Application of nZnO supported with nanoclay for improving shrimp immunity.

This study discloses the nanoscale silicate platelet-supported nZnO (ZnONSP) applied as novel feed additives in aquaculture. The preparation of the nanohybrid (ZnO/NSP = 15/85, w/w) was characterized by UV-visible spectroscopy, powder X-ray diffraction and transmission electron microscope. The effects of ZnONSP on growth, zinc accumulation, stress response, immunity and resistance to Vibrio alginolyticus in white shrimp (Penaeus vannamei) were \demonstrated. To evaluate the safety of ZnONSP, shrimps (2.0 ± 0.3 g) were fed with ZnONSP containing diets (200, 400 and 800 mg/kg) for 56 days. Dietary ZnONSP did not affect the weight gain, specific growth rate, feed conversion ratio, survival rate, zinc accumulation, and the expression of heat shock protein 70 in tested shrimps. To examine the immunomodulatory effect of ZnONSP, shrimps (16.6 ± 2.4 g) were fed with the same experimental diets for 28 days. Dietary ZnONSP improved the immune responses of haemocyte in tested shrimps, including phagocytic rate, phagocytic index, respiratory burst, and phenoloxidase activity, and upregulated the expression of several genes, including lipopolysaccharide, ß-1,3-glucan binding protein, peroxinectin, penaeidin 2/3/4, lysozyme, crustin, anti-lipopolysaccharide factor, superoxide dismutase, glutathione peroxidase, clotting protein and α-2-macroglobulin. In the challenge experiment, shrimps (17.2 ± 1.8 g) were fed with ZnONSP containing diets (400 and 800 mg/kg) for 7 days and then infected with Vibrio alginolyticus. Notably, white shrimps that received ZnONSP (800 mg/kg) showed significantly improved Vibrio resistance, with a survival rate of 71.4 % at the end of 7-day observation. In conclusion, this study discovers that ZnONSP is a new type of immunomodulatory supplement that are effective on enhancing innate cellular and humoral immunities, and disease resistance in white shrimp.

Addition of Preoperative Ultrasound-Guided Suprascapular Nerve Block and Axillary Nerve Block to Parecoxib Is More Effective in Early Postoperative Pain Control After Arthroscopic Rotator Cuff Repair: A Prospective Randomized Controlled Study.

PURPOSE: To prospectively compare pain intensity and patient-reported outcomes (PROs) after arthroscopic rotator cuff repair (ARCR) between patients who received ultrasound-guided suprascapular nerve block (SSNB) and axillary nerve block (ANB) as well as preincisional parecoxib and patients who received preincisional parecoxib only. METHODS: Sixty-one patients receiving ARCR between March 2020 and March 2021 were prospectively enrolled. They were randomly assigned to the peripheral nerve block group (group N, n = 30) or control group (group C, n = 31). Two patients in group C were excluded because of miscommunication. All patients were administered 40 mg of parecoxib intravenously prior to induction of anesthesia. SSNB and ANB were performed after general anesthesia in group N, whereas no nerve block was performed in group C. Pain intensity was compared before surgery, as well as immediately, 24 hours, and 2 weeks after surgery. PROs, including the Oxford Shoulder Score, University of California-Los Angeles shoulder score, and Single Assessment Numeric Evaluation score, were compared before and 6 months after surgery. RESULTS: The numerical rating scale (NRS) score for resting pain was significantly lower in group N (4.9 ± 3.1 vs 7.6 ± 2.5, P < .001) immediately after surgery, but no difference was noted 24 hours after surgery. The resting pain NRS score 2 weeks after surgery was significantly lower in group N (1.4 ± 1.6 vs 2.7 ± 2.7, P = .03), but the scores for movement-evoked pain and night pain were similar. All PROs significantly improved 6 months after surgery in both groups, but there was no difference between the 2 groups. CONCLUSIONS: The addition of preoperative ultrasound-guided SSNB and ANB to parecoxib offered better resting pain control immediately and 2 weeks after ARCR, but there was no benefit for PROs 6 months after surgery. LEVEL OF EVIDENCE: Level II, prospective randomized controlled trial.

