bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Tadalafil on Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia and on Erectile Dysfunction in Sexually Active Men with Both Conditions: Analyses of Pooled Data from Four Randomized, Placebo-Controlled Tadalafil Clinical Studies
Authors: Porst Hartmut , Roehrborn Claus G. , Secrest Roberta J. , Esler Anne , Viktrup Lars 
Published: June 2013

ABSTRACT

Introduction
Erectile dysfunction (ED) and lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) are common in aging males and frequently occur together. Tadalafil has demonstrated efficacy in treating both conditions.

Aim
The study aims to evaluate the efficacy and safety of tadalafil 5 mg once daily vs. placebo over 12 weeks in treating both LUTS/BPH and ED in sexually active men. We also assessed relationships of baseline disease severity and prostate specific antigen (PSA) to outcomes.

Methods
Data were pooled from four multinational, randomized studies of men ≥45 years with LUTS/BPH, with analyses restricted to sexually active men with ED. Randomization (baseline) followed a 4-week placebo run-in; changes from baseline were assessed vs. placebo using analysis of covariance.

Main Outcome Measures
International Prostate Symptom Score (IPSS), IPSS subscores, Quality-of-Life Index (IPSS-QoL), BPH Impact Index (BII), and International Index of Erectile Function-Erectile Function (IIEF-EF) Domain score were used in this study.

Results
Tadalafil (N = 505) significantly improved total IPSS vs. placebo (N = 521); mean changes from baseline were −6.0 and −3.6, respectively (P &lt; 0.001). Improvements in IIEF-EF Domain score (tadalafil, 6.4; placebo, 1.4) were also significant vs. placebo, as were the IPSS storage and voiding subscores, IPSS-QoL, and BII (all P &lt; 0.001).
No significant impact of baseline ED severity or PSA category on IPSS response was observed (interaction P values, 0.463 and 0.149, respectively). Similarly, improvement in IIEF-EF Domain score was not significantly impacted by baseline LUTS/BPH severity or PSA category (interaction P values, 0.926 and 0.230, respectively). Improvements in IPSS and IIEF-EF Domain score during treatment were weakly correlated (r = −0.229). Treatment-emergent adverse events were consistent with previous reports.

Conclusions
Tadalafil was efficacious and well tolerated in treating ED and LUTS/BPH in sexually active men with both conditions. Improvements in both conditions were significant regardless of baseline severity. Improvements in the total IPSS and the IIEF-EF Domain score were weakly correlated.
American Cocker Spaniel Chronic Hepatitis in Japan
Authors: Kanemoto H. , Sakai M. , Sakamoto Y. , Spee B. , van den Ingh T.S.G.A.M. , Schotanus B.A. , Ohno K. , Rothuizen J. 
Published: June 2013

BackgroundAmerican Cocker Spaniels are predisposed to chronic hepatitis.ObjectiveTo describe the clinical and histological features of chronic hepatitis in Japanese American Cocker Spaniels.AnimalsThirteen cases examined from 2003 to 2009.MethodsRetrospective study. Medical records were searched for American Cocker Spaniels with chronic liver diseases. History, physical examination, clinicopathologic features, hepatic ultrasonographic findings, hepatic histopathology, and immunohistochemistry were evaluated.ResultsThe median age was 4.6 (1.9–10.7) years. Clinical signs included inappetence (11/13), ascites (11/13), lethargy (9/13), diarrhea (7/13), and melena (2/13). Only 1/13 dogs was jaundiced. Clinicopathological abnormalities were increased liver enzymes (gamma‐glutamyl transpeptidase: 9/12, aspartate aminotransferase: 7/10, alanine aminotransferase: 6/13, alkaline phosphatase: 6/13), increased total serum bile acid concentrations (10/12), and hypoalbuminemia (10/13). The liver had an irregular surface in all dogs and acquired portosystemic collaterals were verified in 11/13 dogs by abdominal ultrasound (2), laparoscopy (4), or both (5). Liver histology revealed severe fibrosis and cirrhosis in all cases, subdivided in lobular dissecting hepatitis (7), periportal fibrosis (1), micronodular cirrhosis (3), and macronocular cirrhosis (2). Inflammatory activity was low to mild. Immunohistochemical stains showed ductular proliferation. The median survival time was 913 (range: 63–1981) days.Conclusion and Clinical ImportanceHepatitis in Japanese American Cocker Spaniels is clinically silent until an advanced stage and is associated with severe hepatic fibrosis leading to cirrhosis, extensive ductular/putative hepatic progenitor cell proliferation, portal hypertension, and acquired portosystemic collateral shunting, but relatively long survival times. Lobular dissecting hepatitis seems more prevalent than in previously reported cases from other countries.
Systematic Review of Nonsteroidal Anti‐Inflammatory Drug‐Induced Adverse Effects in Dogs
Authors: Monteiro‐Steagall B.P. , Steagall P.V.M. , Lascelles B.D.X. 
Published: June 2013

