bluuebunny/crossref_metadata_2025 huggingface dataset:
Probability of walking, wheeled mobility, and assisted mobility in children and adolescents with cerebral palsy
Authors: PALISANO ROBERT J , HANNA STEVEN E , ROSENBAUM PETER L , TIEMAN BETH
Published: August 2009

Aim  Our aim was to describe how the probability of walking, wheeled mobility, and assisted mobility changes with environmental setting and age in children and adolescents with cerebral palsy (CP).

Method  The parents of a population‐based sample of 642 children and adolescents (360 males, 282 females; age range 16mo–21y) reported their children’s mobility at home, school, and outdoors at 6‐ or 12‐month intervals a mean of 5.2 times. Generalized mixed‐effects analyses were used to model the probabilities.

Results  By age 3 years, children with motor function classified as level I according to the Gross Motor Function Classification System (GMFCS) walked in all three settings. Children/adolescents classified as level V used assisted mobility, with a small number using wheeled mobility. In the case of children classified as GMFCS level II, the probability of walking varied with the environmental setting, which, at age 18, is outdoors 90% of the time. Among children classified as GMFCS level III, the probability of walking was highest at age 9 at school (68%), and at age 18 was approximately 50% in all three settings. Among children/adolescents rated as GMFCS level IV, the probability of wheeled mobility increased with age and, at age 18, 57% of mobility took place outdoors.

Interpretation  The results provide evidence that age and environmental setting influence method of mobility of children/adolescents with CP. The method that is preferred in one setting may not be preferred in another setting or at another age.
Matrix metalloproteinases inhibition provides neuroprotection against hypoxia‐ischemia in the developing brain
Authors: Chen Wanqiu , Hartman Richard , Ayer Robert , Marcantonio Suzanne , Kamper Joel , Tang Jiping , Zhang John H.
Published: August 2009

The present study was designed to investigate the role of matrix metalloproteinases (MMPs) in the immature brain and the long term effects of early MMPs inhibition after hypoxic‐ischemic (HI) injury. HI was induced by unilateral ligation of the right carotid artery followed by hypoxia (8% O2 for 2 h) in P7 rat pups. GM6001, a broad spectrum MMPs inhibitor, was injected (50 mg/kg or 100 mg/kg) intraperitoneally at 2 h and 24 h after HI injury. Blood‐brain barrier (BBB) integrity, brain edema, MMP‐2/‐9 activity, TIMP‐1/‐2 and tight junction protein (TJP) level were evaluated using IgG staining, Evan’s blue extravasation, brain water content, zymography and western blot. Doxycycline, another MMPs inhibitor, was injected (10 mg/kg or 30 mg/kg) intraperitoneally at 2 h after HI, then BBB integrity and brain edema were measured at 48 h post‐HI using brain water content measurement and IgG staining. The long‐term effects of early MMPs inhibition (GM6001, 100 mg/kg) were evaluated by neurobehavioral tests, body weight, and brain atrophy measurement. GM6001 attenuated brain edema and BBB disruption at the dosage of 100 mg/kg. MMP‐2 activity increased at 24 h and peaked at 48 h after HI, whereas MMP‐9 activity peaked at 24 h and tapered by 48 h after HI. MMP‐9/‐2 activities were significantly attenuated by GM6001 at 24 h and 48 h after HI. The degradation of TJPs (ZO‐1 and occludin) at 48 h after HI was reversed by GM6001 treatment. Early MMPs inhibition had long‐term effects that attenuated ipsilateral brain tissue loss, and improved neurobehavioral outcomes after HI. These results suggest that early MMPs inhibition with a broad‐spectrum inhibitor provides both acute and long‐term neuroprotection in the developing brain by reducing TJPs degradation, preserving BBB integrity, and ameliorating brain edema after neonatal HI injury.
Evaluating chemical and physical quality indicators for a structurally fragile tropical soil
Authors: Moura E. G. , Moura N. G. , Marques E. S. , Pinheiro K. M. , Costa Sobrinho J. R. S. , Aguiar A. C. F.
Published: August 2009

In tropical regions with well‐defined wet and dry seasons, repeated wetting and drying cycles can harden exposed soils and inhibit root growth. While this phenomenon has been well documented, the relationships between plant productivity and chemical and physical soil parameters have not been well defined. The current study identifies the abiotic parameters that best relate to measures of plant development, specifically to corn productivity. The primary goal of this research was to provide information to improve agricultural sustainability in humid tropical ecosystems. The effects of using plant residues as a cover on a sandy soil were studied. Four leguminous species were planted in an alley cropping system, Leucaena leucocephala, Cajanus cajan, Clitoria fairchildiana and Acacia mangium, and corn was planted in January 2007 between legume rows. We measured the most important chemical and physical soil parameters. Yield indicators included cob weight and the weight of 100 kernels. The application of plant residues altered soil conditions and increased rootable soil volume. This change was associated with an increase by 10% in water retention above field capacity in the uppermost soil layer of the residue‐covered sections of the experiment. In the control sections cobs were up to three times lighter (31.43–93.38 g) in the bare soil control than those from residue‐covered sections of the experiment. Dynamic indicators related to nutrient absorption and crop evapotranspiration, such as the number of days with water stress and rootable soil volume, were the most suitable indicators for assessing soil quality. The response of corn was best related to complex physical indicators, including the amount of N applied via legume residues.
Proof‐of‐concept study on the suitability of 13C‐urea as a marker substance for assessment of in vivo behaviour of oral colon‐targeted dosage forms
Authors: Schellekens RCA , Olsder GG , Langenberg SMCH , Boer T , Woerdenbag HJ , Frijlink HW , Kosterink JGW , Stellaard F
Published: August 2009

