bluuebunny/crossref_metadata_2025 huggingface dataset:
Normal minimal erythema dose responses in patients with suspected photosensitivity disorders
Authors: Que Syril Keena T. , Brauer Jeremy A. , Soter Nicholas A. , Cohen David E.
Published: November 2012

Purpose

Our study identified the most common diagnoses in patients with a history of photosensitivity or with a photodistributed eruption and normal minimal erythema dose (MED) responses.

Methods

We retrospectively reviewed the diagnoses and phototest results of 319 patients who were phototested at the New York University Photomedicine Section of the Charles C. Harris Skin and Cancer Pavilion from 1993 to 2009. Patients were phototested if they had a history of photosensitivity or had an eruption with a distribution that suggested photosensitivity.

Results

The majority of patients with normal MEDs were diagnosed with polymorphous light eruption, followed by contact or photocontact dermatitis, photodistributed dermatitis not otherwise specified (idiopathic), solar urticaria and photoexacerbated atopic dermatitis.

Discussion

The clinical history of photosensitivity and physical findings remain as important metrics in the diagnosis of patients with photodistributed dermatoses and normal MEDs.
Photoprotective effects of Bifidobacterium breve supplementation against skin damage induced by ultraviolet irradiation in hairless mice
Authors: Sugimoto Saho , Ishii Yuki , Izawa Naoki , Masuoka Norie , Kano Mitsuyoshi , Sone Toshiro , Chiba Katsuyoshi , Miyazaki Kouji , Ishikawa Fumiyasu
Published: November 2012

Background

Probiotics have been considered to affect not only the gut but also the skin. This study aimed at examining whether oral administration of live Bifidobacterium breve strain Yakult (BBY), a typical probiotic, could exert photoprotective effects in hairless mouse skin.

Methods

BBY cell suspensions and fermented milk containing BBY (BBYM) were orally administered to hairless mice for 9 and 14 days, respectively. Mice were irradiated with ultraviolet (UV) light daily for the last four consecutive days. Twenty‐four hours after the final irradiation, skin elasticity, appearance, elastase activity and interleukin (IL)‐1β levels were evaluated in the dorsal skin.

Results

BBY and BBYM significantly prevented UV‐induced deleterious changes in skin elasticity and appearance. BBY suppressed the increases in both elastase activity and IL‐1β levels in the skin. There was a significant negative correlation between elastase activity and the ratio of elastic recovery to total deformation and a significant positive correlation between elastase activity and the area ratio of furrows, independent of UV irradiation or BBY administration.

Conclusion

Our findings suggest that oral administration of probiotic BBY has the potential to prevent UV‐induced skin damage, supporting the hypothesis that probiotics are beneficial not only to the intestine but also to the skin.
Phloroglucinol protects human keratinocytes from ultraviolet B radiation by attenuating oxidative stress
Authors: Kim Ki Cheon , Piao Mei Jing , Cho Suk Ju , Lee Nam Ho , Hyun Jin Won
Published: November 2012

Background

Ultraviolet B generates reactive oxygen species by interacting with water in irradiated skin tissues and cells in turn causes lipid peroxidation, protein modification and further DNA damage.

Purpose

This study examined the cytoprotective effects of phloroglucinol (1,3,5‐trihydroxybenzene) on ultraviolet B‐irradiated cultured human keratinocytes.

Methods

The human keratinocyte cell line HaCaT cells were treated with 10 μM of phloroglucinol. After 1 h, the cells were irradiated with ultraviolet B light at 30 mJ/cm2 and incubated at 37°C.

Results

Phloroglucinol scavenged both the superoxide anion and hydroxyl radical in a cell‐free system and ultraviolet B‐induced intracellular reactive oxygen species. Phloroglucinol reduced ultraviolet B‐generated lipid peroxidation, protein modification and DNA strand breaks. The enzymatic effects of phloroglucinol restored cellular glutathione levels, superoxide dismutase and catalase activities, which were impaired by ultraviolet B radiation.

Conclusion:

Phloroglucinol provides the protective effects in human keratinocyte cell line exposed to ultraviolet B radiation, suggesting that phloroglucinol can be used as a photoprotective agent.
1,25‐Dihydroxyvitamin D3 Inhibits Nuclear Factor Kappa B Activation by Stabilizing Inhibitor IκBα via mRNA Stability and Reduced Phosphorylation in Passively Sensitized Human Airway Smooth Muscle Cells
Authors: Song Y. , Hong J. , Liu D. , Lin Q. , Lai G.
Published: November 2012

Excessive activation of nuclear transcription factor‐κB (NF‐κB) is involved in human airway smooth muscle cells (HASMCs) activities in asthma. We investigated the effects of 1,25 – dihydroxyvitamin D3 [1,25 – (OH) 2D3] on the NF‐ κB signaling pathway in passively sensitized HASMCs and the molecular mechanisms involved. HASMCs were treated with either healthy controls’ serum, asthma patients’ serum or pretreated with 1,25 – (OH) 2D3 prior to treatment with asthmatics’ serum. At 1 h after serum treatment: electrophoretic mobility shift assay (EMSA) was used to detect NF‐κB DNA binding activity; immunocytochemical staining was used to observe the nuclear translocation of NF‐κB p65; Western blots were used for NF‐κB p65, IκBα, and phospho‐IκBα protein levels and the nuclear translocation of NF‐κB p65; real‐time quantitative PCR was used for NF‐κB p65 and IκBα mRNA expressions; and actinomycin D treatment was used to determine IκBα mRNA stability. Our major findings were: (1) 1,25 – (OH) 2D3 significantly reduced asthma serum passively sensitized HASMCs NF‐κB DNA binding activity and inhibited the nuclear translocation of NF‐κB p65; (2) 1,25 – (OH) 2D3 increased the stability of IκBα mRNA with reduced IκBα phosphorylation in asthma serum passively sensitized HASMCs and significantly increased IκBα expression in these HASMCs. Inhibiting NF‐κB signalling with 1,25 – dihydroxyvitamin D3 may be a therapeutic approach for controlling HASMC‐related remodelling in asthma.
Antigenicity and Epitope Specificity of ZnT8 Autoantibodies in Type 1 Diabetes
Authors: Skärstrand H. , Lernmark Å. , Vaziri‐Sani F.
Published: November 2012