The aim of this systematic review was to identify, assess, and critically evaluate the quality of evidence of nonsteroidal anti‐inflammatory drug (NSAID)‐induced adverse effects in dogs. Original prospective studies published in peer‐reviewed journals in English (1990–2012) that reported data on the safety ofNSAIDs administration in dogs were searched. For each study, design type (I, II, III, or IV) and assessment of quality (+, Ø, −) were rated. For each drug, quantity and consistency rating (***, **, *) and strength of evidence (high, moderate, low, or extremely low) were identified and evaluated. The strength of evidence was defined in terms of how applicable and relevant the conclusions were to the target population. Sixty‐four studies met the inclusion criteria. Thirty‐five (55%) research studies and 29 (45%) clinical trials were identified. A high strength of evidence existed for carprofen, firocoxib, and meloxicam; moderate for deracoxib, ketoprofen, and robenacoxib; and low for etodolac. Quality and consistency rating were as follows: carprofen (***/***), deracoxib (**/***), etodolac (*/unable to rate), firocoxib (***/**), ketoprofen (**/***), meloxicam (***/***), and robenacoxib (**/**), respectively. Adverse effects were detected in 35 studies (55%) and commonly included vomiting, diarrhea, and anorexia. Three studies (5%) reported a power analysis related to adverse effects of ≥80%. In randomized, placebo‐controlled, blinded studies (n = 25, 39%), the incidence of adverse effects was not statistically different between treated and control dogs. Finally, most studies were not appropriately designed to determine the safety ofNSAIDs, and involved a healthy nongeriatric population of research dogs.
Neonatal Morbidity and Mortality of 31 Calves Derived from Somatic Cloning
Authors: Brisville A.‐C. , Fecteau G. , Boysen S. , Desrochers A. , Dorval P. , Buczinski S. , Lefebvre R. , Hélie P. , Blondin P. , Smith L.C. 
Published: June 2013

BackgroundThe neonatal period is associated with high morbidity and mortality in cloned calves.ObjectiveTo describe morbidity and mortality in cloned calves from birth to 2 years of age.AnimalsThirty‐one somatic cell‐derivedHolstein calves delivered at a veterinary teaching hospital.MethodsMedical files were retrospectively analyzed.ResultsFour calves were stillborn. Five calves born alive had physical congenital defects. Twenty‐three calves had an enlarged umbilical cord. Laboratory abnormalities included acidemia, respiratory acidosis, hyperlactatemia, anemia, stress leukogram, decreased total protein, albumin and globulins, and increased creatinine. Twenty‐five calves survived the 1st hour of life. Among them, 11 stood without assistance within 6 hours of birth, 10 calves took longer than 6 hours to stand, and 4 never stood. Twenty‐two calves suffered from anorexia. Twelve calves had complications arising from umbilical cord infections. Three calves developed idiopathic hyperthermia (>40°C). Eight calves suffered from gastrointestinal problems, including ruminal distension, abomasal ulcers, neonatal enteritis, intussusception, and abomasal displacement. Mortality between birth and 3 weeks of age was 32% (10/31). Causes of death and reasons for euthanasia included stillbirths, respiratory failure, and limb deformities. Mortality between 3 weeks and 2 years of age was 19% (4/21), with deaths in this group attributed to generalized peritonitis and complications arising from umbilical infections. Overall, mortality rate within 2 years of age was 14/31 (45%).Conclusion and Clinical ImportanceRespiratory problems, limb deformities, and umbilical infections were the most common causes of morbidity and mortality in these cloned calves.
Hepatic stellate cells that coexpress LRAT and CRBP‐1 partially contribute to portal fibrogenesis in patients with human viral hepatitis
Authors: Nagatsuma Keisuke , Hano Hiroshi , Murakami Kazuhiro , Shindo Daisuke , Matsumoto Yoshihiro , Mitobe Jimi , Tanaka Ken , Saito Masaya , Maehashi Haruka , Owada Mamiko , Ikegami Masahiro , Tsubota Akihito , Ohkusa Toshifumi , Aizawa Yoshio , Takagi Ichiro , Tajiri Hisao , Matsuura Tomokazu 
Published: June 2013

