bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel mutation in the AMELX gene and multiple crown resorptions
Authors: Lee Kyung‐Eun , Lee Sook‐Kyung , Jung Seung‐Eun , Song Su Jeong , Cho Sang Hyun , Lee Zang Hee , Kim Jung‐Wook
Published: January 2012

Lee K‐E, Lee S‐K, Jung S‐E, Song SJ, Cho SH, Lee ZH, Kim J‐W. A novel mutation in the AMELX gene and multiple crown resorptions.  Eur J Oral Sci 2011; 119 (Suppl. 1): 324–328. © 2011 Eur J Oral Sci

Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders with regard to genetic aetiology and clinical phenotype and affects tooth enamel with no other non‐oral syndromic conditions. X‐linked AI is caused by mutations in the amelogenin (AMELX) gene, the only AI candidate gene located on the X chromosome. To date, 15 mutations in the AMELX gene have been found to cause AI. We identified a proband with generalized hypoplastic enamel and unusual multiple crown resorption in premolars and molars. Pedigree analysis suggested an X‐linked hereditary pattern. We performed mutational analysis for the AMELX gene based on the candidate gene approach. Sequencing analysis revealed a novel mutation in exon 6 (g.4090delC, c.517delC, p.Pro173LeufsX16). This frameshift mutation produces a premature stop codon within exon 6 and is predicted to replace 33 amino acids at the C‐terminus with 15 novel amino acids if the mutant mRNA escapes the nonsense‐mediated decay system. Although crown resorptions occur frequently in patients with the hypoplastic type of A1, an association with the AMELX mutation has not been previously reported. We believe that these findings will broaden our understanding of the clinical phenotype and pathogenesis of X‐linked AI.
Matrix metalloproteinase 20 promotes a smooth enamel surface, a strong dentino–enamel junction, and a decussating enamel rod pattern
Authors: Bartlett John D. , Skobe Ziedonis , Nanci Antonio , Smith Charles E.
Published: January 2012

Bartlett JD, Skobe Z, Nanci A, Smith CE. Matrix metalloproteinase 20 promotes a smooth enamel surface, a strong dentino–enamel junction, and a decussating enamel rod pattern. Eur J Oral Sci 2011; 119 (Suppl. 1): 199–205. © 2011 Eur J Oral Sci

Mutations of the matrix metalloproteinase 20 (MMP20, enamelysin) gene cause autosomal‐recessive amelogenesis imperfecta, and Mmp20 ablated mice also have malformed dental enamel. Here we showed that Mmp20 null mouse secretory‐stage ameloblasts maintain a columnar shape and are present as a single layer of cells. However, the maturation‐stage ameloblasts from null mouse cover extraneous nodules of ectopic calcified material formed at the enamel surface. Remarkably, nodule formation occurs in null mouse enamel when MMP20 is normally no longer expressed. The malformed enamel in Mmp20 null teeth was loosely attached to the dentin and the entire enamel layer tended to separate from the dentin, indicative of a faulty dentino–enamel junction (DEJ). The enamel rod pattern was also altered in Mmp20 null mice. Each enamel rod is formed by a single ameloblast and is a mineralized record of the migration path of the ameloblast that formed it. The enamel rods in Mmp20 null mice were grossly malformed or absent, indicating that the ameloblasts do not migrate properly when backing away from the DEJ. Thus, MMP20 is required for ameloblast cell movement necessary to form the decussating enamel rod patterns, for the prevention of ectopic mineral formation, and to maintain a functional DEJ.
Enamel proteins and proteases in Mmp20 and Klk4 null and double‐null mice
Authors: Yamakoshi Yasuo , Richardson Amelia S. , Nunez Stephanie M. , Yamakoshi Fumiko , Milkovich Rachel N. , Hu Jan C‐C. , Bartlett John D. , Simmer James P.
Published: January 2012

Yamakoshi Y, Richardson AS, Nunez SM, Yamakoshi F, Milkovich RN, Hu JC‐C, Bartlett JD, Simmer JP. Enamel proteins and proteases in Mmp20 and Klk4 null and double‐null mice. Eur J Oral Sci 2011; 119 (Suppl. 1): 206–216. © 2011 Eur J Oral Sci

Matrix metalloproteinase 20 (MMP20) and kallikrein‐related peptidase 4 (KLK4) are thought to be necessary to clear proteins from the enamel matrix of developing teeth. We characterized Mmp20 and Klk4 null mice to better understand their roles in matrix degradation and removal. Histological examination showed retained organic matrix in Mmp20, Klk4, and Mmp20/Klk4 double‐null mouse enamel matrix, but not in the wild‐type. X‐gal histostaining of Mmp20 null mice heterozygous for the Klk4 knockout/lacZ knockin showed that Klk4 is expressed normally in the Mmp20 null background. This finding was corroborated by zymogram and western blotting, which discovered a 40‐kDa protease induced in the maturation stage of Mmp20 null mice. Proteins were extracted from secretory‐stage or maturation‐stage maxillary first molars from wild‐type, Mmp20 null, Klk4 null, and Mmp20/Klk4 double‐null mice and were analyzed by SDS‐PAGE and western blotting. Only intact amelogenins and ameloblastin were observed in secretory‐stage enamel of Mmp20 null mice, whereas the secretory‐stage matrix from Klk4 null mice was identical to the matrix from wild‐type mice. More residual matrix was observed in the double‐null mice compared with either of the single‐null mice. These results support the importance of MMP20 during the secretory stage and of KLK4 during the maturation stage and show there is only limited functional redundancy for these enzymes.
Fine mapping of dental fluorosis quantitative trait loci in mice
Authors: Everett Eric T. , Yin Zhaoyu , Yan Dong , Zou Fei
Published: January 2012

Everett ET, Yin Z, Yan D, Zou F. Fine mapping of dental fluorosis quantitative trait loci in mice.
 
