Association of an Alphasatellite with Tomato Yellow Leaf Curl Virus and Ageratum Yellow Vein Virus in Japan is Suggestive of a Recent Introduction

Samples were collected in 2011 from tomato plants exhibiting typical tomato leaf curl disease symptoms in the vicinity of Komae, Japan. PCR mediated amplification, cloning and sequencing of all begomovirus components from two plants from different fields showed the plants to be infected by Tomato yellow leaf curl virus (TYLCV) and Ageratum yellow vein virus (AYVV). Both viruses have previously been shown to be present in Japan, although this is the first identification of AYVV on mainland Japan; the virus previously having been shown to be present on the Okinawa Islands. The plant harboring AYVV was also shown to contain the betasatellite Tomato leaf curl Java betasatellite (ToLCJaB), a satellite not previously shown to be present in Japan. No betasatellite was associated with the TYLCV infected tomato plants analyzed here, consistent with earlier findings for this virus in Japan. Surprisingly both plants were also found to harbor an alphasatellite; no alphasatellites having previously been reported from Japan. The alphasatellite associated with both viruses was shown to be Sida yellow vein China alphasatellite which has previously only been identified in the Yunnan Province of China and Nepal. The results suggest that further begomoviruses, and their associated satellites, are being introduced to Japan. The significance of these findings is discussed.     

Prognostic Value of the CHA 2 DS 2 -VASc Score after Endovascular Therapy for Femoral Popliteal Artery Lesions

Aim: Originally developed for predicting the risk of stroke in patients with atrial fibrillation (AF), the CHA ₂ DS ₂ -VASc score also has the potential to predict the risk of other cardiovascular disease. This study aimed to investigate the prognostic value of the CHA ₂ DS ₂ -VASc score in patients with peripheral artery disease (PAD) requiring Femoral popliteal (FP) endovascular therapy (EVT). Methods: This multicenter, retrospective study analyzed the clinical database of 2190 patients who underwent FP EVT for symptomatic PAD (Rutherford categories 2–4) between January 2010 and December 2018. We calculated the CHA ₂ DS ₂ -VASc score and then investigated the association between the score, as well as AF, and their prognosis. Outcome measures were major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs). Results: During a median follow-up of 3.0 years (interquartile range, 1.5–5.0 years), 532 MACEs and 562 MALEs occurred. The CHA ₂ DS ₂ -VASc score and AF were independently associated with an increased risk of MACEs; their adjusted hazard ratios [95% confidence intervals] were 1.28 [1.20–1.36] ( P ＜0.001) per 1-point increase and 1.49 [1.06–2.09] ( P =0.022), respectively. The CHA ₂ DS ₂ -VASc score was almost linearly associated with MACEs, without any clear threshold point. On the other hand, these variables were not associated with MALEs risk ( P =0.32 and 0.48). Conclusion: The CHA ₂ DS ₂ -VASc score and AF were independently associated with the increased risk of MACEs but not of MALEs in patients with symptomatic PAD who underwent FP EVT. The score might be useful in stratifying the MACEs risk in this type of patients.     

Updated Electrocardiographic Classification of Acute Coronary Syndromes

The electrocardiogram (ECG) findings in acute coronary syndrome should always be interpreted in the context of the clinical findings and symptoms of the patient, when these data are available. It is important to acknowledge the dynamic nature of ECG changes in acute coronary syndrome. The ECG pattern changes over time and may be different if recorded when the patient is symptomatic or after symptoms have resolved. Temporal changes are most striking in cases of ST-elevation myocardial infarction. With the emerging concept of acute reperfusion therapy, the concept ST-elevation/non-ST elevation has replaced the traditional division into Q-wave/non-Q wave in the classification of acute coronary syndrome in the acute phase.

Keypoints:

In acute coronary syndrome, in addition to the traditional electrocardiographic risk markers, such as ST depression, the 12-lead ECG contains additional, important diagnostic and prognostic information. Clinical guidelines need to acknowledge certain high-risk ECG patterns to improve patient care.     