The single nucleotide polymorphism (SNP) rs13266634 encodes either an Arginine (R) or a Tryptophan (W) (R325W) at the amino acid position 325 in the Zinc Transporter 8 (ZnT8) protein. Autoantibodies (Ab) that recognize ZnT8R, ZnT8W or both at the polymorphic site are common in newly diagnosed type 1 diabetes (T1D) patients. The epitope specificity and affinity of ZnT8Ab are poorly understood, but may be of importance for the prediction and clinical classification of T1D. Therefore, the aims were to 1) determine the immunogenicity of short (318–331) ZnT8 peptides in mice and 2) test the affinity of short and long (268–369) ZnT8 proteins in T1D patients positive for either ZnT8RAb or ZnT8wAb. Sera from BALB/cByJ mice immunized with short R, W or Q (Glutamine) ZnT8 peptides were tested for ZnT8‐peptide antibodies in ELISA and radiobinding assay (RBA). Using reciprocal permutation experiment, short synthetic ZnT8R and ZnT8W (318–331) and long in vitro transcription translation ZnT8R and ZnT8W (268–369) proteins were tested in competitive RBA with R‐ and W‐monospecific T1D sera samples. All mouse sera developed non‐epitope‐specific peptide antibodies in ELISA and only 6/12 mice had ZnT8‐RWQ antibodies in RBA. Both long ZnT8R and ZnT8W (268–369), but not any short, proteins displaced labelled ZnT8 (268–369) proteins in binding to T1D ZnT8Ab‐specific sera. The reciprocal cross‐over tests showed that half‐maximal displacement varied 2‐ to 11‐fold indicating variable affinity of patient ZnT8Ab, signifying crucial autoantibody epitope spreading. The present approach should make it possible to dissect the importance of the R325W ZnT8 autoantigen epitope in the T1D pathogenesis.
The Ex Vivo Induction of Human CD103+CD25hi Foxp3+CD4+ and CD8+ Tregs is IL‐2 and TGF‐β1 Dependent
Authors: Gunnlaugsdottir B. , Maggadottir S. M. , Skaftadottir I. , Ludviksson B. R.
Published: November 2012

The expression of the integrin αE (CD103), may enhance the retention of regulatory T cells to peripheral inflammatory sites and possibly contribute to their suppressive potential. The aim of this study was to define the regulatory role of IL‐2 and TGF‐β1 on the CD103 expression and the optimal in vitro conditions for the induction/expansion of human CD4+ and CD8+ Tregs. Cord blood mononuclear cells (CBMC) were stimulated under various culture conditions, including anti‐CD3, anti‐CD28, IL‐2 and TGF‐β1. TGF‐β1 and IL‐2 were both required for optimal expression of CD103. In addition, TGF‐β1 and IL‐2 synergistically induced CD103 expression on CD8+ T cells, whereas, only additive induced expression was noted on CD4+ T cells. Surprisingly, CD103 expression was not dependent upon CD28 costimulation. IL‐2 also played a central role in CD103 expression by CD25hi Foxp3+ Tregs. IL‐2, TGF‐β1 and anti‐CD3 defined the optimal stimulatory conditions favouring the induction/expansion of both CD4+ and CD8+ human Tregs from naive CBMC. Thus, this study provides new insights into the regulatory role of IL‐2 upon CD103 expression by human cord blood CD4+ and CD8+ T cells. Furthermore, it identifies the in vitro culture conditions driving the differentiation of the novel phenotype CD4+ and CD8+ CD103+ CD25hi Foxp3+ Tregs from human CBMC.
A new submaximal cycle ergometer test for prediction of VO2max
Authors: Ekblom‐Bak E. , Björkman F. , Hellenius M.‐L. , Ekblom B.
Published: November 2012

Maximal oxygen uptake (VO2max) is an important, independent predictor of cardiovascular health and mortality. Despite this, it is rarely measured in clinical practice. The aim of this study was to create and evaluate a submaximal cycle ergometry test based on change in heart rate (HR) between a lower standard work rate and an individually chosen higher work rate. In a mixed population (n = 143) with regard to sex (55% women), age (21–65 years), and activity status (inactive to highly active), a model included change in HR per unit change in power, sex, and age for the best estimate of VO2max. The association between estimated and observed VO2max for the mixed sample was r = 0.91, standard error of estimate = 0.302 L/min, and mean measured VO2max = 3.23 L/min. The corresponding coefficient of variation was 9.3%, a significantly improved precision compared with one of the most commonly used submaximal exercise tests, the Åstrand test, which in the present study was estimated to be 18.1%. Test–retest reliability analysis over 1 week revealed no mean difference in the estimated VO2max (−0.02 L/min, 95% confidence interval: −0.07–0.03). The new test is low‐risk, easily administered, and valid for a wide capacity range, and is therefore suitable in situations as health evaluations in the general population.
Identification of two novel HLA alleles: HLA‐DRB1*12:03:03 and HLA‐DRB1*13:143
Authors: Kim K. M. , Sung H. Y. , Kang M. S. , Huh J. Y.
Published: November 2012

