bluuebunny/crossref_metadata_2025 huggingface dataset:
Vacuum‐assisted closure improves the incorporation of artificial dermis in soft tissue defects: Terudermis® and Pelnac®
Authors: Eo SuRak , Kim YoongSoo , Cho SangHun
Published: February 2011

As a dermal scaffold, artificial dermal substitutes allow the body to accomplish its own tissue regeneration through infiltration of cells and neovascularisation. However, they show not only rather lower take rates compared to autologous skin grafts alone, but they also require more time for sufficient vascular ingrowth to overlay the skin graft. To accelerate this overlaying, we applied vacuum‐assisted closure negative‐pressure settings over the artificial dermis: Terudermis® and Pelnac® grafts. Fourteen patients with complex tissue defects were treated, including bone exposure in two cases, tendon exposure in seven cases and soft tissue defects in five cases. Nine cases had combined wound infections. The time interval between the first artificial dermis graft and the second split‐thickness skin graft over it was 7·64 days on average. Dermal substitutes took place completely in all cases and there were no graft failures.
Update in Testosterone Therapy for Men (CME)
Authors: Corona Giovanni , Rastrelli Giulia , Forti Gianni , Maggi Mario
Published: February 2011

Introduction

Male hypogonadism is a condition characterized by inadequate testicular production of sex steroids and sperms; however, the term is more commonly used to identify testosterone (T) deficiency. When fertility is not desired, T replacement therapy (TRT) is the gold standard.

Aim

To review the pathogenesis of male hypogonadism and the available preparations for TRT, along with the main clinical outcomes.

Methods

A systematic search of published evidence was performed using Medline (1969 to September 2010). Data from a consecutive series of subjects attending our Andrology Unit were also provided to stress the clinical correlates of low T. Inventories available for detecting hypogonadism (including ANDROTEST) were overviewed.

Main Outcome Measures

The most important studies regarding the pathogenesis of male hypogonadism and the preparations for its treatment were reviewed. To review TRT outcomes, only meta-analytic studies were considered.

Results

The goals of TRT are to alleviate clinical symptoms and to restore serum T levels to the mid-normal range, without significant side effects or safety concerns. Different T formulations have been approved. TRT is associated with a reduction of fat mass, an increase of lean mass, and a possible positive effect on lipid profile and glycometabolic control. Bone density and depressive symptoms are improved by TRT, while effects on cardiovascular risk and frailty are more controversial. No increase of prostate cancer and prostate-related problems has been reported so far. TRT, alone or in combination with phosphodiesterase type 5 inhibitors, is considered the first-line therapy in hypogonadal subjects with erectile dysfunction.

Conclusions

T deficiency is highly prevalent in the aging male and represents a sign of physical and sexual frailty. The significance of low T in elderly men has yet to be completely clarified. Large, prospective intervention trials will help solve this dilemma.
Antibiotic Patterns with Inflatable Penile Prosthesis Insertion
Authors: Wosnitzer Matthew S. , Greenfield Jason M.
Published: February 2011

Introduction

A clear set of guidelines has not been defined in the use of antibiotics in penile prosthesis implantation.

Aim

We surveyed urologists throughout the United States to determine current practice patterns regarding antibiotic use in primary and revision penile prosthesis surgery.

Methods

Fifty-two Sexual Medicine Society of North America (SMS) member urologist and 164 non-SMS member urologist responses were obtained.

Main Outcome Measures

The survey contained 10 questions regarding antibiotic selection for primary and revision inflatable penile prosthesis (IPP) implantation.

Results

One hundred percent of responders in both groups utilize intraoperative antibiotics, most commonly vancomycin and gentamicin in both groups. Of SMS members, 94% prescribed postoperative home oral antibiotics in contrast to 88% of non-SMS members (P =0.3). Among SMS members, the most common antibiotic prescribed postoperatively was levofloxacin 500 mg daily while among non-SMS members, the most common antibiotic postoperatively was cephalexin 500 mg 2–4 times daily. Of SMS members, antibiotic irrigation intraoperatively occurred with 100% and with 92% of non-SMS members (P =0.04). Thirty-seven percent SMS physicians and 15% non-SMS physicians made modifications of intraoperative and postoperative antibiotics for high-risk patients (P =0.001). In the circumstance of revision of a clinically noninfected IPP, 23% SMS and 16% non-SMS member physicians utilized additional antibiotics/treatment (P =0.3). Sixteen of those surveyed admitted that they had been approached by their institution about their antibiotic use and asked to change. In the past 5 years, 29% surveyed have changed their practice patterns in antibiotic use.

Conclusions

There is significant difference between practice patterns of SMS and non-SMS urologists in terms of antibiotic irrigation usage, modifications for high-risk patients, and consensus about the importance of antibiotic use with Coloplast Titan implant (Coloplast, Minneapolis, MN, USA). A significant lack of uniformity exists among urologists performing prosthetic surgery with regard to antibiotic protocols. A standard set of guidelines may prove useful to implanters.
Gamma-ray sources like V407 Cygni in symbiotic stars
Authors: Lü Guoliang , Zhu Chunhua , Wang Zhaojun , Huo Wensheng , Yang Yuangui
Published: February 2011

