bluuebunny/crossref_metadata_2025_split huggingface dataset:
PNPLA3 in end‐stage liver disease: Alcohol consumption, hepatocellular carcinoma development, and transplantation‐free survival
Authors: Friedrich Kilian , Wannhoff Andreas , Kattner Stefan , Brune Maik , Hov Johannes Roksund , Weiss Karl Heinz , Antoni Christoph , Dollinger Matthias , Neumann‐Haefelin Christoph , Seufferlein Thomas , Schemmer Peter , Schirmacher Peter , Stremmel Wolfgang , Gotthardt Daniel Nils 
Published: February 2014

AbstractBackground and AimsThe rs738409 variant (I148M) of the patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) gene is associated with several liver malfunctions. Its impact on end‐stage liver disease has not been addressed yet.MethodsThe I148M polymorphism was genotyped in a well‐characterized cohort of 421 Caucasian patients and retrospectively analyzed from the time of enrollment at Eurotransplant.ResultsThe G allele of the I148M variant was significantly overrepresented in patients with alcoholic liver disease (ALD, P < 0.001) and associated with hepatocellular carcinoma (HCC) development (odds ratio [OR] = 2.399; 95% confidence interval [CI]: 1.292–4.455; P = 0.008) while not affecting the other liver disease entities. Time until hydropic decompensation (P = 0.04) and hepatic encephalopathy (P = 0.043) was significantly impaired for ALD patients carrying either one or two mutated G alleles. Actuarial survival free of liver transplantation was further reduced for ALD carriers of the I148M variant (CC = 30.7 months ± 7.9, 95% CI: 15.1–46.2 vs CG/GG: 17.1 months ± 3.3, 95% CI: 3.3–10.6; P = 0.012) compared with wild‐type patients. Cox multivariate analysis identified the PNPLA3 I148M genotype as an independent predictor actuarial survival free of liver transplantation (OR = 1.77; 95% CI: 1.27–2.47; P = 0.001).ConclusionsIn end‐stage liver disease patients, we identified ALD to be predominantly affected by the PNPLA3 I148M variant resulting in an increased risk of HCC and reduced transplantation free survival. Genetic testing of the I148M genotype in ALD patients awaiting liver transplantation might be beneficial for these patients.
Amyloid‐β concentration and structure influences the transport and immunomodulatory effects ofIVIG
Authors: Wuest Diane M. , Lee Kelvin H. 
Published: February 2014

AbstractIntravenous immunoglobulin (IVIG) contains anti‐amyloid‐β antibodies as well as antibodies providing immunomodulatory effects that may modify chronic inflammation in Alzheimer's disease. Answers to important questions about IVIG transport into the central nervous system and assessments of any impact amyloid‐β has on this transport can be provided byin vitromodels of the blood–brain barrier. In this study, amyloid‐β[1‐42]was pre‐aggregated into fibrillar or oligomeric structures, and various concentrations were incubated in the brain side of the blood–brain barrier model, followed by IVIG administration in the blood side at the therapeutically relevant concentrations of 5 and 20 mg/mL. IVIG accumulated in the brain side at physiologically relevant levels, with amyloid‐β pre‐incubation increasing IVIG accumulation. The increased transport effect was dependent on amyloid‐β structural form, amyloid‐β concentration, and IVIG dose. IVIG was found to decrease monocyte chemotactic protein‐1 levels 6.5–18% when low amyloid‐β levels were present and increase levels 4.2–23% when high amyloid‐β levels were present. Therefore, the presence, concentration, and structure of amyloid‐β plays an important role in the effect of IVIG therapy in the brain.imageThe mechanisms of action and transport across the blood–brain barrier (BBB) for an Alzheimer's disease therapeutic, intravenous immunoglobulin (IVIG), remain unknown. We investigated the transport of IVIG across endothelial cell BBB monolayers pre‐incubated with amyloid‐β peptides. We found that the concentration and structure of amyloid‐β plays an important role in the effect of IVIG on BBB tightening and cytokine neutralization. (Note: Figure not drawn to scale.)
Unique method of tooth replacement in durophagous placodont marine reptiles, with new data on the dentition of Chinese taxa
Authors: Neenan James M. , Li Chun , Rieppel Olivier , Bernardini Federico , Tuniz Claudio , Muscio Giuseppe , Scheyer Torsten M. 
Published: February 2014

