Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning.

Historically, the ribosome has been viewed as a complex ribozyme with constitutive rather than regulatory capacity in mRNA translation. Here we identify mutations of the Ribosomal Protein L38 (Rpl38) gene in mice exhibiting surprising tissue-specific patterning defects, including pronounced homeotic transformations of the axial skeleton. In Rpl38 mutant embryos, global protein synthesis is unchanged; however the translation of a select subset of Homeobox mRNAs is perturbed. Our data reveal that RPL38 facilitates 80S complex formation on these mRNAs as a regulatory component of the ribosome to confer transcript-specific translational control. We further show that Rpl38 expression is markedly enriched in regions of the embryo where loss-of-function phenotypes occur. Unexpectedly, a ribosomal protein (RP) expression screen reveals dynamic regulation of individual RPs within the vertebrate embryo. Collectively, these findings suggest that RP activity may be highly regulated to impart a new layer of specificity in the control of gene expression and mammalian development.

Geriatric Nutritional Risk Index Predicts Cardiovascular Events in Patients at Risk for Heart Failure.

BACKGROUND: The geriatric nutritional risk index (GNRI) is a simple and objective nutritional assessment tool for elderly patients. Lower GNRI values are associated with a worse prognosis in patients with heart failure (HF). However, few data are available regarding the prognostic effect of the GNRI value for risk stratification in patients at risk for HF.Methods and Results:We retrospectively investigated 1,823 consecutive patients at risk for HF (Stage A/B) enrolled in the IMPACT-ABI Study. GNRI on admission was calculated as follows: 14.89×serum albumin (g/dL)+41.7×body mass index/22. Patients were divided into 2 groups according to the median GNRI value (107.1). The study endpoint was a composite of cardiovascular (CV) events, including CV death and hospitalization for worsening HF. Over a 4.7-year median follow-up, CV events occurred in 130 patients. In the Kaplan-Meier analysis, patients with low GNRI (<107.1, n=904) showed worse prognoses than those with high GNRI (≥107.1, n=919) (20.2% vs. 12.4%, P<0.001). In the multivariable Cox proportional hazards analysis, low GNRI was significantly associated with the incidence of CV events (hazard ratio: 1.48, 95% confidence interval: 1.02-2.14; P=0.040). CONCLUSIONS: The simple and practical assessment of GNRI may be useful for predicting CV events in patients with Stage A/B HF.

The usefulness of brachial-ankle pulse wave velocity in predicting long-term cardiovascular events in younger patients.

Brachial-ankle pulse wave velocity (baPWV) is known as a significant predictor of cardiovascular events. However, the previous studies have not considered age, which can affect the baPWV value. We evaluated the predictive value of baPWV for cardiovascular events in various age groups. From January 2005 to December 2012, all patients admitted to our department with any cardiovascular disease and underwent ankle-brachial index (ABI) measurement were enrolled in the IMPACT-ABI registry. The primary endpoints included major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, and stroke). Of the 3131 patients enrolled, 2554 were included in the analysis, whereas 577 were excluded due to missing baPWV data, ABI ≤0.9 and/or >1.4, and the previous endovascular therapy and/or surgical treatment for peripheral artery disease. Patients were divided according to age 30-59 years (n = 580), 60-69 years (n = 730), 70-79 years (n = 862), and ≥80 years (n = 330). The cumulative incidence of MACE through 5 year was significantly higher in the high baPWV group (>1644 cm/s) than in the low baPWV group (≤1644 cm/s; 8.7 vs. 4.6%; log-rank: p < 0.001). However, among the age groups, only the 30-59-year group showed a significant difference in MACE incidence between those with high and low baPWV (7.0 vs. 0.9%; log-rank: p = 0.001). In conclusion, the baPWV could serve as a useful marker to predict cardiovascular events, particularly among younger patients.

Prognostic value of ankle brachial index for future incident heart failure in patients without previous heart failure: data from the impressive predictive value of ankle brachial index for clinical long term outcome in patients with cardiovascular disease examined by ABI study.