Using a simple accelerating model and an assumption that γ-rays originate from p–p collisions for a π0 model, we investigate γ-ray sources like V407 Cygni in symbiotic stars. The upper limit of their occurrence rate in the Galaxy is between 0.5 and 5 yr−1, indicating that they may be important sources of high-energy γ-rays. The maximum energies of the accelerated protons mainly distribute around 1011eV, and barely reach 1015eV. The novae occurring in D-type SSs with ONe white dwarfs and long orbital periods are good candidates for γ-ray sources. Due to a short orbital period which results in a short acceleration duration, the nova occurring in symbiotic star RS Oph cannot produce γ-ray emission like that in V407 Cygni.
Hyperfine excitation of CN by He
Authors: Lique F. , Kłos J.
Published: February 2011

Modelling of molecular emission spectra from interstellar clouds requires the calculation of rates for excitation by collisions with the most-abundant species. We calculate hyperfine structure resolved excitation rate coefficients of the cyano radical (CN) by He. State-to-state rate coefficients between the 37 lowest hyperfine levels of CN were calculated for low temperatures in the range 5–30 K. The new rate coefficients will help significantly in the interpretation of the CN emission lines observed with current and future telescopes, and enable this molecule to become a powerful astrophysical tool.
Sea Water Intrusion by Sea‐Level Rise: Scenarios for the 21st Century
Authors: Loáiciga Hugo A. , Pingel Thomas J. , Garcia Elizabeth S.
Published: February 2011

This study presents a method to assess the contributions of 21st‐century sea‐level rise and groundwater extraction to sea water intrusion in coastal aquifers. Sea water intrusion is represented by the landward advance of the 10,000 mg/L iso‐salinity line, a concentration of dissolved salts that renders groundwater unsuitable for human use. A mathematical formulation of the resolution of sea water intrusion among its causes was quantified via numerical simulation under scenarios of change in groundwater extraction and sea‐level rise in the 21st century. The developed method is illustrated with simulations of sea water intrusion in the Seaside Area sub‐basin near the City of Monterey, California (USA), where predictions of mean sea‐level rise through the early 21st century range from 0.10 to 0.90 m due to increasing global mean surface temperature. The modeling simulation was carried out with a state‐of‐the‐art numerical model that accounts for the effects of salinity on groundwater density and can approximate hydrostratigraphic geometry closely. Simulations of sea water intrusion corresponding to various combinations of groundwater extraction and sea‐level rise established that groundwater extraction is the predominant driver of sea water intrusion in the study aquifer. The method presented in this work is applicable to coastal aquifers under a variety of other scenarios of change not considered in this work. For example, one could resolve what changes in groundwater extraction and/or sea level would cause specified levels of groundwater salinization at strategic locations and times.
MODFLOW‐Style Parameters in Underdetermined Parameter Estimation
Authors: D'Oria Marco , Fienen Michael N.
Published: February 2011

In this article, we discuss the use of MODFLOW‐Style parameters in the numerical codes MODFLOW_2005 and MODFLOW_2005‐Adjoint for the definition of variables in the Layer Property Flow package. Parameters are a useful tool to represent aquifer properties in both codes and are the only option available in the adjoint version. Moreover, for overdetermined parameter estimation problems, the parameter approach for model input can make data input easier. We found that if each estimable parameter is defined by one parameter, the codes require a large computational effort and substantial gains in efficiency are achieved by removing logical comparison of character strings that represent the names and types of the parameters. An alternative formulation already available in the current implementation of the code can also alleviate the efficiency degradation due to character comparisons in the special case of distributed parameters defined through multiplication matrices. The authors also hope that lessons learned in analyzing the performance of the MODFLOW family codes will be enlightening to developers of other Fortran implementations of numerical codes.
Temporal Scaling of Groundwater Level Fluctuations Near a Stream
Authors: Schilling Keith E. , Zhang You‐Kuan
Published: February 2011

Temporal scaling in stream discharge and hydraulic heads in riparian wells was evaluated to determine the feasibility of using spectral analysis to identify potential surface and groundwater interaction. In floodplains where groundwater levels respond rapidly to precipitation recharge, potential interaction is established if the hydraulic head (h) spectrum of riparian groundwater has a power spectral density similar to stream discharge (Q), exhibiting a characteristic breakpoint between high and low frequencies. At a field site in Walnut Creek watershed in central Iowa, spectral analysis of h in wells located 1 m from the channel edge showed a breakpoint in scaling very similar to the spectrum of Q (∼20 h), whereas h in wells located 20 and 40 m from the channel showed temporal scaling from 1 to 10,000 h without a well‐defined breakpoint. The spectral exponent (β) in the riparian zone decreased systematically from the channel into the floodplain as groundwater levels were increasingly dominated by white noise groundwater recharge. The scaling pattern of hydraulic head was not affected by land cover type, although the number of analyses was limited and site conditions were variable among sites. Spectral analysis would not replace quantitative tracer or modeling studies, but the method may provide a simple means of confirming potential interaction at some sites.
Simplified Molecular Input‐Line Entry System and International Chemical Identifier in the QSAR Analysis of Styrylquinoline Derivatives as HIV‐1 Integrase Inhibitors
Authors: Toropova Alla P. , Toropov Andrey A. , Benfenati Emilio , Gini Giuseppina
Published: February 2011

