Test characteristics of a level I or II fetal ultrasound in detecting structural heart disease

At the University of California Davis Medical Center, a screening fetal ultrasound examination (level I or II) incorporates a comprehensive segmental evaluation of the fetal heart. This study evaluated the reliability of the fetal ultrasound exam in the detection of abnormal heart anatomy. Our retrospective study reviewed results of 614 antenatal patients that had a screening fetal ultrasound exam. All patients subsequently underwent a detailed targeted fetal cardiac ultrasound exam performed by a pediatric cardiac sonographer and reviewed by a board-certified pediatric cardiologist. Of these 614 patients, 60 fetuses had structural heart disease by the targeted fetal exam. The screening fetal ultrasound exam correctly identified 55 of the 60, with 5 false negatives (8.3% false-negative rate) and 1 false positive (1.7% false-positive rate). Our study suggests that if a screening fetal ultrasound exam incorporates a segmental evaluation of the fetal heart it can reliably detect abnormal heart anatomy. At our institution a targeted fetal cardiac exam is now used to confirm and provide detailed assessment of the heart anatomy when a screening fetal exam is positive for heart disease.     

Dual enteric and respiratory tropisms of winter dysentery bovine coronavirus in calves

Summary Although winter dysentery (WD), which is caused by the bovine coronavirus (BCoV) is characterized by the sudden onset of diarrhea in many adult cattle in a herd, the pathogenesis of the WD-BCoV is not completely understood. In this study, colostrum-deprived calves were experimentally infected with a Korean WD-BCoV strain and examined for viremia, enteric and nasal virus shedding as well as for viral antigen expression and virus-associated lesions in the small and large intestines and the upper and lower respiratory tract from 1 to 8 days after an oral infection. The WD-BCoV-inoculated calves showed gradual villous atrophy in the small intestine and a gradual increase in the crypt depth of the large intestine. The WD-BCoV-infected animals showed epithelial damage in nasal turbinates, trachea and lungs, and interstitial pneumonia. The WD-BCoV antigen was detected in the epithelium of the small and large intestines, nasal turbinates, trachea and lungs. WD-BCoV RNA was detected in the serum from post-inoculation day 3. These results show that the WD-BCoV has dual tropism and induces pathological changes in both the digestive and respiratory tracts of calves. To our knowledge, this is the first detailed report of dual enteric and respiratory tropisms of WD-BCoV in calves. Comprehensive studies of the dual tissue pathogenesis of the BCoV might contribute to an increased understanding of similar pneumoenteric CoV infections in humans.     

Novel mutations in type 2 Gaucher disease in Chinese and their functional characterization by heterologous expression

We investigated 10 unrelated Chinese patients with type 2 Gaucher disease and performed ex vivo expression for the novel mutations to characterize their functional defects. These patients were diagnosed by enzymatic assays and clinicopathologic features over the past five years in a national centre in China. Genomic DNA was sequenced by a two-stage PCR approach for mutations in the functional GBA gene. Novel mutations were expressed with baculovirus-transfected Sf21 cells. Six novel mutations were found (in traditional nomenclature): P122L, Y363C, N382K, L383R, L385P, and M416V. Review of reported mutations indicated clustering of type 2 mutations in three regions of the GBA gene. Expression of novel mutations revealed that the enzyme defect could arise from one of two mechanisms: loss of catalytic activity (Y363C and M416V) or enzyme instability (P122L and N382K).     

Layered double hydroxide as an efficient drug reservoir for folate derivatives

Folic acid derivatives such as folinic acid and methotrexate (MTX) have been successfully hybridized with layered double hydroxide (LDH) by ion-exchange reaction. The X-ray diffraction patterns and spectroscopic analyses indicate that these molecules intercalated into the hydroxide interlayer space are stabilized in the tilted longitudinal monolayer mode by electrostatic interaction. No significant changes in their structural and functional properties are found in the hybrids. The cellular uptake test of MTX-LDH hybrid is carried out in the fibroblast (human tendon) and SaOS-2 cell line (Osteosarcoma, human) by in vitro MTT (3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide) assay. The initial proliferation of SaOS-2 cell is more strongly suppressed by treatment with MTX-LDH hybrid than with MTX alone. This study clearly shows that LDH not only plays a role as a biocompatible-delivery matrix for drugs but also facilitates a significant increase in the delivery efficiency.     

Coxsackievirus B3-associated myocardial pathology and viral load reduced by recombinant soluble human decay-accelerating factor in mice

Coxsackievirus B3 (CVB3) infection can result in myocarditis, which in turn may lead to a protracted immune response and subsequent dilated cardiomyopathy. Human decay-accelerating factor (DAF), a binding receptor for CVB3, was synthesized as a soluble IgG1-Fc fusion protein (DAF-Fc). In vitro, DAF-Fc was able to inhibit complement activity and block infection by CVB3, although blockade of infection varied widely among strains of CVB3. To determine the effects of DAF-Fc in vivo, 40 adolescent A/J mice were infected with a myopathic strain of CVB3 and given DAF-Fc treatment 3 days before infection, during infection, or 3 days after infection; the mice were compared with virus alone and sham-infected animals. Sections of heart, spleen, kidney, pancreas, and liver were stained with hematoxylin and eosin and submitted to in situ hybridization for both positive-strand and negative-strand viral RNA to determine the extent of myocarditis and viral infection, respectively. Salient histopathologic features, including myocardial lesion area, cell death, calcification and inflammatory cell infiltration, pancreatitis, and hepatitis were scored without knowledge of the experimental groups. DAF-Fc treatment of mice either preceding or concurrent with CVB3 infection resulted in a significant decrease in myocardial lesion area and cell death and a reduction in the presence of viral RNA. All DAF-Fc treatment groups had reduced infectious CVB3 recoverable from the heart after infection. DAF-Fc may be a novel therapeutic agent for active myocarditis and acute dilated cardiomyopathy if given early in the infectious period, although more studies are needed to determine its mechanism and efficacy.     

