Sequence analysis of grapevine isolates of Raspberry ringspot nepovirus

Summary. The nucleotide sequences of RNAs 1 and 2 of a German isolate of Raspberry ringspot virus (RpRSV) infecting grapevine (RpRSV-Grapevine), as well as partial sequences of another grapevine isolate from Switzerland (RAC815) were determined. The sequences of the protease-polymerase region encoded by RNA1, and the movement protein and coat protein genes encoded by RNA 2, of these isolates were compared with those of other isolates available in databases. The coat proteins of the grapevine isolates formed a sister group to all those from other RpRSV isolates, but whether this resulted from divergence or recombination was uncertain.     

Dynamic particle image velocimetry flow analysis of the flow field immediately downstream of bileaflet mechanical mitral prostheses

New dynamic particle image velocimetry (PIV) technology was applied to the study of the flow field associated with prosthetic heart valves. Four bileaflet prostheses, the St. Jude Medical (SJM) valve, the On-X valve with straight leaflets, the Jyros (JR) valve, and the Edwards MIRA (MIRA) valve with curved leaflets, were tested in the mitral position under pulsatile flow conditions to find the effect of the leaflet shape and overall valve design on the flow field, particularly in terms of the turbulent stress distribution, which may influence hemolysis, platelet activation, and thrombus formation. Comparison of the time-resolved flow fields associated with the opening, accelerating, peak, and closing phases of the diastolic flow revealed the effects of the leaflet shape and overall valve design on the flow field. Anatomically and antianatomically oriented bileaflet valves were also compared in the mitral position to study the effects of the orientation on the downstream flow field. The experimental program used a dynamic PIV system utilizing a high-speed, high-resolution video camera to map the true time-resolved velocity field inside the simulated ventricle. Based on the experimental data, the following general conclusions can be made. High-resolution dynamic PIV can capture true chronological changes in the velocity and turbulence fields. In the vertical measuring plane that passes the centers of both the aortic and mitral valves (A-A section), bileaflet valves show clear and simple circulatory flow patterns when the valve is installed in the antianatomical orientation. The SJM, the On-X, and the MIRA valves maintain a relatively high velocity through the central orifice. The curved leaflets of the JR valve generate higher velocities with a divergent flow during the accelerating and peak flow phases when the valve is installed in the anatomical orientation. In the velocity field directly below the mitral valve and normal to the previous measuring plane (B-B section), where characteristic differences in valve design on the three-dimensional flow should be visible, the symmetrical divergent nature of the flow generated by the two inclined half-disks installed in the antianatomical orientation was evident. The SJM valve, with a central downward flow near the valve, is contrasted with the JR valve, which has a peripherally strong downward circulation with higher turbulent stresses. The On-X valve has a strong central downward flow attributable to its large opening angle and flared inlet shape. The MIRA valve also has a relatively strong downward central flow. The MIRA valve, however, diverts the flow three-dimensionally due to its peripherally curved leaflets.     

Acute cytomegalovirus infection modulates the intestinal microbiota and targets intestinal epithelial cells

Primary and recurrent cytomegalovirus (CMV) infections frequently cause CMV colitis in immunocompromised as well as inflammatory bowel disease (IBD) patients. Additionally, colitis occasionally occurs upon primary CMV infection in patients who are apparently immunocompetent. In both cases, the underlying pathophysiologic mechanisms are largely elusive - in part due to the lack of adequate access to specimens. We employed the mouse cytomegalovirus (MCMV) model to assess the association between CMV and colitis. During acute primary MCMV infection of immunocompetent mice, the gut microbial composition was affected as manifested by an altered ratio of the Firmicutes to Bacteroidetes phyla. Interestingly, these microbial changes coincided with high-titer MCMV replication in the colon, crypt hyperplasia, increased colonic pro-inflammatory cytokine levels, and a transient increase in the expression of the antimicrobial protein Regenerating islet-derived protein 3 gamma (Reg3γ). Further analyses revealed that murine and human intestinal epithelial cell lines, as well as primary intestinal crypt cells and organoids represent direct targets of CMV infection causing increased cell death. Accordingly, in vivo MCMV infection disrupted the intestinal epithelial barrier and increased apoptosis of intestinal epithelial cells. In summary, our data show that CMV transiently induces colitis in immunocompetent hosts by altering the intestinal homeostasis.     

Small keyhole transuncal foraminotomy for unilateral cervical radiculopathy

Summary Interbody fusion after anterior discectomy may lead to acceleration of degenerative changes at adjacent levels. Although the posterior approach preserves the motion segment, decompression of the nerve root is indirect if “hard disc prolaps” is the main cause. Recently, a technique of microsurgical anterior cervical foraminotomy for the treatment of radiculopathy with preservation of the segment mobility was published. In this study, we present this technique with several modifications. Thirteen patients – 5 men and 8 women with an average age of 49 years – with unilateral radiculopathy resistant to conservative treatment underwent microsurgical anterior foraminotomy via a small keyhole transuncal approach. The base of the uncinate process (UP) was directly drilled in the trajectory to the intervertebral foramen without destroying the disc tissue. The vertebral artery between the transverse process was not exposed. Furthermore, the functional anatomy of the uncovertebral joint remained largely intact. All patients experienced complete relief of radiating pain. A cervical collar was not used. Mean follow-up time was 19 months. The mobility of the operated segment was preserved in each patient. No instability of the cervical spine was seen. The microsurgical anterior foraminotomy via a small keyhole transuncal approach is safe, minimally invasive, and represents an effective method to treat unilateral cervical radiculopathy caused by disc prolaps and/or uncovertebral osteophytes. Additionally, the segment mobility is preserved and prevents the acceleration of degenerative changes at adjacent levels.     

