bluuebunny/crossref_metadata_2025 huggingface dataset:
Cadherins in Cutaneous Biology
Authors: Furukawa Fukumi , Takigawa Masahiro , Matsuyoshi Norihisa , Shirahama Shigeho , Wakita Hisashi , Fujita Mayumi , Horiguchi Yuji , Imamura Sadao
Published: April 2015

The role of cadherins in cutaneous biology has focused mainly on the classical cadherins, E‐ and P‐cadherin. In this review, roles for cadherins in skin morphogenesis, keratinocyte differentiation, and cancer metastasis are discussed.

E‐cadherin is expressed on the surfaces of whole epidermal layer cells, and P‐cadherin is expressed only on the surfaces of basal cells. Ultrastructural studies have shown that E‐cadherin is distributed on the cytoplasmic membranes of keratinocytes with a condensation in the intercellular space of the desmosomes. During human skin development, P‐cadherin expression is spatiotemporally controlled and closely related to the segregation of basal layers as well as to the arrangement of epidermal cells into eccrine ducts. In human skin diseases, E‐cadherin expression is markedly reduced on the acantholytic cells of tissues in pemphigus and also in Darier's disease.

Keratinocytes cultured in high calcium produce a much more intense immunofluorescence of intercellular E‐ and P‐cadherin than do cells grown in low calcium. Ultrastructural studies show that E‐cadherin on the cytoplasmic membrane of the keratinocytes is shifted to desmosomes under physiological conditions and therein expresses an adhesion function is association with other desmosomal cadherins.

Cell adhesion molecules are now considered to play significant roles in the cellular connections of cancers and metastatic cells. Reduced expression of E‐cadherin on invasive neoplastic cells has been demonstrated for cancers of the stomach, liver, breast, and several other organs. This reduced expression of E‐cadherin is observed in squamous cell carcinoma and Paget's disease.

Soluble E‐cadherins in sera are elevated in various skin diseases, including bullous pemphigoid, pemphigus vulgaris and psoriasis, but not in patients with burns. Markedly high levels in soluble E‐cadherin are demonstrated in patients with metastatic cancers.
Role of Integrins in Cell Adhesion and Polarity in Normal Keratinocytes and Human Skin Pathologies
Authors: De Luca Michele , Pellegrini Graziella , Zambruno Giovanna , Marchisio Pier Carlo
Published: April 2015

In vitro, normal human keratinocytes reconstitute a differentiated stratified epidermis, maintaining the same gene expression pattern as its in vivo counterpart and are suitable for permanent grafting onto patients. Keratinocyte adhesion to basal lamina and lateral interactions among basal epidermal cells are also mediated by integrin receptors that are sorted to defined plasma membrane domains. The hemidesmosome‐associated integrin α6β4 is sharply localized at the basal surface of basal cells and codistributes with laminin and nicein/kalinin; the α2β1 and α3β1 integrins are enriched laterally and play crucial roles in cell‐cell interaction and proper colony morphology. During wound healing, proliferating and migrating keratinocytes express on their plasma membrane αvβ5 and α5β1, which allow keratinocyte attachment and migration over the provisional matrix present in the wound. TGFβ, which is an autocrine and paracrine mediator in wound healing, specifically increases the synthesis and expression of αvβ5 and α5β1, induces the de novo expression of αvβ6, and determines the loss of integrin polarization. In hyperproliferative skin diseases, such as skin cancer or psoriasis vulgaris, and in normal keratinocytes forced into more frequent cell cycles, the polarized expression of integrins is lost, and α5β1 becomes costitutively expressed on the plasma membrane. In addition, the α6β4 integrin becomes associated with focal contacts. Nerve growth factor (NGF) is a potent autocrine stimulator of keratinocyte growth and induces melanocyte migration toward the leading edge of a healing wound. We are currently investigating the NGF‐dependent modulation of integrin expression and function in keratinocytes and melanocytes in both normal epidermis and several hyperproliferative skin diseases.
Novel Experimental Approaches to Melanoma Diagnosis and Therapy
Authors: Hearing Vincent J. , Gersten Douglas M. , Shrayer David , Law Lloyd W.
Published: April 2015

We have investigated the potential use of immune therapies on the growth of melanoma metastases in a new animal model that more closely approximates the clinical situation. We have found that significant benefits towards decreased metastatic growth and subsequent animal survival can be achieved by treatment of tumor‐bearing mice with melanoma‐specific monoclonal antibodies or alternatively, with various types of monovalent or polyvalent vaccines. The beneficial effects of those vaccines can be significantly enhanced by concomitant interleukin‐2 therapy.
Melanogenesis Investigation Leading to Selective Melanoma Neutron Capture Therapy and Diagnosis
Authors: Mishima Yutaka
Published: April 2015

Basic investigation into the nature of melanin monomer and polymer synthesis in pigment cells has revealed many of the new underlying factors involved in its regulation and control by three melanogenesis‐related genes, tyrosinase, TRP‐1 and TRP‐2, and other non‐tyrosinase glycoproteins.