Using Single Peroneal Longus Tendon Graft for Segmental Meniscus Transplantation and Revision Anterior Cruciate Ligament Combined Anterolateral Reconstruction.

This case report describes a new approach to segmental meniscal reconstruction using a peroneal longus autograft in a patient with recurrent traumatic medial meniscus tear and anterior cruciate ligament reconstruction (ACLR) failure. While allograft meniscal transplantation is the preferred method for treating meniscal deficiency, its high cost and various legal regulations have limited its widespread use. Autologous tendon grafts have been proposed as a substitute for allograft meniscus transplantation, but their initial results were poor, leading to little progress in this area. However, recent animal experiments and clinical studies have demonstrated promising results in using autologous tendon grafts for meniscal transplantation, including improvements in pain and quality of life for patients. Further research is needed to evaluate the effectiveness of segmental meniscal reconstruction using autologous tendon grafts, but it could potentially lead to more accessible and cost-effective treatment options for patients with meniscal deficiency.

Arthroscopic Lower Trapezius Tendon Transfer for a Patient with Axillary Nerve Injury and Concomitant Rotator Cuff Tear: A Case Report and Technical Notes.

Introduction: Concomitant nerve injuries with musculoskeletal injuries present a challenging problem. The goals of nerve reconstruction for the shoulder include shoulder abduction and external rotation. When patients fail to achieve acceptable shoulder external rotation and shoulder abduction, tendon transfers such as trapezius transfer offer a reliable option in the subsequent stage. Case Presentation: A 32-year-old male presented with weak external rotation in his left shoulder, after previous axillary nerve reconstruction. He received the ipsilateral lower trapezius transfer with the aim of improving the external rotation. Discussion: The lower trapezius restores a better joint reaction force in both the compressive-distractive and anterior-posterior balancing and provides a centering force through the restoration of the anterior-posterior force couple. Conclusion: We believe that the ipsilateral lower trapezius transfer to the infraspinatus is a good outcome and is effective in improving overall shoulder stability and the shoulder external rotation moment arm or at least maintaining in neutral position with the arm fully adducted in patients with post axillary nerve injuries post unsatisfactory nerve reconstruction to increase the quality of life and activities of daily living.

Application of structural allogenous bone graft in two-stage exchange arthroplasty for knee periprosthetic joint infection: a case control study.

BACKGROUND: Knee prosthetic joint infection (PJI) is a common but devastating complication after knee arthroplasty. The revision surgeries for knee PJI may become more challenging when it is associated with large bone defects. The application of structural bone allograft in knee revision surgeries with large bone defects is not a new technique. However, there is a lack of literature reporting its efficacy in PJI cases. This study aimed to investigate the outcome of structural fresh frozen allogenous bone grafts in treating patients in knee PJI with large bone defects. METHODS: We performed a retrospective cohort analysis of knee PJI cases treated with two-stage exchange arthroplasty at our institution from 2010 to 2016. 12 patients with structural allogenous bone graft reconstructions were identified as the study group. 24 patients without structural allograft reconstructions matched with the study group by age, gender, and Charlson comorbidity index were enrolled as the control group. The functional outcome of the study group was evaluated with the Knee Society Score (KSS). Treatment success was assessed according to the Delphi-based consensus definition. The infection relapse rate and implant survivorship were compared between groups. RESULTS: Revision knees with structural allograft presented excellent improvement in the KSS (33.1 to 75.4). There was no significant difference between infection relapse-free survival rate and prosthesis survival rate in the two groups. The 8-year prosthesis survival rate was 90.9% in the study group and 91% in the control group (p = 0.913). The 8-year infection relapse-free survival rate was 80 and 83.3% in the study group and control group, respectively (p = 0.377). CONCLUSION: The structural fresh frozen allogenous bone graft provided an effective way for bone defect reconstruction in knee PJI with an accountable survival rate. Meanwhile, using structural allografts did not increase the relapse rate of infection.

