Polyhedron-like Inclusion Body Formation by a Mutant Nucleopolyhedrovirus Expressing the Granulin Gene from a Granulovirus

The polyhedrin gene inBombyx morinucleopolyhedrovirus (BmNPV) was replaced with the granulin gene ofTrichoplusia nigranulovirus (TnGV). The substitution was verified by Southern hybridization, and expression of granulin by the mutant virus, BmGran, was demonstrated by sodium dodecyl sulfate–polyacrylamide gel electrophoresis and by amino acid sequencing of the predominant protein of BmGran inclusion bodies (IBs). Light and electron microscopy examination of BmGran-infectedB. moriand BmN cells revealed large, cuboidal, polyhedron-like IBs in the nucleus and cytoplasm, but granules were not seen. IBs contained small, parallel, electron-dense streaks, which defined the geometric pattern of crystallization. Geometric patterns of nuclear IBs were frequently disrupted by occlusion of polyhedron envelope fragments, resulting in IB instability and fracturing. Virions were not embedded in most of the polyhedron-like IBs, but accumulated with polyhedron envelope fragments. Some virions were coated with matrix protein and were partially wrapped by polyhedron envelope. These results suggested that (1) the amino acid sequence of granulin is insufficient for determining IB morphology in TnGV-infected cells, and TnGV may have genes, not present in BmNPV, that control granule formation, and (2) interactions among the virion, the IB envelope, and the matrix protein may be important in virion occlusion and IB morphology and stability.     

Immune responses against a single CD8+-T-cell epitope induced by virus vector vaccination can successfully control Trypanosoma cruzi infection

In order to develop CD8+-T-cell-mediated immunotherapy against intracellular infectious agents, vaccination using recombinant virus vectors has become a promising strategy. In this study, we generated recombinant adenoviral and vaccinia virus vectors expressing a single CD8+-T-cell epitope, ANYNFTLV, which is derived from a Trypanosoma cruzi antigen. Immunogenicity of these two recombinant virus vectors was confirmed by the detection of ANYNFTLV-specific CD8+ T cells in the spleens of immunized mice. Priming/boosting immunization using combinations of these two recombinant virus vectors revealed that the adenovirus vector was efficient for priming and the vaccinia virus vector was effective for boosting the CD8+-T-cell responses. Moreover, we also demonstrated that the ANYNFTLV-specific CD8+-T-cell responses were further augmented by coadministration of recombinant vaccinia virus vector expressing the receptor activator of NFkappaB (RANK) ligand as an adjuvant. By priming with the adenovirus vector expressing ANYNFTLV and boosting with the vaccinia virus vectors expressing ANYNFTLV and RANK ligand, the immunized mice were efficiently protected from subsequent challenge with lethal doses of T. cruzi. These results indicated, for the first time, that the induction of immune responses against a single CD8+-T-cell epitope derived from an intrinsic T. cruzi antigen was sufficient to control lethal T. cruzi infection.     

Differences in diazepam pharmacokinetics in Chinese and white Caucasians – Relation to body lipid stores

Summary We have compared diazepam pharmacokinetics in 16 Chinese and 18 white Caucasian healthy male volunteers, resident in Hong Kong and have correlated them with physical attributes. Serum concentrations of diazepam and desmethyldiazepam were measured in venous blood by an enzyme-linked immunoassay (0–3 h samples) and HPLC (3–72 h samples). Pharmacokinetic parameters were derived assuming a two compartment model, distribution phase <6 h, and 100% oral systemic availability. Compared with the Chinese the white Caucasians were older, heavier, taller, and fatter, as judged by skin fold thickness (SFT) and total body weight to Ideal body weight (TBW/IBW) ratio; respective mean differences being 16%, 27%, 4%, 26%, and 15% (p<0.05). Mean diazepam apparent volume of distribution (V) and V/IBW were larger in the white Caucasians (52% & 39% respectively, p=0.002). SFT and TBW/IBW ratio yielded the best correlations with V, V/TBW and V/IBW (0.50–0.75, p<0.05). Obesity indices contributed most to the overall regressions (R² up to 0.52), and for V there was a further small effect (2%, partial F test) due to ethnic group, possibly reflecting stature. Mean peak diazepam concentration (C_max) was similar in both ethnic groups. Time to C_max (t_max) was more often prolonged in the Chinese (X ² test, p=0.01). Body fat and stature may thus account for these inter-ethnic differences in the apparent volume of distribution of diazepam, a highly lipid-soluble drug.     