Background and purpose:  13C‐urea may be a suitable marker to assess the in vivo fate of colon‐targeted dosage forms given by mouth. We postulated that release in the colon (urease‐rich segment) of 13C‐urea from colon‐targeted capsules would lead to fermentation of 13C‐urea by bacterial ureases into 13CO2. Subsequent absorption into the blood and circulation would lead to detectable 13C (as 13CO2) in breath. If, however, release of 13C‐urea occurred in the small intestine (urease‐poor segment), we expected detectable 13C (as 13C‐urea) in blood but no breath 13C (as 13CO2). The differential kinetics of 13C‐urea could thus potentially describe both release kinetics and indicate the gastrointestinal segment of release.

Experimental approach:  The in vivo study consisted of three experiments, during which the same group of four volunteers participated.

Key results:  The kinetic model was internally valid. The appearance of 13C‐in breath CO2 (Ffermented) and the appearance of 13C in blood as 13C‐urea (Fnot fermented) show a high inverse correlation (Pearson's r=−0.981, P= 0.06). The total recovery of 13C (Ffermented+Fnot fermented) averaged 99%, indicating complete recovery of the administered 13C via breath and blood. 13CO2 exhalation was observed in all subjects. This indicates that 13C‐urea was available in urease‐rich segments, such as the caecum or colon.

Conclusions and implications:  In this proof‐of‐concept study, 13C‐urea was able to provide information on both the release kinetics of a colon‐targeted oral dosage form and the gastrointestinal segment where it was released.
Modulation of cellular redox state underlies antagonism between oxaliplatin and cetuximab in human colorectal cancer cell lines
Authors: Dahan Laetitia , Sadok Amine , Formento Jean‐Louis , Seitz Jean François , Kovacic Hervé
Published: August 2009

Background and purpose:  Oxaliplatin is the first platinum‐based compound effective in the treatment of colorectal cancer. Oxaliplatin combined with cetuximab for metastatic colorectal cancer is under evaluation. The preliminary results seem controversial, particularly for the use of cetuximab in K‐Ras mutated patients. K‐Ras mutation is known to affect redox homeostasis. Here we evaluated how the efficacy of oxaliplatin alone or combined with cetuximab varied according to the Ras mutation and redox status in a panel of colorectal tumour cell lines.

Experimental approach:  Viability was evaluated by methylthiazoletetrazolium assay, reactive oxygen species production by DCFDA and lucigenin on HT29‐D4, Caco‐2, SW480 and SW620 cell lines.

Key results:  Combination of oxaliplatin and cetuximab was less cytotoxic than oxaliplatin alone in colorectal cells harbouring wild‐type Ras and membrane expression of receptors for epidermal growth factor receptor (EGFR), such as HT29‐D4 and Caco‐2 cells. In contrast, cetuximab did not affect oxaliplatin efficiency in cells harbouring K‐RasV12 mutation, irrespective of membrane EGFR expression (SW620 and SW480 cells). Transfection of HT29‐D4 with K‐RasV12 decreased oxaliplatin IC50 and impaired cetuximab sensitivity, without affecting expression of membrane EGFR compared with HT29‐D4 control. Oxaliplatin efficacy relies on endogenous production of H2O2. Cetuximab inhibits H2O2 production inhibiting the EGFR/Nox1 NADPH oxidase pathway. Oxaliplatin efficacy was impaired by short hairpin RNA for Nox1 and by catalase (H2O2 scavenger).

Conclusions and implications:  Cetuximab limited oxaliplatin efficiency by affecting the redox status of cancer cells through Nox1. Such combined therapy might be improved by controlling H2O2 elimination.
On‐the‐fly server‐based aerial imagery management system
Authors: Seguí Ana E. , Lerma José L. , Navarro Santiago , Portalés Cristina
Published: August 2009

Aerial images are valuable products when dealing with both geospatial and geotemporal analysis. Nowadays, they are widely used for many different purposes and by an extensive public, including private companies, official administrations and individual users. Although in the past few years there has been an increasing interest in showing all kinds of geographical information on the World Wide Web, access to aerial imagery and its dissemination are still difficult and lack flexibility. This paper introduces an aerial imagery management system based on client–server principles, operated so as to allow users quick and efficient queries, processing and management of huge sets of photogrammetric imagery stored on raster servers. It is a novel product that is ready to provide image‐based cartographic data available in public and private digital warehouses, facilitating all the required visualisations and queries, as well as geometric and radiometric processing on the fly. This paper shows the design, system architecture and various functionalities of the system in a real‐life scenario.
Performance Management in Insurance Firms by Using Transfer Pricing
Authors: Doff René , Bilderbeek Jan , Bruggink Bert , Emmen Pieter
Published: August 2009

Abstract

In this article, we analyze the asset and liability management and market risk systems of insurance companies. We discuss that the current system is not goal congruent and does not satisfy necessary conditions for effective control. It follows that managers are unable to run their business effectively. We develop a transfer pricing system that allows the clear separation of underwriting and investment activities, both on the risk and return aspects. It creates the appropriate incentive schemes. We illustrate this system with an example indicating the differences in incentives between the traditional embedded value measures and the proposed funds transfer pricing system.
Recent Developments in the Aviation Insurance Industry
Authors: Flouris Triant , Hayes Paul , Pukthuanthong‐Le Kuntara , Thiengtham Dolruedee , Walker Thomas
Published: August 2009

