bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis, Characterization, and High Temperature Stability of Si(B)CN‐Coated Carbon Nanotubes Using a Boron‐Modified Poly(ureamethylvinyl)Silazane Chemistry
Authors: Bhandavat Romil , Singh Gurpreet
Published: February 2012

Carbon nanotubes (CNT) and polymer‐derived ceramics (PDCs) are of interest due to their unique multifunctional properties. CNTs, however, tend to lose their well‐defined structure and geometry at about 400°C in air. PDCs on the other hand are structureless in X‐ray diffraction but show high chemical and thermal stability in air (up to ~1400°C). Herein, we demonstrate synthesis of a composite nanowire structure consisting of polymer‐derived silicon boron‐carbonitride (Si–B–C–N) shell with a multiwalled carbon nanotube core. This was achieved through a novel process involving preparation of a boron‐modified liquid polymeric precursor through a reaction of trimethyl borate and poly (ureamethylvinyl) silazane under normal conditions; followed by conversion of polymer to ceramic on carbon nanotube surfaces through controlled heating. Chemical structure of the polymer was studied by liquid‐Nuclear Magnetic Resonance (NMR) while evolution of various ceramic phases was studied by solid‐NMR, Fourier transform infrared and X‐ray photoelectron spectroscopy. Electron microscopy and X‐ray diffraction confirm presence of amorphous Si(B)CN coating on individual nanotubes for all specimens processed below 1400°C. Thermogravimetric analysis, followed by Raman spectroscopy and transmission electron microscopy revealed high temperature stability of the carbon nanotube core in flowing air up to 1000°C.
Direct Multi‐Scale Modeling of Sintering
Authors: Maximenko Andrey , Kuzmov Andrey , Grigoryev Evgeny , Olevsky Eugene
Published: February 2012

A new multi‐scale numerical approach for the modeling of sintering of macroscopically inhomogeneous materials is put forward. The new approach does not require the formulation of material constitutive equations: it specifies material properties through the definition of macroscopic unit cells. As a result, the influence of any number of material structure parameters on sintering kinetics and on specimen distortion can be investigated. The method is based on the consideration of the sintered body macroscopic behavior in parallel with an online analysis of the mesoscopic evolution of the unit cell structure. The developed modeling approach provides the information on the sintering progress at both macro‐ and meso‐scale levels. The examples of diffusion sintering of ceramic composites and of viscous sintering of a bi‐layer porous specimen containing voids of anisotropic shapes are considered.
Development of a Noninvasive Vitamin D Screening Tool
Authors: Lukaszuk Judith M. , Prawitz Aimee D. , Johnson Kirsten N. , Umoren Josephine , Bugno Terrence J.
Published: February 2012

The purpose was to develop a vitamin D screening tool for use in community health/wellness settings. Fifty‐four healthy Caucasian women of normal weight (body mass index = 18–24.9) and obese weight (body mass index ≥30) had anthropometrics measured, and completed three‐day food records, vitamin D screening tools, and serum 25‐hydroxyvitamin D tests. Findings provided evidence of usefulness of three specific screening tool items (sunscreen use, obesity, dairy consumption) and indicated need for more precision about sunscreen use. Odds for vitamin D inadequacy were 5 times lower with sunscreen use, 6 times higher with low dairy consumption, and 10 times higher with self‐reported obesity, X2 (5, n = 54) = 43.24, P <.01. The study provided initial verification of self‐report items useful in assessing vitamin D inadequacy. Following refinement and testing with larger, less homogeneous samples, the instrument can serve as a useful, cost‐effective vitamin D screening tool in community health/wellness settings.
Reliability of the Scales in the NC1172 Complex Nature of Saving Data Set
Authors: Hayhoe Celia R. , Gutter Michael E.
Published: February 2012

The purpose of this study was to test the reliability of scales measuring the psychological aspects of savings behavior. The data set titled The Complex Nature of Saving: Psychological and Economic Factors was collected under the sponsorship of the North Central (NC) 1172 multistate research program. Researchers from 12 universities developed the questionnaire for the study. The sample consisted of low‐to‐moderate‐income consumers with a respondent (or spouse or partner of the respondent) between the ages of 24 and 66. The scales included in this study consist of Rook & Fisher (1995) Impulsivity Scale and three sub‐scales (distrust, anxiety, and bargain‐conscious) from the revised Yamauchi & Templer (1982) money attitudes scale by Roberts & Sepulveda (1999). Other scales that were included are the Richins & Dawson (1992) materialism scale, Sherer et al. (1982) Self‐efficacy Scale, and Grable & Joo (2004) financial risk‐tolerance scale. Also, these data were used to develop a Financial Management Behavior Score. Based on data from this sample, the results show that the modified scales work as well as the original scales.
Which Low‐ and Moderate‐Income Families Purchase Life Insurance?
Authors: Kim Haejeong , DeVaney Sharon A. , Kim Jinhee
Published: February 2012

The primary reason for buying life insurance is to provide financial protection for family members in case of the unexpected death of the wage earner. The two major types of life insurance are term and cash‐value insurance. Term is believed to be the least expensive. This study examined ownership of life insurance among families with a respondent between the age of 24 and 66 and with incomes below $80,000. About one‐third of the sample of 454 respondents had purchased life insurance on either the respondent or spouse/partner. Although there were some differences in predicting term versus cash‐value insurance, saving regularly and income were the two most consistent predictors of life insurance purchase.
Transepidermal elimination in cutaneous leishmaniasis: a multiregional study
Authors: Karram Sarah , Loya Asif , Hamam Hadi , Habib Robert H. , Khalifeh Ibrahim
Published: February 2012

Background: Transepidermal elimination has been documented in a myriad of infectious diseases; however, its occurrence in cutaneous leishmaniasis has not been evaluated.