Investigating a possible cause of mesh migration during totally extraperitoneal (TEP) repair

Background In experienced hands, laparoscopic inguinal hernia repair has a low rate of recurrence, but it still can recur, and a number of reasons for this have been identified. In published studies, the majority of such cases seem to result from inadequate dissection leading to missed hernias or suboptimal mesh placement. But even with adequate dissection and proper placement of a sufficiently large mesh, recurrence sometimes happens. A number of investigators have cited mesh migration or dislocation as a possible cause, and this study examined how hip flexion affects the position of newly placed meshes and staples in totally extraperitoneal (TEP) repair of inguinal hernia.Methods After completion of the dissection and reduction of discovered hernias, a 15 × 15-cm polypropylene mesh was placed either unilaterally or bilaterally, as indicated. The preperitoneal space then was desufflated. The operating table, in an extended –20° position during surgery, was placed in a 90° position for approximately 15 s. After reinsufflation, the possibility of mesh migration and folding was investigated. Finally, the mesh was stapled, the table again extended and flexed, and the possibility of mesh migration and staple dislodgement investigated once more.Results The mesh did not migrate or become displaced from any potential hernia area, nor did any of the staples become dislodged.Conclusions Concern about mesh migration attributable to patients sitting up immediately after surgery appears to be unfounded, at least according to the findings for the current, small, simulated study group.     

CDK4 expression in chordoma: A potential therapeutic target

Chordomas are rare bone tumors and treatment is commonly based on a combination of surgery and radiotherapy. There is no standard chemotherapy treatment for chordoma. The aim of this study was to determine the expression of cyclin‐dependent kinase 4 (CDK4) in chordoma and its therapeutic implications. We evaluated CDK4 expression both in chordoma cell lines and in chordoma tissues. Also, we investigated the functional roles of CDK4 in chordoma cell growth and proliferation. Furthermore, the therapeutic implications of targeting CDK4 in chordoma were evaluated. We found CDK4 highly expressed in chordoma cell lines and in a majority (97.7%) of chordoma tissues. Higher CDK4 expression correlated with metastasis and recurrence of chordoma. Treatment of chordoma cells using CDK4 inhibitor palbociclib could efficiently inhibit chordoma cells growth and proliferation. These data demonstrate that targeting CDK4 may be useful as a novel strategy in the treatment of chordoma. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1581–1589, 2018.

     

Human coronary laser recanalization

Five patients undergoing distal saphenous vein bypass had an attempt at intraoperative laser vaporization of a proximal coronary stenosis. Laser treatment of three patients was technically successful. One patient's successfully treated native vessel was competing with the graft at angiographic restudy 25 days after the procedure. This first human intraoperative laser recanalization trial generated questions regarding the energy source, power parameters, and catheter modifications required for satisfactory clinical laser therapy. The trial is directing future experiments toward more efficient and complete laser vaporization of atherosclerotic plaques in the human coronary vasculature.     

Combined neonatal stress and young-adult glucocorticoid stimulation in rats reduce BDNF expression in hippocampus: effects on learning and memory

Epidemiological studies suggest that multiple developmental disruptions are involved in the etiology of psychiatric illnesses including schizophrenia. In addition, altered expression of brain-derived neurotrophic factor (BDNF) has been implicated in these illnesses. In the present study, we examined the combined long-term effect of an early stress, in the form of maternal deprivation, and a later stress, simulated by chronic young-adult treatment with the stress hormone, corticosterone, on BDNF expression in the hippocampus of rats. To assess whether there were behavioral effects, which may correlate with the BDNF changes, learning and memory was tested in the Y-maze test for short term spatial memory, the Morris water maze for long-term spatial memory, and the T-maze test for working memory. Four groups of rats received either no stress, maternal deprivation, corticosterone treatment, or both. Dorsal hippocampus sections obtained from parallel groups were used for BDNF mRNA in situ hybridization. Rats which had undergone both maternal deprivation and corticosterone treatment displayed a unique and significant 25-35% reduction of BDNF expression in the dentate gyrus (DG), and similar trends in the CA1 and CA3 regions of the hippocampus. These "two-hit" animals exhibited a learning delay in the Morris water maze test, a marked deficit in the Y-maze, but little change in the T-maze test. However, some aspects of cognition were also altered in rats with either maternal deprivation or corticosterone treatment. This study demonstrates a persistent effect of two developmental disruptions on BDNF expression in the hippocampus, with parallel, but not completely correlative changes in learning and memory.     

Factorial structure and psychometric properties of a brief version of the Reminiscence Functions Scale with Chinese older adults

Objective: The current study aims to examine the factorial structure and psychometric properties of a brief version of the Reminiscence Functions Scale (RFS), a 14-item assessment tool of reminiscence functions, with Chinese older adults.Method: The scale, covering four reminiscence functions (boredom reduction, bitterness revival, problem solving, and identity) was translated from English into Chinese and administered to older adults (N = 675). Confirmatory factor analysis and hierarchical confirmatory factor analysis were conducted to examine its factorial structure, and its psychometric properties and criterion validity were examined.Results: Confirmatory factor analysis supports a second-order model comprising one second-order factor and four first-order factors of RFS. The Cronbach's alpha of the subscales ranged from 0.75 to 0.90.Conclusion: The brief RFS contains a second-order factorial structure. Its psychometric properties support it as a sound instrument for measuring reminiscence functions among Chinese older adults.