Abstract

The aviation industry has been hard hit in recent years. While there are numerous factors that have contributed to the industry's dilemma, rising and volatile insurance premiums—particularly after the events of 9/11—have posed a particular problem for many airline managers. Despite a general trend for accident rates involving commercial passenger airplanes to decrease as aviation technology has advanced over the years and airplanes have become safer, the aviation insurance market has been far from stable. This article provides an overview of how the aviation insurance industry works and how it has changed in recent years. We take a look at how the risk is spread between insurers, how insurers treat deliberate acts of violence, and lastly, how insurers price the risk. Our article shows that the aviation insurance market has undergone considerable changes in recent years and that it has adjusted to the post‐9/11 aviation insurance realities being reasonably ready to handle events of an even more catastrophic magnitude.
Debt Sustainability Under Catastrophic Risk: The Case for Government Budget Insurance
Authors: Borensztein Eduardo , Cavallo Eduardo , Valenzuela Patricio
Published: August 2009

Abstract

Natural disasters are an important source of vulnerability in the Caribbean region. Despite being one of the more disaster‐prone areas of the world, it has the lowest levels of insurance coverage. This article examines the vulnerability of Belize's public finance to the occurrence of hurricanes and the potential impact of insurance instruments in reducing that vulnerability. The article finds that catastrophic risk insurance significantly improves Belize's debt sustainability. In addition, the methodology employed makes it possible to estimate the appropriate level of insurance, which for the case of Belize is a maximum coverage of US$120 million per year. International organizations can play a role in assisting countries to overcome distortions in insurance markets, as well as in helping to relax internal political resistance to the purchase of insurance policies.
Prognostic Evaluation of QT‐Dispersion in Elderly Hypertensive and Normotensive Patients
Authors: DIMOPOULOS STAVROS , NICOSIA FRANCO , TURINI DANIELE , ZULLI ROBERTO
Published: August 2009

Background:

QT‐corrected interval dispersion (QTcD) is an indirect index of increased heterogeneity of ventricular repolarization. However, the prognostic value of (QTcD) in elderly hypertensive and normotensive patients has not been thoroughly investigated yet.

Methods:

The study population consisted of 60 consecutive patients (34 males/26 females; mean age: 63±11 years) with mild to moderate essential arterial hypertension and 48 consecutive age‐matched healthy subjects (24 males/24 females; 65±16 years). QTcD was measured by a 12‐lead electrocardiogram (ECG) as the difference between maximum and minimum QT‐interval, corrected for heart rate. Ventricular arrhythmias were recorded by a 24‐hour Holter ECG and classified by a modified Lown's score (range: 0–6). Left ventricular mass was measured echocardiographically and indexed by body surface area [left ventricular mass index (LVMI)]. Nine patients were lost during the follow‐up period. Patients were followed up for 54±9 months, and the primary end‐point was the major cardiovascular events (including cardiac mortality).

Results:

Major cardiovascular events occurred in 22 patients (22%). Patients with QTcD ≥45 ms (n = 35) had a higher rate of major cardiovascular events (43% vs 11%; log rank: 14.8; P < 0.001), a higher LVMI (146±29 vs 104±21 g/m2; P < 0.001), greater values of systolic and diastolic blood pressure (154±16 vs 144±18 mmHg; P < 0.01 and 92±10 vs 88±8 mmHg; P < 0.05, respectively), a higher number of premature ventricular beats (354±870 vs 113±301; P < 0.05), and a greater Lown's score (3.7±1.9 vs 1.4±1.8; P < 0.05) than patients with QTcD <45 ms. QTcD (≥ or < 45 ms) was an independent predictor of major cardiovascular events (odds ratio: 4.9; 95% confidence interval: 2.0–12.1; P = 0.001) after adjustment for LVMI, Lown's score (≥ or <3), age (≥ or <65 years), and QTc max (≥ or <437 ms).

Conclusions:

QTcD is an independent predictor of major cardiovascular events in elderly hypertensive and normotensive patients and might be used in their risk stratification.
When Water Hurts
Authors: CASELLA FRANCESCO , DIANA ALESSANDRO , BULGHERONI MARA , SOLBIATI MONICA , CERIANI ELISA , PENTIMALLI FRANCESCO , SAGONE ANTONIO , MONTANO NICOLA
Published: August 2009

Deglutition syncope refers to an uncommon cause of neurally mediated syncope induced by swallowing. We briefly review a case of a 66‐year‐old man who experienced recurrent syncope episodes during ingestion of beverages, mainly water. Our investigations documented several short asymptomatic episodes of asystole and one prolonged complete atrioventricular block of around 15 seconds associated with the syncopal events, during swallowing. Barium x‐ray and manometry evaluations revealed only a nonspecific esophageal dysmotility. An underlying sick‐sinus syndrome was found on electrophysiologic study. A DDD pacemaker implantation was performed leading to total disappearance of patient's symptoms.
Does Oxidative Stress Modulate Left Ventricular Diastolic Function in Asymptomatic Subjects with Hereditary Hemochromatosis?
Authors: Shizukuda Yukitaka , Bolan Charles D. , Tripodi Dorothy J. , Sachdev Vandana , Nguyen Tammy T. , Botello Gilberto , Yau Yu‐Ying , Sidenko Stanislav , Inez Ernst , Ali Mir I. , Waclawiw Myron A. , Leitman Susan F. , Rosing Douglas R.
Published: August 2009