Methods: Skin biopsies (n = 212) with cutaneous leishmaniasis in Lebanon (n = 46), Syria (n = 53), Saudi Arabia (n = 45) and Pakistan (n = 68) were evaluated. Clinical data collected included age, gender, eruption type (papule, nodule, verrucous or scar), duration and anatomic location. Histopathologically, multiple parameters were recorded including Ridley's parasitic index and pattern, transepidermal elimination, interface changes, ulceration and necrosis. Transepidermal elimination was defined as the presence of amastigotes in the epidermis in all layers, limited to the basal layer or present in a perforating plug. All cases were confirmed by polymerase chain reaction (PCR) analysis followed by restriction fragment length polymorphism analysis for molecular subspeciation.

Results:
Leishmania tropica was identified in 88.2% and Leishmania major in 11.8% of all cases. Transepidermal elimination was observed in 28.3% of cases (29 perforating plug, 19 all layers and 12 basal layer) with a significant prevalence of L. major in this group (35 vs. 2%, p < 0.001). Cases with transepidermal elimination were associated with interface changes and higher parasitic index (p < 0.001) but not with an increased ulceration rate (p > 0.05). Multivariate analysis showed that transepidermal elimination was independently predicted by L. major [OR (95% confidence interval) = 80 (9–712); p < 0.001], parasitic index [OR = 3.4 (2.1–5.3); p < 0.001], interface changes [OR = 6.24 (2.2–17.8); p < 0.001] and necrosis [OR = 0.2 (0.1–0.8);p = 0.026].

Conclusions: We report the largest multiregional cutaneous leishmaniasis series with a 28.3% documented transepidermal elimination incidence of which 48% were perforating plug; a significant prevalence of L. major was also identified in the transepidermal elimination group. The association of transepidermal elimination with interface changes and a higher parasitic index, without an increased ulceration rate, may reflect a unique biologic alteration in the epidermis, serving to facilitate the extrusion of the parasites through the skin.

Karram S, Loya A, Hamam H, Habib RH, Khalifeh I. Transepidermal elimination in cutaneous leishmaniasis: a multiregional study.
Broad range of adverse cutaneous eruptions in patients on TNF‐alpha antagonists
Authors: Hawryluk Elena B. , Linskey Katy R. , Duncan Lyn M. , Nazarian Rosalynn M.
Published: February 2012

Biologic therapies targeting tumor necrosis factor (TNF)‐alpha have become a mainstay in the management of a number of autoimmune diseases. We report a series of adverse skin eruptions in six patients (four females, two males, age: 21–58 years, mean: 39) receiving 4 months to 10 years (mean 3.1 years) of anti‐TNF‐alpha therapies (infliximab, n = 4; adalimumab, n = 1 or etanercept, n = 1). The following drug‐associated diagnoses were made in eight skin biopsies performed at Massachusetts General Hospital between 3/2007 and 10/2010: pustular folliculitis, psoriasis, interface dermatitis, neutrophilic eccrine hidradenitis, Sweet's syndrome, lupus, vasculitis and palmoplantar pustulosis. The descriptions of neutrophilic eccrine hidradenitis‐like and Sweet's‐like hypersensitivity eruptions induced by anti‐TNF‐alpha therapies are the first such cases described in the literature. Each cutaneous eruption improved or resolved with switching to a different TNF‐alpha inhibitor, discontinuation of the anti‐TNF‐alpha agent, and/or topical or systemic steroids. There was a clear chronologic relationship with, and clinical remission upon withdrawal or steroid suppression of the anti‐TNF‐alpha agents. The mechanism for such diverse cutaneous eruptions among this class of medications remains poorly understood. The cutaneous adverse reaction profile of TNF‐alpha inhibitors is broad and should be considered in the histopathologic differential in this clinical setting.

Hawryluk EB, Linskey KR, Duncan LM, Nazarian RM. Broad range of adverse cutaneous eruptions in patients on TNF‐alpha antagonists.
Quantitative phosphoproteomics identifies filaggrin and other targets of ionizing radiation in a human skin model
Authors: Yang Feng , Waters Katrina M. , Webb‐Robertson Bobbie‐Jo , Sowa Marianne B. , von Neubeck Claere , Aldrich Josh T. , Meng Markillie Lye , Wirgau Rachel M. , Gritsenko Marina A. , Zhao Rui , Camp David G. , Smith Richard D. , Stenoien David L.
Published: February 2012

Abstract:  Our objective here was to perform a quantitative phosphoproteomic study on a reconstituted human skin tissue to identify low‐ and high‐dose ionizing radiation‐dependent signalling in a complex three‐dimensional setting. Application of an isobaric labelling strategy using sham and three radiation doses (3, 10, 200 cGy) resulted in the identification of 1052 unique phosphopeptides. Statistical analyses identified 176 phosphopeptides showing significant changes in response to radiation and radiation dose. Proteins responsible for maintaining skin structural integrity including keratins and desmosomal proteins (desmoglein, desmoplakin, plakophilin 1, 2 and 3) had altered phosphorylation levels following exposure to both low and high doses of radiation. Altered phosphorylation of multiple sites in profilaggrin linker domains coincided with altered profilaggrin processing suggesting a role for linker phosphorylation in human profilaggrin regulation. These studies demonstrate that the reconstituted human skin system undergoes a coordinated response to both low and high doses of ionizing radiation involving multiple layers of the stratified epithelium that serve to maintain tissue integrity and mitigate effects of radiation exposure.
Endozoochory decreases environmental filtering imposed to seedlings
Authors: Cavallero Laura , Aizen Marcelo A. , Raffaele Estela
Published: February 2012

Questions

Recruitment microsites are imposed on plants, first by seed dispersal and then by the environment. Different seed dispersal vectors could decrease or increase the environmental filtering imposed on seedlings, depending on their specificity to deliver seeds to suitable microsites for germination and establishment. We addressed the hypothesis that endozoochory reduces the environmental filtering imposed to seedlings to a larger extent than does anemochory. We predicted that seedlings from animal‐dispersed species should show a higher degree of environmental coupling.