Eur J Oral Sci 2011; 119 (Suppl. 1): 8–12. © 2011 Eur J Oral Sci

Genetic factors underlie the susceptibility and the resistance to dental fluorosis (DF). The A/J (DF susceptible) and 129P3/J (DF resistant) mouse strains have previously been used to detect quantitative trait loci (QTLs) associated with DF on chromosome (Chr) 2 and Chr 11. In the present study, increased marker density genotyping followed by interval mapping was performed to narrow the QTL intervals and improve the logarithm of the odds (to the base 10) (LOD) scores. Narrower intervals were obtained on Chr 2 where LOD ≥ 6.0 (57–84 cM or ∼51 Mb), LOD ≥ 7.0 (62–79 cM or ∼32 Mb), and LOD ≥ 8.0 (65–74 cM or ∼17 Mb); and on Chr 11 where LOD ≥ 6.0 (18–51 cM or ∼53 Mb), LOD ≥ 7.0 (28–48 cM or ∼34 Mb), and LOD ≥ 8.0 (31–45 cM or∼22 Mb). Haplotype analysis between A/J and 129P3/J mice further reduced the QTL intervals. Accn1 was selected as a candidate gene based upon its location near the peak LOD score on Chr 11 and distant homology with the Caenorhabditis elegans fluoride‐resistance gene, flr1. The severity of DF between Accn1−/− and wild‐type mice was not significantly different. Hence, the loss of ACCN1 function does not modify DF severity in mice. Narrowing the DF QTL intervals will facilitate additional candidate gene selections and interrogation.
Is the 32‐kDa fragment the functional enamelin unit in all species?
Authors: Brookes Steven J. , Kingswell Nicola J. , Barron Martin J. , Dixon Michael J. , Kirkham Jennifer
Published: January 2012

Brookes SJ, Kingswell NJ, Barron MJ, Dixon MJ, Kirkham J. Is the 32‐kDa fragment the functional enamelin unit in all species?  Eur J Oral Sci 2011; 119 (Suppl. 1): 345–350. © 2011 Eur J Oral Sci

Enamelin is an extracellular enamel matrix protein essential for normal amelogenesis. After secretion, porcine enamelin is processed to generate several enamelin‐degradation products. The cumulative 32‐kDa enamelin is the most abundant enamelin present, and various roles for this molecule have been suggested. However, the proteolytic cleavage sites in porcine enamelin that generate the 32‐kDa enamelin are not conserved across species, and the 32‐kDa enamelin analogue may not be present in all species. To explore this we studied rat enamelin biochemistry using western blotting with anti‐peptide IgGs to porcine 32‐kDa enamelin and to the putative rat 32‐kDa enamelin analogue. The dominant enamelins in secretory‐stage rat enamel migrated at around 60–70 kDa. In contrast, the dominant enamelins in secretory‐stage porcine enamel migrated at around 32 kDa. In contrast, secretory‐stage porcine‐enamel enamelins were dominated by the 32‐kDa enamelin. Rat enamelin was completely removed from maturation‐stage enamel without any accumulation of 32‐kDa enamelin. We suggest that a discrete 32‐kDa enamelin is not essential for normal amelogenesis in all species, and in pig it may be a processing product of a larger functional enamelin molecule. The pig may be an atypical model in terms of enamelin biochemistry and function, and caution should be exercised when assigning functional roles to the 32‐kDa enamelin as a discrete enamel matrix entity.
Relationships between protein and mineral during enamel development in normal and genetically altered mice
Authors: Smith Charles E. , Hu Yuanyuan , Richardson Amelia S. , Bartlett John D. , Hu Jan C‐C. , Simmer James P.
Published: January 2012

Smith CE, Hu Y, Richardson AS, Bartlett JD, Hu JC‐C, Simmer JP. Relationships between protein and mineral during enamel development in normal and genetically altered mice.  Eur J Oral Sci 2011; 119 (Suppl. 1): 125–135. © 2011 Eur J Oral Sci

The purpose of this study was to quantify and compare the amounts of volatiles (mostly protein) and mineral present in developing incisor enamel in normal mice and in those genetically engineered for absence of intact enamelin, ameloblastin, matrix metalloproteinase 20 (MMP20) or kallikrein‐related peptidase 4 (KLK4). Data indicated that all mice showed peaks in the gross weight of volatiles and a similar weight of mineral at locations on incisors normally associated with early maturation. Thereafter, the content of volatiles on normal incisors declined rapidly by as much as 62%, but not by 100%, over 2 mm, accompanied by increases of ∼threefold in mineral weights. Enamelin heterozygous mice (lower incisors) showed a decrease in volatile content across the maturation stage, yet mineral failed to increase significantly. Mmp20 null mice showed no significant loss of volatiles from maturing enamel, yet the amount of mineral increased. Klk4 null mice showed normal mineral acquisition up to early maturation, but the input of new volatiles in mid to late maturation caused the final mineralization to slow below normal levels. These results suggest that it is not only the amount of protein but also the nature or type of protein or fragments present in the local crystallite environment that affects their volumetric expansion as they mature.
Relationships between dentin and enamel mineral at the dentino–enamel boundary: electron tomography and high‐resolution transmission electron microscopy study
Authors: Fang Ping‐An , Lam Raymond S. K. , Beniash Elia
Published: January 2012

