A Case of a Pulmonary Arteriovenous Malformation With Ebstein's Anomaly

A pulmonary arteriovenous malformation (PAVM) is a rare pulmonary vascular anomaly presenting as dyspnea or recurrent epistaxis. Ebstein's anomaly (EA), a congenital cardiac malformation, is also a rare condition. There have been no reports concerning the co-existence of PAVM with hereditary hemorrhagic telangiectasia (HHT) and EA. A 40-year-old woman was admitted with a 2-month history of increasing dyspnea and several years of recurrent epistaxis. On transthoracic echocardiography, she was diagnosed with EA and agreed to undergo surgical treatment. A chest CT angiography showed a 12-mm serpiginous vascular structure suspicious for a PAVM and a liver CT suggested HTT. Although it is unclear whether or not a concurrent PAVM and EA have an embryologic or genetic relationship, we report a case of a PAVM with EA. Further genetic and embryonic studies are needed to identify a possible relationship of the two medical conditions

Association of Polymorphisms in Monocyte Chemoattractant Protein-1 Promoter with Diabetic Kidney Failure in Korean Patients with Type 2 Diabetes Mellitus

Monocyte chemoattractant protein-1 (MCP-1) is suggested to be involved in the progression of diabetic nephropathy. We investigated the association of the -2518 A/G polymorphism in the MCP-1 gene with progressive kidney failure in Korean patients with type 2 diabetes mellitus (DM). We investigated -2518 A/G polymorphism of the MCP-1 gene in type 2 DM patients with progressive kidney failure (n=112) compared with matched type 2 DM patients without nephropathy (diabetic control, n=112) and healthy controls (n=230). The overall genotypic distribution of -2518 A/G in the MCP-1 gene was not different in patients with type 2 DM compared to healthy controls. Although the genotype was not significantly different between the patients with kidney failure and the diabetic control (p=0.07), the A allele was more frequent in patients with kidney failure than in DM controls (42.0 vs. 32.1%, p=0.03). The carriage of A allele was significantly associated with kidney failure (68.8 vs. 54.5%, OR 1.84, 95% CI 1.07-3.18). In logistic regression analysis, carriage of A allele retained a significant association with diabetic kidney failure. Our result shows that the -2518 A allele of the MCP-1 gene is associated with kidney failure in Korean patients with type 2 DM

Effects of the El Niño Southern Oscillation on Influenza Peak Activity Timing

ObjectiveThis study aimed to explore the effects of El Niño and La Niña events on the timing of influenza A peak activity in European countries.IntroductionInfluenza causes a significant burden to the world every year. In the temperate zone, influenza usually prevalent in the winter season, however, it is hardly predictable when the influenza epidemic will begin and when the peak activity will come. Influenza has a peak in early winter sometimes and a peak in late winter in another year. However, it is not well known what determines these epidemics timing, and the global climate change is expected to influence the timing of influenza epidemics.MethodsThe weekly influenza surveillance data of 5 European countries (UK, Norway, Germany, Greece, and Italy) from January 2005 to July 2018 were retrieved from WHO FluNET database. UK and Norway are considered the northern part of Europe, otherwise Germany, Greece, and Italy are considered western southern part. The El Niño southern oscillation (ENSO) were retrieved from Korean Meteorological Administration. We used the definition of El Niño as the positive sea surface temperature anomalies (≥0.5 degree in Celcius), while La Niña events are negative anomalies (≤-0.5 degree) of 3 months moving average. The weeks with the highest activities of influenza A and B in each season were identified and coded as 1, 2, 3 if the peak appeared the 1st 2nd and 3rd week from the beginning of the year respectively. The influenza data of 2008/2009 and 2009/2010 were excluded from the analysis to eliminate the bias due to a pandemic influenza outbreak. We compared the means of these peak weeks according to the presence of the anomalies using the general linear model with Scheffe multiple comparison and Wilcoxon signed rank sum test.ResultsFrom January 2005 to July 2018, there were 3 El Niño and 5 La Niña events by the ENSO excluding 2009 El Niño. The influenza A peak activity was observed at 9th week (mean±SD, 8.7±4.8) from the beginning of the year in no anomaly event, but the peak appearance timing was significantly shortened to 6th week (6.2±2.7) and 5th week (5.1±3.9) when El Niño and La Niña events occurred, respectively (both p<0.05). Influenza A made the peak at usually 10th week (9.9±5.0) in northern 2 countries in no anomalies, but at 6th (6.4±3.9) week in any events of an anomaly in the surface sea temperature (p=0.072). In the southern 3 countries, influenza peaks were observed at 8th (7.9±4.8 ) week in usual without anomalies, but at 5th (5.0±3.3) week in El Niño or La Niña events (p=0.049).ConclusionsBoth El Niño and La Niña affect the timing of influenza A peak activity; the ENSO associated the early emergency of peak influenza activities in European countries.ReferencesFisman DN, et al. Impact of El Niño Southern Oscillation on infectious disease hospitalization risk in the United States. Proc Natl Acad Sci U S A. 2016; 113(51):14589-14594.Oluwole OSA. Seasonal Influenza Epidemics and El Niños. Front. Public Health 3:250.Zaraket H, et al. Association of early annual peak influenza activity with El Niño southern oscillation in Japan. Influenza andOther Respiratory Viruses 2008; 2(4): 127–130