Location

Northern Patagonian Andean region of Argentina, 40–42° S.

Methods

We characterized the relationship of seedlings, saplings and reproductive individuals to total radiation, air temperature and relative humidity for 16 woody species growing in 25 plant communities of different post‐fire ages in temperate forests of southern South America.

Results

Seedlings and saplings of endozoochorous species occurred under more similar environmental conditions than seedlings and saplings of anemochorous species. Basically, the mean difference in plant–environment correlation coefficients between saplings and seedlings was <0.2 for all endozoochorous species and >0.2 for all anemochorous species for all environmental variables. Comparisons between dispersal modes were also statistically significant before and after controlling for phylogenetic relationships among species. Even though saplings and seedlings of endozochorous species tended to occur under similar environmental conditions, we did not find evidence that saplings and seedlings co‐occur in the same physical microsites. Finally, we did not find evidence either that seedlings of endozoochorous species tended to occur differentially underneath reproductive individuals of the same species (i.e. more seeds falling by gravity beneath maternal plants).

Conclusions

The tighter coupling between seedlings of endozoochorous species and environmental factors persisting to the sapling stage suggests that relying on animals for seed dispersal reduces mortality costs during the early stages of recruitment by reducing the environmental filtering imposed on seedlings.
Characterization of Ursodeoxycholic and Norursodeoxycholic Acid as Substrates of the Hepatic Uptake Transporters OATP1B1, OATP1B3, OATP2B1 and NTCP
Authors: König Jörg , Klatt Sabine , Dilger Karin , Fromm Martin F.
Published: February 2012

Ursodeoxycholic acid (UDCA) is the only approved treatment for primary biliary cirrhosis, and norursodeoxycholic acid (norUDCA) is currently tested in clinical trials for future treatment of primary sclerosing cholangitis because of beneficial effects in cholestatic Mdr2 knock‐out mice. Uptake of UDCA and norUDCA into hepatocytes is believed to be a prerequisite for subsequent metabolism and therapeutic action. However, the molecular determinants of hepatocellular uptake of UDCA and norUDCA are poorly understood. We therefore investigated whether UDCA and norUDCA are substrates of the hepatic uptake transporters OATP1B1, OATP1B3, OATP2B1 and Na+‐taurocholate co‐transporting polypeptide (NTCP), which are localized in the basolateral membrane of hepatocytes. Uptake of [3H]UDCA and [14C]norUDCA into Human embryonic kidney (HEK) cells stably expressing OATP1B1, OATP1B3, OATP2B1 or NTCP was investigated and compared with uptake into vector control cells. Uptake ratios were calculated by dividing uptake into transporter‐transfected cells by uptake into respective control cells. Uptake ratios of OATP1B1‐, OATP1B3‐ and OATP2B1‐mediated UDCA and norUDCA uptake were at maximum 1.23 and 1.49, respectively. Uptake of UDCA was significantly higher into HEK‐NTCP cells only at the lowest tested concentration (1 μM, p < 0.001) compared with the control cells with an uptake ratio of 1.34‐fold. NorUDCA was not significantly transported by NTCP. The low uptake rates suggest that OATP1B1, OATP1B3, OATP2B1 and NTCP are not relevant for hepatocellular uptake and effects of UDCA and norUDCA in human beings.
Oxidation of Styrene to Benzaldehyde by Anhydrous Hydrogen Peroxide on γ‐Alumina‐Supported V2O5 Nanoparticle Catalysts: Optimization Studies Using Response Surface Methodology
Authors: Ahmad, Abdul L. , Koohestani Behnam , Bhatia Subhash , Ooi Seng B.
Published: February 2012

Particles of γ‐alumina‐supported V2O5 with an average particle size of 5‐10 nm and a surface area of 174.8 m2/g were prepared through a wet impregnation method. These materials were found to be effective in the selective oxidation of styrene to benzaldehyde using anhydrous H2O2. Response surface methodology was used to investigate the effect of the oxidant (H2O2) concentration (from 20 to 60 mmol), temperature (from 45 to 75°C), time (from 2.5 to 6 h) and catalyst concentration (from 0.014 to 0.036 g/L) on the styrene conversion and the selectivity of benzaldehyde and styrene oxide. Based on the response surface methodology analysis, the optimal oxidation conditions occur with a reaction temperature of 62.7°C, a reaction time of 5.15 h, a molar ratio of H2O2/styrene of 2.7:1 and a catalyst concentration of 0.024 g/L. These conditions result in maximal styrene conversion (68.23%) and benzaldehyde selectivity (57.32%).
Prevention of relapses of nasal polyposis with intranasal triamcinolone acetonide after polyp surgery: A prospective double‐blind, placebo‐controlled, randomised study with a 9‐month follow‐up
Authors: Vento SI. , Blomgren K. , Hytönen M. , Simola M. , Malmberg H.
Published: February 2012

Clin. Otolaryngol. 2012, 37, 117–123

Objective:  To determine whether intranasal triamcinolone acetonide prevents the regrowth of nasal polyps after polyp surgery.

Study design:  Randomised, double‐blind, placebo‐controlled, prospective study.