The novel alleles DRB1*12:03:03 and DRB1*13:143 differ from DRB1*12:03:02 and DRB1*13:02:01 by one nucleotide in exon 2, respectively.
Sprint interval and traditional endurance training increase net intramuscular triglyceride breakdown and expression of perilipin 2 and 5
Authors: Shepherd S. O. , Cocks M. , Tipton K. D. , Ranasinghe A. M. , Barker T. A. , Burniston J. G. , Wagenmakers A. J. M. , Shaw C. S.
Published: November 2012

Key points

Increases in aerobic capacity and intramuscular triglyceride (IMTG) utilization are well‐described adaptations to endurance training (ET) and contribute to improvements in insulin sensitivity.

Sprint interval training (SIT) also improves aerobic capacity and insulin sensitivity with a lower time commitment than ET.

This study aimed to determine whether SIT also induces improvements in insulin sensitivity and net IMTG breakdown, and to investigate the underlying mechanisms.

Six weeks of ET and SIT increased net IMTG breakdown during moderate‐intensity cycling, and improved insulin sensitivity. A greater concentration of lipid droplet‐associated proteins, perilipin 2 and perilipin 5, was observed following both training modes and contributes to the increases in net IMTG breakdown following training.

The results suggest a novel mechanism for the training‐induced improvements in IMTG breakdown and insulin sensitivity, and clearly demonstrate that SIT is an alternative, time‐efficient training strategy that induces similar beneficial metabolic adaptations.

Abstract  Intramuscular triglyceride (IMTG) utilization is enhanced by endurance training (ET) and is linked to improved insulin sensitivity. This study first investigated the hypothesis that ET‐induced increases in net IMTG breakdown and insulin sensitivity are related to increased expression of perilipin 2 (PLIN2) and perilipin 5 (PLIN5). Second, we hypothesized that sprint interval training (SIT) also promotes increases in IMTG utilization and insulin sensitivity. Sixteen sedentary males performed 6 weeks of either SIT (4–6, 30 s Wingate tests per session, 3 days week−1) or ET (40–60 min moderate‐intensity cycling, 5 days week−1). Training increased resting IMTG content (SIT 1.7‐fold, ET 2.4‐fold; P < 0.05), concomitant with parallel increases in PLIN2 (SIT 2.3‐fold, ET 2.8‐fold; P < 0.01) and PLIN5 expression (SIT 2.2‐fold, ET 3.1‐fold; P < 0.01). Pre‐training, 60 min cycling at ∼65% pre‐training decreased IMTG content in type I fibres (SIT 17 ± 10%, ET 15 ± 12%; P < 0.05). Following training, a significantly greater breakdown of IMTG in type I fibres occurred during exercise (SIT 27 ± 13%, ET 43 ± 6%; P < 0.05), with preferential breakdown of PLIN2‐ and particularly PLIN5‐associated lipid droplets. Training increased the Matsuda insulin sensitivity index (SIT 56 ± 15%, ET 29 ± 12%; main effect P < 0.05). No training × group interactions were observed for any variables. In conclusion, SIT and ET both increase net IMTG breakdown during exercise and increase in PLIN2 and PLIN5 protein expression. The data are consistent with the hypothesis that increases in PLIN2 and PLIN5 are related to the mechanisms that promote increased IMTG utilization during exercise and improve insulin sensitivity following 6 weeks of SIT and ET.
Preserved fertility despite erectile dysfunction in mice lacking the nitric oxide receptor
Authors: Groneberg Dieter , Lies Barbara , König Peter , Jäger Ronald , Friebe Andreas
Published: November 2012

Key points

Erectile dysfunction may result from reduced or non‐functional nitric oxide (NO)/cGMP‐mediated signalling. Mice lacking NO synthases are fertile whereas mice deficient in cGMP‐dependent protein kinase I suffer from erectile dysfunction.

To clarify this discrepancy we performed studies on the corpus cavernosum of male mice lacking the NO receptor NO‐sensitive guanylyl cyclase (NO‐GC) either globally or specifically in smooth muscle cells.

NO released from NO donors as well as from nitrergic neurons failed to relax precontracted corpus cavernosum from mice lacking NO‐GC either globally or specifically in smooth muscle; to our surprise, males from both knockout lines were fertile.

Our data show that deletion of the NO receptor specifically in smooth muscle cells abolishes NO‐induced corpus cavernosum relaxation but does not lead to infertility.

Abstract  Nitric oxide (NO) and cGMP have been shown to be important mediators of penile erection. Erectile dysfunction may result from reduced or non‐functional signal transduction within this cascade. There is, however, some inconsistency in the available data as mice lacking NO synthases (endothelial and neuronal nitric oxide synthase, or both) appear to be fertile whereas mice deficient in cGMP‐dependent protein kinase I (PKGI) suffer from erectile dysfunction. To clarify this discrepancy we performed studies on mice lacking the NO receptor NO‐sensitive guanylyl cyclase (NO‐GC). In addition, we generated cell‐specific NO‐GC knockout (KO) lines to investigate the function of NO in individual cell types. NO‐GC was specifically deleted in smooth muscle or endothelial cells (SM‐guanylyl cyclase knockout (SM‐GCKO) and EC‐GCKO, respectively) and these KO lines were compared with total knockouts (GCKO) and wild‐type animals. We investigated expression of NO‐GC, NO‐induced relaxation of corpus cavernosum smooth muscle and their ability to generate offspring. NO‐GC‐positive immunostaining was detected in smooth muscle and endothelial cells of murine corpus cavernosum but not in interstitial cells of Cajal. NO released from NO donors as well as from nitrergic neurons failed to relax precontracted corpus cavernosum from GCKO mice in organ bath experiments. Similar results were obtained in corpus cavernosum from SM‐GCKO mice whereas deletion of NO‐GC in endothelial cells did not affect relaxation. The lack of NO‐induced relaxation in GCKO animals was not compensated for by guanosine 3′,5′‐cyclic monophosphate (cGMP) signalling. To our surprise, GCKO males were fertile although their ability to produce offspring was decreased. Our data show that deletion of NO‐GC specifically in smooth muscle cells abolishes NO‐induced corpus cavernosum relaxation but does not lead to infertility.
The Effect of Material Models on Elastic Follow-Up
Authors: Boyle James T.
Published: November 2012