Fang P‐A, Lam RSK, Beniash E. Relationships between dentin and enamel mineral at the dentino–enamel boundary: electron tomography and high‐resolution transmission electron microscopy study.  Eur J Oral Sci 2011; 119 (Suppl. 1): 120–124. © 2011 Eur J Oral Sci

To better understand the nature of the relationships between mineral phases at the dentino–enamel boundary (DEB), we performed electron tomography (ET) and high‐resolution transmission electron microscopy (HR‐TEM) of the apical portions of rat incisors. The ET studies of the DEB at the secretory stage of amelogenesis revealed that nascent enamel crystals are co‐aligned and closely associated with dentin crystallites in the mineralized von Korff fibers, with the distances between dentin and enamel crystals in the nanometer range. We have further studied the relationships between dentin and enamel crystals using HR‐TEM lattice imaging of the DEB. Among dozens of high‐resolution micrographs taken from the DEB we were able to identify only one case of lattice continuity between dentin and enamel crystals, indicating direct epitaxy. In other cases, although there was no direct continuity between the crystalline lattices, power spectra analysis of lattice images revealed a very high level of co‐alignment between dentin and enamel crystals. Hence, we propose here that the high degree of alignment and integration between dentin and enamel mineral can be established either by epitaxy or without direct interactions between crystalline lattices, probably via regulation of mineral formation and organization by integrated organic matrices of dentin and enamel at the DEB.
Rescue of the murine amelogenin null phenotype with two amelogenin transgenes
Authors: Gibson Carolyn W. , Li Yong , Suggs Cynthia , Kuehl Melissa A. , Pugach Megan K. , Kulkarni Ashok B. , Wright John T.
Published: January 2012

Gibson CW, Li Y, Suggs C, Kuehl MA, Pugach MK, Kulkarni AB, Wright JT. Rescue of the murine amelogenin null phenotype with two amelogenin transgenes.
 
Eur J Oral Sci 2011; 119 (Suppl. 1): 70–74. © 2011 Eur J Oral Sci

The amelogenin proteins are required for normal enamel development, and the most abundant amelogenins expressed from alternatively spliced mRNAs are M180 and leucine‐rich amelogenin protein (LRAP). The X‐Chromosomal Amelogenin (Amelx) null [knockout (KO)] mouse has an enamel defect similar to human X‐linked amelogenesis imperfecta. The disorganized enamel layer in KO mice is 10–20% of the thickness of wild‐type (WT) enamel and lacks prismatic structures. When the KO mice were mated with mice that express the transgene M180‐87, (TgM180‐87) partial rescue of the phenotype was observed such that enamel thickness, volume, and density increased. A second transgene was introduced by mating TgM180 KO mice with TgLRAP mice, and male offspring were characterized for genotype and tooth phenotype was evaluated by scanning electron microscopy. The molar enamel thickness of TgM180‐LRAP KO mice was further increased, and the structure was improved, with a more defined decussation pattern compared with singly rescued mice. We conclude that TgM180 provides significant rescue of the KO phenotype. Although the effectiveness of the LRAP transgene, alone, to rescue is less obvious, the addition of the LRAP transgene to the M180 transgene in KO enamel leads to an added improvement in both amount and structure and thus these transgenes function in a complementary manner. Together, the two most abundant amelogenins lead to the formation of obvious enamel decussation patterns.
Amelogenin–enamelin association in phosphate‐buffered saline
Authors: Yang Xiudong , Fan Daming , Mattew Shibi , Moradian‐Oldak Janet
Published: January 2012

Yang X, Fan D, Mattew S, Moradian‐Oldak J. Amelogenin–enamelin association in phosphate‐buffered saline.  Eur J Oral Sci 2011; 119 (Supp. 1): 351–356. © 2011 Eur J Oral Sci

The structures and interactions among macromolecules in the enamel extracellular matrix play vital roles in regulating hydroxyapatite crystal nucleation, growth, and maturation. We used dynamic light scattering (DLS), circular dichroism (CD), fluorescence spectroscopy, and transmission electron microscopy (TEM) to investigate the association of amelogenin and the 32‐kDa enamelin, at physiological pH 7.4, in phosphate‐buffered saline (PBS). The self‐assembly behavior of amelogenin (rP148) was altered following addition of the 32‐kDa enamelin. Dynamic light scattering revealed a trend for a decrease in aggregate size in the solution following the addition of enamelin to amelogenin. A blue‐shift and intensity increase of the ellipticity minima of rP148 in the CD spectra upon the addition of the 32‐kDa enamelin, suggest a direct interaction between the two proteins. In the fluorescence spectra, the maximum emission of rP148 was red‐shifted from 335 to 341 nm with a marked intensity increase in the presence of enamelin as a result of complexation of the two proteins. In agreement with DLS data, TEM imaging showed that the 32‐kDa enamelin dispersed the amelogenin aggregates into oligomeric particles and stabilized them. Our study provides novel insights into understanding the possible cooperation between enamelin and amelogenin in macromolecular co‐assembly and in controlling enamel mineral formation.
Root surface treatment using diode laser in delayed tooth replantation: radiographic and histomorphometric analyses in rats
Authors: Carvalho Erica dos Santos , Costa Felipe Toledo Souza , Campos Marcia Sampaio , Anbinder Ana Lia , Neves Ana Christina Claro , Habitante Sandra Márcia , Lage‐Marques José Luiz , Raldi Denise Pontes
Published: January 2012

Abstract –  Background aim:  The aim of this study was to evaluate, by radiographic and histomorphometric analyses, the effects of high‐power diode laser irradiation on the root surfaces of delayed replanted rat teeth.