AbstractBackground & AimsPrecisely what type of cells mainly contributes to portal fibrosis, especially in chronic viral hepatitis, such as hepatic stellate cells (HSCs) in the parenchyma or myofibroblasts in the portal area, still remains unclear. It is necessary to clarify the characteristics of cells that contribute to portal fibrosis in order to determine the mechanism of portal fibrogenesis and to develop a therapeutic target for portal fibrosis. This study was undertaken to examine whether LRAT+/CRBP‐1+ HSCs contribute to portal fibrosis on viral hepatitis.MethodsAntibodies to lecithin:retinol acyltransferase (LRAT), cellular retinol‐binding protein‐1 (CRBP‐1) and widely ascertained antibodies to HSCs (alpha‐smooth muscle actin, neurotrophin‐3) and endothelial cells (CD31) were used for immunohistochemical studies to assess the distribution of cells that contribute to the development of portal fibrosis with the aid of fluorescence microscopy. A quantitative analysis of LRAT+/CRBP‐1+ HSCs was performed.ResultsThe number of LRAT+/CRBP‐1+ HSCs was increased in fibrotic liver in comparison with normal liver in the portal area and fibrous septa. The number of double positive cells was less than 20% of all cells/field in maximum.ConclusionThis study provides evidence that functional HSCs coexpressing both LRAT and CRBP‐1 that continue to maintain the ability to store vitamin A contribute in part to the development of portal fibrogenesis in addition to parenchymal fibrogenesis in patients with viral hepatitis.
Role of Urodynamic Study in Nocturnal Enuresis: Urodynamic Findings and Treatment Outcome Correlation in Children with Pharmacotherapy‐resistant Monosymptomatic Nocturnal Enuresis or Severe Non‐monosymptomatic Nocturnal Enuresis
Authors: RYU Dong Soo , LEE Hye Won , KWAK Kyung Won , PARK Kwan Hyun , BAEK Minki 
Published: June 2013