Background: Little is known about the early mechanisms mediating left ventricular (LV) diastolic dysfunction in patients with hereditary hemochromatosis (HH). However, the increased oxidative stress related to iron overload may be involved in this process, and strain rate (SR), a sensitive echocardiography‐derived measure of diastolic function, may detect such changes. Aim: we evaluated the relationship between left ventricular diastolic function measured with tissue Doppler SR and oxidative stress in asymptomatic HH subjects and control normal subjects. Materials and Methods: Ninety‐four consecutive visits of 43 HH subjects, age 30–74 (50 ± 10, mean ± SD), and 37 consecutive visits of 21 normal volunteers, age 30–63 (48 ± 8), were evaluated over a 3‐year period. SR was obtained from the basal septum in apical four‐chamber views. All patients had confirmed C282Y homozygosity, a documented history of iron overload, and were New York Heart Association functional class I. Normal volunteers lacked HFE gene mutations causing HH. Results: In the HH subjects, the SR demonstrated moderate but significant correlations with biomarkers of oxidative stress; however, no correlations were noted in normal subjects. The biomarkers of iron overload per se did not show significant correlations with the SR. Conclusion: Although our study was limited by the relatively small subject number, these results suggest that a possible role of oxidative stress to affect LV diastolic function in asymptomatic HH subjects and SR imaging may be a sensitive measure to detect that effect. (ECHOCARDIOGRAPHY, Volume 26, November 2009)
Human Rights Barriers for Displaced Persons in Southern Sudan
Authors: Pavlish Carol , Ho Anita
Published: August 2009

Purpose:This community‐based research explores community perspectives on human rights barriers that women encounter in a postconflict setting of southern Sudan.

Methods:An ethnographic design was used to guide data collection in five focus groups with community members and during in‐depth interviews with nine key informants. A constant comparison method of data analysis was used. Atlas.ti data management software facilitated the inductive coding and sorting of data.

Findings:Participants identified three formal and one set of informal community structures for human rights. Human rights barriers included shifting legal frameworks, doubt about human rights, weak government infrastructure, and poverty.

Conclusions:The evolving government infrastructure cannot currently provide adequate human rights protection, especially for women. The nature of living in poverty without development opportunities includes human rights abuses. Good governance, protection, and human development opportunities were emphasized as priority human rights concerns. Human rights framework could serve as a powerful integrator of health and development work with community‐based organizations.

Clinical Relevance:Results help nurses understand the intersection between health and human rights as well as approaches to advancing rights in a culturally attuned manner.
The Use of Liquid Latex for Soot Removal from Fire Scenes and Attempted Fingerprint Development with Ninhydrin*
Authors: Clutter Susan Wright , Bailey Robert , Everly Jeff C. , Mercer Karl
Published: August 2009

Abstract:  Throughout the United States, clearance rates for arson cases remain low due to fire’s destructive nature, subsequent suppression, and a misconception by investigators that no forensic evidence remains. Recent research shows that fire scenes can yield fingerprints if soot layers are removed prior to using available fingerprinting processes. An experiment applying liquid latex to sooted surfaces was conducted to assess its potential to remove soot and yield fingerprints after the dried latex was peeled. Latent fingerprints were applied to glass and drywall surfaces, sooted in a controlled burn, and cooled. Liquid latex was sprayed on, dried, and peeled. Results yielded usable prints within the soot prior to removal techniques, but no further fingerprint enhancement was noted with Ninhydrin. Field studies using liquid latex will be continued by the (US) Virginia Fire Marshal Academy but it appears that liquid latex application is a suitable soot removal method for forensic applications.
A conjunctival lesion with histological features similar to large‐cell acanthoma of the skin
Authors: Ghazi Nicola G. , Patel Bina S. , Olsakovsky Leslie A. , White Kevin , Patterson James W. , Carter Bruce
Published: August 2009

Large‐cell acanthoma (LCA) is a sharply demarcated epidermal lesion composed of large keratinocytes and characterized by hyperkeratosis, hypergranulosis and orthokeratosis. It usually affects actinically damaged skin. LCA is currently believed to be a distinct entity with an unclear pathogenesis and a benign biologic behavior. Here, we describe the first occurrence of LCA in the conjunctiva. The lesion recurred following initial excision, and later recurred as a carcinoma in situ following a second excision. This case suggests that LCA may have a malignant and transformation potential.