Material and methods:  Maxillary right incisors were extracted from 60 Wistar rats and kept dry for 60 min. Subsequently, the root canals were prepared and filled with calcium hydroxide paste. According to the root surface treatment before the replantation, the teeth were assigned to four groups (n = 15): G1 (negative control) – no root surface treatment; G2 (positive control) – treated with 2% sodium fluoride solution; G3 – irradiated with a high‐power diode laser (810 nm, continuous mode, 1.0 W, 30 s); and G4 – irradiated with a diode laser using the same parameters as those used for G3 but in pulsed mode. The rats were euthanized after 15, 30, and 60 days of replantation. The specimens were digitally radiographed and processed for histomorphometric analysis to determine the average root resorption areas and to evaluate the histological events.

Results:  The percentage of root resorption was in the following order: G1 > G2 > G4 > G3. Both histomorphometric and radiographic analyses showed significantly lower means (P < 0.05) of the occurrence of root resorption in the irradiated groups (G3 and G4) when compared to the control groups (G1 and G2). Replacement resorption and ankylosis were observed in histological sections only after 30 and 60 days; however, such events were not observed in G3.

Conclusion:  Root surface treatments with high‐powered diode laser irradiation prior to delayed replantation reduced the occurrence of external root resorption compared to no treatment or sodium fluoride treatment at up to 60 days.
Effect of iodine, selenium and cobalt rumen boluses given to dry dairy cows on the immunoglobulin and thyroid hormone status of calves
Authors: ROSE Michael , PEARSON Sam , CRATCHLEY Tom
Published: January 2012

The objective was to determine the effect of rumen boluses containing 6800 mg iodine, 1000 mg selenium and 1000 mg cobalt given to dry dairy cows on the efficiency of colostral immunoglobulin G (IgG) absorption in calves. Thirteen cows received the bolus approximately 58 days before calving. A further 12 cows received no bolus and were used as controls. The cows were housed as one group. Calves were prevented from suckling for the first 24 h of life, and were given three feeds of a fixed quantity of colostrum. At 24 h, the average plasma concentrations of IgG in the calves were 15.5 and 13.4 g/L for the control and bolus groups, respectively; these were not significantly different (P = 0.212). Bolus treatment was associated with higher levels of free and total tri‐iodothyronine (T3) and thyroxine (T4) in the dams (all P < 0.001), although it had no effect on thyroid hormone levels in the calves. There were nevertheless positive and negative relationships between the efficiency with which colostral IgG was absorbed at 24 h and, respectively, total T3 at 24 h (P < 0.05) and total T4 at 1 h of age (P < 0.05). The underlying basis for these relationships remains to be established.
Regional and circadian variations of sweating rate and body surface temperature in camels (Camelus dromedarius)
Authors: ABDOUN Khalid A. , SAMARA Emad M. , OKAB Aly B. , AL‐HAIDARY Ahmed A.
Published: January 2012

It was the aim of this study to investigate the regional variations in surface temperature and sweating rate and to visualize body thermal windows responsible for the dissipation of excess body heat in dromedary camels. This study was conducted on five dromedary camels with mean body weight of 450 ± 20.5 kg and 2 years of age. Sweating rate, skin and body surface temperature showed significant (P < 0.001) circadian variation together with the variation in ambient temperature. However, daily mean values of sweating rate, skin and body surface temperature measured on seven regions of the camel body did not significantly differ. The variation in body surface temperature compared to the variation in skin temperature was higher in the hump compared to the axillary and flank regions, indicating the significance of camel's fur in protecting the skin from daily variation in ambient temperature. Infrared thermography revealed that flank and axillary regions had lower thermal gradients at higher ambient temperature (Ta) and higher thermal gradients at lower Ta, which might indicate the working of flank and axillary regions as thermal windows dissipating heat during the night. Sweating rate showed moderate correlation to skin and body surface temperatures, which might indicate their working as potential thermal drivers of sweating in camels.
MRI FEATURES OF CERVICAL ARTICULAR PROCESS DEGENERATIVE JOINT DISEASE IN GREAT DANE DOGS WITH CERVICAL SPONDYLOMYELOPATHY
Authors: Gutierrez‐Quintana Rodrigo , Penderis Jacques
Published: January 2012

Cervical spondylomyelopathy or Wobbler syndrome commonly affects the cervical vertebral column of Great Dane dogs. Degenerative changes affecting the articular process joints are a frequent finding in these patients; however, the correlation between these changes and other features of cervical spondylomyelopathy are uncertain. We described and graded the degenerative changes evident in the cervical articular process joints from 13 Great Danes dogs with cervical spondylomyelopathy using MRimaging, and evaluated the relationship between individual features of cervical articular process joint degeneration and the presence of spinal cord compression, vertebral foraminal stenosis, intramedullary spinal cord changes, and intervertebral disc degenerative changes. Degenerative changes affecting the articular process joints were common, with only 13 of 94 (14%) having no degenerative changes. The most severe changes were evident between C4–C5 and C7–T1 intervertebral spaces. Reduction or loss of the hyperintense synovial fluid signal on T2‐weighted MR images was the most frequent feature associated with articular process joint degenerative changes. Degenerative changes of the articular process joints affecting the synovial fluid or articular surface, or causing lateral hypertrophic tissue, were positively correlated with lateral spinal cord compression and vertebral foraminal stenosis. Dorsal hypertrophic tissue was positively correlated with dorsal spinal cord compression. Disc‐associated spinal cord compression was recognized less frequently.
Current state of US breastfeeding laws
Authors: Nguyen Thu T. , Hawkins Summer Sherburne
Published: January 2012