Setting:  Helsinki University Central Hospital.

Participants:  Sixty patients with nasal polyps entered the study. Patients were included upon arrival for elective polyp operations determined according to our standard clinical criteria. The recurrence of nasal polyposis was followed up for 9 months after surgical treatment at 3‐month intervals.

Main outcome measures:  Anterior rhinoscopy, nasal endoscopy, olfactory threshold measurement, active anterior rhinomanometry and acoustic rhinometry were performed at every follow‐up visit.

Results:  On the whole, there was a significant inter‐group difference in the change in polyp size of acetylsalicylic acid (ASA)‐tolerant patients during the follow‐up. In patients with acetylsalicylic acid intolerance, there was no inter‐group difference (P = 0.28). No significant differences were noted for nasal resistance, nasal cavity volume, sense of smell and nasal symptoms.

Conclusion:  Triamcinolone acetonide prevents regrowth of nasal polyps after polyp surgery in acetylsalicylic acid‐tolerant patients, but not in acetylsalicylic acid‐intolerant patients.
Determination of the Usage of Shade Structures via a Dosimetry Technique
Authors: Parisi Alfio V. , Eley Robert , Downs Nathan
Published: February 2012

A measurement system is described that allows an objective review and evaluation of the amount of use by different population groups of provided shade structures. It employs the comparison of the erythemal UV exposure measured with dosimeters to either the vertex or forehead to that in full sun. The technique has been developed using three shade structures and found to provide a linear relationship with an R2 of 0.99 between the exposure ratio and the time spent in the shade for the solar zenith angle range of 19–53o and for both low‐ and high‐cloud levels. It provides an objective determination of the amount of shade use by population groups that have set periods of time outdoors.
Photodynamic Therapy Can Improve Warts’ Discomfort in Renal Transplant Patients Prospective Multicenter Study
Authors: Sparsa Agnès , Blaise Sophie , Tack Brigitte , Dalmay François , Leroy Dominique , Bonnetblanc Jean‐Marie , Béani Jean‐Claude , Bédane Christophe
Published: February 2012

Many studies have been conducted showing that aminolevulinic acid (ALA)‐photodynamic therapy (PDT) can be an alternative treatment for recalcitrant warts. Recently, we performed a study evaluating methyl‐aminolevulinic acid (MAL)‐PDT for the treatment of hand warts in a population of renal transplant patients. Two symmetrical targets were selected on each hand and randomly assigned to chemical keratolytic treatment followed by three cycles of ALA‐PDT (75 J cm−² red light). Patients were evaluated after 3 months and a second run of PDT was performed if the total area and number of warts decreased less than 50%, with evaluation every 3 months for 1 year. Twenty patients were included and 16 were evaluable (9 M, 7 F). After 6 months the reduction of warts’ area was 48.4% on the treated side versus 18.4% in the control area (P = 0.021). The decrease in the total number of warts was 41%versus 19.4% (P = NS). The global tolerance of the treatment was good with acceptable pain during irradiation. These results suggest that ALA‐PDT is a safe and efficient treatment for transplanted patient warts. The improvement between treated and control zone is 20% due to the decrease in untreated warts’ area and number.
Misdiagnosis of Aortic Dissection: Experience of 361 Patients
Authors: Zhan Sun , Hong Shen , Shan‐shan Li , Chen‐ling Yao , Lai Wei , Dong‐wei Shi , Chao‐yang Tong , Xian‐hong Shu , Chun‐Sheng Wang
Published: February 2012

J Clin Hypertens (Greenwich). 2012;14:256–260. ©2012 Wiley Periodicals, Inc.

Aortic dissection (AD) is a life‐threatening condition that requires immediate diagnosis and surgical correction. Patients with acute AD usually present clinically with an insignificant medical history, leading to a high probability of misdiagnosis. The aim of the present study was to investigate the number of misdiagnoses of patients with AD in order to understand this problem and to avoid future misdiagnosis in the emergency department. Clinical data from 361 patients with AD admitted between January 2003 and June 2008 were reviewed as part of a retrospective chart review. Diagnosis of AD was made using either chest x‐ray, computed tomography, magnetic resonance imaging, or angiography. Fifty‐one patients had an initial misdiagnosis (14.1%), later found to have experienced AD. The condition may clinically present in a varied number of manifestations, including syncope, chest pain, abdominal pain, back pain, acute congestive heart failure, or alternatively with minimal symptoms. Persons of any age can experience an AD, with key clinical manifestations of pain. Echocardiography can be used for primary examination of patients with suspected AD; however, a definite diagnosis is usually made using computed tomographic or magnetic resonance angiography. Care should be taken, particularly in the emergency department, to maintain a level of suspicion for AD diagnosis in order to avoid the potential for misdiagnosis.
Efficacy and safety of the long‐acting muscarinic antagonist GSK233705 delivered once daily in patients with COPD
Authors: Bateman Eric , Feldman Gregory , Kilbride Sally , Brooks Jean , Mehta Rashmi , Harris Stephanie , Maden Claire , Crater Glenn
Published: February 2012

Introduction:  GSK233705 is a recently developed inhaled anticholinergic being investigated for the potential treatment of chronic obstructive pulmonary disease (COPD).

Objectives:  This dose‐ranging, parallel‐group, double‐blind study compared the bronchodilator efficacy, safety and pharmacokinetics of GSK233705 with placebo in patients with moderate‐to‐severe COPD.

Methods:  Patients were randomised to receive 12.5 µg, 25 µg, 50 µg, 100 µg or 200 µg of GSK233705 or placebo once daily for 28 days. The primary endpoint was change from baseline in trough forced expiratory volume in 1 s (FEV1) on day 29.