The ankle brachial index (ABI) is regarded as a predictor of future cardiovascular events. However, the relationship between ABI and incident heart failure (HF) in patients without previous HF is poorly understood. This study aimed to assess the prognostic value of ABI for incident HF in patients without previous HF. The IMPACT-ABI study was a retrospective, single-center, cohort study that enrolled and measured ABI in 3131 patients hospitalized for cardiovascular disease between January 2005 and December 2012. From this cohort, 307 patients were excluded because of previous HF and high (>1.4) ABI. The remaining 2824 patients were stratified into three groups: low ABI (≤0.9), borderline ABI (0.91-0.99), and normal ABI (1.0-1.4). The primary endpoint was hospitalization for HF. Over a mean 4.8-year follow-up, 105 cases of HF occurred. The cumulative incidence of HF was significantly higher in patients with low and borderline ABIs than in those with normal ABI (19.3 vs. 21.0 vs. 10.4 %, log rank P <0.001). In multivariate Cox proportional hazard analysis, low ABI and borderline ABI were independent predictors of incident HF [hazard ratio (HR) 3.00; 95 % confidence interval (CI) 1.70-5.28; P < 0.001 and HR 2.68; 95 % CI 1.35-5.34; P = 0.005, respectively]. In conclusion, low and borderline ABI were strong predictors for future incident HF in patients without previous HF.

Prognostic Impact of Diastolic Wall Strain in Patients at Risk for Heart Failure.

Diastolic wall strain (DWS) is based on the linear elastic theory, according to which decreased wall thinning during diastole reflects reduced left ventricular compliance and thus increased diastolic stiffness. Increased diastolic stiffness as assessed by DWS is associated with a worse prognosis in patients who have heart failure (HF) with preserved ejection fraction. However, there are no data about the prognostic value of DWS derived by M-mode echocardiography in patients at risk for HF. We retrospectively enrolled 1829 consecutive patients without prior HF who were hospitalized for cardiovascular (CV) diseases in our hospital between 2005 and 2012. Patients were divided into two groups stratified by DWS (median value 0.34). The study endpoint was the composite of major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, stroke, and hospitalization for HF. Over a 4.2-year median follow-up, adverse events were observed in 322 patients (17.6%). In Kaplan-Meier analysis, patients with low DWS (≤ 0.34, n = 915) showed worse prognoses than those with high DWS (> 0.34, n = 914) (MACE incidence 39.4% versus 31.9%, P = 0.011). In multivariate Cox proportional hazards analysis after the adjustment for age, sex, and echocardiographic parameters, low DWS (≤ 0.34) was significantly associated with the incidence of MACE (hazard ratio: 1.26, 95% confidence interval: 1.01-1.59; P = 0 .045). In patients without prior HF, DWS is an independent predictor of MACE. Simple assessment of DWS might improve risk stratification for CV events in those patients.

[TUBERCULOUS CONSTRICTIVE PERICARDITIS DETECTED ON POSITRON EMISSION TOMOGRAPHY].

A 72-year-old man presented with fever, dyspnea, and weight loss. He was referred to our hospital for further examination of the cause of the pleural effusions. Chest computed tomography showed pleural effusions, a pericardial effusion, and enlarged lymph nodes in the carina tracheae. We administered treatment for heart failure and conducted analyses for a malignant tumor. The pericardial effusion improved, but the pericardium was thickened. Positron emission tomography-computed tomography (PET-CT) showed fluorine-18 deoxyglucose accumulation at the superior fovea of the right clavicle, carina tracheae, superior mediastinum lymph nodes, and a thickened pericardium. Because these findings did not suggest malignancy, we assumed this was a tuberculous lesion. Echocardiography confirmed this finding as constrictive pericarditis; therefore, pericardiolysis was performed. Pathological examination showed features of caseous necrosis and granulomatous changes. Hence, the patient was diagnosed with tuberculous constrictive pericarditis. PET-CT serves as a useful tool for the diagnosis of tuberculous pericarditis.

Cystic fibrosis with multiple pulmonary arteriovenous malformations: A case report.

Cystic fibrosis is an autosomal recessive genetic disorder that damages the exocrine function of the body, resulting in alterations of multiple organs. In the respiratory system, it is known to cause bronchiectasis, recurrent bronchitis, and pneumonia; however, to the best of our knowledge, there are no reported cases of pulmonary arteriovenous malformations associated with this disease. Herein, we report a case of cystic fibrosis with multiple pulmonary arteriovenous malformations. A 16-year-old girl, who has been monitored since childhood for pancreatitis of unknown cause, experienced respiratory symptoms and hypoxemia (PaO2 = 57 mmHg). At 13 years of age, chest computed tomography revealed bronchiectasis, bronchial wall thickening, and tree-in-bud sign. Genetic testing was performed, and the patient was diagnosed with cystic fibrosis. However, the computed tomography scan also showed incidental nodular lesions in the left superior and both the inferior pulmonary lobes, suggesting multiple arteriovenous malformations. Dynamic computed tomography was performed which, confirmed the presence of 3 pulmonary arteriovenous malformations. Coil embolization was performed on all lesions, and the hypoxemia was corrected. Marked hypoxemia in a patient with cystic fibrosis may not be explained only by the presence of bronchiectasis and/or bronchial wall thickening; in such cases, it may be necessary to examine possible additional findings on computed tomography images, such as arteriovenous malformations.