Ghazi NG, Patel BS, Olsakovsky Leslie A, White K, Patterson JW. A conjunctival lesion with histological features similar to large‐cell acanthoma of the skin.
Exploring the role of stem cells in cutaneous wound healing
Authors: Lau Katherine , Paus Ralf , Tiede Stephan , Day Philip , Bayat Ardeshir
Published: August 2009

Abstract:  The skin offers a perfect model system for studying the wound healing cascade, which involves a finely tuned interplay between several cell types, pathways and processes. The dysregulation of these factors may lead to wound healing disorders resulting in chronic wounds, as well as abnormal scars such as hypertrophic and keloid scars. As the contribution of stem cells towards tissue regeneration and wound healing is increasingly appreciated, a rising number of stem cell therapies for cutaneous wounds are currently under development, encouraged by emerging preliminary findings in both animal models and human studies. However, we still lack an in‐depth understanding of the underlying mechanisms through which stem cells contribute to cutaneous wound healing. The aim of this review is, therefore, to present a critical synthesis of our current understanding of the role of stem cells in normal cutaneous wound healing. In addition to summarizing wound healing principles and related key molecular and cellular players, we discuss the potential participation of different cutaneous stem cell populations in wound healing, and list corresponding stem cells markers. In summary, this review delineates current strategies, future applications, and limitations of stem cell‐based or stem cell‐targeted therapy in the management of acute and chronic skin wounds.
Olfaction in dentistry
Authors: Bromley SM , Doty RL
Published: August 2009

Oral Diseases (2010) 16, 221–232

Practitioners of oral medicine frequently encounter patients with complaints of taste disturbance. While some such complaints represent pathological processes specific to the gustatory system, per se, this is rarely the case. Unless taste‐bud mediated qualities such as sweet, sour, bitter, salty, umami, chalky, or metallic are involved, ‘taste’ dysfunction inevitably reflects damage to the sense of smell. Such ‘taste’ sensations as chicken, chocolate, coffee, raspberry, steak sauce, pizza, and hamburger are dependent upon stimulation of the olfactory receptors via the nasopharynx during deglutition. In this paper, we briefly review the anatomy, physiology, and pathophysiology of the olfactory system, along with means for clinically assessing its function. The prevalence, etiology, and nature of olfactory disorders commonly encountered in the dental clinic are addressed, along with approaches to therapy and patient management.
Spatial patterns of association at local and regional scales in coastal sand dune communities
Authors: Forey Estelle , Lortie Christopher J. , Michalet Richard
Published: August 2009

Questions: Are positive understorey‐dominant associations important in physically severe dune communities and does the strength of positive associations vary with disturbance at the local scale and with stress at the regional scale? Do associational patterns observed at the neighbourhood scale predict diversity at higher scales?

Location: Coastal sand dunes, Aquitaine (France).

Methods: Associational patterns with five dominant species were recorded along a local gradient of disturbance and a 240‐km long regional gradient. Density, richness, cover and variance ratio of understorey species were recorded in quadrats located in dominant and in open areas. Spatial pattern of dominant plant species was recorded using a distance‐based method.

Results: Positive understorey‐dominant associations were most frequent at both regional and local scale, although negative associations with understorey species were observed for one of the five dominants. At the regional scale, there was a shift in the magnitude of spatial associations, with higher positive associations in the most stressful sites, whereas spatial associations where not affected by the local disturbance gradient. Positive associations were not related to the size of the dominants but rather influenced by the identity of the dominant species.

Conclusions: Our study highlights the potential crucial role of facilitation together with the importance of turnover of the dominants in explaining large‐scale variation in diversity. However, because positive associations may also be attributed to environmental heterogeneity or co‐occurrence of microhabitat preferences of species, experiments are needed to fully assess the relative importance of facilitation versus other drivers of community diversity.
Simplified yet highly accurate enzyme kinetics for cases of low substrate concentrations
Authors: Härdin Hanna M. , Zagaris Antonios , Krab Klaas , Westerhoff Hans V.
Published: August 2009

Much of enzyme kinetics builds on simplifications enabled by the quasi‐steady‐state approximation and is highly useful when the concentration of the enzyme is much lower than that of its substrate. However, in vivo, this condition is often violated. In the present study, we show that, under conditions of realistic yet high enzyme concentrations, the quasi‐steady‐state approximation may readily be off by more than a factor of four when predicting concentrations. We then present a novel extension of the quasi‐steady‐state approximation based on the zero‐derivative principle, which requires considerably less theoretical work than did previous such extensions. We show that the first‐order zero‐derivative principle, already describes much more accurately the true enzyme dynamics at enzyme concentrations close to the concentration of their substrates. This should be particularly relevant for enzyme kinetics where the substrate is an enzyme, such as in phosphorelay and mitogen‐activated protein kinase pathways. We illustrate this for the important example of the phosphotransferase system involved in glucose uptake, metabolism and signaling. We find that this system, with a potential complexity of nine dimensions, can be understood accurately using the first‐order zero‐derivative principle in terms of the behavior of a single variable with all other concentrations constrained to follow that behavior.
Structural origins for selectivity and specificity in an engineered bacterial repressor–inducer pair
Authors: Klieber Michael A. , Scholz Oliver , Lochner Susanne , Gmeiner Peter , Hillen Wolfgang , Muller Yves A.
Published: August 2009