Simultaneous interstitial pneumonitis and cardiomyopathy induced by venlafaxine

Venlafaxine is a serotonin-norepinephrine reuptake inhibitor used as an antidepressant. Interindividual variability and herb-drug interactions can lead to drug-induced toxicity. We report the case of a 35-year-old female patient diagnosed with synchronous pneumonitis and acute cardiomyopathy attributed to venlafaxine. The patient sought medical attention due to dyspnea and dry cough that started three months after initiating treatment with venlafaxine for depression. The patient was concomitantly taking Centella asiatica and Fucus vesiculosus as phytotherapeutic agents. Chest CT angiography and chest X-ray revealed parenchymal lung disease (diffuse micronodules and focal ground-glass opacities) and simultaneous dilated cardiomyopathy. Ecocardiography revealed a left ventricular ejection fraction (LVEF) of 21%. A thorough investigation was carried out, including BAL, imaging studies, autoimmune testing, right heart catheterization, and myocardial biopsy. After excluding other etiologies and applying the Naranjo Adverse Drug Reaction Probability Scale, a diagnosis of synchronous pneumonitis/cardiomyopathy associated with venlafaxine was assumed. The herbal supplements taken by the patient have a known potential to inhibit cytochrome P450 enzyme complex, which is responsible for the metabolization of venlafaxine. After venlafaxine discontinuation, there was rapid improvement, with regression of the radiological abnormalities and normalization of the LVEF. This was an important case of drug-induced cardiopulmonary toxicity. The circumstantial intake of inhibitors of the CYP2D6 isoenzyme and the presence of a CYP2D6 slow metabolism phenotype might have resulted in the toxic accumulation of venlafaxine and the subsequent clinical manifestations. Here, we also discuss why macrophage-dominant phospholipidosis was the most likely mechanism of toxicity in this case.     

Pulmonary function in advanced uncomplicated singleton and twin pregnancy

Objective:

Pregnancy brings about significant changes in respiratory function, as evidenced by alterations in lung volumes and capacities, which are attributable to the mechanical impediment caused by the growing foetus. This study was undertaken in order to identify changes in respiratory function during normal pregnancy and to determine whether such changes are more pronounced in twin pregnancy than in singleton pregnancy.

Methods:

Respiratory function was assessed in 50 women with twin pregnancies and in 50 women with singleton pregnancies (during the third trimester in both groups), as well as in 50 non-pregnant women. We measured the following pulmonary function test parameters: FVC; FEV₁; PEF rate; FEV₁/FVC ratio; FEF_25-75%; and maximal voluntary ventilation.

Results:

All respiratory parameters except the FEV₁/FVC ratio were found to be lower in the pregnant women than in the non-pregnant women. We found no significant differences between women with twin pregnancies and those with singleton pregnancies, in terms of respiratory function.

Conclusions:

Despite its higher physiological demands, twin pregnancy does not appear to impair respiratory function to any greater degree than does singleton pregnancy.     

Mycobacterium tuberculosis resistance to antituberculosis drugs in Mozambique,

OBJECTIVE:

To determine the drug resistance profile of Mycobacterium tuberculosis in Mozambique.

METHODS:

We analyzed secondary data from the National Tuberculosis Referral Laboratory, in the city of Maputo, Mozambique, and from the Beira Regional Tuberculosis Referral Laboratory, in the city of Beira, Mozambique. The data were based on culture-positive samples submitted to first-line drug susceptibility testing (DST) between January and December of 2011. We attempted to determine whether the frequency of DST positivity was associated with patient type or provenance.

RESULTS:

During the study period, 641 strains were isolated in culture and submitted to DST. We found that 374 (58.3%) were resistant to at least one antituberculosis drug and 280 (43.7%) were resistant to multiple antituberculosis drugs. Of the 280 multidrug-resistant tuberculosis cases, 184 (65.7%) were in previously treated patients, most of whom were from southern Mozambique. Two (0.71%) of the cases of multidrug-resistant tuberculosis were confirmed to be cases of extensively drug-resistant tuberculosis. Multidrug-resistant tuberculosis was most common in males, particularly those in the 21-40 year age bracket.