Comparison of lesion characteristics between conventional and high-power short-duration ablation using contact force-sensing catheter in patients with paroxysmal atrial fibrillation.

BACKGROUND: Transmural lesion creation is essential for effective atrial fibrillation (AF) ablation. Lesion characteristics between conventional energy and high-power short-duration (HPSD) setting in contact force-guided (CF) ablation for AF remained unclear. METHODS: Eighty consecutive AF patients who received CF with conventional energy setting (power control: 25-30 W, force-time integral = 400 g s, n = 40) or with HPSD (power control: 40-50 W, 10 s, n = 40) ablation were analyzed. Of them, 15 patients in each conventional and HPSD group were matched by age and gender respectively for ablation lesions analysis. Type A and B lesions were defined as a lesion with and without significant voltage reduction after ablation, respectively. The anatomical distribution of these lesions and ablation outcomes among the 2 groups were analyzed. RESULTS: 1615 and 1724 ablation lesions were analyzed in the conventional and HPSD groups, respectively. HPSD group had a higher proportion of type A lesion compared to conventional group (P < 0.01). In the conventional group, most type A lesions were at the right pulmonary vein (RPV) posterior wall (50.2%) whereas in the HPSD group, most type A lesions were at the RPV anterior wall (44.0%) (P = 0.04). The procedure time and ablation time were significantly shorter in the HPSD group than that in the conventional group (91.0 ± 12.1 vs. 124 ± 14.2 min, P = 0.03; 30.7 ± 19.2 vs. 57.8 ± 21 min, P = 0.02, respectively). At a mean follow-up period of 11 ± 1.4 months, there were 13 and 7 patients with recurrence in conventional and HPSD group respectively (P = 0.03). CONCLUSION: Optimal ablation lesion characteristics and distribution after conventional and HPSD ablation differed significantly. HPSD ablation had shorter ablation time and lower recurrence rate than did conventional ablation.

Distribution of triggers foci and outcomes of catheter ablation in atrial fibrillation patients in different age groups.

BACKGROUND: Atrial fibrillation (AF) prevalence increases with age. Aging affects the substrate properties of the left atrium (LA) and the outcomes of catheter ablation for treating AF. We investigated the AF trigger distribution and catheter ablation outcomes in patients of different ages with AF. METHODS: 1585 patients with AF (1181 paroxysmal and 404 non- paroxysmal AF) who had undergone catheter ablation were enrolled. The patients were divided into young (20-40 year-old, n = 175), middle-aged (41-64 year-old, n = 1134), and old (≥ 65 year-old, n = 276) groups. Electrophysiological characteristics and AF trigger sites were recorded. RESULT: The incidence of AF with only non-pulmonary vein (non-PV) foci was higher in the young group than in the other groups (8.6% vs. 3.6% vs. 3.3%, p < 0.01). Non-PV foci were more commonly located in the superior vena cava (SVC) in the young group than in the other groups (13.1% vs. 7.8% vs. 6.5%, p = 0.03). The left atrium (LA) mean voltage was higher and the incidence of very late recurrence after AF ablation was lower in the young group than in the other groups. However, the final AF recurrence rate after multiple procedures and complication rates were similar among all the groups at a mean follow-up of 5.6 years. CONCLUSION: The young patients with AF had a higher incidence of only non-PV foci, mostly located in SVC, than the middle-aged and old patients. Our study highlights the importance of identifying the non-PV foci in catheter ablation of young patients with AF.

Effects of Good Pain Management (GPM) ward program on patterns of care and pain control in patients with cancer pain in Taiwan.