The simplified molecular input‐line entry system (SMILES) and IUPAC International Chemical Identifier (InChI) were examined as representations of the molecular structure for quantitative structure–activity relationships (QSAR), which can be used to predict the inhibitory activity of styrylquinoline derivatives against the human immunodeficiency virus type 1 (HIV‐1). Optimal SMILES‐based descriptors give a best model with n = 26, r2 = 0.6330, q2 = 0.5812, s = 0.502, F = 41 for the training set and n = 10, r2 = 0.7493,  = 0.6235,  = 0.537, s = 0.541, F = 24 for the validation set. Optimal InChI‐based descriptors give a best model with n = 26, r2 = 0.8673, q2 = 0.8456, s = 0.302, F = 157 for the training set and n = 10, r2 = 0.8562,  = 0.7715,  = 0.819, s = 0.329, F = 48 for the validation set. Thus, the InChI‐based model is preferable. The described SMILES‐based and InChI‐based approaches have been checked with five random splits into the training and test sets.
CoMSIA Study on Substituted Aryl Alkanoic Acid Analogs as GPR40 Agonists
Authors: Bhatt Aaditya , Patel Pallav D. , Patel Maulik R. , Singh Satyakam , Lau‐Cam Cesar A. , Talele Tanaji T.
Published: February 2011

GPR40, a G‐protein‐coupled receptor has been well established to play a crucial role in regulating blood glucose levels. Hence, GPR40 is a potential target for future antidiabetic agents. The present 3D QSAR study is aimed at delineating structural parameters governing GPR40 agonistic activity. To meet this objective, a comparative molecular similarity indices analysis for 63 different GPR40 agonists was performed using two methods; a ligand‐based 3D QSAR model employing the atom fit alignment method and a receptor‐based 3D QSAR model that was derived from the predicted binding conformations obtained by docking all the GPR40 agonists at the active site of GPR40. The results of these studies showed the ligand‐based model to be superior ( value of 0.610) to the receptor‐based model ( value of 0.519) in terms of statistical data. The predictive ability of these models was evaluated using a test set of 15 compounds not included in the preliminary training set of 48 compounds. The predictive r2 values for the ligand‐ and the receptor‐based models were found to be 0.863 and 0.599, respectively. Further, interpretation of the comparative molecular similarity indices analysis contour maps with reference to the active site of GPR40 provided an insight into GPR40‐agonist interactions.
Comparison of the Non‐Nucleoside Reverse Transcriptase Inhibitor Lersivirine with its Pyrazole and Imidazole Isomers
Authors: Jones Lyn H. , Allan Gill , Corbau Romuald , Middleton Donald S. , Mowbray Charles E. , Newman Sandra D. , Phillips Chris , Webster Rob , Westby Mike
Published: February 2011

Lersivirine is a potent non‐nucleoside reverse transcriptase inhibitor with exceptional mutant resilience. Here, we compare the pharmacological and pharmacokinetic profile of lersivirine with its pyrazole and imidazole isomers and briefly explore the profile of these series. This work establishes lersivirine as the outstanding molecule in this set.
Changes in spatial and temporal distribution and vocal behavior of Blainville's beaked whales (Mesoplodon densirostris) during multiship exercises with mid‐frequency sonar
Authors: McCarthy Elena , Moretti David , Thomas Len , DiMarzio Nancy , Morrissey Ronald , Jarvis Susan , Ward Jessica , Izzi Annamaria , Dilley Ashley
Published: February 2011

Abstract

The number and distribution of vocalizing groups of Blainville's beaked whales (Mesoplodon densirostris) were analyzed before, during, and after multiship mid‐frequency active sonar operations at the US Navy's Atlantic Undersea Test and Evaluation Center (AUTEC) in the Bahamas. Groups of foraging animals were isolated by detecting their echolocation clicks using an array of bottom‐mounted hydrophones. Two data sets were evaluated consisting of 115 and 240 h of acoustic data in May 2007 and 2008, respectively. Vocal activity was observed to decline during active sonar exercises and increase upon cessation of sonar transmissions in both data sets. Vocal activity did not recover to preexposure levels in the postexposure time period in 2007 nor in the initial postexposure period in the 2008 data set. Clicks detected during sonar operations were generally found to be on the periphery of the hydrophone field and vocal durations declined for those groups that remained on the range in that time period. Receive levels were calculated for several vocal groups of whales and indicated that animals continued to forage when exposed to sonar at levels as high as 157 dB re: μPa.
Respiratory hygiene practices by the public during the 2009 influenza pandemic: an observational study
Authors: Barry Tasmin , Manning Stephanie , Lee Mei S. , Eggleton Russell , Hampton Simon , Kaur Jasveen , Baker Michael G. , Wilson Nick
Published: February 2011

Please cite this paper as: Barry et al. (2011) Respiratory hygiene practices by the public during the 2009 influenza pandemic: an observational study. Influenza and Other Respiratory Viruses 5(5), 317–320.

Aims  To describe the public use of respiratory hygiene behaviours during the 2009 influenza pandemic and to test the feasibility of an observational method.

Methods  Respiratory behaviour was systematically observed at three public settings during August 2009 in the capital city of New Zealand (Wellington). Data on each coughing or sneezing event were collected.

Results  A total of 384 respiratory events were observed, at a rate of 0·8 cough/sneeze per observed‐person‐hour. Around a quarter of respiratory events (27·3%) were uncovered, and there was infrequent use of the responses recommended by health authorities (i.e., covering with a tissue or handkerchief at 3·4% and covering with elbow or arm at 1·3%). Respiratory event rates were higher in all settings that were ‘high flow’ (for people movement) compared to ‘low flow’ settings. Uncovered events were more common among people at the hospital entrance versus the hospital café [risk ratio (RR) = 7·8, 95% confidence interval (CI): 1·1–52·6] and when a person was located within 1 m of others (RR = 1·5, 95% CI: 1·1–1·9).