Pigment cells can undergo clinically and biologically recognizable progressive multi‐step carcinogenesis. Generally parallel to this progressive cancerization is accentuated melanogenesis. Using this accentuated melanogenesis to develop a specific diagnosis and cure for melanoma (Mm) has long been a challenge. However, until recently, no success was achieved.

As an example, attempting to utilize the fact that dopa accumulates as a melanin substrate within Mm cells, hybrid compounds of dopa and cytotoxic drugs were developed. However, these compounds were found to have severe systemic side effects and were therefore unusable. Another newer Mm treatment involves high energy radiation such as fast neutrons. But this is quite non‐selective, killing both the target cancer and the normal surrounding tissue.

Since 1972, I have developed the idea of coupling the high energy releasing system of thermal neutron irradiation with the non‐toxic 10B‐dopa analogue, 10B1‐l‐p‐boronophenylalanine (10B1‐l‐BPA). Thermal neutrons are essentially harmless, but, after specific absorption by 10B, release high LET α‐particles and 7Li‐atoms with an energy of 2.33 MeV up to a distance of 14 μ, the diameter of Mm cells, thus selectively killing them without damaging surrounding normal tissue.

After the synthesis of 10B1‐l‐BPA, exhaustive in vitro and in vivo radiological studies on its enhanced killing effect were done to develop optimal Mm Boron Neutron Capture Therapy (NCT). We have successfully treated 14 Mm cases to date. Our Mm NCT can be a prototype for the treatment of many other cancers which synthesize specific proteins.

Following our progress with NCT, we recently developed a powerful, novel method for accurate diagnosis and 3‐dimensional imaging of Mm using Positron Emission Tomography with new 18F‐10B‐BPA. We can also determine the 10B concentration in target melanomas and blood essential for most effective NCT.
Movimientos alternativos de protección de los trabajadores en los Estados Unidos
Authors: FINE Janice
Published: April 2015

Los Estados Unidos están entre los países desarrollados con mayor declive de la sindicación y la negociación colectiva. Sus instituciones laborales tradicionales, basadas en la relación de empleo «estándar», llevan mucho tiempo sufriendo la erosión de una legislación restrictiva y de la oposición de los empleadores, al tiempo que el empleo precario, las malas condiciones de trabajo y la marginación se han generalizado, conduciendo a la emergencia espontánea de iniciativas alternativas, con frecuencia cívicas, para proteger a los trabajadores vulnerables mediante estrategias muy innovadoras. Un buen ejemplo son los «centros de trabajadores», que suelen colaborar con sindicatos tradicionales para lograr sus objetivos.
Ideas, paradojas y factores de cambio determinantes de las relaciones laborales futuras en la UE
Authors: KEUNE Maarten
Published: April 2015

El autor ve el futuro de las relaciones laborales en Europa dependiente de la resolución de tres paradojas actuales relacionadas con los mercados de trabajo, la dinámica sindical y la política de la UE: la individualización de la relación de trabajo frente a la falsa autonomía del individuo y su vulnerabilidad en aumento; el número cada vez mayor de trabajadores precarios necesitados de protección frente a su baja tasa de sindicación y la incapacidad de los sindicatos de conectar con ellos a pesar de la disminución de sus miembros, y la posición actual de la UE, orientada al mercado, que alienta condiciones de empleo conducentes a un revés político contra sí misma.
Characterization of phenotype variations of luminescent and non‐luminescent variants of Vibrio harveyi wild type and quorum sensing mutants
Authors: Hong N T X , Baruah K , Vanrompay D , Bossier P
Published: April 2015