Results:  The intent‐to‐treat population consisted of 576 patients (mean predicted FEV1 51%; mean age 62 years). Treatment with GSK233705 produced statistically significant improvements in pulmonary function compared with placebo. Only the 200 µg dose exceeded the predefined target threshold of 130‐mL difference compared with placebo for the primary endpoint of change from baseline in trough FEV1 on day 29. No clear pattern of dose response was observed for the other doses. Serial FEV1 (0–24 h) showed a peak effect around 2 h postdose and tended to decline to clinically insignificant levels compared with placebo at 23 and 24 h.

Each dose of GSK233705 was well tolerated. The incidence of adverse events was low and similar across all treatment groups. There were no clinically significant effects on laboratory parameters, vital signs or electrocardiograms.

Conclusion:  All doses of GSK233705 demonstrated bronchodilatory activity and were well tolerated. Although the onset of bronchodilation was rapid, it was not sustained over 24 h making it unsuitable for once‐daily dosing.

Please cite this paper as: Bateman E, Feldman G, Kilbride S, Brooks J, Mehta R, Harris S, Maden C and Crater G. Efficacy and safety of the long‐acting muscarinic antagonist GSK233705 delivered once daily in patients with COPD. Clin Respir J 2012; DOI:10.1111/j.1752‐699X.2011.00278.x.
SIMULTANEOUS PANCREAS AND KIDNEY TRANSPLANTATION IN DIABETES WITH RENAL FAILURE: THE GOLD STANDARD?
Authors: Augustine Titus
Published: February 2012

Simultaneous Pancreas and Kidney (SPK) transplantation in the 21st century is a proven therapeutic intervention for diabetes with renal failure. Although it is a major invasive procedure, successful transplantation leads to an overall improvement in the quality of life of the recipient, freedom from insulin and dialysis, along with stabilisation and improvement in several of the multi‐system complications associated with long‐term diabetes. It is also associated with improved longevity when compared to diabetics who have had a kidney transplant alone. The combined transplant could be considered a curative procedure albeit at the expense of long‐term immunosuppression. In essence, successful SPK transplantation may be considered the gold standard against which all other therapeutic interventions may be measured in diabetes with end‐stage renal failure.
EXPLORING THE PROCESS OF ADJUSTING TO DIABETIC KIDNEY DISEASE
Authors: Reid Katherine , Morris Marianne , Cormack Margaret , Marchant Karen
Published: February 2012

The psychological process of adjusting to diabetic kidney disease (DKD) has been afforded little attention within previous literature. This study aimed to explore the process of adjusting to DKD as a secondary condition to type 1 diabetes. A qualitative method was used in the study design. Eleven participants were interviewed using a semi‐structured and exploratory approach. Through inductive thematic analysis, three super‐ordinate themes were identified from the data: coming to an understanding over time, managing the impact of DKD and facing the future. The themes demonstrate that the DKD population has complex physical and psychological needs at all stages of their condition. Making sense of kidney disease as a secondary condition and integration of this information with existing beliefs was integral to the adjustment process. Attempts to manage uncertainty and change included asserting control of the situation and use of cognitive strategies. The results support the use of psychological models of adjustment in conceptualising the ‘process’ of adjustment and suggest the need for psychological interventions to support this population.
THE DIETARY MANAGEMENT OF PATIENTS WITH DIABETES AND RENAL DISEASE: CHALLENGES AND PRACTICALITIES
Authors: Willingham Fiona
Published: February 2012

Diabetes Mellitus is one of the major causes of chronic kidney disease and end‐stage renal disease. Diet and lifestyle modification are vital components of optimal treatment for both conditions. This paper will address appropriate and often diverse treatment for each individual, understanding that advising changes which positively impact both conditions is a major challenge for health care professionals working within either speciality. It will also highlight where overlap can be contradictory rather than complementary, and offers practical guidance to support patients in making the necessary lifestyle changes to have maximal positive impact upon both conditions and their overall health.
Calibrate Before You Collaborate: Five Questions to Guide Group Work
Authors: Dunne Alex M. , Peck Tonya M.
Published: February 2012

In which we learn that the how of collaboration is just as important as the what.
Function and expression of ryanodine receptors and inositol 1,4,5‐trisphosphate receptors in smooth muscle cells of murine feed arteries and arterioles
Authors: Westcott Erika B. , Goodwin Erica L. , Segal Steven S. , Jackson William F.
Published: February 2012

Key points 

Feed arteries and arterioles, respectively, control the magnitude and distribution of blood flow to skeletal muscle but regional differences in the regulation of vasomotor tone are poorly understood.

To provide this insight, we investigated functional roles and molecular expression of the calcium‐release channels, ryanodine receptors (RyRs) and inositol 1,4,5‐trisphosphate receptors (IP3Rs) in smooth muscle cells (SMCs) of isolated pressurized vessels of mice.

In feed arteries, SMCs displayed localized calcium sparks and more global calcium waves. In arterioles, SMCs exhibited only calcium waves.

Calcium signalling and vasomotor tone were governed by both RyRs and IP3Rs in feed arteries, while only IP3Rs were functional in arterioles. Regional differences were also manifest in the expression profile of RyR isoforms.

This new perspective offers the potential for developing novel strategies to target therapeutic interventions to selective regions of vascular beds.
Cardiac output and sympathetic vasoconstrictor responses during upright tilt to presyncope in healthy humans
Authors: Fu Qi , Verheyden Bart , Wieling Wouter , Levine Benjamin D.
Published: February 2012

Key points 

Syncope is a common clinical condition occurring even in healthy people without manifest cardiovascular disease; we determined the role of cardiac output and sympathetic vasoconstriction in neurally mediated (pre)syncope.