This study systematically examined state‐level laws protecting breastfeeding, including their current status and historical development, as well as identified gaps across US states and regions. The National Conference of State Legislatures summarised breastfeeding laws for 50 states and DC as of September 2010, which we updated through May 2011. We then searched LexisNexis and Westlaw to find the full text of laws, recording enactment dates and definitions. Laws were coded into five categories: (1) employers are encouraged or required to provide break time and private space for breastfeeding employees; (2) employers are prohibited from discriminating against breastfeeding employees; (3) breastfeeding is permitted in any public or private location; (4) breastfeeding is exempt from public indecency laws; and (5) breastfeeding women are exempt from jury duty. By May 2011, 1 state had enacted zero breastfeeding laws, 10 had one, 22 had two, 12 had three, 5 had four and 1 state had laws across all five categories. While 92% of states allowed mothers to breastfeed in any location and 57% exempted breastfeeding from indecency laws, 37% of states encouraged or required employers to provide break time and accommodations, 24% offered breastfeeding women exemption from jury duty and 16% prohibited employment discrimination. The Northeast had the highest proportion of states with breastfeeding laws and the Midwest had the lowest. Breastfeeding outside the home is protected to varying degrees depending on where women live; this suggests that many women are not covered by comprehensive laws that promote breastfeeding.
Outer membrane protein A and OprF: versatile roles in Gram‐negative bacterial infections
Authors: Krishnan Subramanian , Prasadarao Nemani V.
Published: January 2012

Outer membrane protein A (OmpA) is an abundant protein of Escherichia coli and other enterobacteria and has a multitude of functions. Although the structural features and porin function of OmpA have been well studied, its role in the pathogenesis of various bacterial infections has emerged only during the last decade. The four extracellular loops of OmpA interact with a variety of host tissues for adhesion to and invasion of the cell and for evasion of host‐defense mechanisms when inside the cell. This review describes how various regions present in the extracellular loops of OmpA contribute to the pathogenesis of neonatal meningitis induced by E. coli K1 and to many other functions. In addition, the function of OmpA‐like proteins, such as OprF of Pseudomonas aeruginosa, is discussed.
A Multi-Institutional Observational Study of Testosterone Levels After Testosterone Pellet (Testopel®) Insertion
Authors: McCullough Andrew R. , Khera Mohit , Goldstein Irwin , Hellstrom Wayne J.G. , Morgentaler Abraham , Levine Laurence A.
Published: January 2012

Introduction

Implantable testosterone pellets were approved by the Food and Drug Administration in 1972 for the treatment of testosterone deficiency syndrome (TDS). Clinical use of this testosterone delivery modality has been limited until its recent reintroduction (Testopel®, Slate Pharmaceuticals, Durham, NC, USA). Six academic institutions collaborated and combined their databases to more fully characterize serum testosterone levels after the pellet implantations.

Aims

To assess the time-dependent serum testosterone levels after subcutaneous testosterone pellets in clinical practice for the treatment of TDS.

Methods

Data were retrospectively pooled and analyzed from data in six academic institutions. Variables included patient age, total testosterone concentrations before and after implantation, the number of testosterone pellets implanted, and the time from implantation to measurement of serum testosterone concentrations. Three hundred eighty men undergoing 702 insertions were included for analysis using JMP (version 4.0.4; SAS Institute, Cary, NC, USA).

Main Outcome Measures

Main outcome measures were postimplantation total testosterone levels and investigator-reported adverse events. Testosterone levels as a function of the number of pellets implanted and time from implantation were assessed.

Results

Implantation of six to ≥10 testosterone pellets (450 to ≥750 mg) increased total testosterone into the therapeutic range at 1 month postimplantation and sustained therapeutic levels (>300) for 4–6 months. Higher pellet numbers (10–12 pellets) were associated with higher, more consistent, and longer maintenance of testosterone levels within the therapeutic range. Four extrusions and three hematomas were reported early in our experience; other investigator-reported adverse events were generally mild to moderate in nature and transient in duration. No subjects required analgesics.

Conclusions

Testosterone pellets (Testopel®, Slate Pharmaceuticals) provide sustained levels of testosterone for at least 4 months and up to 6 months in men with TDS. Implantation of ≥8 pellets achieved optimal results with respect to peak mean testosterone level and duration of effect. Testosterone pellets were generally well tolerated.
A retrospective cohort study of metastatic colorectal cancer patients treated with oxaliplatin‐based chemotherapy, with an exploratory analysis of changing serum carcinoembryonic antigen levels
Authors: NG Say Liang , BURNS William I , SNYDER Raymond D , NEWNHAM Genni M , MCLACHLAN Sue‐Anne , LIEW Danny , DOWLING Anthony J
Published: January 2012

Aim:  To examine the relationship between changes in serum carcinoembryonic antigen (CEA) levels and survival during oxaliplatin‐based chemotherapy for metastatic colorectal cancer (mCRC).

Methods:  A retrospective review of 142 patients with mCRC who were treated with oxaliplatin‐based chemotherapies (mostly FOLFOX 6 or XELOX) by St Vincent's Hospital, from October 1999 until 30 November 2007. Survival analysis was used to determine median overall survival (OS) from commencement of chemotherapy. A CEA response was defined by ≥50% decline compared with baseline, maintained on two consecutive occasions at least 4 weeks apart. The Cox proportional hazard model and a landmark analysis at 3 months were used to evaluate survival differences between CEA responders (rCEA) and non‐responders (non‐rCEA).