The phenomenon of elastic follow-up in high temperature piping has a long history and rules to limit its significance in design are well established. However, most design rules, and numerous associated supporting studies, have been limited to a simple power-law of creep, with variations to account for time- or strain-hardening in primary creep. A common feature of the most studies of elastic follow-up in structures subject to power-law creep is that a plot of (maximum) stress against strain—a so-called isochronous stress– strain trajectory—is almost insensitive to the creep law (in particular, the stress exponent in the power-law) and is almost linear (until perhaps the later stages of stress relaxation). A limitation of the power-law is that it assumes to be valid across all stress ranges, from low through moderate to high, yet it is well known that this is not generally the case. This paper aims to investigate the effect of stress-range dependent material models on the nature of elastic follow-up: both a simple two-bar structure (common in studies of elastic follow-up) and a detailed finite element analysis of a piping elbow are examined. It is found that stress-range dependent material models can have a significant effect on the accepted characteristics of elastic follow-up.
Non‐Gaussian statistical properties of breast images
Authors: Abbey Craig K. , Nosratieh Anita , Sohl‐Dickstein Jascha , Yang Kai , Boone John M.
Published: November 2012

Purpose:

Several studies have shown that the power spectrum of x‐ray breast images is well described by a power‐law at lower frequencies where anatomical variability dominates. However, an image generated from a Gaussian process with this spectrum is easily distinguished from an image of actual breast tissue by eye. This demonstrates that higher order non‐Gaussian statistical properties of mammograms are readily accessible to the visual system. The authors’ purpose is to quantify and characterize non‐Gaussian statistical properties of breast images as influenced by processing of a digital mammogram, different imaging modalities, and breast density.

Methods:

To quantify non‐Gaussian statistical properties, the authors consider histograms of filter responses from the interior of a breast image that have similar properties to receptive fields in the early visual system. They quantify departure from a Gaussian distribution by the relative entropy of the histogram compared to a best‐fit Gaussian distribution. This entropy is normalized by the relative entropy of a best‐fit Laplacian distribution into a measure they refer to as Laplacian fractional entropy (LFE). They test the LFE on a set of 26 patients recalled at screening for which they have available full‐field digital mammography (FFDM), digital breast tomosynthesis (DBT), and dedicated breast CT (bCT) images as well as breast density scores and biopsy results.

Results:

A study of LFE in FFDM comparing the raw “for‐processing” transmission data from the device to log‐converted density estimates and the processed “for‐display” data shows that processing mammographic image data enhances the non‐Gaussian content of the image. A check of the methodology using a Gaussian process with a power‐law power spectrum shows relatively little bias from the finite extent of the region of interests used. A second study comparing LFE across FFDM, DBT, and bCT modalities shows that each maximized the non‐Gaussian content of the image for different ranges of spatial frequency. FFDM is optimal at high spatial frequencies (>0.7 mm−1), DBT is optimal at mid‐range frequencies (0.3–0.7 mm−1), and bCT is optimal at low spatial frequency (<0.3 mm−1). A third study of breast density in FFDM and bCT shows that LFE generally rises slightly going from the low‐to moderate density, and then falls considerably at higher densities.

Conclusions:

Non‐Gaussian statistical structure in breast images that is manifest in the responses of Gabor filters similar to receptive fields of the early visual system is dependent on how the image data are processed, the modality used to acquire the image, and the density of the breast tissue being imaged. Higher LFE corresponds with expected improvements from image processing and 3D imaging.
Automated size‐specific CT dose monitoring program: Assessing variability in CT dose
Authors: Christianson Olav , Li Xiang , Frush Donald , Samei Ehsan
Published: November 2012

Purpose:

The potential health risks associated with low levels of ionizing radiation have created a movement in the radiology community to optimize computed tomography (CT) imaging protocols to use the lowest radiation dose possible without compromising the diagnostic usefulness of the images. Despite efforts to use appropriate and consistent radiation doses, studies suggest that a great deal of variability in radiation dose exists both within and between institutions for CT imaging. In this context, the authors have developed an automated size‐specific radiation dose monitoring program for CT and used this program to assess variability in size‐adjusted effective dose from CT imaging.

Methods:

The authors radiation dose monitoring program operates on an independent health insurance portability and accountability act compliant dosimetry server. Digital imaging and communication in medicine routing software is used to isolate dose report screen captures and scout images for all incoming CT studies. Effective dose conversion factors (k‐factors) are determined based on the protocol and optical character recognition is used to extract the CT dose index and dose‐length product. The patientˈs thickness is obtained by applying an adaptive thresholding algorithm to the scout images and is used to calculate the size‐adjusted effective dose (EDadj). The radiation dose monitoring program was used to collect data on 6351 CT studies from three scanner models (GE Lightspeed Pro 16, GE Lightspeed VCT, and GE Definition CT750 HD) and two institutions over a one‐month period and to analyze the variability in EDadj between scanner models and across institutions.