BACKGROUND: The undertreatment of cancer pain is a global issue although many international guidelines and various studies bloom to explore the approaches in pain management. However, there is no standard care for cancer pain in routine practices. To set up a standardized procedure for improving cancer pain management in Taiwan, the Good Pain Management (GPM) program is explored to provide treatments following the US National Cancer Care Network (NCCN) Adult Cancer Pain Guideline. METHOD: Patients diagnosed with moderate-to-severe cancer pain were eligible and randomized into the GPM or control arm and observed the first 48 h to evaluate the effects of pain management between 2 arms. Pain control, adequacy of treatments, patient satisfaction, and quality of life (QoL) of eligible patients were analyzed. Ad hoc analyses based on the pain medication category were also conducted. RESULT: Fifty-one patients were enrolled, with 26 and 25 assigned to the GPM and control arms, respectively. Significant differences among the GPM and control arms were found including a greater decrease in the mean numerical rating scale (NRS) score in the GPM arm (- 4.6 vs. - 2.8), a lower proportion of moderate-to-severe pain in the GPM arm (23.2% vs. 39.8%), and a higher pain management index (PMI) score in the GPM arm (0.64 points vs. 0.33 points) (all p < 0.05). Ad hoc analyses revealed that the patient subgroups using strong opioids showed better patient satisfaction in GPM arm when compared with the same subgroup in the control arm. CONCLUSION: In summary, our study demonstrated that the implementation of a standardized pain assessment and management approach (GPM ward program) showed significant improvements on pain relief, decreased the portion of moderate-to-severe cancer pain, and increased patient satisfaction in the 1st 48 h after admission. The implementation of the GPM approach in the cancer ward may provide sooner and better improvement of cancer pain management for patients who suffered moderate-to-severe cancer pain. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT03155516).

Association between ß2-Adrenoreceptor Medications and Risk of Parkinson's Disease: A Meta-Analysis.

Background and Objective: Parkinson's disease (PD) is a progressive neurological disorder characterized by an accumulation of Lewy bodies and degeneration of dopaminergic neurons in the substantia nigra. The treatment options currently available are only partly effective and fail to restore the lost dopaminergic neurons or slow the progression. ß2-adrenoceptors (ß2AR) are widely expressed in various human tissues and organs, regulate many important metabolic functions, and are targeted for treatment of various diseases. Studies have reported a link between chronic use of the ß2AR antagonist propranolol and an increased risk of PD, and chronic use of ß2AR agonists has been associated with a decreased risk of PD. We conducted a meta-analysis on the association between both ß2AR agonist level and ß2AR antagonist level and the risk of PD. Materials and Methods: A comprehensive electronic search was conducted on the databases of PubMed, ScienceDirect, ProQuest, Cochrane Library, and ClinicalKey from the start of each database until 30 June 2021. The objective was to identify prospective cohort and case-control studies that have reported on the association between ß-adrenoceptor agonist level, antagonist level, and PD risk. Results: A meta-analysis of the data extracted from eight studies revealed that ß2AR agonist use was associated with reduced PD risk (RR = 0.859, 95% confidence interval [CI] 0.741-0.995. p = 0.043). Compared with the control group, ß2AR antagonist use was associated with an increased risk of PD (RR = 1.490, 95% CI, 1.195 to 1.857. p < 0.005). Propranolol, a type of ß2AR antagonist, was related to an increased risk of PD (RR = 2.820, 95% CI, 2.618 to 3.036. p < 0.005). Conclusions: In this meta-analysis, ß2AR agonists were associated with a decreased risk of PD, and ß2AR antagonists were related with an increased risk of PD. However, further studies with larger sample sizes and an evaluation of the long-term effects of varying dosages of medications are needed.

Identification of critical isthmus using coherent mapping in patients with scar-related atrial tachycardia.