远视性屈光不正儿童屈光状态远期变化

目的探讨远视性屈光不正儿童屈光状态远期变化规律.方法对162例(324只眼)3～12岁远视性屈光不正儿童进行5～12.5年的观察,分别按性别、眼别、子午线、远视程度及不同年龄阶段进行分级,计算各组的年均下降远视屈光度,用u检验和方差分析.结果男女两组年均下降屈光度分别为0.34±0.17D和0.35±0.17D,左右眼为0.35±0.L7D、0.33±0.16D,平均90°和180°子午线轴为0.35±0.L6D、0.36±0.17D,无显著性差异;轻、中、高度远视为0.45±0.19D、0.27±0.16D、0.36±0.17D,中度远视下降最慢,轻、高度远视差异无显著性;＜6岁,6～9岁和≥9岁三组分别为0.46±0.15、0.37±020D、0.15±0.06D,有显著性差异.结论远视性屈光不正儿童的屈光随年龄的增长逐年下降,9岁以后趋于稳定,但散光无明显改变;远视下降速度以中度远视最慢,高度和轻度远视下降较快,后者易发展为近视眼.下降速度与性别、眼别无关.     

ASO Author Reflections: Do Shorter Tumor-to-Nipple Distances Compromise the Local Oncologic Safety of Nipple-Sparing Mastectomy?

Annals of Surgical Oncology -     

Effect of QT interval prolongation on cardiac arrest following liver transplantation and derivation of a risk index

Liver transplantation (LT) has a 4-fold higher risk of periprocedural cardiac arrest and ventricular arrhythmias (CA/VAs) compared with other noncardiac surgeries. Prolongation of the corrected QT interval (QTc) is common in patients with liver cirrhosis. Whether it is associated with an increased risk of CA/VAs following LT is unclear. Rates of 30-day CA/VAs post-LT were assessed in consecutive adults undergoing LT between 2010 and 2017. Pretransplant QTc was measured by a cardiologist blinded to clinical outcomes. Among 408 patients included, CA/VAs occurred in 26 patients (6.4%). QTc was significantly longer in CA/VA patients (475 ± 34 vs 450 ± 34 ms, P < .001). Optimal QTc cut-off for prediction of CA/VAs was ≥480 ms. After adjustment, QTc ≥480 ms remained the strongest predictor for the occurrence of CA/VAs (odds ratio [OR] 5.2, 95% confidence interval [CI] 2.2-12.6). A point-based cardiac arrest risk index (CARI) was derived with the bootstrap method for yielding optimism-corrected coefficients (2 points: QTc ≥480, 1 point: Model for End-Stage Liver Disease [MELD] ≥30, 1 point: age ≥65, and 1 point: male). CARI score ≥3 demonstrated moderate discrimination (c-statistic 0.79, optimism-corrected c-statistic 0.77) with appropriate calibration. QTc ≥480 ms was associated with a 5-fold increase in the risk of CA/VAs. The CARI score may identify patients at higher risk of these events. Whether heightened perioperative cardiac surveillance, avoidance of QT prolonging medications, or beta blockers could mitigate the risk of CA/VAs in this population merits further study.     