AbstractThe placodonts of the Triassic period (~252–201 mya) represent one of the earliest and most extreme specialisations to a durophagous diet of any known reptile group. Exceptionally enlarged crushing tooth plates on the maxilla, dentary and palatine cooperated to form functional crushing areas in the buccal cavity. However, the extreme size of these teeth, combined with the unusual way they occluded, constrained how replacement occurred. Using an extensive micro‐computed tomographic dataset of 11 specimens that span all geographic regions and placodont morphotypes, tooth replacement patterns were investigated. In addition, the previously undescribed dental morphologies and formulae of Chinese taxa are described for the first time and incorporated into the analysis. Placodonts have a unique tooth replacement pattern and results follow a phylogenetic trend. The plesiomorphic Placodus species show many replacement teeth at various stages of growth, with little or no discernible pattern. On the other hand, the more derived cyamodontoids tend to have fewer replacement teeth growing at any one time, replacing teeth unilaterally and/or in functional units, thus maintaining at least one functional crushing area at all times. The highly derived placochelyids have fewer teeth and, as a result, only have one or two replacement teeth in the upper jaw. This supports previous suggestions that these taxa had an alternative diet to other placodonts. Importantly, all specimens show at least one replacement tooth growing at the most posterior palatine tooth plates, indicating increased wear at this point and thus the most efficient functional crushing area.
Treatment of Radial Artery Occlusions Using Balloon Angioplasty and Localized Intra‐Arterial Abciximab
Authors: JARADAT ZIAD , BASIR BABAR , REVTYAK GEORGE 
Published: February 2014

ObjectivesTo study an alternative strategy for the treatment of radial artery occlusion (RAO) using balloon angioplasty and intrathrombus administration of abciximab.BackgroundRAO is a well‐described complication of transradial procedures. The optimal method to restore the patency of the radial artery following its occlusion remains unclear. Spontaneous recanalization can occur in some patients and systemic anticoagulation can be recommended but is often unsuccessful.MethodsA retrospective review of all patients in our database from 2009 to 2013 with RAO who underwent treatment with balloon angioplasty and intra‐arterial abciximab administered directly at the site of occlusion.ResultsFour patients with symptomatic RAO following transradial catheterization were treated with balloon angioplasty and a 90‐second intrathrombus infusion of abciximab. All procedures were successful and patency was documented the following day with duplex sonography and again at follow‐up (mean 189 days). The patients also remained free of symptoms at follow‐up. The fifth patient was treated with balloon angioplasty alone. This patient suffered symptomatic reocclusion of the radial artery.ConclusionsBalloon angioplasty and intrathrombus administration of abciximab via a catheter appears to be a safe, effective, and durable technique for reestablishing the patency of an occluded radial artery following transradial catheterization. Larger studies are needed to confirm our findings and establish the role for this technique in an algorithm for treatment of RAO. (J Interven Cardiol 2014;27:217–222)
The efficacy and safety of levetiracetam in paediatric patients treated with chemotherapeutic agents for haematologic disorders
Authors: Bayram Erhan , Topcu Yasemin , Tufekci Ozlem , Karaoglu Pakize , Yis Uluc , Oren Hale , Kurul Semra Hiz 
Published: February 2014

AimWe aimed to describe the efficacy and safety of levetiracetam in paediatric patients receiving chemotherapy for haematologic disorders.MethodsChildren with haematologic disorders who were receiving chemotherapy agents and developed seizure during treatment and treated with levetiracetam were included in the study. The clinical data of the patients were retrospectively evaluated. Primary haematologic diagnosis, chemotherapeutic agents, age at first seizure, seizure type, interictal electroencephalography findings, magnetic resonance imaging findings, response to the levetiracetam treatment, dose of levetiracetam, levetiracetam side effects and treatment period were recorded.ResultsTen patients with a mean age 12.4 ± 2.96 years were included in the study. Possible triggering factors for seizures were chemotherapeutic agents in 60% (n = 6), posterior reversible encephalopathy syndrome in 20% (n = 2) and central nervous system involvement of the primary disease in 20% (n = 2). Nine patients received levetiracetam monotherapy, and one patient received levetiracetam that was added on oxcarbazepine due to the intractable seizures. The mean duration of antiepileptic treatment that overlapped with chemotherapy was 7.3 ± 3.5 months. Nine patients (90%) were seizure free after levetiracetam monotherapy, and one patient (10%) had ≥50% seizure reduction after levetiracetam who was previously treated with oxcarbazepine. No side effects were observed for levetiracetam during treatment.ConclusionLevetiracetam treatment is safe and effective to prevent seizures in children receiving chemotherapy for haematologic disorders.
Pigment epithelium-derived factor as a natural matrix metalloproteinase inhibitor: a comparison with classical matrix metalloproteinase inhibitors used for cancer treatment
Authors: Alcantara Marice B , Dass Crispin R 
Published: February 2014