Our data showed that a moderate fall in cardiac output with coincident vasodilatation occurred in the majority (64%) of the presyncopal subjects, while a marked fall in cardiac output, driven predominantly by a decrease in heart rate, with no changes in total peripheral resistance at presyncope, occurred in a smaller (36%) subset.

Sympathetic withdrawal occurred late, after the onset of hypotension.

Sympathetic vasoconstriction and baroreflex sensitivity during symptom‐free upright posture were well preserved and, thus, an intrinsic impairment of sympathetic neural control and vasomotor responsiveness was not the cause of neurally mediated (pre)syncope in this population.

These results help us better understand the mechanisms for syncope in humans.
The role of the TRPV6 channel in cancer
Authors: Lehen’kyi V’yacheslav , Raphaël Maylis , Prevarskaya Natalia
Published: February 2012

Abstract  The TRPV6 channel belongs to the superfamily of transient receptor potential (TRP) channels, subfamily vanilloid, member 6. Its expression in health is mainly confined to epithelial tissue of different organs such as digestive tract, kidney, testis, ovaries and skin. Due to its high calcium selectivity over other TRP channels, this channel was shown to participate in close regulation of calcium homeostasis in the body. In cancer a number of pieces of evidence demonstrate its upregulation and correlation with the advanced stages in prostate, colon, breast, thyroid, and ovarian carcinomas. Little is known about its role in initiation or progression for most of cancers, though in prostate cancer its oncogenic potential in vitro has been suggested. The most probable mechanisms involve calcium signalling in the control of processes such as proliferation and apoptosis resistance, though in some cases first evidence was reported as to its likely protective role in some cancers such as colon cancer. Further studies are needed to confirm whether this channel does really have an oncogenic potential or is just the last hope for transformed cells/tissues to stop cancer.
Excitation of Single Phonon Modes in Nanoscale Waveguides
Authors: Cheney Drew A. , Lukes Jennifer R.
Published: February 2012

We present a new computational method that excites guided phonon modes in nanoscale waveguides at a specific frequency and wavenumber. The method uses nonequilibrium molecular dynamics and Fourier analysis of particle displacements to extract mode shapes from single frequency excitations consisting of superposed spatial modes. These mode shapes are used to excite the waveguide inlet boundary so that single phonon modes are generated in the structure. Mode shapes and phonon spectra for a silicon planar waveguide with rigid wall boundaries are calculated to demonstrate the viability of the technique. This method improves upon molecular dynamics techniques that activate all possible phonon modes and are thus not able to isolate the contribution of any single phonon excitation. Application of our method will enable the computational investigation of single phonon mode propagation in nanostructures of varying geometry.
In Vitro
Efficacy of Diallyl Sulfides against the Periodontopathogen Aggregatibacter actinomycetemcomitans
Authors: Velliyagounder Kabilan , Ganeshnarayan Krishnaraj , Velusamy Senthil Kumar , Fine Daniel H.
Published: February 2012

The
in vitro
antibacterial effects of diallyl sulfide (DAS) against the Gram-negative periodontopathogen
Aggregatibacter actinomycetemcomitans
, the key etiologic agent of the severe form of localized aggressive periodontitis and other nonoral infections, were studied.
A. actinomycetemcomitans
was treated with garlic extract, allicin, or DAS, and the anti-
A. actinomycetemcomitans
effects of the treatment were evaluated. Garlic extract, allicin, and DAS significantly inhibited the growth of
A. actinomycetemcomitans
(greater than 3 log;
P
< 0.01) compared to control cells. Heat inactivation of the garlic extracts significantly reduced the protein concentration; however, the antimicrobial effect was retained. Purified proteins from garlic extract did not exhibit antimicrobial activity. Allicin lost all its antimicrobial effect when it was subjected to heat treatment, whereas DAS demonstrated an antimicrobial effect similar to that of the garlic extract, suggesting that the antimicrobial activity of garlic extract is mainly due to DAS. An
A. actinomycetemcomitans
biofilm-killing assay performed with DAS showed a significant reduction in biofilm cell numbers, as evidenced by both confocal microscopy and culture. Scanning electron microscopy (SEM) analysis of DAS-treated
A. actinomycetemcomitans
biofilms showed alterations of colony architecture indicating severe stress. Flow cytometry analysis of OBA9 cells did not demonstrate apoptosis or cell cycle arrest at therapeutic concentrations of DAS (0.01 and 0.1 μg/ml). DAS-treated
A. actinomycetemcomitans
cells demonstrated complete inhibition of glutathione (GSH)
S
-transferase (GST) activity. However, OBA9 cells, when exposed to DAS at similar concentrations, showed no significant differences in GST activity, suggesting that DAS-induced GST inhibition might be involved in
A. actinomycetemcomitans
cell death. These findings demonstrate that DAS exhibits significant antibacterial activity against
A. actinomycetemcomitans
and that this property might be utilized for exploring its therapeutic potential in treatment of
A. actinomycetemcomitans
-associated oral and nonoral infections.
Pulmonary Disposition of Tedizolid following Administration of Once-Daily Oral 200-Milligram Tedizolid Phosphate in Healthy Adult Volunteers
Authors: Housman Seth T. , Pope J. Samuel , Russomanno John , Salerno Edward , Shore Eric , Kuti Joseph L. , Nicolau David P.
Published: February 2012