Observing respiratory hygiene was found to be feasible in all of the selected public locations. There was good agreement between observing pairs about whether or not respiratory events occurred (inter‐observer correlation = 0·81) and for uncovered versus covered events (total Cohen’s kappa score = 0·70).

Conclusions  It was feasible to document respiratory hygiene behaviour in public urban settings during a influenza pandemic. Respiratory hygiene advice was not being adequately followed by this population towards the end of the first wave of the pandemic.
Coordination Assembly and Characterization of Red‐Emitting Europium (III) Organic/Inorganic Polymeric Hybrids
Authors: Li Ying , Chian Wei , Wang Xia , Sha Wentian , Zhang Yiwen , Jiang Wenkai
Published: February 2011

Novel luminescent ternary organic–inorganic–polymeric hybrid material has been assembled by Eu3+ complex incorporating into poly (methyl methacrylate) (PMMA) matrix. The functionalized silylated precursor PDC‐Si derived from PDC (2,6‐pyridinedicarboxylic acid chloride) behaves as the coordination units of Eu3+ ion. The organic polymer was introduced into the system by directly dissolving PMMA in solution of Eu(PDC‐Si)3 complex and N‐N‐Dimethyl Formamide (DMF) with subsequent addition of tetraethoxysilane to promote hydrolysis and condensation. The structure and photophysical properties of the resulting hybrids are characterized by Fourier transform infrared spectra, X‐ray diffraction (XRD), scanning electronic microscopy and photoluminescence spectra. The luminescence quantum yield was calculated based on the emission spectra and luminescence lifetimes. XRD reveals its amorphous structure. Efficient energy transfer process occurs between PMMA and Eu3+, and replacement of water molecule by PMMA in the first coordination sphere was confirmed by comparing with the binary hybrid.
Successful Combined Therapy with Tamoxifen and Lithium in a Paradoxical Sleep Deprivation‐Induced Mania Model
Authors: Armani Fernanda , Andersen Monica L. , Andreatini Roberto , Frussa‐Filho Roberto , Tufik Sergio , Fernandes Galduróz José Carlos
Published: February 2011

Background: Previous studies have suggested that manic states and sleep deprivation could contribute to the pathophysiology of bipolar disorder (BD) through protein kinase C (PKC) signaling abnormalities. Moreover, adjunctive therapy has become a standard strategy in the management of BD patients who respond poorly to current pharmacological treatments. Aim: Thus, the aim of this study was to investigate the possible involvement of PKC inhibition by tamoxifen both separately or in combination with lithium, in paradoxical sleep deprivation (PSD)‐induced hyperactivity, one facet of mania‐like behavior. Materials & Methods: Adult male C57BL/6J mice were randomly distributed (n = 7/group) in 24‐h PSD or control groups and injected intraperitoneally (i.p.) with vehicle, lithium (50, 100, or 150 mg/kg) or tamoxifen (0.5, 1.0, or 2.0 mg/kg – experiment 1). In a second experiment, mice were injected i.p. with vehicle or a combination of subeffective doses of lithium and tamoxifen. Animals were subjected to a protocol based on repetitive PSD conditions, followed by assessment of locomotion activity in the open‐field task. Results: PSD significantly increased locomotor activity in both experiments. These behavioral changes were prevented by a treatment with lithium or tamoxifen, or a combined treatment with both lithium and tamoxifen. Discussion: Therefore, our findings suggest that lithium and tamoxifen exert reversal effects against PSD‐induced hyperactivity in mice. Conclusion: Furthermore, tamoxifen as an adjunct to lithium therapy provides support for an alternative treatment of individuals who either do not respond adequately or cannot tolerate the adverse effects associated with therapeutic doses of lithium.
Muscarinic Receptors: Their Roles in Disorders of the Central Nervous System and Potential as Therapeutic Targets
Authors: Scarr Elizabeth
Published: February 2011

Phylogenetically, acetylcholine is an ancient neurochemical. Therefore, it is not surprising that cholinergic neurons project extensively throughout the central nervous system, innervating a wide range of structures within the brain. In fact, acetylcholine is involved in processes that underpin some of our most basic central functions. Both muscarinic and nicotinic receptor families, which mediate cholinergic transmission, have been implicated in the pathophysiology of psychiatric and neurological disorders. The question that remains to be definitively answered is whether or not these receptors are viable targets for the development of future therapeutic agents.
MicroRNA, epigenetic machinery and lung cancer
Authors: Kumar Rajeev , Xi Yaguang
Published: February 2011

Lung cancer is the leading cause of cancer deaths worldwide and over 80% of lung cancer patients are classified as having non‐small cell lung cancer. Although there have been technological advancements in the early detection and standard treatment of lung cancer, it is often diagnosed at an advanced stage and is chemoresistant to most available drugs. A number of studies have demonstrated that microRNA is able to modulate various tumorigenic processes, including progression and metastasis, in various mechanisms. In this review we examine the most recent achievements in microRNA and lung cancer treatment and summarize the research progress on the reciprocal regulation between microRNA and epigenetic modifications, as both have been intensively studied in lung cancer. Epigenetic modifications on the human genome regulate gene and microRNA expression at the transcriptional level; inversely, microRNA can also transcriptionally cleave and/or translationally repress the expression of several key enzymes involved in epigenetic processes such as DNA methylation and histone modification. Better understanding of reciprocal regulation between microRNA and epigenetic modifications will underlie the development of novel microRNA orientated diagnostic and therapeutic strategies relating to lung cancer in the near future.
Morphometric analysis of conformational changes in hepatic venous system after right lobe living donor liver transplantation
Authors: Takahashi Masanori , Fukumoto Takumi , Kido Masahiro , Tsuchida Shinobu , Takebe Atsushi , Kuramitsu Kaori , Komatsu Shohei , Yamada Isamu , Hori Yuichi , Ku Yonson
Published: February 2011

Aim:  After living donor liver transplantation (LDLT), the graft liver regenerates to the standard liver volume. However, little is known about the influence of this phenomenon on the hepatic venous system.