Abstract

Objectives
In the 1990s, the discovery of the important role of matrix metalloproteinases (MMPs) in cancer angiogenesis, growth and metastasis galvanised research efforts to search for ways to inhibit these MMPs. To date, this has resulted in the investigation of approximately 50 MMPIs which have undergone various phases of clinical trials. However, despite a large body of research being devoted to discovery and development of MMPIs, results have largely not been supportive of this approach to anticancer treatment.

Key findings
The reasons for the general failure of these drugs in clinical trials include various unwanted side-effects, the use of healthy volunteers to provide drug dosages which did not correctly reflect dosages for cancer patients, and the exclusion of patients with early stage cancer in clinical trials despite MMPs being determined to be critical for the angiogenic switch, a process associated with early tumour growth. In contrast, a naturally-occurring endogenous protein and a non-functional serine protease inhibitor (serpin), pigment epithelium-derived factor (PEDF), has been proposed for cancer therapy partly due to its ability to regulate specific MMPs central to cancer progression.

Summary
PEDF has been found to specifically downregulate membrane-type I matrix metalloproteinase (MT1-MMP) and furthermore, potentially matrix metalloproteinase-2 (MMP-2), two of the most commonly implicated MMPs in neoplasia.
Preparation, characteristic and pharmacological study on inclusion complex of sulfobutylether-β-cyclodextrin with glaucocalyxin A
Authors: Ren Lili , Jing Jianghui , Chen Guoguang , Miao Yanfei , Wei Ping 
Published: February 2014

Abstract

Objectives
The objective of this study was to improve the water solubility and solubility of glaucocalyxin A (GLA) by producing its inclusion complex with sulfobutylether-β-cyclodextrin (SBE-β-CD).

Methods
The formation of its 1 : 1 complex with SBE-β-CD in solution was confirmed by phase-solution and spectral-shift studies. The interaction of GLA and SBE-β-CD was examined by differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy and ultraviolet-visible spectroscopy to determine the formation of the GLA–SBE-β-CD inclusion complex.

Key findings
The solubilities of GLA and its complexes were 2.38 × 102 and 1.82 × 104 μg/ml, respectively, and the values of the inclusion complexes were significantly improved by 76-fold compared with the solubility of free GLA. Moreover, a higher area under the curve0–∞ after inclusion technique was observed in the pharmacokinetics study.

Conclusions
The aforementioned results indicate that GLA–SBE-β-CD could be useful with a better solubility and sustained function in drug delivery.
Effects of topical indomethacin, bromfenac and nepafenac on lipopolysaccharide-induced ocular inflammation
Authors: Bucolo Claudio , Marrazzo Giuseppina , Platania Chiara Bianca Maria , Romano Giovanni Luca , Drago Filippo , Salomone Salvatore 
Published: February 2014

Abstract

Objectives
To evaluate the effects of topical non-steroidal anti-inflammatory drugs (NSAIDs) on retinal vascular leakage, and inflammatory markers in endotoxin-induced uveitis (EIU) in rats.

Methods
EIU was induced in rats by lipopolysaccharide (LPS). Topical 0.5% indomethacin, 0.09% bromfenac and 0.1% nepafenac were given before and after LPS. Twenty-four hours after LPS, the animals were euthanized and plasma along with retina were collected to assess prostaglandin-E2 (PGE2) and C-reactive protein (CRP) levels using enzyme-linked immunosorbent assay. Retinal vascular leakage was assessed by Evans blue. Molecular modelling was used to evaluate interaction of compounds with cyclooxygenase-2 (COX-2).