牛津单髁膝关节置换：长期结果

牛津膝置换是使用最广泛的膝关节单髁置换（UKR）。牛津膝在37年前开始应用,拥有一个全匹配的活动衬垫,因而磨损率非常低。牛津膝最主要的使用指征是膝关节前内侧骨关节炎,这种病人至少占所有需要行膝关节置换术患者的50％。由于这一系统的设计特点,传统UKR的反指征,如年龄、活动量、肥胖、髌股关节损害和软骨钙质沉着症等对于牛津膝均不是反指征。与全膝关节置换（TKR）相比,牛津膝提供更快的康复、更好的功能、更大的活动度和更好的术后满意度,发生并发症更少、程度更轻,病残率和死亡率更低。一个持续超过30年的研究显示在90％的病例中,牛津膝为患者终生提供了优或良的临床结果,且不需要翻修。在最近15年,牛津膝通过微创手术入路植入,涉及6000多例使用该入路牛津膝置换的9个研究报道显示,10年生存率约95％。在许多这样的研究中,医生们在拟行膝关节置换的患者中约50％使用了牛津单髁膝置换。     

ER and PR Immunohistochemistry and HER2 FISH versus Oncotype DX: Implications for Breast Cancer Treatment

Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor (HER2) concordance between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and Oncotype DX, a commercially available RT‐PCR‐based assay which recently began reporting biomarker results was assessed. ER concordance was 98.9% (262/265), Pearson correlation coefficient (r) = 0.42, and Spearman's rank correlation (ρ) = 0.25. Positive percent agreement for ER was 98.9% (262/265). One patient with discordant ER results was not offered hormone therapy based on the preferential use of Oncotype DX. PR was concordant in 91.3% (242/265), r = 0.80, ρ = 0.75, and Cohen's kappa (κ) = 0.63. Positive percent agreement for PR was 90.5% (218/241) and negative percent agreement was 100% (24/24). HER2 concordance was 99.2% (245/247), r = 0.35, ρ = 0.28, and κ = 0.12. Positive percent agreement for HER2 was 0% (0/2) and negative percent agreement was 100% (245/245). Of the three FISH HER2‐amplified cases, two were negative and one was equivocal, and all FISH HER2‐equivocal cases (n = 3) were negative by Oncotype DX. Patients that were FISH HER2‐amplified, Oncotype DX HER2‐negative did not receive trastuzumab. Although our results demonstrated high concordance between IHC and Oncotype DX for ER and PR, our data showed poor positive percent agreement for HER2. Compared to FISH, Oncotype DX does not identify HER2‐positive breast carcinomas. The preferential use of Oncotype DX biomarker results over IHC and FISH is discouraged.     

A longitudinal immunologic evaluation of hemophiliac patients

Over an average span of one year, we performed a prospective clinical and immunologic evaluation of 30 patients with hemophilia. No patient developed life-threatening opportunistic infection or malignancy; however, the immunologic abnormalities and lymphadenopathy initially present in nine patients (lymphadenopathy group) persisted. In addition, five patients, representing 24% of the initial group without lymphadenopathy, developed generalized lymphadenopathy (converter group). One episode of idiopathic thrombocytopenia (ITP) and one episode of staphylococcal sepsis occurred in this "converter" group; one episode of ITP also occurred in the lymphadenopathy group. Sixteen patients remained asymptomatic. At the time of the follow-up evaluation, those differences in mononuclear cell (MNC) percentages and numbers noted initially among the three hemophiliac groups were no longer present. Natural killer cell function alone or in the presence of biologic response modifiers was not different among hemophiliac and control groups. Before developing lymphadenopathy, the converter group of patients had significantly better lymphocyte mitogenic function than did the other two groups of patients with hemophilia. However, lymphocyte mitogenic responses of all groups of patients with hemophilia significantly deteriorated over the course of the study. The abnormal mitogenic responses noted in these patients was explained in part by higher levels of spontaneous suppressor cell activity in mononuclear cell preparations from patients with hemophilia. We conclude that long-term immunologic studies of this patient population requires both quantitative and qualitative evaluations. Our data show that patients with hemophilia have progressive dysfunction of cell- mediated immunity.     

Atrial Arrhythmias in Long-QT Syndrome under Daily Life Conditions: A Nested Case Control Study

Background: The long-QT syndromes (LQTS) are inherited electrical cardiomyopathies characterized by prolonged ventricular repolarization and ventricular arrhythmias. Several genetic reports have associated defects in LQTS-causing genes with atrial fibrillation (AF). We therefore studied whether atrial arrhythmias occur in patients with LQTS under daily-life conditions.
Methods: We systematically assessed atrial arrhythmias in LQTS patients and matched controls using implanted defibrillators or pacemakers as monitors of atrial rhythm in a nested case-control study. Twenty-one LQTS patients (3 male; 39 ± 18 years old; 18 on β blocker, ICD therapy duration 6.3 ± 2.7 years; 4 LQT1, 6 LQT2, 2 LQT3) were matched to 21 control subjects (13 male; 50 ± 19 years old; 3 on β blocker; pacemaker therapy duration 8.5 ± 5.5 years; 19 higher-degree AV block, 2 others). LQTS patients were identified by a systematic search of the LQTS patient databases in Münster and Munich.
Results: One-third (7 of 21) of the LQTS patients developed self-terminating atrial arrhythmias (atrial cycle lengths <250 ms). Only one control patient developed a single episode of postoperative AF (P < 0.05 vs LQTS).
Conclusions: LQTS patients at high risk for ventricular arrhythmias may develop short-lasting atrial arrhythmias under daily-life conditions, suggesting that prolonged atrial repolarization may contribute to the initiation of AF.