The bacterial tetracycline transcription regulation system mediated by the tetracycline repressor (TetR) is widely used to study gene expression in prokaryotes and eukaryotes. To study multiple genes in parallel, a triple mutant TetR(K64L135I138) has been engineered that is selectively induced by the synthetic tetracycline derivative 4‐de‐dimethylamino‐anhydrotetracycline (4‐ddma‐atc) and no longer by tetracycline, the inducer of wild‐type TetR. In the present study, we report the crystal structure of TetR(K64L135I138) in the absence and in complex with 4‐ddma‐atc at resolutions of 2.1 Å. Analysis of the structures in light of the available binding data and previously reported TetR complexes allows for a dissection of the origins of selectivity and specificity. In all crystal structures solved to date, the ligand‐binding position, as well as the positioning of the residues lining the binding site, is extremely well conserved, irrespective of the chemical nature of the ligand. Selective recognition of 4‐ddma‐atc is achieved through fine‐tuned hydrogen‐bonding constraints introduced by the His64→Lys substitution, as well as a combination of hydrophobic effect and the removal of unfavorable electrostatic interactions through the introduction of Leu135 and Ile138.
Vardenafil Allows Successful Intercourse initiated Rapidly After Dosing in Japanese Patients with Diabetes Mellitus and Erectile Dysfunction
Authors: Nagao Koichi , Kobayashi Hideyuki , Fujikawa Keita , Tachibana Takashi , Iwamoto Yasuhiko , Ishii Nobuhisa , Turek Paul J. , Brant William O. , Kamidono Sadao
Published: August 2009

Introduction

Vardenafil is reported to improve success rates in the maintenance of an erection sufficient for completion of intercourse (SEP-3) compared with placebo in erectile dysfunction (ED) patients who attempted intercourse from as early as 15 minutes after dosing. However, these data were based on general ED patients, using time from administration to initiation of intercourse. It is unclear whether the results can be applied to difficult-to-treat ED patients, such as those with diabetes mellitus (DM), with the time between dosing and insertion into vagina.

Aim

To determine whether early onset of activity with vardenafil is also achievable in ED patients with DM.

Methods

Data from a 12-week Phase III clinical trial (randomized, placebo-controlled, double-blind, parallel-group comparison) in Japanese men with ED and DM was used for analysis. In this study, patients received vardenafil 10 mg, 20 mg, or placebo, and were instructed to start sexual activity 1 hour after dosing. Mean per-patient SEP-3 success rates (intent-to-treat; ITT population), based on patient diary question, were calculated by the time between dosing and insertion. The least-squares means and nominal P values for differences versus placebo were derived by analysis of covariance with terms for baseline.

Main Outcome Measures

SEP-3 success rates in each time interval.

Results

The majority of inserts occurred between 60–90 minutes after dosing, but 100 of inserts in 52 patients occurred in the first 30 minutes. SEP-3 success rates in patients who inserted in each interval from 0–15 minutes (P = 0.0268), 15–30 minutes (P = 0.0094) through > 120 minutes were all higher in vardenafil-treated patients than those in placebo.

Conclusions

In this retrospective analysis, a rapid onset of activity was also demonstrated in difficult-to-treat ED patients. Vardenafil improved successful intercourse rates compared with placebo in Japanese DM patients who inserted from as early as 15 minutes to >120 minutes after dosing.
II. Slow Oscillations in Vaginal Blood Flow: Regulation of Vaginal Blood Flow Patterns in Rat by Central and Autonomic Mechanisms
Authors: Allers Kelly A. , Richards Natalie , Scott Liam , Sweatman Catherine , Cheung Jolenta , Reynolds David , Casey James H. , Wayman Chris
Published: August 2009

Introduction

A new method for assessing female sexual arousal through changes in slow oscillatory patterns in vaginal blood flow was first described in the previous manuscript [1]. This method was translational and discriminated between normal healthy volunteers and women with female sexual arousal disorder.

Aim

These studies addressed the influence of autonomic and central nervous systems on slow vaginal blood flow oscillations in rats.

Methods

Vaginal blood flow oscillations were measured in urethane-anesthetized rodents using laser Doppler flowmetry. Acquired data were filtered for frequency analysis range of 0.013–2.5 Hz.

Main Outcome Meaures

Data were assessed for changes in a high frequency range (HF=0.6–2.5 Hz), and low frequency range (LF=0.013–0.6 Hz).

Results

The basal HF oscillatory component of vaginal blood flow was primarily vagally mediated, although could be modulated pharmacologically with p-chloroamphetamine in the absence of vagal innervation. The LF component could be modulated by antagonists of noradrenergic receptors but did not appear to be dependent upon tonic activation of sympathetic circuitry. The non-selective dopamine receptor agonist apomorphine induced changes in vaginal blood flow oscillations consistent with sexual arousal during metestrus in the presence of the peripheral antagonist domperidone but not in the presence of the centrally acting antagonist haloperidol. Electrical stimulation of the paraventricular nucleus (PVN) of the hypothalamus induced an anti-arousal response in vaginal blood flow oscillations. These data demonstrated that manipulation of the central nervous system alone (via centrally acting apomorphine or electrical stimulation of the PVN) could produce either a pro-arousal or an anti-arousal response in vaginal blood flow oscillations. Alterations in the LF/HF ratio measured from vaginal laser Doppler flowmetry were independently regulated from vasculature in the trunk, the tongue, and electrocardiogram-derived heart rate variability, and were independent of overall vasocongestion of the vagina as measured by mean blood flow.