Vibrio harveyi, a luminescent Gram‐negative motile marine bacterium, is an important pathogen responsible for causing severe diseases in shrimp, finfish and molluscs leading to severe economic losses. Non‐luminescent V. harveyi obtained by culturing luminescent strains under static and dark condition were reported to alter the levels of virulence factors and metalloprotease gene and luxR expression when compared to their luminescent variants. Presently, we conducted an in vitro study aiming at the characterization of virulence‐related phenotypic traits of the wild‐type V. harveyi BB120 strain and its isogenic quorum sensing mutants before and after switching to the non‐luminescent status. We measured the production of caseinase, haemolysin and elastase and examined swimming motility and biofilm formation. Our results showed that switching from the bioluminescent to the non‐luminescent state changed the phenotypic physiology or behaviour of V. harveyi resulting in alterations in caseinase and haemolytic activities, swimming motility and biofilm formation. The switching capacity was to a large extent independent from the quorum sensing status, in that quorum sensing mutants were equally capable of making the phenotypic switch.
Co‐infection of Nucleospora cyclopteri (Microsporidia) and Kudoa islandica (Myxozoa) in farmed lumpfish, Cyclopterus lumpus L., in Norway: a case report
Authors: Alarcón M , Thoen E , Poppe T T , Bornø G , Mohammad S N , Hansen H
Published: April 2015

This study describes a co‐infection of Kudoa islandica (Myxozoa) and Nucleospora cyclopteri (Microsporida) in farmed lumpfish, Cyclopterus lumpus L., in Norway. Several other parasites (Cryptocotyle sp., protozoan ciliates and Gyrodactylus sp.) were also found in gills. In June 2013, the mortality in a farmed lumpfish population increased to 65%. Lumpfish showed erratic swimming behaviour and loss of weight. At necropsy, nodules in the kidney were the only visible lesions. Histologically, all fish showed severe changes with gill inflammation and necrosis in the spleen, kidney and liver. Haemorrhages and necrosis were observed in some hearts. Intracellular microsporidians associated with the lesions were detected in most organs using histological examination and Calcofluor White. Kudoa spores were diagnosed in the skeletal muscle, but no inflammatory response was associated with the presence of the plasmodia. Comparison of 18S ribosomal DNA sequences showed 100% similarity to Kudoa islandica and Nucleospora cyclopteri. Kudoa islandica and N. cyclopteri have previously been described associated with lesions in wild lumpfish in Iceland. In the present case, N. cyclopteri is believed to be the main cause of systemic pathology. This is the first description of K. islandica and N. cyclopteri causing pathology in farmed lumpfish in Norway.
Aβ1–42oligomer‐induced leakage in anin vitroblood–brain barrier model is associated with up‐regulation ofRAGEand metalloproteinases, and down‐regulation of tight junction scaffold proteins
Authors: Wan Wenbin , Cao Lan , Liu Lumei , Zhang Chunyan , Kalionis Bill , Tai Xiantao , Li Yaming , Xia Shijin
Published: April 2015

Accumulating evidence indicates that abnormal deposition of amyloid‐β (Aβ) peptide in the brain is responsible for endothelial cell damage and consequently leads to blood–brain barrier (BBB) leakage. However, the mechanisms underlyingBBBdisruption are not well described. We employed an monolayerBBBmodel comprisingbEnd.3 cell and found thatBBBleakage was induced by treatment with Aβ1–42,and the levels of tight junction (TJ) scaffold proteins (ZO‐1, Claudin‐5, and Occludin) were decreased. Through comparisons of the effects of the different components of Aβ1–42, including monomer (Aβ1–42‐Mono), oligomer (Aβ1–42‐Oligo), and fibril (Aβ1–42‐Fibril), our data confirmed that Aβ1–42‐Oligo is likely to be the most important damage factor that results inTJdamage andBBBleakage in Alzheimer's disease. We found that the incubation ofbEnd.3 cells with Aβ1–42significantly up‐regulated the level of receptor for advanced glycation end‐products (RAGE). Co‐incubation of a polyclonal antibody toRAGEand Aβ1–42‐Oligo inbEnd.3 cells blockedRAGEsuppression of Aβ1–42‐Oligo‐induced alterations inTJscaffold proteins and reversed Aβ1–42‐Oligo‐induced up‐regulation ofRAGE, matrix metalloproteinase (MMP)‐2, andMMP‐9. Furthermore, we found that these effects induced by Aβ1–42‐Oligo treatment were effectively suppressed by knockdown ofRAGEusing small interferingRNA(siRNA) transfection. We also found thatGM6001, a broad‐spectrumMMPinhibitor, partially reversed the Aβ1–42‐Oligo‐induced inhibitor effects inbEnd.3 cells. Thus, these results suggested thatRAGEplayed an important role in Aβ‐inducedBBBleakage and alterations ofTJscaffold proteins, through a mechanism that involved up‐regulation ofMMP‐2 and MMP‐9.