Results:

No significant difference was found between computer measurements of patient thickness and observer measurements (p = 0.17), and the average difference between the two methods was less than 4%. Applying the size correction resulted in EDadj that differed by up to 44% from effective dose estimates that were not adjusted by patient size. Additionally, considerable differences were noted in EDadj distributions between scanners, with scanners employing iterative reconstruction exhibiting significantly lower EDadj (range: 9%–64%). Finally, a significant difference (up to 59%) in EDadj distributions was observed between institutions, indicating the potential for dose reduction.

Conclusions:

The authors developed a robust automated size‐specific radiation dose monitoring program for CT. Using this program, significant differences in EDadj were observed between scanner models and across institutions. This new dose monitoring program offers a unique tool for improving quality assurance and standardization both within and across institutions.
Quantitative 90Y image reconstruction in PET
Authors: Willowson Kathy , Forwood Nicholas , Jakoby Bjoern W. , Smith Anne M. , Bailey Dale L.
Published: November 2012

Purpose:

Positron emission tomography (PET) imaging is increasingly used to confirm localization of90Y microspheres in the treatment of liver cancer. The aim of this work was to evaluate the quantification of 90Y PET data on a current generation time‐of‐flight extended axial field‐of‐view PET/CT camera.

Methods:

The International Electrotechnical Commission (IEC) body phantom was used to image six spheres of varying diameters containing a high concentration of90Y solution in a lower concentration background. Multiple PET studies were acquired of the phantom over a number of days during decay. The effect of reconstruction parameters in OSEM was evaluated both qualitatively and quantitatively. Expected values of total phantom activity, hot‐sphere, and background concentration were compared to measured values from the reconstructed data as well as misplaced events in a cold insert. The partial volume effect was measured and the effects of time‐of‐flight during reconstruction on hot contrast recovery and background variability were evaluated according to NEMA‐NU2‐2007 protocol, and compared to that for 18F. The method was applied to a patient study following radioembolization to estimate actual implanted radioactivity.

Results:

Increasing the number of OSEM iterations visually deteriorated image data and resulted in a larger overall difference of hot concentration measures when considering both count high and count poor data. The average difference between measured and true total activity and background concentration was found to be +5% and +5%, respectively. Measured hot‐sphere concentration was linear across all datasets, and while estimated to be within error of expected values, was consistently underestimated by an average of 23%, 12%, and 8%, when using a CT‐derived, 50% threshold‐derived, and 70% threshold‐derived volume of interest, respectively. Partial volume effects were evident in all but the largest sphere, following an expected relationship between object size and recovery coefficient, inferior to that of18F. Time‐of‐flight improved contrast of hot‐spheres but resulted in a deterioration of background variability, following a similar trend to that seen with 18F. The patient data estimated a total implanted activity of 1643 MBq, compared to the intended dose of 1780 MBq, with a difference most likely due to residual and error in the initial dose calibration.

Conclusions:

Quantitative90Y PET with a state‐of‐the‐art PET/CT scanner with time‐of‐flight and standard corrections for photon interactions demonstrates consistent and acceptable measures of total activity and radionuclide concentration across a range of realistic count statistics. The method is suitable for measuring the radioactivity delivered at the time of 90Y therapy with the potential for absorbed dose calculation.
Proliferative and Antiapoptotic Signaling Stimulated by Nuclear-Localized PDK1 Results in Oncogenesis
Authors: Kikani Chintan K. , Verona Erik V. , Ryu Jiyoon , Shen Yanying , Ye Qingqing , Zheng Li , Qian Ziliang , Sakaue Hiroshi , Nakamura Kyoko , Du Jie , Ji Qunsheng , Ogawa Wataru , Sun Lu-Zhe , Dong Lily Q. , Liu Feng
Published: November 2012

PDK1 in the nucleus drives oncogenesis in mice and correlates with human prostate tumor grade.
Key Roles for the Lipid Signaling Enzyme Phospholipase D1 in the Tumor Microenvironment During Tumor Angiogenesis and Metastasis
Authors: Chen Qin , Hongu Tsunaki , Sato Takanobu , Zhang Yi , Ali Wahida , Cavallo Julie-Ann , van der Velden Adrianus , Tian Huasong , Di Paolo Gilbert , Nieswandt Bernhard , Kanaho Yasunori , Frohman Michael A.
Published: November 2012

Genetic ablation or pharmacological inhibition of a lipid signaling enzyme attenuates tumor growth and metastasis.
Sexy DEG/ENaC Channels Involved in Gustatory Detection of Fruit Fly Pheromones
Authors: Pikielny Claudio W.
Published: November 2012

DEG/ENaC channels allow male fruit flies to “taste” their mates.
Necrophilic Bandit Fungi
Authors: Hines Pamela J.
Published: November 2012

Cochliobolus victoriae
, a necrotrophic fungal pathogen with devastating effects on oat crops, reveals its strategies.
Estrogens Block p53 in Breast Cancer
Authors: Foley John F.
Published: November 2012

In estrogen receptor–dependent breast cancer cells, estrogen signaling antagonizes the proapoptotic function of the tumor suppressor p53.
The Therapeutic Effect of Tigecycline, Unlike That of Ceftazidime, Is Not Influenced by whether the Klebsiella pneumoniae Strain Produces Extended-Spectrum β-Lactamases in Experimental Pneumonia in Rats
Authors: Goessens Wil H. F. , Mouton Johan W. , ten Kate Marian T. , Sörgel Fritz , Kinzig Martina , Bakker-Woudenberg Irma A. J. M.
Published: November 2012