Key findings
All NSAIDs tested significantly prevented PGE2 production with higher effect of indomethacin and bromfenac in comparison with nepafenac. The three drugs did not affect plasma CRP levels. The analysis of retinal vascular leakage revealed a significant (P &lt; 0.01) decrease after treatment with indomethacin, but no significant changes were observed after treatment with bromfenac and nepafenac. Indomethacin had a different interaction with COX-2 in comparison with bromfenac and amfenac (active metabolite of nepafenac).

Conclusions
Topical treatment with indomethacin, bromfenac and nepafenac has significant anti-inflammatory effects. However, only indomethacin was able to prevent retinal vascular leakage in LPS-injected rats, likely due to the distinctive molecular mechanism.
Sexual Health Discussions with Older Adult Patients During Periodic Health Exams
Authors: Ports Katie A. , Barnack-Tavlaris Jessica L. , Syme Maggie L. , Perera Robert A. , Lafata Jennifer Elston 
Published: February 2014

Abstract

Introduction
Sexual health is an integral part of overall health across the lifespan. In order to address sexual health issues, such as sexually transmitted infections (STIs) and sexual functioning, the sexual history of adult patients should be incorporated as a routine part of the medical history throughout life. Physicians and health-care professionals cite many barriers to attending to and assessing the sexual health needs of older adult patients, underscoring the importance of additional research to improve sexual history taking among older patients.

Aim
The purpose of this article is to explore the content and context of physician–patient sexual health discussions during periodic health exams (PHEs) with adults aged 50–80 years.

Methods
Patients completed a pre-visit telephone survey and attended a scheduled PHE with their permission to audio-record the exam. Transcribed audio recordings of 483 PHEs were analyzed according to the principles of qualitative content analysis.

Main Outcome Measures
Frequency of sexual history taking components as observed in transcripts of PHEs. Physician characteristics were obtained from health system records and patient characteristics were obtained from the pre-visit survey.

Results
Analyses revealed that approximately one-half of the PHEs included some discussion about sexual health, with the majority of those conversations initiated by physicians. A two-level logistic regression model revealed that patient–physician gender concordance, race discordance, and increasing physician age were significantly associated with sexual health discussions.

Conclusion
Interventions should focus on increasing physician self-efficacy for assessing sexual health in gender discordant and race/ethnicity concordant patient interactions. Interventions for older adults should increase education about sexual health and sexual risk behaviors, as well as empower individuals to seek information from their health-care providers.
Powerful Relaxation of Phosphodiesterase Type 4 Inhibitor Rolipram in the Pig and Human Bladder Neck
Authors: Ribeiro Ana S.F. , Fernandes Vítor S. , Martínez-Sáenz Ana , Martínez Pilar , Barahona María Victoria , Orensanz Luis M. , Blaha Igor , Serrano-Margüello Daniel , Bustamante Salvador , Carballido Joaquín , García-Sacristán Albino , Prieto Dolores , Hernández Medardo 
Published: February 2014

Abstract

Introduction
Phosphodiesterase type 5 (PDE5) inhibitors act as effective drugs for the treatment of lower urinary tract symptom (LUTS). There is a poor information, however, about the role of the PDE4 inhibitors on the bladder outflow region contractility.

Aim
To investigate PDE4 expression and the relaxation induced by the PDE4 inhibitor rolipram versus that induced by the PDE5 blockers sildenafil and vardenafil, in the pig and human bladder neck.

Methods
Immunohistochemistry for PDE4 expression, myographs for isometric force recordings and fura-2 fluorescence for simultaneous measurements of intracellular Ca2+ concentration ([Ca2+]i) and tension for rolipram in bladder neck samples were used.

Main Outcome Measures
PDE4 expression and relaxations to PDE4 and PDE5 inhibitors and simultaneous measurements of [Ca2+]i and tension.

Results
PDE4 expression was observed widely distributed in the smooth muscle layer of the pig and human bladder neck. On urothelium-denuded phenylephrine (PhE)-precontracted strips of pig and human, rolipram, sildenafil and vardenafil produced concentration-dependent relaxations with the following order of potency: rolipram&gt; &gt; sildenafil&gt;vardenafil. In pig, the adenylyl cyclase activator forskolin potentiated rolipram-elicited relaxation, whereas protein kinase A (PKA) blockade reduced such effect. On potassium-enriched physiological saline solution (KPSS)-precontracted strips, rolipram evoked a lower relaxation than that obtained on PhE-stimulated preparations. Inhibition of large (BKCa) and intermediate (IKCa) conductance Ca2+-activated K+ channels, neuronal voltage-gated Ca2+ channels, nitric oxide (NO) and hydrogen sulfide (H2S) synthases reduced rolipram responses. Rolipram inhibited the contractions induced by PhE without reducing the PhE-evoked [Ca2+]i increase.