ObjectivesThis study aimed to determine whether or not a urodynamic study (UDS) is beneficial for management of pediatric nocturnal enuresis (NE), especially in pharmacoresistant monosymptomatic nocturnal enuresis (PRMNE) or severe non‐monosymptomatic nocturnal enuresis (NMNE) patients.MethodsChildren with PRMNE or severe NMNE who underwent a UDS for the process of NE treatment were retrospectively reviewed. The UDS findings of patients and treatment outcomes of subsequent tailored therapies according to the UDS findings were analyzed.ResultsA total of 80 children (50 boys and 30 girls, mean age 8.4 ± 2.2 years), 19 of which were diagnosed with PRMNE and 61 of which were diagnosed with NMNE, were included in the final analysis. Of the 19 PRMNE children, 12 (63.2%) demonstrated abnormal UDS findings. Ten demonstrated detrusor overactivity (DO) with or without decreased cystometric bladder capacity (CBC); the treatment outcomes markedly improved in all of the children after anticholinergics were added to the initial desmopressin therapy. Biofeedback was found to be helpful for two children with detrusor‐sphincter dyssynergia. All of the total 61 children with NMNE demonstrated abnormal urodynamic findings of DO with or without decreased CBC, and 42 (68.9%) achieved more than partial response (> 50% decrease in the number of wet nights) when given a combination therapy of anticholinergics and desmopressin.ConclusionsThe urodynamic findings were helpful for guiding children with PRMNE in the proper choice of further treatment strategies. A routine UDS should not be recommended prior to a first‐line combination treatment in children with NMNE.
Comparison of the effectiveness of a milk‐free soy‐maize‐sorghum‐based ready‐to‐use therapeutic food to standard ready‐to‐use therapeutic food with 25% milk in nutrition management of severely acutely malnourished Zambian children: an equivalence non‐blinded cluster randomised controlled trial
Authors: Irena Abel H. , Bahwere Paluku , Owino Victor O. , Diop ElHadji I. , Bachmann Max O. , Mbwili‐Muleya Clara , Dibari Filippo , Sadler Kate , Collins Steve 
Published: June 2013

AbstractCommunity‐based Management of Acute Malnutrition using ready‐to‐use therapeutic food (RUTF) has revolutionised the treatment of severe acute malnutrition (SAM). However, 25% milk content in standard peanut‐based RUTF (P‐RUTF) makes it too expensive. The effectiveness of milk‐free RUTF has not been reported hitherto. This non‐blinded, parallel group, cluster randomised, controlled, equivalence trial that compares the effectiveness of a milk‐free soy–maize–sorghum‐based RUTF (SMS‐RUTF) with P‐RUTF in treatment of children with SAM, closes the gap. A statistician randomly assigned health centres (HC) either to the SMS‐RUTF (n = 12; 824 enrolled) or P‐RUTF (n = 12; 1103 enrolled) arms. All SAM children admitted at the participating HCs were enrolled. All the outcomes were measured at individual level. Recovery rate was the primary outcome. The recovery rates for SMS‐RUTF and P‐RUTF were 53.3% and 60.8% for the intention‐to‐treat (ITT) analysis and 77.9% and 81.8% for per protocol (PP) analyses, respectively. The corresponding adjusted risk difference (ARD) and 95% confidence interval, were −7.6% (−14.9, 0.6%) and −3.5% (−9,6., 2.7%) for ITT (P = 0.034) and PP analyses (P = 0.257), respectively. An unanticipated interaction (interaction P < 0.001 for ITT analyses and 0.0683 for PP analyses) between the study arm and age group was observed. The ARDs were −10.0 (−17.7 to −2.3)% for ITT (P = 0.013) and −4.7 (−10.0 to 0.7) for PP (P = 0.083) analyses for the <24 months age group and 2.1 (−10.3,14.6)% for ITT (P = 0.726) and −0.6 (−16.1, 14.5) for PP (P = 0.939) for the ≥24 months age group. In conclusion, the study did not confirm our hypothesis of equivalence between SMS‐RUTF and P‐RUTF in SAM management.
A mutation in the expansin‐like A2 gene enhances resistance to necrotrophic fungi and hypersensitivity to abiotic stress in Arabidopsis thaliana
Authors: Abuqamar Synan , Ajeb Suad , Sham Arjun , Enan Mohamed Rizq , Iratni Rabah 
Published: June 2013