Influence of surgery involving tendons around the knee joint on ankle motion during gait in patients with cerebral palsy

Category: Ankle Introduction/Purpose: The gastrocnemius, a biarticular muscle that crosses the knee and ankle, acts as a knee flexor as well as an ankle plantar flexor. Although simultaneous motion of the knee and ankle joints is required for many activities including standing, running, swimming, and cycling, the change in ankle motion during gait has not been described in patients with cerebral palsy who underwent distal hamstring lengthening or distal hamstring lengthening with rectus femoris transfer. Therefore, we aimed to evaluate the influence of surgery involving tendons around the knee on ankle motion during gait in cerebral palsy patients. Methods: The analysis included data regarding 55 limbs from 34 patients with spastic cerebral palsy, who were followed-up after they had undergone distal hamstring lengthening with or without additional rectus femoris transfer. Mean age of the patients at time of the knee surgery was 11.2 ± 4.7 years. Preoperative and postoperative kinematic variables that were extracted from three-dimensional gait analyses were compared to assess the change in ankle motion after surgery involving tendons around the knee. The postoperative 3D gait analysis was performed at a mean of 0.9 ± 1.3 years after the surgery. The outcome measures were relevant kinematics parameters including peak ankle dorsiflexion at initial contact, peak ankle dorsiflexion during stance, ankle peak dorsiflexion during swing, and dynamic range of motion of the ankle. A linear mixed model was constructed to estimate the changes in ankle motion after adjusting for multiple factors. Results: We estimated that peak ankle dorsiflexion at initial contact, peak ankle dorsiflexion during stance, ankle peak dorsiflexion during swing, and dynamic range of motion of the ankle decreased, respectively, by 0.4º (p=0.016), 0.6º (p<0.001), 0.2º (p=0.038), and 0.5º (p=0.006) per degree increase in total range of motion of the knee after knee surgery (Table). Estimated ankle peak dorsiflexion in the swing phase increased by 0.4º per degree increased in postoperative peak knee flexion in the swing phase (Table). Age at the time of the knee surgery did not significantly affect ankle kinematics. Conclusion: Improvement in total knee range of motion was correlated with a decrease in ankle kinematics after surgery involving tendons around the knee. Knee surgery may reduce the need for an additional surgical procedure involving the ankle joint. Because the simultaneous motion of the knee and ankle joints is cross-linked, surgeons should be aware of potential changes in the ankle joint after knee surgery

Screening of Human CYP1A2 and CYP3A4 Inhibitors from Seaweed In Silico and In Vitro

Phenolic compounds and carotenoids are potential inhibitors of cytochrome P450s. Sixteen known compounds, phenolic compounds and carotenoids from seaweed were examined for potential inhibitory capacity against CYP1A2 and CYP3A4 in silico and in vitro. Morin, quercetin, and fucoxanthin inhibited the enzyme activity of CYP1A2 and CYP3A4 in a dose-dependent manner. The IC50 values of morin, quercetin, and fucoxanthin were 41.8, 22.5, and 30.3 &mu;M for CYP1A2 and 86.6, 16.1, and 24.4 &mu;M for CYP3A4, respectively. Siphonaxanthin and hesperidin did not show any significant effect on CYP1A2, but they slightly inhibited CYP3A4 activity at high concentrations. In silico modeling of CYP&rsquo;s binding site revealed that the potential inhibitors bound in the cavity located above the distal surface of the heme prosthetic group through the 2a or 2f channel of CYPs. This study presents an approach for quickly predicting CYP inhibitory activity and shows the potential interactions of compounds and CYPs through in silico modeling

Sex differences in pedobarographic findings and relationship between radiographic and pedobarographic measurements in young healthy adults