Conclusions
PDE4 is present in the pig and human bladder neck smooth muscle, where rolipram exerts a much more potent relaxation than that elicited by PDE5 inhibitors. In pig, rolipram-induced response is produced through the PKA pathway involving BKCa and IKCa channel activation and [Ca2+]idesensitization-dependent mechanisms, this relaxation also being due to neuronal NO and H2S release.
Detection of Clinically Relevant Pain Relief in Cats with Degenerative Joint Disease Associated Pain
Authors: Gruen M.E. , Griffith E. , Thomson A. , Simpson W. , Lascelles B.D.X. 
Published: February 2014

BackgroundDetection of clinically relevant pain relief in cats with degenerative joint disease (DJD) is complicated by a lack of validated outcome measures and a placebo effect.Hypothesis/ObjectivesTo evaluate a novel approach for detection of pain relief in cats with DJD.AnimalsFifty‐eight client‐owned cats.MethodsProspective, double‐masked, placebo‐controlled, stratified, randomized, clinical study. Enrolled cats were 6–21 years of age, with owner‐observed mobility impairment, evidence of pain in at least 2 joints during orthopedic examination, and overlapping radiographic evidence of DJD, and underwent a 2‐week baseline period, 3‐week treatment period with placebo or meloxicam, and 3‐week masked washout period. Outcome measures were evaluated at days 0, 15, 36, and 57.ResultsBoth groups significantly improved after the treatment period (day 36) on client‐specific outcome measures (CSOM) and feline musculoskeletal pain index (FMPI) (P < .0001 for both); there was no difference between the groups on CSOM or FMPI score improvement. After the masked washout period, more cats that received meloxicam during the treatment period had a clinically relevant decrease in CSOM score (P = .048) and FMPI score (P = .021) than cats that received placebo.Conclusions and Clinical ImportanceUsing both a client‐specific and a general clinical metrology instrument, owners of cats with DJD were able to detect evident recurrence of clinical signs after withdrawal of active medication than after withdrawal of placebo, and that this study design might be a novel and useful way to circumvent the placebo effect and detect the efficacy of pain‐relieving medications.
Comparison of Carboplatin and Doxorubicin‐Based Chemotherapy Protocols in 470 Dogs after Amputation for Treatment of Appendicular Osteosarcoma
Authors: Selmic L.E. , Burton J.H. , Thamm D.H. , Withrow S.J. , Lana S.E. 
Published: February 2014

BackgroundMany chemotherapy protocols have been reported for treatment of canine appendicular osteosarcoma (OSA), but outcome comparisons in a single population are lacking.ObjectiveTo evaluate the effects of protocol and dose intensity (DI) on treatment outcomes for carboplatin and doxorubicin‐based chemotherapy protocols.AnimalsFour hundred and seventy dogs with appendicularOSA.MethodsA retrospective cohort study was performed comprising consecutive dogs treated (1997–2012) with amputation followed by 1 of 5 chemotherapy protocols: carboplatin 300 mg/m2IVq21d for 4 or 6 cycles (CARBO6), doxorubicin 30 mg/m2IVq14d or q21d for 5 cycles, and alternating carboplatin 300 mg/m2IVand doxorubicin 30 mg/m2IVq21d for 3 cycles. Adverse events (AE) andDIwere evaluated. Kaplan–Meier survival curves and Cox proportional hazards regression were used to compare disease‐free interval (DFI) and survival time (ST) among protocols.ResultsThe overall medianDFIandSTwere 291 days and 284 days, respectively. A lower proportion of dogs prescribedCARBO6 experiencedAEs compared to other protocols (48.4% versus 60.8–75.8%;P = .001).DIwas not associated with development of metastases or death. After adjustment for baseline characteristics and prognostic factors, none of the protocols provided a significant reduction in risk of development of metastases or death.Conclusions and Clinical ImportanceAlthough choice of protocol did not result in significant differences inDFIorST, theCARBO6 protocol resulted in a lower proportion of dogs experiencingAEs, which could be advantageous in maintaining high quality of life during treatment.DIwas not a prognostic indicator in this study.