SummaryExpansins are cell wall loosening agents, known for their endogenous function in cell wall extensibility. The Arabidopsis expansin‐like A2 (EXLA2) gene was identified by its down‐regulation in response to infection by the necrotrophic pathogen Botrytis cinerea, and by the reduced susceptibility of an exla2 mutant to the same pathogen. The exla2 mutant was equally susceptible to Pseudomonas syringae pv. tomato, but was more resistant to the necrotrophic fungus Alternaria brassicicola, when compared with the wild‐type or with transgenic, ectopic EXLA2‐overexpressing lines. The exla2 mutants also enhanced tolerance to the phytoprostane‐A1. This suggests that the absence or down‐regulation of EXLA2 leads to increased resistance to B. cinerea in a CORONATINE INSENSITIVE 1 (COI1)‐dependent manner, and this down‐regulation can be achieved by phytoprostane‐A1 treatment. EXLA2 is induced significantly by salinity and cold, and by the exogenous application of abscisic acid. The exla2 mutant also showed hypersensitivity towards increased salt and cold, and this hypersensitivity required a functional abscisic acid pathway. The differential temporal expression of EXLA2 and the phenotypes in transgenic plants with altered expression of EXLA2 indicate that plant cell wall structure is an important player during Arabidopsis developmental stages. Our results indicate that EXLA2 appears to be important in response to various biotic and abiotic stresses, particularly in the pathogenesis of necrotrophic pathogens and in the tolerance to abiotic stress.
Self‐interaction of the cucumber mosaic virus 2b protein plays a vital role in the suppression of RNA silencing and the induction of viral symptoms
Authors: Xu Aixia , Zhao Zhijing , Chen Wenhu , Zhang Hengmu , Liao Qiansheng , Chen Jishuang , Carr John P. , Du Zhiyou 
Published: June 2013

SummaryThe cucumber mosaic virus (CMV) 2b protein is an RNA silencing suppressor protein that can also play direct and indirect roles in symptom induction. Previous work has shown that a hybrid virus, FRad352b‐CMV (renamed here as CMV‐FRad2b‐Pro), generated by replacement of the 2b gene of strain Fny‐CMV with that from Rad35‐CMV, displays markedly lower pathogenicity than Fny‐CMV on Nicotiana species. However, the replacement of proline with leucine at position 55 of the 2b protein of CMV‐FRad2b‐Pro (protein Rad2b‐Pro) created a virus (CMV‐FRad2b‐Leu) that induced severe symptoms. Infection of Arabidopsis thaliana mutants defective in the expression of DICER‐like (DCL) endoribonucleases 2 and 4, which mediate antiviral RNA silencing, as well as of dcl3 and dcl2/3/4 triple‐mutant plants, indicated that Rad2b‐Pro was a weaker RNA silencing suppressor than the protein Rad2b‐Leu. This was confirmed in Nicotiana benthamiana using agroinfiltration assays, showing that, compared with either Rad2b‐Leu or the Fny2b protein, Rad2b‐Pro was ineffective at inhibiting local or systemic silencing of expression of a green fluorescent protein reporter gene. Transgenic expression of Rad2b‐Leu, but not of Rad2b‐Pro, in Arabidopsis induced symptom‐like phenotypes and rescued the accumulation of the 2b‐deletion mutant Fny‐CMVΔ2b. Bimolecular fluorescent complementation indicated that, in planta, Rad2b‐Leu, but not Rad2b‐Pro, self‐interacts. Thus, self‐interaction is crucial to the ability of the 2b protein to suppress silencing and induce a symptom‐like phenotype, and is dependent on the properties of the residue at position 55.
Fitness penalty in susceptible host is associated with virulence of Soybean mosaic virus on Rsv1‐genotype soybean: a consequence of perturbation of HC‐Pro and not P3
Authors: Khatabi B. , Wen R.‐H. , Hajimorad M. R. 
Published: June 2013