The efficacies of tigecycline and ceftazidime against fatal pneumonia in rats caused by an extended-spectrum β-lactamase (ESBL)-positive
Klebsiella pneumoniae
strain or its wild-type (WT) progenitor were compared. Ceftazidime at 12.5 or 50 mg/kg of body weight twice daily (b.i.d.) was effective (50% or 100% rat survival) in pneumonia caused by the WT isolate but unsuccessful (100% rat mortality) in pneumonia caused by the ESBL-positive variant. In contrast, tigecycline at 6.25, 12.5, or 25 mg/kg b.i.d. showed dosage-dependent efficacy up to 100% rat survival irrespective of the ESBL character of the infecting organism.
Evaluation of an Expanded Microarray for Detecting Antibiotic Resistance Genes in a Broad Range of Gram-Negative Bacterial Pathogens
Authors: Card Roderick , Zhang Jiancheng , Das Priya , Cook Charlotte , Woodford Neil , Anjum Muna F.
Published: November 2012

A microarray capable of detecting genes for resistance to 75 clinically relevant antibiotics encompassing 19 different antimicrobial classes was tested on 132 Gram-negative bacteria. Microarray-positive results correlated >91% with antimicrobial resistance phenotypes, assessed using British Society for Antimicrobial Chemotherapy clinical breakpoints; the overall test specificity was >83%. Microarray-positive results without a corresponding resistance phenotype matched 94% with PCR results, indicating accurate detection of genes present in the respective bacteria by microarray when expression was low or absent and, hence, undetectable by susceptibility testing. The low sensitivity and negative predictive values of the microarray results for identifying resistance to some antimicrobial resistance classes are likely due to the limited number of resistance genes present on the current microarray for those antimicrobial agents or to mutation-based resistance mechanisms. With regular updates, this microarray can be used for clinical diagnostics to help accurate therapeutic options to be taken following infection with multiple-antibiotic-resistant Gram-negative bacteria and prevent treatment failure.
Genotypic and Phenotypic Analyses of Hepatitis C Virus from Patients Treated with JTK-853 in a Three-Day Monotherapy
Authors: Ogura Naoki , Toyonaga Yukiyo , Ando Izuru , Hirahara Kunihiro , Shibata Tsutomu , Turcanu Gabriela , Pai Sudhakar , Yee Kan , Gerhardt Barbara , Rodriguez-Torres Maribel , Noguchi Toru
Published: November 2012

JTK-853, a palm site-binding NS5B nonnucleoside polymerase inhibitor, shows antiviral activity
in vitro
and in hepatitis C virus (HCV)-infected patients. Here, we report the results of genotypic and phenotypic analyses of resistant variants in 24 HCV genotype 1-infected patients who received JTK-853 (800, 1,200, or 1,600 mg twice daily or 1,200 mg three times daily) in a 3-day monotherapy. Viral resistance in NS5B was investigated using HCV RNA isolated from serum specimens from the patients. At the end of treatment (EOT) with JTK-853, the amino acid substitutions M414T (methionine [M] in position 414 at baseline was replaced with threonine [T] at EOT), C445R (cysteine [C] in position 445 at baseline was replaced with arginine [R] at EOT), Y448C/H (tyrosine [Y] in position 448 at baseline was replaced with cysteine [C] or histidine [H] at EOT), and L466F (leucine [L] in position 466 at baseline was replaced with phenylalanine [F] at EOT), which are known to be typical resistant variants of nonnucleoside polymerase inhibitors, were observed in a clonal sequencing analysis. These substitutions were also selected by a treatment with JTK-853
in vitro
, and the 50% effective concentration of JTK-853 in the M414T-, C445F-, Y448H-, and L466V-harboring replicons attenuated the susceptibility by 44-, 5-, 6-, and 21-fold, respectively, compared with that in the wild-type replicon (Con1). These findings suggest that amino acid substitutions of M414T, C445R, Y448C/H, and L466F are thought to be viral resistance mutations in HCV-infected patients receiving JTK-853 in a 3-day monotherapy.
Antimicrobial Photodynamic Inactivation Inhibits Candida albicans Virulence Factors and Reduces
In Vivo
Pathogenicity
Authors: Kato Ilka Tiemy , Prates Renato Araujo , Sabino Caetano Padial , Fuchs Beth Burgwyn , Tegos George P. , Mylonakis Eleftherios , Hamblin Michael R. , Ribeiro Martha Simões
Published: November 2012

The objective of this study was to evaluate whether
Candida albicans
exhibits altered pathogenicity characteristics following sublethal antimicrobial photodynamic inactivation (APDI) and if such alterations are maintained in the daughter cells.
C. albicans
was exposed to sublethal APDI by using methylene blue (MB) as a photosensitizer (0.05 mM) combined with a GaAlAs diode laser (λ 660 nm, 75 mW/cm
2
, 9 to 27 J/cm
2
).
In vitro
, we evaluated APDI effects on
C. albicans
growth, germ tube formation, sensitivity to oxidative and osmotic stress, cell wall integrity, and fluconazole susceptibility.
In vivo
, we evaluated
C. albicans
pathogenicity with a mouse model of systemic infection. Animal survival was evaluated daily. Sublethal MB-mediated APDI reduced the growth rate and the ability of
C. albicans
to form germ tubes compared to untreated cells (
P
< 0.05). Survival of mice systemically infected with
C. albicans
pretreated with APDI was significantly increased compared to mice infected with untreated yeast (
P
< 0.05). APDI increased
C. albicans
sensitivity to sodium dodecyl sulfate, caffeine, and hydrogen peroxide. The MIC for fluconazole for
C. albicans
was also reduced following sublethal MB-mediated APDI. However, none of those pathogenic parameters was altered in daughter cells of
C. albicans
submitted to APDI. These data suggest that APDI may inhibit virulence factors and reduce
in vivo
pathogenicity of
C. albicans
. The absence of alterations in daughter cells indicates that APDI effects are transitory. The MIC reduction for fluconazole following APDI suggests that this antifungal could be combined with APDI to treat
C. albicans
infections.
Population Pharmacokinetic-Pharmacodynamic Analysis of Anidulafungin in Adult Patients with Fungal Infections
Authors: Liu Ping
Published: November 2012