Results:  The median OS was 14.7 months. Using an intention‐to‐treat analysis, 76 (53.5%) patients achieved a CEA response, while 66 (46.5%) did not. Using the landmark analysis at 3 months, rCEA had a longer survival than non‐rCEA (median 16.0 vs 7.8 months, P < 0.0001). The hazard ratio for patients dying of mCRC in non‐rCEA was 2.2 (P < 0.0001). In multivariate analysis, CEA response and better baseline Eastern Cooperative Oncology Group (ECOG) predicted for survival (P < 0.0001 for both), while age, gender and histology grade did not.

Conclusion:  The median OS of our patients is similar to published randomized trials. A CEA response of ≥50% at 3 months and good ECOG were independent predictors of OS of patients with mCRC treated with oxaliplatin‐based chemotherapies.
Benefits of the LTCC Substrate Configuration with an Air‐Gap for Realization of RF Inductor with High Q‐Factor and SRF
Authors: Radosavljević Goran J. , Marić Andrea M. , Smetana Walter , Živanov Ljiljana D.
Published: January 2012

This article offers a detail description of design, simulation, fabrication and characterization of inductors on different substrate configurations intended for application in radio frequency range. The presented inductors are meander type structures fabricated using low temperature co‐fired ceramic technology. Different substrate configurations incorporate placement of an air‐gap beneath the inductor. Obtained results present over 30% increase in quality factor and widening of the operating frequency range by over 55% in comparison with inductors on standard substrate configurations.
Magnetic jet model for GRBs and the delayed arrival of >100 MeV photons
Authors: Bošnjak Ž. , Kumar P.
Published: January 2012

Photons of energy larger than 100 MeV from long GRBs arrive a few seconds after <10 MeV photons do. We show that this delay is a natural consequence of a magnetic-dominated relativistic jet. The much slower acceleration of a magnetic jet with radius (compared with a hot baryonic outflow) results in high-energy γ-ray photons to be converted to electron–positron pairs out to a larger radius, whereas lower energy γ-rays of energy less than ∼10 MeV can escape when the jet crosses the Thomson photosphere. The resulting delay for the arrival of high-energy photons is found to be similar to the value observed by the Fermi satellite for a number of GRBs. A prediction of this model is that the delay should increase with photon energy (E) as ∼E0.17 for E > 100 MeV. The delay depends almost linearly on burst redshift, and on the distance from the central compact object where the jet is launched (R0). Therefore, the delay in arrival of >102 MeV photons can be used to estimate burst redshift if the magnetic jet model for γ-ray generation is correct and R0 is roughly the same for long GRBs.
Cross‐Cultural Analysis of Cognitive Attributions of Smoking in Thai and South Korean Adolescents
Authors: Page Randy M. , Park Sunhee , Suwanteerangkul Jiraporn , Park Hyunju , Kemeny Maria , Philips Lynn
Published: January 2012

BACKGROUND: Understanding the cognitive attributions of smoking has the potential to advance youth smoking prevention efforts; however, research on this subject is limited in Asian countries. We attempted to determine the degree to which cognitive attributions of smoking differ among adolescents in 2 Asian countries, Thailand and South Korea.

METHODS: We surveyed 10th‐ to 12th‐grade students in Chiang Mai, Thailand (N = 2516) and Seoul, South Korea (N = 1166). Logistic regression determined association of attributions and current smoking and differences in attributions between Thai and South Korean students.

RESULTS: Items with the highest agreement among South Koreans were “helps me to deal with stress” and “helps relax” and among Thai were “feel like I am making my own decisions” and “keeps from being bored.” Significant predictors of current smoking were different between samples. Only 1 cognitive attribution predicted current smoking in both samples (“helps me to deal with stress”).

CONCLUSION: The pattern of relevant cognitive attributions of smoking for the 2 samples was distinct, suggesting that cross‐cultural differences merit consideration when designing prevention and cessation programs. Health education should strive to dispel the use of smoking as a coping strategy for dealing with stressful situations and distressful feelings and teach adolescents alternative healthy strategies for dealing with stress.
Synthesis of 5‐ and 6‐N‐heterocyclic Methylenebisphosphonate Derivatives and Evaluation of their Cytogenetic Activity in Normal Human Lymphocyte Cultures
Authors: Abdou Wafaa M. , Kamel Azza A. , Khidre Rizk E. , Geronikaki Athina , Ekonomopoulou Maria T.
Published: January 2012

Methods for the preparation of various aminomethylene bisphosphonates were developed. The required bisphosphonates were obtained by applying tetraethyl methylenebisphosphonate reagent to different types of oxazinones and the relevant Schiff base derivatives. Based on the prediction results (Pass program), we further estimated the sister chromatid exchange frequency and proliferation rate index values of human lymphocyte cultures after the administration of four newly synthesized bisphosphonates in order to evaluate their cytotoxic/cytostatic and possible antineoplastic potency. The results showed that all four bisphosphonates cause a dose‐dependent increase in sister chromatid exchange frequency, followed by a decrease in proliferation rate index in both experiments compared to the control.
End‐use analysis of household water by metering: the case study in Korea
Authors: Lee Doo‐Jin , Park No‐Suk , Jeong Woochang
Published: January 2012