CONCLUSIONS:

M. tuberculosis resistance to antituberculosis drugs is high in Mozambique, especially in previously treated patients. The frequency of M. tuberculosis strains that were resistant to isoniazid, rifampin, and streptomycin in combination was found to be high, particularly in samples from previously treated patients.     

Combined pulmonary fibrosis and emphysema: an increasingly recognized condition

Combined pulmonary fibrosis and emphysema (CPFE) has been increasingly recognized in the literature. Patients with CPFE are usually heavy smokers or former smokers with concomitant lower lobe fibrosis and upper lobe emphysema on chest HRCT scans. They commonly present with severe breathlessness and low DLCO, despite spirometry showing relatively preserved lung volumes. Moderate to severe pulmonary arterial hypertension is common in such patients, who are also at an increased risk of developing lung cancer. Unfortunately, there is currently no effective treatment for CPFE. In this review, we discuss the current knowledge of the pathogenesis, clinical characteristics, and prognostic factors of CPFE. Given that most of the published data on CPFE are based on retrospective analysis, more studies are needed in order to address the role of emphysema and its subtypes; the progression of fibrosis/emphysema and its correlation with inflammation; treatment options; and prognosis.     

Stromal cell-derived factors in Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is characterized by increased muscle damage and an abnormal blood flow after muscle contraction leading to a state of functional ischemia. Abundant evidence suggests that endothelial circulating progenitor cells (EPCs) play an important role in mediating vascular and muscle repair mechanisms and that the stromal cell-derived factor (SDF)-1 α chemokine is responsible for both progenitor cell mobilization from the bone marrow to peripheral blood and homing to the sites of vascular and tissue injury. Since normal neovascularization is disrupted in DMD pathogenesis and may contribute ultimately to heart failure and sudden death, the aim of the present study is to investigate whether the (SDF)-1 α, and EPCs surface receptors in terms of CD34, CD133 and kinase domain receptor (KDR) are involved in DMD pathophysiology. In the present study, peripheral blood concentrations of circulating CD34, CD133, and CD34/ CD 133 progenitor cells were measured by flow cytometry, together with serum levels of (SDF)-1α and hypoxia inducible factor (HIF-1α.), in 28 DMD patients vs. 20 healthy age and socioeconomic matching controls. Results showed a significant increase in the number of mononuclear cells bearing EPC markers, HIF-1α mRNA expression and serum (SDF)-1 α, indicating that regeneration is an ongoing process in these patients. However, this regeneration cannot counterbalance the damage induced by dystrophine mutation.Key words: Duchenne dystrophy, stromal cell-derived factors, EPCs surface receptors     

Comparison of Endothelial Dysfunction in Coronary Arteries with Bare Metal and 2 nd -Generation Drug-Eluting Stents

Aims: Previous studies suggested that implantation with a 1st-generation DES was associated with coronary endothelial dysfunction, which was associated with Rho-kinase activation. Second-generation drug-eluting stents (DESs) may preserve coronary endothelial function in stented coronary arteries; however, because of methodological limitations, further study is needed to clarify the association between 2 ^nd -generation DESs and coronary endothelial dysfunction. Methods: We retrospectively analysed the CuVIC trial database, where we identified 112 patients who underwent coronary stenting in the left coronary arteries with either a bare metal stent (BMS, n =53) or 2 ^nd -generation DES ( n =59). We compared vasomotions of target vessels with stents and non-target vessels without stents. Furthermore, we measured the Rho-kinase activation detected in mononucleocytes from aortic and coronary sinus blood. Results: ACh-induced vasoconstrictive responses of target vessels were not enhanced with a 2 ^nd -generation DES (45±21% vs. 44±20%, P =0.56, paired t -test), but significantly enhanced in the coronary arteries with a BMS (50±18% vs. 42±20%, P =0.002). Rho-kinase activation did not differ between patients with a BMS and 2 ^nd -generation DES. In the target vessels with a BMS, large late lumen loss and acute coronary syndrome (ACS) at the index percutaneous coronary intervention (PCI) were associated with ACh-induced enhanced coronary vasoconstrictive responses. Conclusions: Evaluation of ACh-induced vasomotion of target vessels comparing with non-target vessels revealed that 2 ^nd -generation DESs were not associated with coronary endothelial dysfunction in target vessels, nor activation of Rho-kinase in the coronary sinus blood 6-8 months after stenting.     