Methods:  Fourteen right lobe LDLT without the middle hepatic vein were included in this study. Computed tomography before and 1 month after LDLT was performed to measure the inflow angle of the right hepatic vein (RHV), the aspect ratio of the inferior vena cava (IVC), the coordinate position of IVC and diameter of RHV. In addition, the regeneration index (RI) was determined on each liver segment.

Results:  RHV showed a clockwise rotation at early postoperative months, the average increase of the inflow angle being 14.5 ± 15.6 (mean ± standard deviation) degrees. IVC was shifted from right to left with a deformity to a long oval shape on horizontal sections. The center of IVC moved dorsally at an average of 0.55 ± 0.77 cm and leftward at an average of 0.82 ± 0.89 cm. Diameter of RHV decreased at an average of 0.65 ± 0.39 cm at its root. The extent of liver regeneration was more prominent in the posterior segment as compared to the anterior segment, the average RI values being 1.65 ± 0.65 and 1.17 ± 0.44, respectively (P < 0.05). Hepatic vein outflow block (HVOB) was encountered in two patients with a marked conformational deformity observed in the hepatic venous system at early postoperative months after LDLT.

Conclusion:  After right lobe LDLT, the hepatic venous system exhibits a profound conformational change, which most likely plays a role in the onset of HVOB.
Higher discontinuation and lower survival rates are likely in elderly Japanese patients with advanced hepatocellular carcinoma receiving sorafenib
Authors: Morimoto Manabu , Numata Kazushi , Kondo Masaaki , Hidaka Hisashi , Takada Juichi , Shibuya Akitaka , Kobayashi Satoshi , Ohkawa Shinichi , Okuse Chiaki , Morita Satoshi , Taguri Masataka , Tanaka Katsuaki
Published: February 2011

Aim:  Sorafenib is approved for the treatment of advanced hepatocellular carcinoma (HCC) in Japan; however, its tolerability and efficacy in elderly patients with HCC have not been clarified. We aimed to evaluate the tolerability and efficacy of sorafenib with increasing age.

Methods:  As part of a retrospective, multicenter cohort study conducted between May 2009 and February 2010, patients with advanced HCC received 400 mg sorafenib twice daily (standard dosage) or once daily (half‐dosage) until disease progression or treatment intolerance.

Results:  The mean age of the enrolled patients (n = 76) was 70.3 years, and 24 of them were ≥75 years old. The prognostic factors for survival were age < 75 years, performance status score zero, α‐fetoprotein level < 1000 ng/mL, des‐gamma‐carboxy prothrombin level < 1000 ng/mL, and treatment duration ≥ 1 month. The median treatment duration and overall incidence of adverse drug reactions (ADRs) were not statistically different with increasing age. However, subgroup analysis revealed that treatment discontinuation because of ADRs was more frequent among the ≥75‐year‐old patients (41.7%) than among the <75‐year‐old ones (15.0%) with the standard dosage (P = 0.047); this trend was not observed among those who received the half‐dose regimen.

Conclusions:  Sorafenib has modest efficacy and acceptable toxicity in younger (<75 years) patients with HCC; however, elderly patients experience some side effects when it is administered at the standard dosage.
Urinary bile acid sulfate levels in patients with primary biliary cirrhosis
Authors: Miura Ryo , Tanaka Atsushi , Takikawa Hajime
Published: February 2011

Aim:  Urinary bile acids are mainly conjugated with sulfuric acid. In a previous work, we demonstrated that the levels of urinary sulfated bile acids (USBA) and serum total bile acids (TBA) were correlated very well and also that USBA was considered to be a more useful indicator of hepatic fibrosis than TBA in patients with hepatitis C virus (HCV)‐related liver diseases. In the current study we aimed to confirm these finding in patients with primary biliary cirrhosis (PBC), a prototypic cholestatic liver disease.

Methods:  Urinary sulfated bile acids were measured using an automatic assay kit in 50 patients with PBC, of whom 11 were diagnosed as having cirrhosis. We obtained specimens before ursodeoxycholic acid (UDCA) administration in four patients, and during UDCA in 46 patients. The correlations between USBA and various laboratory tests were studied.

Results:  The median USBA level was 67.9 µmol/g creatinine in PBC; 27.7 without cirrhosis and 210.3 with cirrhosis (P = 0.001). The number of PBC patients with elevated USBA was significantly higher than those with elevated TBA (82% vs. 56%). This significance was remarkable especially in early stages, non‐cirrhotic patients (77% vs. 49%). USBA level was well correlated with TBA (rs = 0.72), and negatively correlated with platelet (rs = −0.34) and albumin (rs = −0.31).

