Embryonic Stage of Congenital Zika Virus Infection Determines Fetal and Postnatal Outcomes in Mice

Zika virus (ZIKV) infection during pregnancy causes a wide spectrum of congenital abnormalities and postnatal developmental sequelae such as fetal loss, intrauterine growth restriction (IUGR), microcephaly, or motor and neurodevelopmental disorders. Here, we investigated whether a mouse pregnancy model recapitulated a wide range of symptoms after congenital ZIKV infection, and whether the embryonic age of congenital infection changed the fetal or postnatal outcomes. Infection with ZIKV strain PRVABC59 from embryonic day 6.5 (E6.5) to E8.5, corresponding to the mid-first trimester in humans, caused fetal death, fetal resorption, or severe IUGR, whereas infection from E9.5 to E14.5, corresponding to the late-first to second trimester in humans, caused stillbirth, neonatal death, microcephaly, and postnatal growth deficiency. Furthermore, 4-week-old offspring born to dams infected at E12.5 showed abnormalities in neuropsychiatric state, motor behavior, autonomic function, or reflex and sensory function. Thus, our model recapitulated the multiple symptoms seen in human cases, and the embryonic age of congenital infection was one of the determinant factors of offspring outcomes in mice. Furthermore, maternal neutralizing antibodies protected the offspring from neonatal death after congenital infection at E9.5, suggesting that neonatal death in our model could serve as criteria for screening of vaccine candidates.     

Relationships between Alcohol Intake and Ischemic Stroke Severity in Sex Stratified Analysis for Japanese Acute Stroke Patients

BackgroundThe aim of this study is to evaluate in the relationships between alcohol intake and ischemic stroke severity in Japanese stroke patients.MethodsOf a total of 101,165 registered cases of stroke in Japan, patient data of total strokes (n = 60,836), cardiogenic strokes (n = 11,894), and noncardiogenic strokes (n = 29,129) were extracted. The National Institutes of Health Stroke Scale (NIHSS) score at admission and the modified Rankin Scale (mRS) score at discharge were used. Significant alcohol consumption in regard to stroke severity at admission and discharge was identified by multivariate adjusted logistic regression analysis.ResultsAmong all subject and males, nondrinkers had significantly poorer NIHSS scores of cardiogenic strokes as did those consuming greater than or equal to 60 g/day, whereas there was a significant difference in past heavy drinkers with noncardiogenic strokes. Among females, nondrinkers had a significance of cardiogenic stroke and non-cardiogenic strokes. Among all subjects and males, 20-39 g/day and 40-59 g/day were significantly associated with protective effects on mRS severity of cardiogenic strokes, whereas 40-59 g/day also had significant protective effects for noncardiogenic strokes. Among females, greater than or equal to 60 g/day had a significant protective effect for cardiogenic strokes.ConclusionsFor males, alcohol intake of less than 60 g/day played a protective role in functional prognosis at discharge and showed a J-shape relationship. For females, although there was a limitation that the number of female drinkers was small, negative effects were shown at admission with less consumption than males.     

Frequency,Severity, and Risk Factors for Acute Pancreatitis After Percutaneous Transhepatic Biliary Stent Placement Across the Papilla of Vater

Purpose

To clarify the frequency, severity, and risk factors for acute pancreatitis after percutaneous biliary stent placement across the papilla of Vater for malignant biliary obstruction.

Materials and Methods

This retrospective study included 95 patients who underwent percutaneous biliary metallic stent placement (64 [67.4%] bare stents and 31 [32.6%] covered stents) across the papilla of Vater for malignant biliary obstruction between January 2010 and December 2012. The incidence of acute pancreatitis (Atlanta classification of acute pancreatitis) and its severity (Common Terminology Criteria for Adverse Events, version 4) were reviewed. Additionally, the characteristics of the patients and biliary stents, and the computed tomography findings of the pancreas were evaluated.

Results

Grade 3 acute pancreatitis was observed in 23 patients (24.2%); acute pancreatitis of grade 4 or higher was not observed. The incidence of acute pancreatitis was lower in patients with atrophic pancreas than in those with non-atrophic pancreas (7.5 vs. 36.4%, p = 0.004). It was also lower in patients with main pancreatic duct (MPD) obstruction than in those without MPD obstruction (12.5 vs. 36.2%, p = 0.026). There was no difference in the incidence of acute pancreatitis between bare and covered stents.

Conclusion

Percutaneous biliary stent placement across the papilla of Vater for malignant biliary stricture caused acute pancreatitis requiring medication in 24.2% of patients. Atrophy of the pancreas and the presence of a dilated MPD may be associated with a decreased risk of acute pancreatitis.

Level of Evidence

Level 4, Case Series.

     

Molecular target therapy in cancer

Many molecular target drugs have been developed based on the progress in the study of molecular biology. Majority of treatment for common malignancy include molecular target drugs. Patients selection has become possible by pharmacogenomical tests in some molecular target therapy. Development of active molecular target therapy will enable the increment of curative populations even in advanced malignancies. Intensive proof of principle study will open doors for the identification of new molecular targets.     

Mechanical and biochemical effect of monopolar radiofrequency energy on human articular cartilage: an in vitro study

BACKGROUND: There are growing concerns about thermal chondroplasty using radiofrequency energy to treat partial-thickness cartilage defects. However, most studies emphasize effects on chondrocyte viability, and other factors such as mechanical properties are less studied. HYPOTHESIS: Radiofrequency energy may cause significant effects on articular cartilage other than chondrocyte viability. STUDY DESIGN: Controlled laboratory study. METHODS: Human osteoarthritic cartilage samples were obtained from total knee arthroplasty, and monopolar radiofrequency energy was applied using commercially available equipment. Material properties (compressive stiffness, surface roughness, and thickness) just before and after thermal treatment were determined using ultrasound. A series of biochemical analyses were also performed after explant culture of the samples. RESULTS: The cartilage surface became smoother by radiofrequency energy, whereas cartilage stiffness or thickness was not altered significantly. Collagen fibrils, especially in the superficial layers, were converted to denatured form, whereas proteoglycan contents released in the media as well as retained in the tissue remained unchanged. The concentrations of matrix metalloproteinases (MMP-1 and MMP-2) were reduced remarkably. CONCLUSION: Radiofrequency energy is able to create a smooth cartilage surface and reduce catabolic enzymes at the cost of collagen denaturation and chondrocyte death in the superficial layers. The stiffness of the cartilage is not changed at time zero. CLINICAL RELEVANCE: Further animal as well as clinical studies will be necessary to fully evaluate the long-term effects of radiofrequency energy.