULTS: Compared to those neurons in normal medium (with 0.1ng/ml estrogen), null-estrogen cultures or neurons treated by estrogen receptor blocker (ICI 182,780) both had significant suppressed Kir currents. The expression level of G protein-gated inwardly rectifying K+ channel subunit 1 (GIRK1) was significantly decreased in spaying animals. Furthermore, a GIRK channel inhibitor (TPQ) similarly suppressed the Kir currents. Lastly, estrogen deficiency, estrogen receptor blocker and GIRK channel inhibitor all promoted the epileptiform bursting activities in neurons, as a result of Kir current suppression. CONCLUSION: Taken together, 17-ß-estradiol, by the activation of estrogen receptors, is essential for the maintenance of Kir currents, and thus has an inhibitory effect on the epileptiform bursting activities in cultured hippocampal neurons, whereas GIRK1 is the major intermedial mediator. This research provides a new mechanism for the pathogenesis of catamenial epilepsy, particularly in the menstrual period and the early section of follicular phase.

Root morphological responses of five soybean [Glycine max (L.) Merr] cultivars to cadmium stress at young seedlings.

To examine the differences in root morphological responses of soybean cultivars with different cadmium (Cd) tolerance and accumulation to Cd stress, the biomass, Cd concentration, and root morphological features of five soybean cultivars were determined under 0, 9, 23, 45, and 90 µM Cd stress via hydroponic experiments. Significantly genotypic differences in Cd tolerance and Cd concentration were observed between five soybean cultivars at four Cd levels. For Cd tolerance, HX3 showed a strong Cd tolerance with tolerance indexes of shoot biomass at 92.49, 76.44, 60.21, and 46.45% after 18 days at four Cd levels, and others had similar weak tolerance at young seedling. For Cd accumulation, Cd concentration in roots showed far higher than that in shoots. The different accumulation features in roots and shoots among five cultivars were found at four Cd levels. Comparing with the control, the total root length (RL), root surface area (SA), and root volume (RV) of all cultivars were decreased significantly at four Cd levels. Tolerant cultivar HX3 had the largest root system and sensitive cultivar BX10 had the smallest root system at young seedling stage. Correlation analysis indicated that RL, SA, and RV were positively correlated with root biomass and shoot biomass under 9 and 23 µM Cd treatments, but root average diameter (RD) was negatively correlated with shoot biomass and root biomass only under 9 µM Cd treatments, while RL and SA were negatively correlated with root Cd concentration under 23 and 45 µM Cd treatments. The results suggested that root morphological traits were closely related to Cd tolerance at young seedlings under Cd treatments.

Comparison of subcellular distribution and chemical forms of cadmium among four soybean cultivars at young seedlings.

The hydroponic experiment was carried out to investigate the Cd subcellular distribution and chemical forms in roots and shoots among four soybean seedling cultivars with two Cd treatments. HX3 and GC8, two tolerant and low-grain-Cd-accumulating cultivars, had the lowest Cd concentration in roots and high Cd concentration in shoots, while BX10 and ZH24, two sensitive and high-grain-Cd-accumulating cultivars, had the highest Cd concentration in roots and the lowest Cd concentration in shoots at young seedling stage. Furthermore, the sequence of Cd subcellular distribution in roots at two Cd levels was cell wall (53.4-75.5 %) > soluble fraction (15.8-40.4 %) > organelle fraction (2.0-14.7 %), but in shoots, was soluble fraction (39.3-74.8 %) > cell wall (16.0-52.0 %) > organelle (4.8-19.5 %). BX10 and ZH24 had higher Cd concentration in all subcellular fractions in roots, but HX3 and GC8 had higher Cd concentration of soluble fraction in shoots. The sequence of Cd chemical forms in roots was FNacl (64.1-79.5 %) > FHAC (3.4-21.5 %) > Fd-H2O (3.6-13.0 %) > Fethanol (1.4-21.8) > FHCl (0.3-1.6 %) > Fother (0.2-1.4 %) at two Cd levels but, in shoots, was FNacl (19.7-51.4 %) ≥ FHAC (10.2-31.4 %) ≥ Fd-H2O (8.8-28.2 %) ≥ Fethanol (8.9-38.6 %) > FHCl (0.2-9.6 %) > Fother (2.5-11.2 %). BX10 and ZH24 had higher Cd concentrations in each extracted solutions from roots, but from shoots for GC8 and HX3. Taken together, the results uncover that root cell walls and leaf vacuoles might play important roles in Cd detoxification and limiting the symplastic movement of Cd.

Estrogen suppresses epileptiform activity by enhancing Kv4.2-mediated transient outward potassium currents in primary hippocampal neurons.

Catamenial epilepsy is a common phenomenon in female epileptic patients that is, in part, influenced by the 17-ß-estradiol level during the menstrual cycle, which modulates the strength of the epileptic seizures. However, the underlying mechanism(s) for catamenial epilepsy remains unknown. In the present study, the effect of 17­ß­estradiol on modulating epileptiform activities was investigated in cultured hippocampal neurons by focusing on the transient outward potassium current. Using the patch clamp technique, 17­ß­estradiol was demonstrated to have a dose­dependent U­shape effect on epileptiform bursting activities in cultured hippocampal neurons; only the low dose (~0.1 ng/ml) of 17­ß­estradiol had a suppressive effect on the epileptiform activities. The blockade effect of the low dose 17­ß­estradiol could be suppressed by phrixotoxin2 (PaTx2), a selective channel blocker for voltage­gated potassium channel type 4.2 (Kv4.2), which mediates the transient outward potassium current. Furthermore, the 17­ß­estradiol bell­shape­like dose­dependently enhanced the transient outward potassium current, which was inhibited by the estrogen receptor antagonist ICI 182,780. In conclusion, these results indicate that reduced activation of the transient outward potassium current by a high (or none) 17­ß­estradiol level may enhance the epileptiform bursting activities in neurons, which may be one of the triggering causes for catamenial epilepsy, and therefore, maintaining a certain low 17­ß­estradiol level may aid in the control of catamenial epilepsy.

Identification and comparative analysis of cadmium tolerance-associated miRNAs and their targets in two soybean genotypes.

MicroRNAs (miRNAs) play crucial roles in regulating the expression of various stress responses genes in plants. To investigate soybean (Glycine max) miRNAs involved in the response to cadmium (Cd), microarrays containing 953 unique miRNA probes were employed to identify differences in the expression patterns of the miRNAs between different genotypes, Huaxia3 (HX3, Cd-tolerant) and Zhonghuang24 (ZH24, Cd-sensitive). Twenty six Cd-responsive miRNAs were identified in total. Among them, nine were detected in both cultivars, while five were expressed only in HX3 and 12 were only in ZH24. The expression of 16 miRNAs was tested by qRT-PCR and most of the identified miRNAs were found to have similar expression patterns with microarray. Three hundred and seventy six target genes were identified for 204 miRNAs from a mixture degradome library, which was constructed from the root of HX3 and ZH24 with or without Cd treatment. Fifty five genes were identified to be cleaved by 14 Cd-responsive miRNAs. Gene ontology (GO) annotations showed that these target transcripts are implicated in a broad range of biological processes. In addition, the expression patterns of ten target genes were validated by qRT-PCR. The characterization of the miRNAs and the associated target genes in response to Cd exposure provides a framework for understanding the molecular mechanism of heavy metal tolerance in plants.