Conclusion:  Urinary sulfated bile acids and TBA are well correlated, and together with the findings that USBA is not affected by meals, USBA is considered to be more beneficial and convenient than TBA for earlier detection of fibrosis in PBC.
Respiratory Disease in Neonatal Cloned Calves
Authors: Brisville A.C. , Fecteau G. , Boysen S. , Dorval P. , Buczinski S. , Blondin P. , Smith L.C.
Published: February 2011

Background: Numerous clinical abnormalities occur in cloned calves during the neonatal period.

Objectives: Describe respiratory diseases affecting cloned calves.

Animals: Twenty‐five cloned Holstein calves.

Methods: Retrospective clinical study of the cloned calves born at the Veterinary Teaching Hospital, Saint‐Hyacinthe, QC.

Results: Records of 31 cloned calves were reviewed. Twenty‐five records were included. Four stillborn calves and 2 calves euthanized at birth were excluded. Twenty‐two calves suffered from respiratory diseases. Nineteen calves received intranasal oxygen treatment (INO). They were tachypneic (78 breaths per minute) and 5 of them were hypoxemic (PaO2 < 55 mmHg). Two of 19 calves remained hypoxemic despite INO. Thirteen calves were weaned from INO after a median of 70 hours and were discharged at a median of 5 days of age. Nine calves required ventilatory support: 3 from birth and 6 after INO. Five were successfully weaned from the ventilator after a median of 32 hours and were discharged at a median of 8 days of age. Three calves died and 1 was euthanized because of respiratory disease. Necropsy revealed atelectasis, pulmonary congestion, and alveolar damages.

Conclusion and Clinical Importance: Respiratory disease occurs frequently in cloned calves. The most frequent abnormality is hypoxemia because of V/Q mismatch. It is possible to successfully support these calves by INO and mechanical ventilation.
Mortality in North American Dogs from 1984 to 2004: An Investigation into Age‐, Size‐, and Breed‐Related Causes of Death
Authors: Fleming J.M. , Creevy K.E. , Promislow D.E.L.
Published: February 2011

Background: Anecdotal beliefs and limited research suggest variable patterns of mortality in age, size, and breed cohorts of dogs. Detailed knowledge of mortality patterns would facilitate development of tailored health‐maintenance practices and contribute to the understanding of the genetic basis of disease.

Hypothesis/Objectives: To describe breed‐specific causes of death in all instances of canine mortality recorded in the Veterinary Medical Database (VMDB)a between 1984 and 2004. We hypothesized that causes of death, categorized by organ system (OS) or pathophysiologic process (PP), would segregate by age, body mass, and breed.

Animals: 74,556 dogs from the VMDB for which death was the outcome of the recorded hospital visit.

Methods: Retrospective study. Causes of death from abstracted VMDB medical records were categorized by OS and PP and analyzed by age, breed, and breed‐standard mass of dog.

Results: Causes of death, categorized by OS or PP, segregated by age, breed, and breed‐standard mass. Young dogs died more commonly of gastrointestinal and infectious causes whereas older dogs died of neurologic and neoplastic causes. Increasing age was associated with an increasing risk of death because of cardiovascular, endocrine, and urogenital causes, but not because of hematopoietic or musculoskeletal causes. Dogs of larger breeds died more commonly of musculoskeletal and gastrointestinal causes whereas dogs of smaller breeds died more commonly of endocrine causes.

Conclusions and Clinical Importance: Not all causes of death contribute equally to mortality within age, size, or breed cohorts. Documented patterns now provide multiple targets for clinical research and intervention.
Fe‐Ni metal and sulfide minerals in CM chondrites: An indicator for thermal history
Authors: KIMURA M. , GROSSMAN J. N. , WEISBERG M. K.
Published: February 2011

Abstract– CM chondrites were subjected to aqueous alteration and, in some cases, to secondary metamorphic heating. The effects of these processes vary widely, and have mainly been documented in silicate phases. Herein, we report the characteristic features of Fe‐Ni metal and sulfide phases in 13 CM and 2 CM‐related chondrites to explore the thermal history of these chondrites. The texture and compositional distribution of the metal in CM are different from those in unequilibrated ordinary and CO chondrites, but most have similarities to those in highly primitive chondrites, such as CH, CR, and Acfer 094. We classified the CM samples into three categories based on metal composition and sulfide texture. Fe‐Ni metal in category A is kamacite to martensite. Category B is characterized by pyrrhotite grains always containing blebs or lamellae of pentlandite. Opaque mineral assemblages of category C are typically kamacite, Ni‐Co‐rich metal, and pyrrhotite. These categories are closely related to the degree of secondary heating and are not related to degree of the aqueous alteration. The characteristic features of the opaque minerals can be explained by secondary heating processes after aqueous alteration. Category A CM chondrites are unheated, whereas those in category B experienced small degrees of secondary heating. CMs in category C were subjected to the most severe secondary heating process. Thus, opaque minerals can provide constraints on the thermal history for CM chondrites.
Chemoprotective effect of the tetrahydrofuran lignan grandisin in the in-vivo rodent micronucleus assay
Authors: Valadares Marize C , de Oliveira Júnior Luiz Marcos , de Carvalho Flávio S , Andrade Lorenna V S , dos Santos Alexandre P , de Oliveira Valéria , de Souza Gil Eric , Kato Massuo J
Published: February 2011

Objectives

The chemoprotective effect of the tetrahydrofuran lignan grandisin against DNA damage induced by cyclophosphamide (200 mg/kg) has been evaluated using the in vitro rodent micronucleus assay.