INTRODUCTION: Accurate identification of slow conducting regions in patients with scar-related atrial tachycardia (AT) is difficult using conventional electrogram annotation for cardiac electroanatomic mapping (EAM). Estimating delays between neighboring mapping sites is a potential option for activation map computation. We describe our initial experience with CARTO 3 Coherent Mapping (Biosense Webster Inc,) in the ablation of complex ATs. METHODS: Twenty patients (58 ± 10 y/o, 15 males) with complex ATs were included. We created three-dimensional EAMs using CARTO 3 system with CONFIDENSE and a high-resolution mapping catheter (Biosense Webster Inc). Local activation time and coherent maps were used to aid in the identification of conduction isthmus (CI) and focal origin sites. System-defined slow or nonconducting zones and CI, defined by concealed entrainment (postpacing interval < 20 ms), CV < 0.3 m/s and local fractionated electrograms were evaluated. RESULTS: Twenty-six complex ATs were mapped (mean: 1.3 ± 0.7 maps/pt; 4 focal, 22 isthmus-dependent). Coherent mapping was better in identifying CI/breakout sites where ablation terminated the tachycardia (96.2% vs 69.2%; P = .010) and identified significantly more CI (mean/chamber 2.0 ± 1.1 vs 1.0 ± 0.7; P < .001) with narrower width (19.8 ± 10.5 vs 43.0 ± 23.9 mm; P < .001) than conventional mapping. Ablation at origin and CI sites was successful in 25 (96.2%) with long-term recurrence in 25%. CONCLUSIONS: Coherent mapping with conduction velocity vectors derived from adjacent mapping sites significantly improved the identification of CI sites in scar-related ATs with isthmus-dependent re-entry better than conventional mapping. It may be used in conjunction with conventional mapping strategies to facilitate recognition of slow conduction areas and critical sites that are important targets of ablation.

Transthoracic echocardiography monitoring during ASD closure using an artificial hand system.

AIM: Continuous real-time echocardiographic monitoring is essential for guidance during ASD closure. However, transthoracic echocardiography (TTE) can only be implemented intermittently during fluoroscopy. We evaluate a novel approach to provide real-time imaging during the entire procedure. FINDING: We developed a custom-made TTE monitoring apparatus using artificial hand (AH-TTE) that enables real-time TTE images during atrial septal defect (ASD) closure. Thirty-two patients underwent successful device implantation using AH-TTE monitoring without complications. The median duration for real-time AH-TTE monitoring was 22 min and the median fluoroscopy time was 7.2 min. One case of pericardial effusion and one of transient bradycardia event due to air embolism was detected. All patients had uneventful recoveries. CONCLUSIONS: Our simple and novel monitoring technique with AH-TTE provides TEE-like monitoring and may be a new alternative method for ASD closure. It gives real-time stable TTE images and minimizes radiation exposure for the interventional team during fluoroscopy.

Use of Extended Pedicled Transverse Rectus Abdominis Myocutaneous Flap for Extensive Chest Wall Defect Reconstruction After Mastectomy for Locally Advanced Breast Cancer.

BACKGROUND: The reconstruction of a large postmastectomy chest wall defect for patients with stage III/IV breast cancer is a challenge for plastic surgeons. In this study, we present the application of an extended transverse rectus abdominis myocutaneous (TRAM) flap to easily and safely reconstruct these defects. PATIENTS AND METHODS: A retrospective review from November 1997 to November 2016 revealed that 65 patients with stage III/IV breast cancer immediately underwent postmastectomy TRAM flap reconstruction. In total, 16 patients were enrolled in this study based on the inclusion criteria of a postmastectomy chest skin defect size of greater than or equal to 100 cm and a TRAM flap size of greater than or equal to 80% of the lower abdominal area for reconstruction. RESULTS: Eleven (68.9%) and 5 patients (31.3%) were diagnosed with stage III and stage IV breast cancer, respectively. The chest wall skin defects ranged from 135 to 440 cm. All flap areas exceeded 80% of the lower abdominal area. Overall, 100% of the harvested flaps were used in 3 patients, and only 1 patient had marginal necrosis in zone IV. No total flap loss was observed. The average length of hospital stay was 5.8 days, and the mean follow-up duration was 46.6 months (range, 4.5-117.7 months). On a Likert scale, the mean follow-up satisfaction score of 10 patients was 4.7. CONCLUSIONS: Even when the flap area exceeded 80% of the lower abdominal area, the extended TRAM flap proved an effective and viable method for the immediate reconstruction of extensive postmastectomy chest wall skin defects, resulting in few minor complications and high follow-up satisfaction scores.