Treatment of Recurrent Hemarthrosis Following Total Knee Arthroplasty Using Surgical Interventions

BackgroudRecurrent hemarthrosis following total knee arthroplasty (TKA) is a rare complication. Its pathophysiology and standard treatments have not yet been established. In this study, we report 7 cases of recurrent hemarthrosis after TKA in which failure of the initial conservative treatment was followed by angiographic embolization; in 1 of the 7 cases, arthroscopic electrocauterization was also performed after treatment failure with selective embolization.MethodsFrom January 2015 to May 2018, 7 patients visited our hospital due to recurrent hemarthrosis after TKA. Their medical records and serologic test results were reviewed to check for the presence of any bleeding disorder and history of anticoagulant use. Implant malalignment and instability were checked using X-ray. In all cases, the conservative treatment failed, so interventional angiography with selective embolization was performed, which was also followed by arthroscopic electrocauterization if the outcome was unsatisfactory.ResultsThe interval between TKA and the onset of hemarthrosis ranged from 3 to 76 months (average, 34.1 months). There was no coagulopathy and instability. All patients underwent conservative treatment at an interval of 4.3 months and the rate of relapse was 3.1 on average. On the interventional angiography, 6 cases showed vascular blush, and 1 case had pulsatile bleeding. The average duration for interventional angiography was 90.9 minutes. The average length of follow-up was 38.8 months. Embolization was successfully performed in 4 cases. In 2 of 3 failed cases, the symptoms improved without further treatment. In the remaining 1 failed case, the patient had a relapse of hemarthrosis, so an arthroscopic procedure was performed, which led to identification of the suspicious bleeding point by using preoperative angiographic findings. Electrocauterization was performed and active bleeding was stopped. All cases with recurrent hemarthrosis achieved improvement.ConclusionsInterventional angiography was used to aid in the diagnosis of recurrent hemarthrosis, and therapeutic selective embolization provided satisfactory clinical results. Even if selective embolization fails, interventional angiography may be helpful for further surgical procedures because it reveals vascular blush of a bleeding site. Therefore, interventional angiography and selective embolization should be considered to be a useful treatment for recurrent hemarthrosis after TKA.     

Efficacy and tolerability of anti-asthma herbal medicine intervention in adult patients with moderate-severe allergic asthma

BACKGROUND: Chinese herbal medicine has a long history of human use. A novel herbal formula, anti-asthma herbal medicine intervention (ASHMI), has been shown to be an effective therapy in a murine model of allergic asthma. OBJECTIVE: This study was undertaken to compare the efficacy, safety, and immunomodulatory effects of ASHMI treatment in patients with moderate-severe, persistent asthma with prednisone therapy. METHODS: In a double-blind trial, 91 subjects underwent randomization. Forty-five subjects received oral ASHMI capsules and prednisone placebo tablets (ASHMI group) and 46 subjects received oral prednisone tablets and ASHMI placebo capsules (prednisone group) for 4 weeks. Spirometry measurements; symptom scores; side effects; and serum cortisol, cytokine, and IgE levels were evaluated before and after treatment. RESULTS: Posttreatment lung function was significantly improved in both groups as shown by increased FEV(1) and peak expiratory flow findings (P<.001). The improvement was slightly but significantly greater in the prednisone group (P<.05). Clinical symptom scores, use of beta(2)-bronchodilators, and serum IgE levels were reduced significantly, and to a similar degree in both groups (P<.001). T(H)2 cytokine levels were significantly reduced in both treated groups (P<.001) and were lower in the prednisone-treated group (P<.05). Serum IFN-gamma and cortisol levels were significantly decreased in the prednisone group (P<.001) but significantly increased in the ASHMI group (P<.001). No severe side effects were observed in either group. CONCLUSION: Anti-asthma herbal medicine intervention appears to be a safe and effective alternative medicine for treating asthma. In contrast with prednisone, ASHMI had no adverse effect on adrenal function and had a beneficial effect on T(H)1 and T(H)2 balance.     

Facilitating visuospatial attention for the contralateral hemifield by repetitive TMS on the posterior parietal cortex

Previous studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) could modulate the visuospatial functions. In this study, we investigated the effect of off-line high frequency subthreshold rTMS, when applied over the right or left posterior parietal cortex (PPC), on the visuospatial attention of the bilateral hemispaces. The subjects underwent visuospatial tasks before and immediately after receiving 1000 pulses of 10 Hz rTMS for a period of 20 min, and their responses were recorded. Our results demonstrated that the high frequency rTMS applied over the PPC produced facilitative effects on the visuospatial attention to the contralateral hemispace. The inhibitory effect to the ipsilateral hemispace was noticeable only in the left PPC.