Methods

The effects of a daily oral administration of grandisin (2, 4, or 8 mg/kg) for five days before exposure to cyclophosphamide on the frequency of micronucleus in the bone marrow of normal mice exposed and unexposed to cyclophosphamide were investigated (n = 5 per group). Electrochemical measurements were applied to investigate whether the antimutagenic effects of grandisin could be, at least in part, a consequence of its or its metabolite's antioxidant properties.

Key findings

Grandisin did not show mutagenic effects on the bone marrow cells of exposed mice. On the other hand, the oral administration of grandisin (2, 4, or 8 mg/kg) per day reduced dose-dependently the frequency of micronucleus, induced by cyclophosphamide, in all groups studied. Cyclic voltammograms showed two peaks for a grandisin metabolite, which were absent for grandisin.

Conclusions

Under the conditions tested herein, this study has shown that mice treated with grandisin presented, in a dose-dependent manner, a protective effect against cyclophosphamide-induced mutagenicity. This effect could be, at least in part, associated to grandisin bioactivation. These data open new perspectives for further investigation into the toxicology and applied pharmacology of grandisin.
Formulation development and systematic optimization of solid lipid nanoparticles of quercetin for improved brain delivery
Authors: Dhawan Sanju , Kapil Rishi , Singh Bhupinder
Published: February 2011

Objective

This study aims at formulating solid lipid nanoparticles (SLNs) of quercetin, a natural flavonoid with established antioxidant activity, for intravenous administration in order to improve its permeation across the blood–brain barrier into the CNS, and eventually to improve the therapeutic efficacy of this molecule in Alzheimer's disease.

Methods

The SLNs of quercetin were formulated using Compritol as the lipid and Tween 80 as the surfactant through a microemulsification technique, and optimized employing a 32 central composite design (CCD). Selection of the optimized SLN formulation, using brute-force methodology and overlay plots, was based on its efficiency of entrapping quercetin inside the lipophilic core, particle size, surface charge potential and ability of the SLNs to release the entrapped drug completely. The optimized formulation was subjected to various in-vivo behavioral and biochemical studies in Wistar rats.

Key findings

The optimized formulation exhibited a particle size of less than 200 nm, 85.73% drug entrapment efficiency and a zeta potential of 21.05 mV. In all the in-vivo behavioral and biochemical experiments, the rats treated with SLN-encapsulated quercetin showed markedly better memory-retention vis-à-vis test and pure quercetin-treated rats.

Conclusions

The studies demonstrated successful targeting of the potent natural antioxidant, quercetin, to brain as a novel strategy having significant therapeutic potential to treat Alzheimer's disease.
Supersaturated dissolution data and their interpretation: the TPGS–carbamazepine model case
Authors: Charkoftaki Georgia , Dokoumetzidis Aristides , Valsami Georgia , Macheras Panos
Published: February 2011

Objectives

This study was undertaken to investigate the effect of d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) on the dissolution of carbamazepine (CBZ) commercial tablets (Tegretol®) as a function of temperature and to modify the reaction-limited model of dissolution for the description of classical supersaturated dissolution data.

Methods

Solubility studies were performed using various concentrations of (i) TPGS and (ii) silicon dioxide and microcrystalline cellulose, which are excipients of Tegretol® at 10, 25 and 37°C. Dissolution studies were carried out using Tegretol® tablets, 200 mg/tab.

Key findings

The solubility of CBZ in the presence of TPGS was found to increase in a concentration-dependent manner at all temperatures studied. Classical supersaturated dissolution curves with concentration maxima higher than the corresponding solubility values in the presence of TPGS were observed only at 10°C. The model developed was based on a time-dependant expression for the forward microconstant of the CBZ-TPGS reaction at the solid–liquid interface and it was fitted successfully to the dissolution data of CBZ in the presence of TPGS at 10°C.

Conclusions

Vitamin E TPGS increased the solubility of CBZ at all temperatures studied. The modification of the reaction-limited model of dissolution allowed us to describe classical supersaturated dissolution curves.
Inhalable, bioresponsive microparticles for targeted drug delivery in the lungs
Authors: Sivadas Neeraj , Cryan Sally-Ann
Published: February 2011

Objective

There is a growing interest in developing bioresponsive drug delivery systems to achieve greater control over drug release than can be achieved with the conventional diffusion controlled polymeric delivery systems. While a number of such systems have been studied for oral or parenteral delivery, little or no work has been done on bioresponsive delivery systems for inhalation. Using the raised elastase levels present at sites of lung inflammation as a proof-of-concept model, we endeavoured to develop a prototype of inhalable elastase sensitive microparticles (ESMs).

Methods

Microparticles degradable by the enzyme elastase were formed by crosslinking the polymer alginate in the presence of an elastase substrate, elastin, using Ca+2 ions and subsequent spray drying.

Key findings

The bioresponsive release of a protein cargo in the presence of elastase demonstrated the enzyme-specific degradability of the particles. The microparticles showed favorable properties such as high drug encapsulation and good powder dispersibility. Potential polymer toxicity in the lungs was assessed by impinging the microparticles on Calu-3 cell monolayers and assessing changes in transepithelial permeability and induction of cytokine release. The microparticles displayed no toxic or immunogenic effects.