To evaluate the exposure-response relationships for efficacy and safety of intravenous anidulafungin in adult patients with fungal infections, a population pharmacokinetic-pharmacodynamic (PK-PD) analysis was performed with data from 262 patients in four phase 2/3 studies. The plasma concentration data were fitted with a previously developed population PK model. Anidulafungin exposures in patients with weight extremities (e.g., 40 kg and 150 kg) were simulated based on the final PK model. Since the patient population, disease status, and efficacy endpoints varied in these studies, the exposure-efficacy relationship was investigated separately for each study using logistic regression as appropriate. Safety data from three studies (
n
= 235) were pooled for analysis, and one study was excluded due to concomitant use of amphotericin B as a study treatment and different disease populations. The analysis showed that the same dosing regimen of anidulafungin can be administered to all patients regardless of body weight. Nonetheless, caution should be taken for patients with extremely high weight (e.g., >150 kg). There was a trend of positive association between anidulafungin exposure and efficacy in patients with esophageal candidiasis or invasive candidiasis, including candidemia (ICC); however, adequate characterization of the effect of anidulafungin exposure on response could not be established due to the relatively small sample size. No threshold value for exposure could be established, since patients with low exposure also achieved successful outcomes (e.g., area under the curve < 40 mg · h/liter in ICC patients). There was no association between anidulafungin exposure and the treatment-related adverse events or all-causality hepatic laboratory abnormalities.
Novel Aminoglycoside 2″-Phosphotransferase Identified in a Gram-Negative Pathogen
Authors: Toth Marta , Frase Hilary , Antunes Nuno T. , Vakulenko Sergei B.
Published: November 2012

Aminoglycoside 2″-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci. We describe a novel aminoglycoside 2″-phosphotransferase from the Gram-negative pathogen
Campylobacter jejuni
, which shares 78% amino acid sequence identity with the APH(2″)-Ia domain of the bifunctional aminoglycoside-modifying enzyme aminoglycoside (6′) acetyltransferase-Ie/aminoglycoside 2″-phosphotransferase-Ia or AAC(6′)-Ie/APH(2″)-Ia from Gram-positive cocci, which we called APH(2″)-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin, but not to any of the 4,5-disubstituted antibiotics tested. Steady-state kinetic studies demonstrated that GTP, and not ATP, is the preferred cosubstrate for APH(2″)-If. The enzyme phosphorylates the majority of 4,6-disubstituted aminoglycosides with high catalytic efficiencies (
k
cat
/

K
m

= 10
5
to 10
7
M
−1
s
−1
), while the catalytic efficiencies against the 4,6-disubstituted antibiotics amikacin and isepamicin are 1 to 2 orders of magnitude lower, due mainly to the low apparent affinities of these substrates for the enzyme. Both 4,5-disubstituted antibiotics and the atypical aminoglycoside neamine are not substrates of APH(2″)-If, but are inhibitors. The antibiotic susceptibility and substrate profiles of APH(2″)-If are very similar to those of the APH(2″)-Ia phosphotransferase domain of the bifunctional AAC(6′)-Ie/APH(2″)-Ia enzyme.
Acute Sheehan's syndrome presenting as centraldiabetes insipidus
Authors: Robalo Raquel , Pedroso Célia , Agapito Ana , Borges Augusta
Published: November 2012

Sheehan's syndrome occurs as a result of ischaemic pituitary necrosis due to severe postpartum haemorrhage. Improvements in obstetrical care have significantly reduced its incidence in developed countries, but postpartum pituitary infarction remains a common cause of hypopituitarism in developing countries. We report a case of severe postpartum haemorrhage followed by headache, central diabetes insipidus and failure to lactate, which prompted us to investigate and identify both anterior and posterior pituitary deficiency compatible with Sheehan's syndrome. A timely diagnosis allowed us to implement an adequate treatment and follow-up plan, which are known to improve clinical status and patient outcome.
Bifid mandibular condyle
Authors: Katti Girish , Najmuddin Mohammed , Fatima Syeda , Unnithan Jayesh
Published: November 2012

A 20-year-old young male patient presented with limited mouth opening and cosmetic disfigurement since childhood. On examination, marked mandibular hypoplasia resulting in a convex facial profile was noted. Further radiographic investigation using orthopantomograph and CT scan with three-dimensional reconstruction revealed bifid mandibular condyle of the right side.
Decomposing the association between the amount of exposure and the frequency of self-reported involvement in a road crash
Authors: Jiménez-Mejías Eladio , Lardelli-Claret Pablo , Jiménez-Moleón José Juan , Amezcua-Prieto Carmen , Pulido Manzanero José , Luna-del-Castillo Juan de Dios
Published: November 2012