Clinical efficacy of open-irrigated electrode cooled with half-normal saline for initially failed radiofrequency ablation of idiopathic outflow tract ventricular arrhythmias.

BACKGROUND: Acute failure of radiofrequency ablation (RFA) of ventricular arrhythmias (VAs) occur in 10%-20% of patients and is partly attributed to inadequate lesion depth acquired with standard ablation protocols. Half-normal saline (HNS)-irrigation is a promising strategy to improve the success rate of VA ablation. OBJECTIVE: This study investigated the efficacy of HNS-irrigated ablation after a failed standard plain normal saline solution (PNSS)-irrigated ablation on idiopathic outflow tract ventricular arrhythmia (OT-VA). METHOD: This is a prospective observational study of consecutive patients undergoing RFA of idiopathic OT-VA comparing the efficacy of additional HNS-irrigated ablation for failed standard PNSS-irrigated ablation. Acute failure was defined as persistence of spontaneous VA or persistent inducibility of the clinical VA. RESULTS: Out of 160 OT-VA cases (51 ± 15-year-old, 62 males), 31 underwent HNS irrigation after a failed standard PNSS-irrigated ablation. The HNS group had a significantly longer procedure time (60.06 ± 43.83 vs 37.51 ± 33.40 minutes; P = .013) and higher radiation exposure (31.45 ± 20.24 vs 17.22 ± 15.25 minutes; P = .001) than the PNSS group but provided an additional acute success in 21 of 31 (67.7%) patients. Over a follow-up duration of 7.8 ± 4.6 months, 24 recurrences were identified, including 8 (25.8%) in the HNS and 16 (12.4%) in the PNSS group, with lower freedom from recurrence in the HNS group (log rank P = .009). No major complication was observed. CONCLUSION: HNS-irrigated ablation after failed standard PNSS-irrigated ablation is safe and additionally improves acute ablation success by 67.7% for idiopathic OT-VA but with a higher rate of recurrence on follow-up. Whether the application of HNS as initial irrigant could result in better outcome requires further investigation.

Long-term efficacy and safety of adjunctive ethanol infusion into the vein of Marshall during catheter ablation for nonparoxysmal atrial fibrillation.

INTRODUCTION: We aimed to clarify the effect of vein of Marshall (VOM) ethanol infusion for treating VOM triggers and/or mitral flutter after first-attempt endocardial ablation in patients with nonparoxysmal atrial fibrillation (AF). METHODS AND RESULTS: Of the 254 consecutive patients (age, 56 ± 10 years; 221 male) undergoing catheter ablation for drug-refractory nonparoxysmal AF, 32 (12.6%) received VOM ethanol infusion. The patients were stratified into group 1 (pulmonary vein isolation [PVI], substrate modification, VOM ethanol infusion), group 2 (PVI, substrate modification), and group 3 (PVI alone). Propensity-matched analysis (N = 128) of long-term outcomes (3.9 ± 0.5 years) revealed a higher AF recurrence risk in group 2 (hazard ratio [HR], 4.17; 95% confidence interval [95% CI], 1.63-10.69; P = .003) and group 3 (HR, 1.82; 95% CI, 1.09-3.04; P = .021) than in group 1, as well as a higher atrial arrhythmia recurrence risk in group 2 than in group 1 (HR, 2.42; 95% CI, 1.16-5.03; P = .018). A higher procedural termination rate was observed in group 1 than groups 2 and 3 (41.7% vs 17.2% vs 18.8%; P = .042). On multivariate analysis, VOM ethanol injection was an independent predictor of freedom from recurrence of AF (HR, 0.20; 95% CI, 0.08-0.52; P = .001) and atrial arrhythmia (HR, 0.35; 95% CI, 0.17-0.74; P = .005), whereas a left atrial diameter >45 mm and hypertension were independent risk factors for recurrence. Periprocedural complications rates were comparable among the groups. CONCLUSION: Adjunctive VOM ethanol infusion is effective and safe for treating nonparoxysmal AF in patients with VOM triggers and/or refractory mitral flutter, providing good long-term freedom from AF and atrial arrhythmia.