The purpose of this study is to estimate the real water use for a person per day by analysing water use trend of respective metered data. To investigate the unit amount used and component ratio of residential water usage in households, 146 households nationwide were selected as ‘representative samples’, and each end‐use usage was monitored by actual metering from 2002 to 2006. From the results of analysing the acquired data, it was found that the unit amount used in a household was 165.8 litres per capita day (lpcd). Additionally, the unit amount used consisted of six end‐uses; toilet water was the greatest, at 25% (38.5 lpcd), laundry water represented 20% (30.8 lpcd), kitchen water was 19% (28.4 lpcd), bathtub water was 16% (24.7 lpcd), washbowl water was 10% (15.4 lpcd) and miscellaneous use of water represented 9% (13.5%). Comparing the unit amount used according to housing type, 141 lpcd was shown in the case of single houses, and 155 and 159 lpcd were derived in the cases of multi‐unit houses and apartments, respectively. Moreover, the proportions of the aged (50 and over) among the total number of members in single, multihouse and apartment houses were 68.2, 38.1 and 32.4%, respectively. In addition, comparing the amount used and the component ratio among United Kingdom, United States and Korea, the end‐use amount and component ratio in Korea are similar to those in the United States. The total amount of water use in the United Kingdom was less than that in both Korea and the United States.
Problems for Temporary Existence in Tense Logic
Authors: Sullivan Meghan
Published: January 2012

A‐theorists of time postulate a deep distinction between the present, past and future. Settling on an appropriate logic for such a view is no easy matter. ThisPhilosophy Compassarticle describes one of the most vexing formal problems facing A‐theorists. It is commonly thought that A‐theories can only be formally expressed in a tense logic: a logic with operators likeP(“it was the case that”) andF(“it will be the case that”). And it seems natural to think that we live in a world where objects come to exist and cease to exist as time passes. Indeed, this is typically a key component of the most prominent kind of A‐theory, presentism. But the temporary existence assumption cannot be upheld in any tense logic with a standard quantification theory. I will explain the problem and outline the philosophical and logical considerations that generate it. I will then consider two possible solutions to the problem – one that targets our logic of quantification and one that targets our assumptions about change. I survey the costs of each solution.
Regulation of mature T cell responses by the Wnt signaling pathway
Authors: Xue Hai‐Hui , Zhao Dong‐Mei
Published: January 2012

The canonical Wnt signaling pathway is evolutionarily conserved and plays key roles during development of many organ systems. This pathway utilizes TCF/LEF transcription factors, β‐catenin coactivator, and TLE/GRG corepressors to achieve balanced regulation of its downstream gene expression. It is well established that several Wnt ligands and their effector proteins are crucial for normal T cell development. Recent studies have also revealed critical requirements for TCF‐1 in generation and persistence of functional memory CD8+ T cells, and in promoting Th2‐differentiation and suppressing Th17‐differentiation of activated CD4+ T cells. Activation of β‐catenin facilitated CD8+ memory T cell formation, with enhanced protective capacity and extended survival of CD4+CD25+ regulatory T cells. Upregulation of Wnt ligands was observed in Drosophila in response to Toll signaling as well as in mammalian dendritic cells and macrophages upon microbial stimulation. These new findings suggest that modulating the activity of Wnt pathway may be a powerful approach to enhance protective immunity and treat autoimmune diseases.
Modeling population dynamics, landscape structure, and management decisions for controlling the spread of invasive plants
Authors: Caplat Paul , Coutts Shaun , Buckley Yvonne M.
Published: January 2012

Invasive plants cause substantial economic and environmental damage throughout the world. However, eradication of most invasive species is impossible and, in some cases, undesirable. An alternative is to slow the spread of an invasive species, which can delay impacts or reduce their extent. We identify three main areas where models are used extensively in the study of plant spread and its management: (i) identifying the key drivers of spread to better target management, (ii) determining the role spatial structure of landscapes plays in plant invasions, and (iii) integrating management structures and limitations to guide the implementation of control measures. We show how these three components have been approached in the ecological literature as well as their potential for improving management practices. Particularly, we argue that scientists can help managers of invasive species by providing information about plant invasion on which managers can base their decisions (i and ii) and by modeling the decision process through optimization and agent‐based models (iii). Finally, we show how these approaches can be articulated for integrative studies.
Lighting up the brain's reward circuitry
Authors: Lobo Mary Kay
Published: January 2012

The brain's reward circuit is critical for mediating natural reward behaviors including food, sex, and social interaction. Drugs of abuse take over this circuit and produce persistent molecular and cellular alterations in the brain regions and their neural circuitry that make up the reward pathway. Recent use of optogenetic technologies has provided novel insights into the functional and molecular role of the circuitry and cell subtypes within these circuits that constitute this pathway. This perspective will address the current and future use of light‐activated proteins, including those involved in modulating neuronal activity, cellular signaling, and molecular properties in the neural circuitry mediating rewarding stimuli and maladaptive responses to drugs of abuse.
Epitope specificity of anti‐HA2 antibodies induced in humans during influenza infection
Authors: Staneková Zuzana , Mucha Vojtech , Sládková Tatiana , Blaškovičová Hana , Kostolanský František , Varečková Eva
Published: January 2012

Please cite this paper as:Stanekováet al.(2012) Epitope specificity of anti‐HA2 antibodies induced in humans during influenza infection. Influenza and Other Respiratory Viruses 6(6), 389–395.

Background The conserved, fusion‐active HA2 glycopolypeptide (HA2) subunit of influenza A hemagglutinin comprises four distinct antigenic sites. Monoclonal antibodies (MAbs) recognizing three of these sites are broadly cross‐reactive and protective.

Objectives This study aimed to establish whether antibodies specific to these three antigenic sites were elicited during a natural influenza infection or by vaccination of humans.

Methods Forty‐five paired acute and convalescent sera from individuals with a confirmed influenza A (subtype H3) infection were examined for the presence of HA2‐specific antibodies. The fraction of antibodies specific to three particular antigenic sites (designated IIF4, FC12, and CF2 here) was investigated using competitive enzyme immunoassay.