Nanoparticle-Mediated Delivery of Pitavastatin to Monocytes/Macrophages Inhibits Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Apoe −/− Mice

Aim: Abdominal aortic aneurysm (AAA) is a lethal and multifactorial disease. To prevent a rupture and dissection of enlarged AAA, prophylactic surgery and stenting are currently available. There are, however, no medical therapies preventing these complications of AAA. Statin is one of the candidates, but its efficacy on AAA formation/progression remains controversial. We have previously demonstrated that nanoparticles (NPs) incorporating pitavastatin (Pitava-NPs)—clinical trials using these nanoparticles have been already conducted—suppressed progression of atherosclerosis in apolipoprotein E-deficient ( Apoe ^−/− ) mice. Therefore, we have tested a hypothesis that monocytes/macrophages-targeting delivery of pitavastatin prevents the progression of AAA. Methods: Angiotensin II was intraperitoneally injected by osmotic mini-pumps to induce AAA formation in Apoe ^−/− mice. NPs consisting of poly(lactic-co-glycolic acid) were used for in vivo delivery of pitavastatin to monocytes/macrophages. Results: Intravenously administered Pitava-NPs (containing 0.012 mg/kg/week pitavastatin) inhibited AAA formation accompanied with reduction of macrophage accumulation and monocyte chemoattractant protein-1 (MCP-1) expression. Ex vivo molecular imaging revealed that Pitava-NPs not only reduced macrophage accumulation but also attenuated matrix metalloproteinase activity in the abdominal aorta, which was underpinned by attenuated elastin degradation. Conclusion: These results suggest that Pitava-NPs inhibit AAA formation associated with reduced macrophage accumulation and MCP-1 expression. This clinically feasible nanomedicine could be an innovative therapeutic strategy that prevents devastating complications of AAA.     

Range of motion exercise of temporo-mandibular joint with hot pack increases occlusal force in patients with Duchenne muscular dystrophy

The purpose of this study is to evaluate whether the range of motion exercise of the temporo-mandibular joint (jaw ROM exercise) with a hot pack and massage of the masseter muscle improve biting disorder in Duchenne muscular dystrophy (DMD). The subjects were 18 DMD patients (21.3 ± 4.1 years old). The jaw ROM exercise consisted of therapist-assisted training (2 times a week) and self-training (before each meal every day). The therapist-assisted training consisted of the application of a hot pack on the cheek of the masseter muscle region (15 minutes), the massage of the masseter (10 minutes), and jaw ROM exercise (5 minutes). The self-training involved jaw ROM exercise by opening the mouth to the maximum degree, ten times. These trainings continued for six months. Outcomes were evaluated by measuring the greatest occlusal force and the distance at the maximum degree of mouth opening between an incisor of the top and that of the bottom. Six months later, the greatest occlusal force had increased significantly compared with that at the start of jaw ROM exercise (intermediate values: from 73.8N to 97.3N) (p = 0.005) as determined by the Friedman test and Scheffé''s nonparametric test. The patients'' satisfaction with meals increased. However, the maximum degree of mouth opening did not change after six months of jaw ROM exercise. Jaw ROM exercise in DMD is effective for increasing the greatest occlusal force.Key words: Duchenne muscular dystrophy, exercise, occlusal force