Electrophysiological and clinical characteristics of catheter ablation for isolated left side atrial tachycardia over a 10-year period.

AIMS: Most left atrial tachycardia (LAT) is associated with atrial fibrillation (AF). The clinical and electrophysiological characteristics and outcomes of LAT without AF have not been investigated. This study sought to determine the long-term ablation outcomes and predictors of recurrence of isolated LAT. METHODS: This is a single-center study of consecutive patients with isolated LAT. Atrial arrhythmia recurrence was determined from follow-up records of patients who underwent LAT ablation from 2008 to 2017. Clinical and electrophysiologic characteristics associated with atrial arrhythmia recurrence were identified. RESULTS: A total of 50 patients (53 ± 19 years, 46% male) with 59 LAT (1.16 ± 0.47 per patient) were enrolled. Over a mean follow-up of 37 ± 33 months, atrial arrhythmia recurrence occurred in 22 (44%) patients, 11 with atrial tachycardia (AT) only, five with AF only, and six with concurrent AT and AF. The incidence of pulmonary vein (PV) origins increased significantly in the repeat procedure (P = 0.036). Multivariate analysis identified left ventricular ejection fraction (LVEF) as the only predictor of any atrial arrhythmia recurrence and LAT recurrence, while smoking and identified macroreentrant LAT in the index procedure predicted AF recurrence. CONCLUSION: This study demonstrated a higher rate of atrial arrhythmia recurrence, including AF, among patients with initially isolated LAT. A lower LVEF predicted any atrial arrhythmia and LAT recurrence, whereas smoking and index macroreentrant AT mechanism predicted long-term AF. PV ATs were frequently observed in recurrent patients irrespective of index procedure origin.

Effect of eribulin on patients with metastatic breast cancer: multicenter retrospective observational study in Taiwan.

PURPOSE: The aim of this study was to confirm the therapeutic role of eribulin on Taiwanese women with metastatic breast cancer. METHODS: This retrospective study examined 449 females who received eribulin between March 2014 and June 2017 at 14 hospitals in Taiwan for treatment of locally advanced or metastatic breast cancer. RESULTS: The survival rate at 24 months was 57.2% (95% CI 51.0-62.9%) and the median time to treatment failure (TTF) was 3.91 months (95% CI 3.45-3.94). A total of 175 patients (40.1%) received eribulin for fewer than 90 days and the others received it for 90 days or more. Eight patients (1.83%) had complete remission, 82 (18.8%) had partial remission, 202 (46.3%) had stable disease, and 144 (33.0%) had progressive disease (PD). Patients' tumors with the luminal A subtype had a significantly better objective response rate. Kaplan-Meier analysis indicated that hormone receptor positivity, luminal A subtype, receipt of eribulin as the 1st to 3rd line therapy, and metastasis to fewer than 4 organs were significantly associated with longer TTF. Stepwise multivariate analysis showed that only receipt of eribulin as the 1st to 3rd line therapy was significantly associated with TTF (HR 1.49, p < 0.001). All toxicities were manageable and only 18 patients (4.1%) discontinued treatment due to adverse events. CONCLUSIONS: Eribulin appears to have better efficacy and cause fewer adverse events, especially neutropenia, in Taiwanese women than Western women.

Tubacin, an HDAC6 Selective Inhibitor, Reduces the Replication of the Japanese Encephalitis Virus via the Decrease of Viral RNA Synthesis.