We tried to obtain preliminary evidence to test the hypothesis that the association between driving exposure and the frequency of reporting a road crash can be decomposed into two paths: direct and indirect (mediated by risky driving patterns). In a cross-sectional study carried out between 2007 and 2010, a sample of 1114 car drivers who were students at the University of Granada completed a questionnaire with items about driving exposure during the previous year, risk-related driving circumstances and involvement in road crashes. We applied the decomposition procedure proposed by Buis for logit models. The indirect path showed a strong dose-response relationship with the frequency of reporting a road crash, whereas the direct path did not. The decomposition procedure was able to identify the indirect path as the main explanatory mechanism for the association between exposure and the frequency of reporting a road crash.
Evaluating the prevalence of tail biting and carcase condemnations in slaughter pigs in the Republic and Northern Ireland, and the potential of abattoir meat inspection as a welfare surveillance tool
Authors: Harley S. , More S. J. , O'Connell N. E. , Hanlon A. , Teixeira D. , Boyle L.
Published: November 2012

Despite extensive utilisation in epidemiological investigations of animal health, to date there has been little consideration of the value of abattoir meat inspection as a pig welfare surveillance tool. This study measured the prevalence of tail‐docking, tail biting, carcase condemnations and associated financial losses of the latter (Northern Ireland only) in 36,963 pigs slaughtered in six abattoirs from the Republic of Ireland and Northern Ireland in July and August 2010. Over 99 per cent of inspected pigs had been tail‐docked, while 58.1 per cent and 1.03 per cent had detectable and severe tail lesions, respectively. Producer losses resulting from carcase condemnation were estimated to be €0.37 per pig slaughtered. Enhanced capture and utilisation of meat inspection data for use in animal welfare surveillance schemes has the potential to drive improvements in production efficiency and animal welfare. However, significant differences were detected in the prevalence of carcase condemnation conditions between abattoirs and judiciaries (Republic and Northern Ireland). This reflects variation in the criteria and methods of data capture used in meat inspection in different abattoirs. Thus, the meat inspection process needs to be standardised and reformed before it can be reliably utilised in large‐scale pig welfare surveillance schemes.
Effect of salinity and temperature on seed germination inLimonium cossonianum
Authors: Giménez Luque Esther , Delgado Fernández Isabel C. , Gómez Mercado Francisco
Published: November 2012

Limonium cossonianum Kuntze is an interesting endemic plant in the southeastern Iberian Peninsula and the Balearic Islands that can be used in wetland restoration and as an ornamental species in saline areas. Experiments were carried out to investigate seed germination responses in L. cossonianum at different levels of salinity (0, 100, 200, and 400 mmol/L NaCl) and under different temperature regimes (20/10, 25/15, 30/20, and 35/25 °C, day/night), both in a 14 h light – 10 h dark photoperiod. Seed germination in L. cossonianum was significantly affected by salinity levels, temperature, and the interaction of both parameters. Maximum germination was recorded in the lowest saline media (100 mmol/L NaCl) and distilled water (0 mmol/L NaCl) at 20/10 °C. No seeds germinated in concentrations above 200 mmol/L NaCl at the higher temperatures. The increase in salinity delayed the beginning and end of germination, reduced final germination percentage, and increased mean time to germination. The rate of germination decreased with an increase in salinity and temperature.
Contrasting decadal trends in mortality between large and small individuals in skate populations in Atlantic Canada
Authors: Swain Douglas P. , Jonsen Ian D. , Simon James E. , Davies Trevor D.
Published: November 2012

Mature thorny (Amblyraja radiata), winter (Leucoraja ocellata), and smooth (Malacoraja senta) skates have declined to very low abundance in the southern Gulf of St. Lawrence (SGSL) and on the eastern Scotian Shelf (ESS). We used stage-structured state-space models to examine decadal patterns in mortality rates in these skates. Mortality at early life stages (embryos in egg cases, hatchlings, and (or) small juveniles) appeared to decrease between the 1970s and the 2000s. In contrast, estimated mortality rates increased for larger individuals over this period. Although potentially confounded in models with effects of any changes in juvenile growth, the estimated increases in mortality could not instead be attributed solely to changes in growth. Increases in the mortality of large individuals appeared to reflect increases in natural mortality, possibly due to predation by grey seals. Increases in natural mortality were not evident for skates on the neighbouring western Scotian Shelf, where grey seal abundance has remained lower. Even in the absence of fishing, recovery of skates is unlikely under current ecosystem conditions in the SGSL and on the ESS.
Changes in blister rust infection and mortality in whitebark pine over time
Authors: Smith Cyndi M. , Shepherd Brenda , Gillies Cameron , Stuart-Smith Jon
Published: November 2012

Whitebark pine (Pinus albicaulis Engelm.), a keystone species in subalpine ecosystems of western North America, is under threat across its range from white pine blister rust, mountain pine beetle, fire exclusion, and climate change. Loss of whitebark pine is predicted to have cascading effects on many ecosystem services. We remeasured 115 whitebark pine plots in the Canadian Rocky Mountains to determine whether infection and mortality rates from blister rust were changing over time and (or) latitude. Average rust infection of trees among plots increased from 42% in 2003–2004 to 52% in 2009, while mortality increased from 18% to 28%. In eight plots that have been measured three times, infection increased from 43% of live trees in 1996 to 70% in 2003 and 78% in 2009. Mortality increased from 26% to 65% in the same time period. Overall, infection and mortality have increased 3%/year over the 13 years of the study. Incidence of infection and mortality was highest among plots in the southern part of the study area, particularly on the western side of the Continental Divide. The slowing rates of infection and mortality that we found suggest that some level of natural selection may already be occurring in areas with high levels of both.