Idiopathic Pulmonary Hemosiderosis Associated with Emphysematous Change in an Adult Who Underwent Lung Transplantation.

Idiopathic pulmonary hemosiderosis is characterized by repeated alveolar hemorrhaging. We herein report a 52-year-old Japanese woman who had shortness of breath, diffuse small nodules, thin-walled cysts, and bronchiolectasis. A surgical lung biopsy revealed peribronchial hemosiderosis, centrilobular emphysema, and fragile elastic fibers of the alveolar septa and small vessels. She ultimately underwent living-donor lung transplantation five years after the first visit.

Use of Electric Discharge for Simultaneous Control of Weeds and Houseflies Emerging from Soil.

An electrostatic apparatus was developed to control weeds and houseflies emerging from ground soil in a greenhouse simultaneously. Identical iron plates were placed in parallel at a defined interval and fixed in an iron frame. Two sets of fixed iron plates were used, one for weed control and one for fly control. For weed control, all of the iron plates were negatively charged, and negative charges accumulated on the plates were released to weed shoots through arc discharge. Houseflies were introduced into the space between the negatively charged and grounded plates, then subjected to arc discharge from the charged plates. Both plant shoots and adult houseflies are electrically conductive; thus, they were killed by discharge-exposure in the electric field between the charged iron plate and the ground soil, and between the charged and grounded plates, respectively. In practical use, these two devices were assembled as a two-level apparatus for simultaneous control of both targets. Several apparatuses were linked together, which increased the total electricity charge on the plates and produced a stronger discharge force sufficient to kill all targets. Thus, this study provides an electrostatics-based pest-control method for pesticide-independent greenhouse farming.

Airway-centered Interstitial Fibrosis Involving Smooth Muscle Hyperplasia with Severe Pulmonary Hypertension.

In the 2013 updated classification of the American Thoracic Society/European Respiratory Society, airway-centered interstitial fibrosis (ACIF) is included as a bronchiolocentric pattern of interstitial pneumonia (IP) among idiopathic IPs. We encountered a case of severe pulmonary hypertension (PH) with chronic IP. The patient initially presented with shortness of breath and often lost consciousness due to PH, and seven years after his first visit, he ultimately died. An autopsy revealed ACIF and usual IP. In particular, the ACIF comprised non-atypical smooth muscle hyperplasia, and pulmonary hypertensive vascular degeneration was detected. This case may represent a new pathological feature of ACIF.

Myocarditis with Advanced Atrioventricular Block after Allogeneic Stem Cell Transplantation: A Case Report and Literature Review.

A 51-year-old woman with Philadelphia chromosome-positive acute lymphoblastic leukemia underwent a second cord blood transplantation followed by maintenance therapy with interferon-α. After 33 months, she developed cardiogenic shock caused by advanced atrioventricular block. Laboratory tests revealed increased myocardium enzymes, and ultrasonic cardiography demonstrated mild thickening of the left ventricular wall. She was diagnosed with myocarditis and successfully treated using prednisolone. Myocarditis after allogeneic stem cell transplantation is a rare but potentially fatal complication. However, it is important for physicians to be aware of this complication because all of the symptoms may be reversed with immunosuppressive treatment.

[Usefulness of FDG-PET for the diagnosis of postoperative recurrence of lung cancer].

No standardized postoperative follow-up strategy has been established for lung cancer patients, although CT and tumor markers are often employed. We conducted a retrospective study evaluating fluoro-2-deoxyglucose positron emission tomography (FDG-PET) for the diagnosis of postoperative recurrence of lung cancer. We evaluated 28 patients with suspected postoperative recurrence of lung cancer, who underwent FDG-PET between July 2004 and November 2005. Of these, 15 showed positive PET finings. Recurrence of lung cancer cases confirmed in 14 of these and the remaining case showed a postoperative scar. Thirteen patients with no findings on PET scan have demonstrated no evidence of recurrence during follow-up periods between 10 to 23 months. The negative predictive value was therefore 100%. FDG-PET in addition to chest CT and tumor markers for the diagnosis of the postoperative recurrence of lung cancer is considered to be beneficial in terms of avoiding excessive radiation exposure and limiting medical costs, but further evaluation in more patients is necessary.