Conclusions

These data indicated that slow oscillations in vaginal blood flow from rodents may be utilized as an animal model of female sexual arousal. Changes in these oscillations are driven by the central nervous system and modulated by the autonomic nervous system.
The OsDHODH1 Gene is Involved in Salt and Drought Tolerance in Rice
Authors: Liu Wen‐Ying , Wang Mei‐Mei , Huang Ji , Tang Hai‐Juan , Lan Hong‐Xia , Zhang Hong‐Sheng
Published: August 2009

In the present paper, we identified and cloned OsDHODH1 encoding a putative cytosolic dihydroorotate dehydrogenase (DHODH) in rice. Expression analysis indicated that OsDHODH1 is upregulated by salt, drought and exogenous abscisic acid (ABA), but not by cold. By prokaryotic expression, we determined the enzymatic activity of OsDHODH1 and found that overproduction of OsDHODH1 significantly improved the tolerance of Escherichia coli cells to salt and osmotic stresses. Overexpression of the OsDHODH1 gene in rice increased the DHODH activity and enhanced plant tolerance to salt and drought stresses as compared with wild type and OsDHODH1‐antisense transgenic plants. Our findings reveal, for the first time, that cytosolic dihydroorotate dehydrogenase is involved in plant stress response and that OsDHODH1 could be used in engineering crop plants with enhanced tolerance to salt and drought.
Osmopriming‐Regulated Changes of Plasma Membrane Composition and Function were Inhibited by Phenylarsine Oxide in Soybean Seeds
Authors: Zhuo Jiajin , Wang Weixiang , Lu Yun , Sen Wu , Wang Xiaofeng
Published: August 2009

The aim of the present work was to investigate the effects of osmoconditioning on chilling injury in chilling‐sensitive soybean (Glycine max (L.) Merr. Zhonghuang No. 22) seeds during imbibition. Low temperatures reduced the germination rate and no seed germinated at 1 °C. Osmoconditioning of seeds at 20 °C with a polyethylene glycol‐8000 (PEG8000) solution at 1.5 MPa for 72 h followed by drying back to their initial moisture content (MC) reduced their chilling sensitivity. The phenylarsine oxide (PAO), an inhibitor of protein tyrosinephosphatases, was used to investigate the possible involvement of phosphorylation‐dephosphorylation of Tyr residues in the plasma membrane composition and function when seeds were osmoconditioned. The results showed the germination of osmoconditioned seeds decreased significantly when PAO was added in PEG solution after chilling treatment. PAO inhibited changes in composition of plasma membrane phospholipids and fatty acid induced by osmocondition, indicated that tyrosine protein phosphorylation is involved in the regulatory mechanisms of osmocondition‐responsive chilling in soybean seeds. Western blot result further indicated that osmocondition treatment improved the activity of plasma membrane H+‐ATPase after chilling treatment, but this effect was abolished by PAO. The possible regulation mechanism by Tyr protein phosphorylation is discussed.
A Comparative Study on the Role of Cytokinins in Caryopsis Development in the Maize miniature1 Seed Mutant and Its Wild Type
Authors: Rijavec Tomaž , Kovač Maja , Kladnik Aleš , Chourey Prem S. , Dermastia Marina
Published: August 2009

We report here on a comparative developmental profile of plant hormone cytokinins in relation to cell size, cell number and endoreduplication in developing maize caryopsis of a cell wall invertase‐deficient miniature1 (mn1) seed mutant and its wild type, Mn1, genotype. Both genotypes showed extremely high levels of total cytokinins during the very early stages of development, followed by a marked and genotype specific reduction. While the decrease of cytokinins in Mn1 was associated with their deactivation by 9‐glucosylation, the absolute and the relative part of active cytokinin forms was higher in the mutant. During the exponential growth phase of endosperm between 6 d after pollination and 9 d after pollination, the mean cell doubling time, the absolute growth rate and the level of endoreduplication were similar in the two genotypes. However, the entire duration of growth was longer in Mn1 compared with mn1, resulting in a significantly higher cell number in the Mn1 endosperm. These data correlate with the previously reported peak levels of the Mn1‐encoded cell wall invertase‐2 (INCW2) at 12 d after pollination in the Mn1 endosperm. A model showing possible crosstalk among cytokinins, cell cycle and cell wall invertase as causal to increased cell number and sink strength of the Mn1 developing endosperm is discussed.
Stars with planets and the thick disc
Authors: Gonzalez Guillermo
Published: August 2009

We employ three samples of nearby stars that include stars hosting Doppler-detected planets to test a recent finding by Haywood that the incidence of planets is greater among transition and thick disc stars than it is among thin disc stars in the range [Fe/H]≤−0.20 dex; this implies that distance from the Galactic Centre is the causative factor for planet formation, not [Fe/H]. Thick disc stars with planets do have a smaller mean [Fe/H] value than thin disc stars over this range in [Fe/H], and the most [Fe/H]-poor stars with planets tend to have more negative Vlsr values. However, if we compare stars with planets according to mass abundance of the refractory elements important for planet formation (Mg, Si, Fe), then thick disc and [Fe/H]-poor thin disc stars with planets have similar distributions. There is no need to invoke a new mechanism for giant planet formation to account for the distributions of stars with planets among dwarf stars.
Off-Label Prescribing: A Call for Heightened Professional and Government Oversight
Authors: Dresser Rebecca , Frader Joel
Published: August 2009

Off-label prescribing is an integral part of contemporary medicine. Many patients benefit when they receive drugs or devices under circumstances not specified on the label approved by the Food and Drug Administration (FDA). An off-label use may provide the best available intervention for a patient, as well as the standard of care for a particular health problem. In oncology, pediatrics, geriatrics, obstetrics, and other practice areas, patient care could not proceed without off-label prescribing. When scientific and medical evidence justify off-label uses, physicians promote patients’ interests by prescribing products off label.