Background: Although pedobarographic measurement is increasingly used for clinical and research purposes, relatively few published studies have investigated normative data. This study examined pedobarographic findings in young healthy adults with regard to sex-related differences and correlations among measurement indices. Methods: Twenty young healthy adults (mean age, 22.4 years; standard deviation, 1.2 years; and 10 males and 10 females) were included. Weight bearing anteroposterior (AP) and lateral foot radiographs were taken, and dynamic pedobarographic data during treadmill walking and maximum ankle dorsiflexion were obtained. AP talo-first metatarsal angle, naviculocuboid overlap, lateral talo-first metatarsal angle, and plantar soft tissue thickness were measured on foot radiographs. Pedobarographic data including peak pressure and pressure-time integral were measured on five plantar segments: medial forefoot (MFF), lateral forefoot (LFF), medial midfoot (MMF), lateral midfoot (LMF), and heel. Results: Male and female subjects significantly differed in body mass index (BMI, p &lt; 0.001), AP talo-first metatarsal angle (p = 0.018), soft tissue thickness under the metatarsal head (p = 0.040) and calcaneal tuberosity (p &lt; 0.001), maximum dorsiflexion during stance phase (p = 0.041), peak pressure on the MFF (p = 0.005) and LFF (p = 0.004), and pressure-time integral on the MFF (p = 0.018) and heel (p = 0.001). BMI was significantly correlated with soft tissue thickness under the metatarsal head (r = 0.521, p = 0.018) and calcaneal tuberosity (r = 0.585, p = 0.007), peak pressure on the MFF (r = 0.601, p = 0.005) and LFF (r = 0.487, p = 0.029), pressure-time integral on the heel (r = 0.552, p = 0.012), and total pressure-time integral (r = 0.755, p &lt; 0.001). Maximum dorsiflexion demonstrated significant negative correlations with pressure-time integral on the MFF (r = -0.595, p = 0.007) and total pressure-time integral (r = -0.492, p = 0.032). Pressure-time integral varus/valgus index was significantly correlated with pressure-time integral forefoot/heel index (r = 0.472, p = 0.036). Conclusions: Sex-related differences in pedobarographic examination were observed, which could provide useful information in setting appropriate treatment goals and obtaining appropriate control data. The effects of subtalar motion in distributing plantar pressure should be investigated in a future study.Y

Scopolin Attenuates Osteoporotic Bone Loss in Ovariectomized Mice

Bone remodeling is a renewal process regulated by bone synthesis (osteoblasts) and bone destruction (osteoclasts). A previous study demonstrated that Lycii radicis cortex (LRC) extract inhibited ovariectomized (OVX)-induced bone loss in mice. This study investigated the anti-osteoporotic effects of bioactive constituent(s) from the LRC extract. The effective compound(s) were screened, and a single compound, scopolin, which acts as a phytoalexin, was chosen as a candidate component. Scopolin treatment enhanced alkaline phosphatase activity and increased mineralized nodule formation in MC3T3-E1 pre-osteoblastic cells. However, osteoclast differentiation in primary-cultured monocytes was reduced by treatment with scopolin. Consistently, scopolin treatment increased osteoblast differentiation in the co-culture of monocytes (osteoclasts) and MC3T3-E1 (osteoblast) cells. Scopolin treatment prevented bone mineral density loss in OVX-induced osteoporotic mice. These results suggest that scopolin could be a therapeutic bioactive constituent for the treatment and prevention of osteoporosis

Regulation of Chitinase-3-like-1 in T cell elicits Th1 and cytotoxic responses to inhibit lung metastasis

Chitinase-3-like-1 (Chi3l1) is known to play a significant role in the pathogenesis of Type 2 inflammation and cancer. However, the function of Chi3l1 in T cell and its clinical implications are largely unknown. Here we show that Chi3l1 expression was increased in activated T cells, especially in Th2 cells. In addition, Chi3l1-deficient T cells are hyper-responsive to TcR stimulation and are prone to differentiating into Th1 cells. Chi3l1-deficient Th1 cells show increased expression of anti-tumor immunity genes and decreased Th1 negative regulators. Deletion of Chi3l1 in T cells in mice show reduced melanoma lung metastasis with increased IFNγ and TNFα-producing T cells in the lung. Furthermore, silencing of Chi3l1 expression in the lung using peptide-siRNA complex (dNP2-siChi3l1) efficiently inhibit lung metastasis with enhanced Th1 and CTL responses. Collectively, this study demonstrates Chi3l1 is a regulator of Th1 and CTL which could be a therapeutic target to enhance anti-tumor immunity.1