[Case of pulmonary aspergillosis associated with inappropriate antidiuretic hormone syndrome caused by voriconazole therapy].

A 75-year-old man presented with hemoptysis. Consolidation was identified in the left lower lobe around multiple bullae. He was found to have chronic necrotizing pulmonary aspergillosis based on a high titer of aspergillus antigen and positive antibody. He was treated with 400 mg/day voriconazole. However, liver dysfunction and hyponatremia developed at 21 days after beginning administration of voriconazole. Serum sodium levels were 122 mEq/l. but urinary sodium showed a high level of 135 mEq/l. The serum sodium level improved 10 days after voriconazole was discontinued. Serum levels of voriconazole on day 15 were high at 18 microg/ml (safe effective serum level: 1.5 to 4.5 microg/ml). An analysis of genetic polymorphism showed a mutation of cytochrome P450 (CYP2C19*2 G681A). We report the first case of a voriconazole-induced syndrome of inappropriate antidiuretic hormone caused by a polymorphism mutation of cytochrome P450.

Ankle-brachial Index for the Prognosis of Cardiovascular Disease in Patients with Mild Renal Insufficiency.

Objective A low ankle-brachial index (ABI) is a known predictor for future cardiovascular events and mortality in patients with chronic kidney disease (CKD). While most prior studies have defined CKD as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, recent reports have suggested that the cardiovascular risk may be increased even in early stages of renal insufficiency. We hypothesized that a low ABI may predict future cardiovascular morbidity and mortality in patients with mild impairment of the renal function. Methods The IMPACT-ABI study was a retrospective, single-center, cohort study that enrolled and obtained ABI measurements for 3,131 patients hospitalized for cardiovascular disease between January 2005 and December 2012. From this cohort, we identified 1,500 patients with mild renal insufficiency (eGFR =60-89 mL/min/1.73 m2), and stratified them into 2 groups: ABI ≤0.9 (low ABI group; 9.2%) and ABI >0.9 (90.8%). The primary outcome measured was the cumulative incidence of major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, and stroke). Results Over a mean follow-up of 5.0 years, 101 MACE occurred. The incidence of MACE was significantly higher in patients with low ABI than in those with ABI >0.9 (30.2% vs. 14.4%, log rank p<0.001). A low ABI was associated with MACE in a univariate Cox proportional hazard analysis. A low ABI remained an independent predictor of MACE in a multivariate analysis adjusted for cardiovascular risk factors (hazard ratio (HR): 2.27; 95% confidence interval (CI): 1.33-3.86; p=0.002). Conclusion Low ABI was an independent predictor for MACE in patients with mild renal insufficiency.

Failure of steroid withdrawal guided by 18F-FDG PET in a patient with cardiac sarcoidosis.

A 71-year-old man diagnosed with cardiac sarcoidosis (CS) 11 years previously underwent implantation of an implantable cardioverter defibrillator due to sustained ventricular tachycardia. Over past decade, his condition of CS did not progress on the maintenance steroid dose of 7.5 mg per day. We attempted to taper and discontinue steroids according to the results of fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET). On the basis of the results, we reduced the oral steroid dose slowly. In spite of no abnormal 18F-FDG uptake in the myocardium, advanced atrioventricular conduction block and deterioration of the ventricular pacing threshold occurred during the course of steroid withdrawal. Plasma brain natriuretic peptide (BNP) increased from 94 to 842 pg/ml. It was necessary to add new ventricular and atrial leads to synchronize atrial and ventricular contractions, and the pacing mode for bradycardia was changed to dual-chamber DDD-60 ppm. Fatigue disappeared, and BNP levels decreased to 147 pg/ml. 18F-FDG PET might have a limit to detect small scattered inflammatory foci. This case highlights the need for caution when reducing steroid doses in CS patients, guided by 18F-FDG PET only. .

A new spore precipitator with polarized dielectric insulators for physical control of tomato powdery mildew.