Conclusions

With a manufacturing method that is amenable to scale-up, the ability to be aerosolised efficiently from a first-generation inhaler device, enzyme-specific degradability and lack of toxicity, the ESMs show significant promise as pulmonary drug carriers.
Demographic risk factors affecting emergency room visits caused by benzodiazepine poisoning in Kansas City, Missouri, from 2001 to 2007
Authors: Liu Yifei , Cai Jinwen , Hoff Gerald L , Hong Liang , Okah Felix A
Published: February 2011

Objective

The study objective was to identify demographic risk factors associated with emergency room visits caused by benzodiazepine poisoning.

Methods

A retrospective study was conducted utilizing Missouri Hospital Discharge Data for Kansas City, Missouri, USA, for 2001–2007. The data included patients' demographics such as racial group, age, sex, health insurance status and annual income. Emergency room visits due to benzodiazepine poisoning were identified by ICD-9 code 969.4. The frequencies of patient visits were calculated according to categories of each demographic variable. Chi-square tests were used to assess the difference of emergency room visits among categories of each demographic variable. A multiple logistic regression analysis was performed, where the outcome variable was emergency room visits due to benzodiazepine poisoning (yes/no), and the independent variables were the demographic variables.

Key findings

Of 1 317 566 emergency room visits over the 7-year period, 562 were due to benzodiazepine poisoning. Seventy-seven per cent of these visits were made by patients who were white, of whom 53% were 30–49 years old, 56% were female, 74% had health insurance and 44% lived in zip codes with median family incomes of $40 000–59 999. Chi-square tests were significant for racial group, age and annual income (P < 0.01). In the logistic regression white patients were 73% more likely than black patients to have emergency room visits caused by benzodiazepine poisoning (P < 0.01), with an odds ratio (95% confidence interval) of 5.63 (4.33–7.30). Compared with those aged 0–19 years, the odds ratio for patients aged 30–39 to have such visits was 2.73 (2.09–3.57), and the odds ratio for patients aged 40–49 was 2.84 (2.17–3.71).

Conclusions

White patients and patients aged 30–49 years were at higher risk for emergency room visits due to benzodiazepine poisoning. Health interventions such as medication review by pharmacists may reduce the risk of benzodiazepine poisoning for these patients.
Redefining synaesthesia?
Authors: Cohen Kadosh Roi , Terhune Devin B.
Published: February 2011

In a thought‐provoking paper, Simner (2012) highlights and criticizes a number of assumptions concerning synaesthesia. She specifically takes issue with the following assumptions: (1) synaesthesia is strictly a sensory‐perceptual phenomenon; (2) consistency of inducer‐concurrent pairs is the gold standard for establishing the authenticity of an individual's synaesthesia; and (3) synaesthesia is not heterogeneous. In the wake of this critique, Simner advances a working definition of synaesthesia as a neurological hyper‐association that aims to be more inclusive of its variants. We are very sympathetic to Simner's approach and believe that it raises important points that will advance our understanding of synaesthesia. Here we supplement, and sometimes challenge, some of these ideas.
Interhemispheric interaction and egocentrism: The role of handedness in social comparative judgement
Authors: Rose Jason P. , Jasper John D. , Corser Ryan
Published: February 2011

Previous research has shown that people are egocentrically biased when making judgements that require a self‐to‐peer comparison – leading to above‐/below‐average effects and comparative optimism/pessimism. Two experiments examined whether interhemispheric brain connectivity (assessed via strength of handedness) is associated with egocentrism in the comparative judgement process. In Experiment 1, strong handers (SH) and mixed handers (MH) made percentile rank judgements about their abilities in easy and hard domains. In Experiment 2, SH and MH judged their likelihoods of outperforming a co‐participant in easy and hard tasks. Both experiments showed that SH were more egocentric than MH and thus showed (a) more above‐ and below‐average effects when estimating their abilities (Experiment 1) and (b) generally larger optimism biases when predicting performances in a competition (Experiment 2). Taken together, these experiments provide evidence that underlying interhemispheric connectivity shapes egocentrism in comparative judgement.
Childhood trauma in obsessive compulsive disorder: The roles of alexithymia and attachment
Authors: Carpenter Leanne , Chung Man Cheung
Published: February 2011

Objective. The aim of this study was to investigate the interrelationships between childhood trauma, attachment, alexithymia, and the severity of obsessive compulsive disorder (OCD) in a cohort of participants with OCD.

Rationale. There is a growing body of research linking traumatic experiences in childhood with the development of OCD. The mechanisms involved in this association are not yet clear.

Methods. The sample was comprised of 82 people with OCD and 92 comparison participants. A cross‐sectional design was used, utilizing internet‐mediated administration of the Childhood Trauma Questionnaire – revised (CTQ‐R); the Yale‐Brown Obsessive Compulsive Scale – Self‐Report (Y‐BOCS‐SR); the Experiences in Close Relationships Scale (ECR); and Toronto Alexithymia Scale (TAS‐20). Partial least squares (PLS) analysis was used to determine significant paths between the constructs.

Results. Results of PLS analysis supported all of the hypotheses made: there was a significant positive correlation between childhood trauma and attachment avoidance, which in turn was significantly positively associated with alexithymia. Alexithymia was significantly associated with the severity of OCD symptoms and the number of OCD symptoms. Mediational analysis showed that alexithymia significantly carried an influence from attachment avoidance to the severity of obsessions and the number of obsession symptoms.

Conclusions. There is a relationship between childhood trauma and OCD, however this relationship is not direct in nature but is influenced by peoples’ past experiences with significant others and associated difficulties in emotional processing.