Japanese encephalitis virus (JEV), a neurotropic flavivirus, annually causes over 30,000 Japanese Encephalitis (JE) cases in East and Southeast Asia. Histone deacetylases (HDACs) modulate lysine acetylation of histones and non-histone proteins, regulating many processes including inflammation and antiviral immune response. This study investigated antiviral activity of pan- and selective-HDAC inhibitors as host-targeting agents against JEV. Among HDAC inhibitors, selective HDAC6 inhibitors (tubastatin-A (TBSA) and tubacin) concentration-dependently inhibited JEV-induced cytopathic effect and apoptosis, as well as reduced virus yield in human cerebellar medulloblastoma cells. The 50% inhibitory concentration (IC50) values of virus yield was 0.26 µM for tubacin and 1.75 µM for TBSA, respectively. Tubacin (IC50 of 1.52 µM), but not TBSA, meaningfully blocked the production of intracellular infectious virus particles. In time-of-addition assays, the greatest potency of antiviral activity was observed in the mode of pre-treatment with tubacin (IC50 of 1.89 µM) compared to simultaneous (IC50 of 4.88 µM) and post-treatment (IC50 of 2.05 µM) modes. Interestingly, tubacin induced the hyperacetylation of a HDAC6 substrate Hsp90 and reduced the interaction of Hsp90 with JEV NS5 protein. Novobiocin, an Hsp90 inhibitor, diminished the NS5 protein amount and virus replication in JEV-infected cells. Meantime, tubacin suppressed the NS5 expression and antisense RNA genome synthesis in infected cells. Tubacin-induced Hsp90 hyperacetylation was suggested to influence the NS5 activity in JEV replication. Therefore, tubacin had a high potential of a host-targeting agent against JEV, exhibiting preventive and therapeutic activities against JEV infection.

Comparative genomics of grass EST libraries reveals previously uncharacterized splicing events in crop plants.

BACKGROUND: Crop plants such as rice, maize and sorghum play economically-important roles as main sources of food, fuel, and animal feed. However, current genome annotations of crop plants still suffer false-positive predictions; a more comprehensive registry of alternative splicing (AS) events is also in demand. Comparative genomics of crop plants is largely unexplored. RESULTS: We performed a large-scale comparative analysis (ExonFinder) of the expressed sequence tag (EST) library from nine grass plants against three crop genomes (rice, maize, and sorghum) and identified 2,879 previously-unannotated exons (i.e., novel exons) in the three crops. We validated 81% of the tested exons by RT-PCR-sequencing, supporting the effectiveness of our in silico strategy. Evolutionary analysis reveals that the novel exons, comparing with their flanking annotated ones, are generally under weaker selection pressure at the protein level, but under stronger pressure at the RNA level, suggesting that most of the novel exons also represent novel alternatively spliced variants (ASVs). However, we also observed the consistency of evolutionary rates between certain novel exons and their flanking exons, which provided further evidence of their co-occurrence in the transcripts, suggesting that previously-annotated isoforms might be subject to erroneous predictions. Our validation showed that 54% of the tested genes expressed the newly-identified isoforms that contained the novel exons, rather than the previously-annotated isoforms that excluded them. The consistent results were steadily observed across cultivated (Oryza sativa and O. glaberrima) and wild (O. rufipogon and O. nivara) rice species, asserting the necessity of our curation of the crop genome annotations. Our comparative analyses also inferred the common ancestral transcriptome of grass plants and gain- and loss-of-ASV events. CONCLUSIONS: We have reannotated the rice, maize, and sorghum genomes, and showed that evolutionary rates might serve as an indicator for determining whether the identified exons were alternatively spliced. This study not only presents an effective in silico strategy for the improvement of plant annotations, but also provides further insights into the role of AS events in the evolution and domestication of crop plants. ExonFinder and the novel exons/ASVs identified are publicly accessible at http://exonfinder.sourceforge.net/ .