ABSTRACT In an attempt to physically protect greenhouse tomato plants from the powdery mildew fungus Oidium neolycopersici, we developed a new electrostatic spore precipitator in which a copper wire conductor is linked to an electrostatic generator and covered with a transparent acrylic cylinder (insulator). The conductor was negatively charged by the generator, and the electrostatic field created by the conductor was used to dielectrically polarize the insulator cylinder. The dielectrically polarized cylinder also produced an electrostatic force without a spark discharge. This force was directly proportional to the potential applied to the conductor and was used to attract conidia of the pathogen. The efficacy of this spore precipitator in protecting hydroponically cultured tomato plants from powdery mildew was evaluated in the greenhouse. The hydroponic culture troughs were covered with a cubic frame installed with the spore precipitator, and the disease progress on precipitator-guarded and unguarded seedlings was traced after the conidia were disseminated mechanically from inoculum on tomato plants. Seedlings in the guarded troughs remained uninfected during the entire experiment, in spite of rapid spread of the disease to all leaves of the unguarded seedlings.

In vivo neurochemical evidence that delta1-, delta2- and mu2-opioid receptors, but not mu1-opioid receptors, inhibit acetylcholine efflux in the nucleus accumbens of freely moving rats.

Cholinergic neurons in the nucleus accumbens express delta- and mu-opioid receptors that are thought to inhibit neural activity. Delta- and mu-opioid receptors are divided into delta1- and delta2-opioid receptors and mu1- and mu2-opioid receptors, respectively. We analysed the roles of delta- and mu-opioid receptor subtypes in regulating accumbal acetylcholine efflux of freely moving rats using in vivo microdialysis. Other than naloxonazine, given intraperitoneally, delta- and mu-opioid receptor ligands were administered intracerebrally through the dialysis probe. Doses of these compounds indicate total amount (mol) over an infusion time of 30-60min. To monitor basal acetylcholine, a low concentration of physostigmine (50nM) was added to the perfusate. The delta1-opioid receptor agonist DPDPE (3 and 300pmol) and delta2-opioid receptor agonist deltorphin II (3 and 30pmol) decreased accumbal acetylcholine in a dose-related manner. DPDPE (300pmol)- and deltorphin II (3pmol)-induced reductions in acetylcholine were each inhibited by the delta1-opioid receptor antagonist BNTX (0.3pmol) and delta2-opioid receptor antagonist naltriben (15pmol), respectively. The mu-opioid receptor agonists endomorphin-1 and endomorphin-2 (6 and 30nmol) decreased acetylcholine in a dose-related manner. Endomorphin-1- and endomorphin-2 (30nmol)-induced reductions in acetylcholine were prevented by the mu-opioid receptor antagonist CTOP (3nmol). The mu1-opioid receptor antagonist naloxonazine (15mg/kg ip), which inhibits endomorphin-1 (15nmol)-induced accumbal dopamine efflux, did not alter endomorphin-1- or endomorphin-2 (30nmol)-induced reductions in acetylcholine efflux. This study provides in vivo evidence for delta1-, delta2- and mu2-opioid receptors, but not mu1-opioid receptors, that inhibit accumbal cholinergic neural activity.

Clinical Characteristics and Outcomes of Patients with High Ankle-Brachial Index from the IMPACT-ABI Study.

BACKGROUND: Reduced ankle-brachial index (ABI) is a predictor of cardiovascular events. However, the significance of high ABI remains poorly understood. This study aimed to assess the characteristics and outcomes of patients with high ABI. METHODS: The IMPACT-ABI study was a retrospective cohort study that enrolled and examined ABI in 3,131 patients hospitalized for cardiovascular disease between January 2005 and December 2012. From this cohort, 2,419 patients were identified and stratified into two groups: high ABI (> 1.4; 2.6%) and normal ABI (1.0-1.4; 97.3%). The primary endpoint was the cumulative incidence of major adverse cardiovascular events (MACE), including cardiovascular-associated death, myocardial infarction, and stroke. RESULTS: Compared with the normal ABI group, patients in the high ABI group showed significantly lower body mass index (BMI) and hemoglobin level, but had higher incidence of chronic kidney disease and hemodialysis. Multivariate logistic regression analysis revealed that hemodialysis was the strongest predictor of high ABI (odds ratio, 6.18; 95% confidence interval (CI), 3.05-12.52; P < 0.001). During the follow-up (median, 4.7 years), 172 cases of MACE occurred. Cumulative MACE incidence in patients with high ABI was significantly increased compared to that in those with normal ABI (32.5% vs. 14.5%; P = 0.005). In traditional cardiovascular risk factors-adjusted multivariate Cox proportional hazard analysis, high ABI was an independent predictor of MACE (hazard ratio, 2.07; 95% CI, 1.02-4.20; P = 0.044). CONCLUSION: Lower BMI, chronic kidney disease, and hemodialysis are more frequent in patients with high ABI. Hemodialysis is the strongest predictor of high ABI. High ABI is a parameter that independently predicts MACE.