SummaryThe multigenic Rsv1 locus in the soybean plant introduction (PI) ‘PI96983’ confers extreme resistance against the majority of Soybean mosaic virus (SMV) strains, including SMV‐N, but not SMV‐G7 and SMV‐G7d. In contrast, in susceptible soybean cultivars lacking a functional Rsv1 locus, such as ‘Williams82’ (rsv1), SMV‐N induces severe disease symptoms and accumulates to a high level, whereas both SMV‐G7 and SMV‐G7d induce mild symptoms and accumulate to a significantly lower level. Gain of virulence by SMV‐N on Rsv1‐genotype soybean requires concurrent mutations in both the helper‐component proteinase (HC‐Pro) and P3 cistrons. This is because of the presence of at least two resistance (R) genes, probably belonging to the nucleotide‐binding leucine‐rich repeat (NB‐LRR) class, within the Rsv1 locus, independently mediating the recognition of HC‐Pro or P3. In this study, we show that the majority of experimentally evolved mutational pathways that disrupt the avirulence functions of SMV‐N on Rsv1‐genotype soybean also result in mild symptoms and reduced accumulation, relative to parental SMV‐N, in Williams82 (rsv1). Furthermore, the evaluation of SMV‐N‐derived HC‐Pro and P3 chimeras, containing homologous sequences from virulent SMV‐G7 or SMV‐G7d strains, as well as SMV‐N‐derived variants containing HC‐Pro or P3 point mutation(s) associated with gain of virulence, reveals a direct correlation between the perturbation of HC‐Pro and a fitness penalty in Williams82 (rsv1). Collectively, these data demonstrate that gain of virulence by SMV on Rsv1‐genotype soybean results in fitness loss in a previously susceptible soybean genotype, this being a consequence of mutations in HC‐Pro, but not in P3.
Cerebral white matter hyperintensity predicts cardiovascular events in haemodialysis patients
Authors: Naganuma Toshihide , Takemoto Yoshiaki , Shoji Tetsuo , Shima Hideaki , Ishimura Eiji , Okamura Mikio , Nakatani Tatsuya 
Published: June 2013

AbstractAimCerebral white matter hyperintensities (WMHs), comprised of periventricular hyperintensity (PVH) and deep and subcortical white matter hyperintensity (DSWMH), have been presumed to be predictors for future stroke, cognitive impairment and dementia in the general population. However, no longitudinal studies have been performed to determine the clinical significance of WMHs in haemodialysis (HD) patients. In the present study, we investigated the influence of WMHs as a predictor of future cardiovascular disease in HD patients.MethodsCranial magnetic resonance imaging was performed on 179 HD patients with no past history of stroke from April 2006 to October 2009, and the prevalence of WMHs was investigated. The patients were followed prospectively until March 2012 or death or renal transplantation. The influence of WMHs on cardiovascular events was investigated using the Kaplan–Meier method and Cox proportional hazards analysis.ResultsThe patients with advanced PVH and DSWMH had a significantly higher incidence of cardiovascular morbidity than those without advanced PVH and DSWMH by Kaplan–Meier analysis. By multivariate Cox proportional hazards analysis, the presence of advanced PVH and DSWMH increased the risk of cardiovascular events, independent of other cardiovascular risk factors. In addition, the present study revealed that of the subtypes of WMHs, PVH was a stronger predictor of cardiovascular events compared to DSWMH.ConclusionsThe present study indicates that the presence of WMHs is a novel predictor of cardiovascular events in HD patients, and that PVH is more closely associated with incident cardiovascular disease.
Aborted sudden cardiac death in a child with left ventricular non‐compaction
Authors: Ergul Yakup , Nisli Kemal , Bilge Ahmet Kaya , Dindar Aygun 
Published: June 2013

AbstractLeft ventricular non‐compaction is a rare form of cardiomyopathy believed to be the result of intrauterine arrest of compaction of the endomyocardial morphogenesis, leading to persistence of the embryonic myocardium. Clinical manifestations are highly variable, ranging from no symptoms to a progressive deterioration in cardiac function that results in congestive heart failure, systemic thromboemboli, arrhythmias, and sudden cardiac death. Presented here is the case of a 4‐year‐old child with a history of aborted sudden cardiac death. Following resuscitation, he was admitted to the intensive care unit with neurologic sequelae that regressed later on. Transthoracic echocardiography and magnetic resonance imaging showed numerous prominent trabeculations and deep intertrabecular recesses at the apical and anterolateral region of the left ventricle. Electrophysiologic study showed polymorphic ventricular tachycardia. An implantable cardioverter–defibrillator (ICD) was implanted following clinical recovery. Five months after implantation, appropriate ICD shock due to ventricular fibrillation was documented.