This study assessed the pulmonary disposition of tedizolid, an oxazolidinone, in adult volunteers receiving 200 mg of the prodrug tedizolid phosphate orally every 24 h for 3 days to steady state. Plasma samples were collected over the dosing interval, and participants were randomized to undergo bronchoalveolar lavage (BAL) at 2, 6, 12, or 24 h after the last dose. Drug concentrations in plasma, BAL fluid, and alveolar macrophages (AM) were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the urea correction method was used to calculate epithelial lining fluid (ELF) concentrations. Pharmacokinetic parameters were estimated by noncompartmental methods followed by compartmental population pharmacokinetics. Penetration was calculated as the area under the concentration-time curve during the dosing interval (AUC
0–24
) for ELF and AM relative to the free AUC
0–24
(
f
AUC
0–24
) in plasma. The half-life and volume of distribution in plasma were 9.23 ± 2.04 h and 108.25 ± 20.53 liters (means ± standard deviations), respectively. Total AUC
0–24
in plasma was 25.13 ± 5.78 μg · h/ml. Protein binding was 89.44% ± 1.58%, resulting in a mean
f
AUC
0–24
of 2.65 ± 0.72 μg · h/ml in plasma. Mean concentrations (μg/ml) at 2, 6, 12, and 24 h were 9.05 ± 3.83, 4.45 ± 2.18, 5.62 ± 1.99, and 1.33 ± 0.59 in ELF and 3.67 ± 1.02, 4.38 ± 2.18, 1.42 ± 0.63, and 1.04 ± 0.52 in AM. ELF and AM penetration ratios were 41.2 and 20.0. The mean ELF penetration ratio after population analyses was 39.7. This study demonstrates that tedizolid penetrates into ELF and AM to levels approximately 40-fold and 20-fold, respectively, higher than free-drug exposures in plasma.
Efficacy of Posaconazole in Murine Experimental Sporotrichosis
Authors: Fernández-Silva Fabiola , Capilla Javier , Mayayo Emilio , Guarro Josep
Published: February 2012

We developed a murine model of systemic sporotrichosis by using three strains of each of the two commonest species causing sporotrichosis, i.e.,
Sporothrix schenckii
sensu stricto and
Sporothrix brasiliensis
, in order to evaluate the efficacy of posaconazole (PSC). The drug was administered at a dose of 2.5 or 5 mg/kg of body weight twice a day by gavage, and one group was treated with amphotericin B (AMB) as a control treatment. Posaconazole, especially at 5 mg/kg, showed good efficacy against all the strains tested, regardless of their MICs, as measured by prolonged survival, tissue burden reduction, and histopathology.
Sustained Release of the CCR5 Inhibitors CMPD167 and Maraviroc from Vaginal Rings in Rhesus Macaques
Authors: Malcolm R. Karl , Veazey Ronald S. , Geer Leslie , Lowry Deborah , Fetherston Susan M. , Murphy Diarmaid J. , Boyd Peter , Major Ian , Shattock Robin J. , Klasse Per Johan , Doyle Lara A. , Rasmussen Kelsi K. , Goldman Laurie , Ketas Thomas J. , Moore John P.
Published: February 2012

Antiretroviral entry inhibitors are now being considered as vaginally administered microbicide candidates for the prevention of the sexual transmission of human immunodeficiency virus. Previous studies testing the entry inhibitors maraviroc and CMPD167 in aqueous gel formulations showed efficacy in the macaque challenge model, although protection was highly dependent on the time period between initial gel application and subsequent challenge. In this paper, we describe the sustained release of maraviroc and CMPD167 from matrix-type silicone elastomer vaginal rings both
in vitro
and
in vivo
. Both inhibitors were released continuously during 28 days from rings
in vitro
at rates of 100 to 2,500 μg/day. In 28-day pharmacokinetic studies in rhesus macaques, the compounds were measured in the vaginal fluid and vaginal tissue; steady-state fluid concentrations were ∼10
6
-fold greater than the 50% inhibitory concentrations (IC
50
s) for simian human immunodeficiency virus 162P3 inhibition in macaque lymphocytes
in vitro
. Plasma concentrations for both compounds were very low. The pretreatment of macaques with Depo-Provera (DP), which is commonly used in macaque challenge studies, was shown to significantly modify the biodistribution of the inhibitors but not the overall amount released. Vaginal fluid and tissue concentrations were significantly decreased while plasma levels increased with DP pretreatment. These observations have implications for designing macaque challenge experiments and also for ring performance during the human female menstrual cycle.
Therapeutic Equivalence Requires Pharmaceutical, Pharmacokinetic, and Pharmacodynamic Identities: True Bioequivalence of a Generic Product of Intravenous Metronidazole
Authors: Agudelo M. , Vesga O.
Published: February 2012

Animal models of infection have been used to demonstrate the therapeutic failure of “bioequivalent” generic products, but their applicability for this purpose requires the accurate identification of those products that are truly bioequivalent. Here, we present data comparing one intravenous generic product of metronidazole with the innovator product in a neutropenic mouse thigh anaerobic infection model. Simultaneous experiments allowed comparisons (generic versus innovator) of potency and the concentration of the active pharmaceutical ingredient (API), analytical chemistry (liquid chromatography/mass spectrometry [LC/MS]),
in vitro
susceptibility testing, single-dose serum pharmacokinetics (PK) in infected mice, and
in vivo
pharmacodynamics (PD) against
Bacteroides fragilis
ATCC 25825 in synergy with
Escherichia coli
SIG-1 in the neutropenic mouse thigh anaerobic infection model. The Hill dose-response model followed by curve-fitting analysis was used to calculate and compare primary and secondary PD parameters. The generic and the innovator products were identical in terms of the concentration and potency of the API, chromatographic and spectrographic profiles, MIC and minimal bactericidal concentrations (MBC) (2.0 mg/liter), and mouse PK. We found no differences between products in bacteriostatic doses (BD) (15 to 22 mg/kg of body weight per day) or the doses needed to kill 1 log (1LKD) (21 to 29 mg/kg per day) or 2 logs (2LKD) (28 to 54 mg/kg per day) of
B. fragilis
under dosing schedules of every 12 h (q12h), q8h, or q6h. The area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) was the best PD index to predict the antibacterial efficacy of metronidazole (adjusted coefficient of determination [AdjR
2
] = 84.6%), and its magnitude to reach bacteriostasis
in vivo
(56.6 ± 5.17 h) or to kill the first (90.8 ± 9.78 h) and second (155.5 ± 22.2 h) logs was the same for both products. Animal models of infection allow a thorough demonstration of the therapeutic equivalence of generic antimicrobials.
Pharmacokinetics of Rifampin in Peruvian Tuberculosis Patients with and without Comorbid Diabetes or HIV
Authors: Requena-Méndez Ana , Davies Geraint , Ardrey Alison , Jave Oswaldo , López-Romero Sonia L. , Ward Stephen A. , Moore David A. J.
Published: February 2012