Results Increased levels of antibodies specific to an ectodomain of HA2 (EHA2: N‐terminal residues 23–185 of HA2) were detected in 73% of tested convalescent sera (33/45), while an increased level of antibodies specific to the HA2 fusion peptide (N‐terminal residues 1–38) was induced in just 15/45 individuals (33%). Competitive assays confirmed that antibodies specific to the IIF4 epitope (within HA2 residues 125–175) prevailed in 86% (13/15) over those specific to the other two epitopes during infection. However, only a negligible increase in HA2‐specific antibodies was detectable following vaccination with a current subunit vaccine.

Conclusions We observed that the antigenic site localized within N‐terminal HA2 residues 125–175 was more immunogenic than that within residues 1–38 (HA2 fusion protein), although both are weak natural immunogens. We suggest that new anti‐influenza vaccines should include HA2 (or specific epitopes localized within this glycopolypeptide) to enhance their cross‐protective efficacy.
Effects of Carbon Dioxide (CO2) Laser Perforation as Skin Pretreatment to Improve Sugar Infusion Process of Frozen Blueberries
Authors: Fujimaru Tomomi , Ling Qingyue , Morrissey Michael T.
Published: January 2012

Abstract:  Sugar infusion is a widely used osmotic treatment for fruit preservation, but the process is inherently slow and the waxy skins of some fruits hinder mass transfer during the process. This work examined the utility of perforation by a carbon dioxide (CO2) laser as a novel skin treatment to improve the infusion process. In 2 experiments, individually quick frozen (IQF) blueberries were subjected to varying degrees of laser perforation (3 levels of perforation density × 3 levels of perforation depth), and then infused stepwise with high fructose corn syrup (HFCS) to a final °Brix of 70 using varying solution concentration increment (5, 10, 20, and 30 °Brix/d). At each concentration, increasing perforation density and depth promoted solute migration into the fruit with increased fruit weight (P < 0.05; up to 24.15%, 37.23%, 52.89%, 65.34% wt. increase at 5, 10, 20, and 30 °Brix/d compared to the controls). Laser‐treated blueberries maintained the original shape without excessive shrinkage and texture hardening due to enhanced solute incorporation, while the controls and mechanically treated samples were ruptured and wrinkled at the end of the process. Increasing solution concentrations shortened the process duration but decreased final fruit weight due to greater osmotic gradients. However, negative effects of using higher solution concentrations on final fruit weight were significantly alleviated with moderate‐to‐high doses of laser perforation (P < 0.001). Overall, the results demonstrate that laser perforation can be a viable skin pretreatment technique, offering marked improvement on final process yield, process efficiency, and product quality.

Practical Application:  CO2 laser perforation as a novel skin pretreatment for sugar infusion of individually quick frozen (IQF) blueberries is presented. The technique markedly improves the product yield and quality. Although further investigation is needed, the method may potentially be used for other waxy skin fruits such as cranberries and cherries.
Molecular Response to Ultraviolet Radiation Exposure in Fish Embryos: Implications for Survival and Morphological Development
Authors: Torres Nuñez Eva , Sobrino Cristina , Neale Patrick J. , Ceinos Rosa Maria , Du ShaJun , Rotllant Josep
Published: January 2012

UVR exposure is known to cause developmental defects in a variety of organisms including aquatic species but little is known about the underlying molecular mechanisms. In this work we used zebrafish (Danio rerio) embryos as a model system to characterize the UVR effects on fish species. Larval viability was measured for embryos exposed to several UVR spectral treatments by using a solar simulator lamp and an array of UV cutoff filters under controlled conditions in the laboratory. Survival rate and occurrence of development abnormalities, mainly caudal (posterior) notochord bending/torsion, were seriously affected in UV‐exposed larvae reaching values of 53% and 72%, respectively, compared with non–UV‐exposed larvae after 6 days postfertilization (dpf). In order to elucidate the molecular mechanisms involved, a matricellular glycoprotein named osteonectin and the expression of a DNA‐repair related gene, p53, were studied in relation to UVR exposure. The results indicate that osteonectin and p53 expression were increased under UVR exposure due to wavelengths shorter than 335 nm (i.e. mainly UVB) and 350 nm (i.e. short UVA and UVB), respectively. Furthermore, parallel experiments with microinjections of osteonectin‐capped RNA showed that malformations induced by osteonectin overexpression were similar to those observed after a UVR exposure. Consequently this study shows a potential role of osteonectin in morphological deformities induced by solar UV radiation in zebrafish embryos.
The PSS‐SR as a screening tool for PTSD in first‐episode psychosis patients
Authors: Sin Gwen‐Li , Abdin Edimansyah , Lee Jimmy
Published: January 2012

Aim: We examined the validity of the PTSD Symptom Scale – Self‐Report (PSS‐SR) as a screening instrument for post‐traumatic stress disorder (PTSD) in patients recovering from first‐episode psychosis.

Methods: Sixty‐one patients from the Early Psychosis Intervention Programme in Singapore completed the PSS‐SR questionnaire. The Clinician‐Administered PTSD Scale was administered by a blinded interviewer as the ‘gold standard’ to identify patients with PTSD. The sensitivity, specificity and receiver operating characteristic curve were used to determine the screening performance of the PSS‐SR.

Results: The score representing the optimal cut‐off point for the PSS‐SR was 14, with a sensitivity and specificity of 0.83 and 0.71, respectively. The area under the curve was determined to be 0.82 (95% CI: 0.70–0.95).

Conclusion: These data suggest that the PSS‐SR can be a useful screening instrument for PTSD in patients recovering from their first psychotic episode.