Off-label prescribing can also harm patients, however. The potential for harm is greatest when an offlabel use lacks a solid evidentiary basis. A 2006 study examining prescribing practices for 169 commonly prescribed drugs found high rates of off-label use with little or no scientific support. Researchers examining off-label use in U.S. children’s hospitals concluded, “[W]e still have incomplete knowledge about the safety and efficacy of many medications commonly used to treat children across a range of drug classes and clinical diagnoses.”
Data and Safety Monitoring Boards: Some Enduring Questions
Authors: Kowalski Charles J. , Hewett Jan L.
Published: August 2009

Data Safety and Monitoring Boards (DSMBs) were introduced in the 1960s to monitor data in clinical trials to ensure subject safety. It was thought important that DSMB members be experts in the field(s) of interest, but not otherwise involved in the study (e.g., sponsors and investigators) in order to maximize objectivity. Since then, the use of DSMBs has increased dramatically, and their scope has expanded to include scientific issues — in particular, to avoid bias that can result when trials are stopped early because of evidence that one treatment has greater efficacy or causes greater harm than another; or that no treatment is likely to do better than any other.
The Constitutionality of Mandates to Purchase Health Insurance
Authors: Hall Mark A.
Published: August 2009

Many proposals to reform health care finance and delivery require individuals or private employers to pay for private health insurance. Senators Ron Wyden and Robert Bennett’s Healthy Americans Act, for instance, would require every adult person who is not covered by a public program to purchase health insurance. Similarly, President Obama’s campaign proposal requires that parents arrange for coverage of their minor children and that all but small employers pay a tax if they do not provide their workers health insurance.

This paper addresses the constitutionality of such proposals. Compulsory health insurance might raise constitutional concerns because there is no existing social legislation that serves as a perfect legal analogy to an individual mandate for private health insurance. Insurance mandates are familiar in other contexts, such as automobile liability, but they present an easier case for constitutionality because they are a condition of exercising a privilege, such as driving a car.
The Role of ERISA Preemption in Health Reform: Opportunities and Limits
Authors: Jacobson Peter D.
Published: August 2009

It should come as no surprise to any observer of health policy debates that the preemption provisions of the Employee Retirement Income Security Act (ERISA) will play a major role in determining the contours of any health reform initiative. For the past few years, many states have been aggressively pursuing health reform experiments, while congressional action has essentially been deadlocked along partisan political lines. Yet after the 2008 election results, there is reason to expect considerable congressional attention to health reform. President Obama has made health reform a priority of his administration, and several members of Congress have long been waiting for an opportunity to pursue health reform legislation.
Insurance Discrimination on the Basis of Health Status: An Overview of Discrimination Practices, Federal Law, and Federal Reform Options
Authors: Rosenbaum Sara
Published: August 2009

This is an important time to focus on the question of insurance discrimination based on health status. The nation once again is poised to embark on a major health care reform debate. Even as the number of uninsured stands at some 45 million persons, millions more may be poised to lose coverage during the worst economic downturn in generations. In addition, a large number of persons may be seriously under-insured, with coverage falling significantly below the cost of necessary health care. In recent years, the proportion of insured persons who are underinsured has grown by 60% since 2003, reaching an estimated 25 million persons in 2007. Health care costs experienced by insured persons now account for more than 75% of all personal bankruptcies related to medical care. Underlying these figures is a national approach to health care financing for the non-elderly that effectively increases the odds that those who are in poor health status will be uninsured or underinsured.
Privacy and Health Information Technology
Authors: McGraw Deven
Published: August 2009

In discussions of health reform, the increased use of health information technology (health IT) is a common element of nearly every serious proposal on the table. Health IT includes electronic health records kept by providers, personal health records offered by health insurance plans or owned by consumers, and electronic health information exchanges. Although health reform initiatives being discussed contain little detail regarding health IT, in general they promote health IT to facilitate the electronic sharing of health information to improve individual and population health. During the 2008 presidential campaign, the health care proposals of both President Obama and Senator McCain discussed health IT. President Obama’s proposal invests $50 billion over the next five years to promote the adoption of health IT with privacy safeguards. Senator McCain’s plan also encouraged the adoption of health IT, with an emphasis on coordination.
A Traditional Tibetan Medical Response to Advancements in Basic Longevity Research
Authors: Dakpa Tenzing , Dodson‐Lavelle Brooke
Published: August 2009

This paper is intended to serve as a traditional Tibetan medical response to advancements in basic longevity research, with particular attention to current models of caloric restriction. This is a complicated task, as Tibetan medicine traditionally approaches dietary modification from a radically different perspective, and relies upon a complex model of health and balance in the treatment and prevention of disease. This paper offers a brief overview of the traditional Tibetan medicine (TTM) model and suggests potential areas for collaborative research on dietary modification.
The Cross‐Cultural Evidence on “Extreme Behaviors”
Authors: Jackson Jean E.
Published: August 2009

Many kinds of body/mind practices are capable of producing remarkable behaviors and altered body states. A typology of such behaviors and states, defined as observable and intentional “extreme” alterations to the body, is presented. Epistemological and methodological issues are discussed: limitations of observational data, and role of meaning, intentionality, and consciousness. Rapprochement between Western medicine and Indo‐Tibetan medicine requires rethinking biomedicine's radical grounding in physicality and reliance on “evidence‐based medicine,” and guarding against an ethnocentric Western intellectual hegemony motivating medical science and clinical practice to colonize and subvert non‐Western traditions like Indo‐Tibetan Buddhist medicine.