image

To reveal the role of RAGE in blood–brain barrier (BBB) disruption in Alzheimer's disease (AD), we employed an monolayer BBB model comprising bEnd.3 cell and found that BBB leakage was induced by treatment with amyloid‐β (Aβ), and the levels of tight junction (TJ) scaffold proteins including ZO‐1, Claudin‐5, and Occludin were decreased. Using receptor for advanced glycation end‐products (RAGE) neutralizing polyclonal antibody and siRNA, we confirmed that RAGE played an important role in Aβ‐induced BBB leakage and alterations of TJ scaffold proteins and in the up‐regulation of matrix metalloproteinase‐2 (MMP‐2) and matrix metalloproteinase‐9 (MMP‐9). NF‐κB, nuclear factor kappa‐light‐chain‐enhancer of activated B cells.
Dendrochronological reconstruction reveals a mixed‐intensity fire regime in Pinus sylvestris‐dominated stands of Białowieża Forest, Belarus and Poland
Authors: Zin Ewa , Drobyshev Igor , Bernacki Dmitrij , Niklasson Mats
Published: April 2015

Questions

What were the features of the historical forest fire regime, fire intensity in particular, in Pinus sylvestris‐dominated stands of Białowieża Forest? Did tree recruitment patterns relate to the fire history?

Location

Białowieża Forest, western Belarus and northeast Poland.

Methods

We used dendrochronological methods to reconstruct the fire regime in a 8.5‐ha mixed coniferous (Pinus sylvestris–Picea abies) forest stand located in the Belarusian part of Białowieża Forest. We analysed fire frequency at stand and point scale, seasonal distribution of fires and fire intensity. We compared the results to a previous study done in a 13.0‐ha site of similar habitat and stand structure, located in the Polish part of Białowieża Forest.

Results

We reconstructed fires back to 1655, the most recent fire dating to 1918. Mean fire interval at stand scale during 1645–2010 was 9 ± 7.8 yrs (±SD). Fire frequency gradually declined after 1811, with mean fire interval at stand scale increasing from 5 ± 2.5 yrs prior to 1811 to 18 ± 9.3 yrs thereafter. Most fires were likely of low intensity, as suggested by (1) small average tree diameter (5.1 ± 2.9 cm) at the first scar, (2) absence of strong negative growth reactions after fire, and (3) high fire frequency likely limiting fuel build‐up. However, a fire in 1718 was intense and resulted in a wave of P. sylvestris regeneration. The reconstructed fire history in the Belarusian part of Białowieża Forest showed many similarities with that done in the Polish section of this forest. Similarities included dominance of low‐intensity dormant and early‐season fires, sporadic occurrence of high‐intensity fires, high fire frequencies between the 1650s and the early 1800s, and cessation of fires since the early 20th century. Six out of 50 fire dates reconstructed in both sites were common and represented a level of synchrony that was significantly higher than expected under a random pattern of fire occurrence.

Conclusions

Low‐intensity surface fires dominated the historical fire regime of Białowieża Forest. However, occasional high‐intensity stand‐replacing fires led to successional changes at the stand scale.
Molecular tools and bumble bees: revealing hidden details of ecology and evolution in a model system
Authors: Woodard S. Hollis , Lozier Jeffrey D. , Goulson David , Williams Paul H. , Strange James P. , Jha Shalene
Published: April 2015

Bumble bees are a longstanding model system for studies on behaviour, ecology and evolution, due to their well‐studied social lifestyle, invaluable role as wild and managed pollinators, and ubiquity and diversity across temperate ecosystems. Yet despite their importance, many aspects of bumble bee biology have remained enigmatic until the rise of the genetic and, more recently, genomic eras. Here, we review and synthesize new insights into the ecology, evolution and behaviour of bumble bees that have been gained using modern genetic and genomic techniques. Special emphasis is placed on four areas of bumble bee biology: the evolution of eusociality in this group, population‐level processes, large‐scale evolutionary relationships and patterns, and immunity and resistance to pesticides. We close with a prospective on the future of bumble bee genomics research, as this rapidly advancing field has the potential to further revolutionize our understanding of bumble bees, particularly in regard to adaptation and resilience. Worldwide, many bumble bee populations are in decline. As such, throughout the review, connections are drawn between new molecular insights into bumble bees and our understanding of the causal factors involved in their decline. Ongoing and potential applications to bumble bee management and conservation are also included to demonstrate how genetics‐ and genomics‐enabled research aids in the preservation of this threatened group.
Management of sleep apnea: a critical look at intra‐oral appliances
Authors: Conley R. S.
Published: April 2015