For drug-compliant patients, poor responses to tuberculosis (TB) treatment might be attributable to subtherapeutic drug concentrations. An impaired absorption of rifampin was previously reported for patients with diabetes mellitus (DM) or HIV. The objectives of this study were to determine whether TB drug pharmacokinetics differed in Peruvian TB patients with DM or HIV. In this cross-sectional study, TB patients, recruited from health centers in Lima, Peru, had blood samples taken at 2 and 6 h after directly observed TB drug ingestion, to determine plasma concentrations of rifampin. Of 105 patients, 50 had TB without a comorbidity, 26 had coexistent DM, and 29 had coexistent HIV. Unexpectedly, the overall median 2- and 6-h levels of rifampin were 1.6 and 3.2 mg/liter, respectively, and the time to the peak concentration was 6 h (slow absorber) instead of 2 h (fast absorber) for 61 patients (62.2%). The geometric mean peak concentration of drug in serum (
C
max
) was significantly higher in fast absorbers than in slow absorbers (5.0 versus 3.8 mg/liter;
P
= 0.05). The rifampin
C
max
was significantly lower in male patients than in female patients (3.3 versus 6.3 mg/liter;
P
< 0.001). Neither slow nor fast absorbers with comorbidities (DM or HIV) had significantly different
C
max
results compared to those of TB patients without comorbidities. An analysis of variance regression analysis showed that female gender (
P
< 0.001) and the time to maximum concentration of drug in serum (
T
max
) at 2 h (
P
= 0.012) were independently correlated with increased exposure to rifampin. Most of this Peruvian study population exhibited rifampin pharmacokinetics different from those conventionally reported, with delayed absorption and low plasma concentrations, independent of the presence of an HIV or DM comorbidity.
Effect of Natural Polymorphisms in the HIV-1 CRF02_AG Protease on Protease Inhibitor Hypersusceptibility
Authors: Santos André F. A. , Tebit Denis M. , Lalonde Matthew S. , Abecasis Ana B. , Ratcliff Annette , Camacho Ricardo J. , Diaz Ricardo S. , Herchenröder Ottmar , Soares Marcelo A. , Arts Eric J.
Published: February 2012

Hypersusceptibility (HS) to inhibition by different antiretroviral drugs (ARVs) among diverse HIV-infected individuals may be a misnomer because clinical response to treatment is evaluated in relation to subtype B infections while drug susceptibility of the infecting virus, regardless of subtype, is compared to a subtype B HIV-1 laboratory strain (NL4-3 or IIIB). Mounting evidence suggests that HS to different ARVs may result in better treatment outcome just as drug resistance leads to treatment failure. We have identified key amino acid polymorphisms in the protease coding region of a non-B HIV-1 subtype linked to protease inhibitor HS, namely, 17E and 64M in CRF02_AG. These HS-linked polymorphisms were introduced in the BD6-15 CRF02_AG molecular clone and tested for inhibition using a panel of protease inhibitors. In general, suspected HS-linked polymorphisms did increase susceptibility to specific protease inhibitors such as amprenavir and atazanavir, but the combination of the 17E/64M polymorphisms showed greater HS. These two mutations were found at low frequencies but linked in a sequence database of over 700 protease sequences of CRF02_AG. In direct head-to-head virus competitions, CRF02_AG harboring the 17E/64M polymorphisms also had higher replicative fitness than did the 17E or the 64M polymorphism in the CFR02_AG clone. These findings suggest that subtype-specific, linked polymorphisms can result in hypersusceptibility to ARVs. Considering the potential benefit of HS to treatment outcome, screening for potential HS-linked polymorphisms as well as preexisting drug resistance mutations in treatment-naïve patients may guide the choice of ARVs for the best treatment outcome.
Intention, procedure, outcome and personhood in palliative sedation and euthanasia
Authors: Materstvedt Lars Johan
Published: February 2012

Palliative sedation at the end of life has become an important last-resort treatment strategy for managing refractory symptoms as well as a topic of controversy within palliative care. Furthermore, palliative sedation is prominent in the public debate about the possible legalisation of voluntary assisted dying (physician-assisted suicide and euthanasia). This article attempts to demonstrate that palliative sedation is fundamentally different from euthanasia when it comes to intention, procedure, outcome and the status of the person. Nonetheless, palliative sedation in its most radical form of terminal deep sedation parallels euthanasia in one respect: both end the experience of suffering. However, only the latter intentionally ends life and also has this as its goal. There is the danger that deep sedation could bring death forward in time due to particular side effects of the treatment. Still that would, if it happens, not be intended, and accordingly is defensible in view of the doctrine of double effect.