With so many disciplines of both medicine and dentistry involved in the treatment of obstructive sleep apnea (OSA), several forms of therapy are available. The orthodontist is rarely considered when the diagnosis of chronic obstructive sleep apnea (OSA) is delivered. However, the scope of orthodontic care today is much broader than the mere alignment of teeth. While the current gold standard for OSA care remains continuous positive air pressure (CPAP), the patient may be given a prescription for an intra‐oral sleep appliance. When orthodontists work in concert with their medical colleagues to provide a sleep appliance, several considerations must be made including the evidence regarding oral appliance efficacy. For some patients, oral appliances are highly successful; however, even for responsive patients, there are risks associated with oral appliance therapy. The aim of the paper was to present a critical review of the current level of evidence for the use of oral appliances in the treatment of OSA. A substantial number of publications ranging from case reports, uncontrolled and controlled case series, prospective randomized studies, and even a small number of systematic reviews were available. The existing systematic reviews were based on either a limited number of prospective studies with limited numbers of patients or in some cases were based on subjective data only. As a result, a narrative review of the literature was performed that discusses objective clinically testable criteria and recent developments that may aid future research investigations.
Mechanical environment change in root, periodontal ligament, and alveolar bone in response to two canine retraction treatment strategies
Authors: Jiang F. , Xia Z. , Li S. , Eckert G. , Chen J.
Published: April 2015

Structured Abstract

Objective

To investigate the initial mechanical environment (ME) changes in root surface, periodontal ligament (PDL), and alveolar bone due to two treatment strategies, low or high moment‐to‐force ratio (M/F).

Setting and Sample Population

Indiana University‐Purdue University Indianapolis. Eighteen patients who underwent maxillary bilateral canine retraction.

Material and method

Finite element models of the maxillary canines from the patients were built based on their cone beam computed tomography scans. For each patient, the canine on one side had a specially designed T‐loop spring with the M/F higher than the other side. Four stress invariants (1st principal/dilatational/3rd principal/von Mises stress) in the tissues were calculated. The stresses were compared with the bone mineral density (BMD) changes reported previously for linking the ME change to bone modeling/remodeling activities. The correlation was tested by the mixed‐model anova.

Results

The alveolar bone in the direction of tooth movement is primarily in tension, while the PDL is in compression; the stresses in the opposite direction have a reversed pattern. The M/F primarily affects the stress in root. Three stress invariants (1st principal/3rd principal/dilatational stress) in the tooth movement direction have moderate correlations with BMD loss.

Conclusions

The stress invariants may be used to characterize what the osteocytes sense when ME changes. Their distributions in the tissues are significantly different, meaning the cells experience different stimuli. The higher bone activities along the direction of tooth movement may be related to the initial volumetric increase and decrease in the alveolar bone.
Genetic and treatment‐related risk factors associated with external apical root resorption (EARR) concurrent with orthodontia
Authors: Sharab L. Y. , Morford L. A. , Dempsey J. , Falcão‐Alencar G. , Mason A. , Jacobson E. , Kluemper G. T. , Macri J. V. , Hartsfield J. K.
Published: April 2015

Structured Abstract

Objective

As genetic variation accounts for two‐thirds of the variation in external apical root resorption (EARR) concurrent with orthodontic treatment, we analyzed the association of selected genetic and treatment‐related factors with EARR concurrent with orthodontic treatment.

Setting and sample population

This case–control study of 134 unrelated, orthodontically treated Caucasian individuals was conducted in part at an Indiana Private Practice, Indiana University and the University of Kentucky.

Methods

Utilizing a research data bank containing information from ~1450 orthodontically treated patients, pre‐ and post‐treatment radiographs from 460 individuals were evaluated for EARR of the four permanent maxillary incisors. Sixty‐seven unrelated Caucasians with moderate to severe EARR were identified and were age‐/sex‐matched with orthodontically treated Caucasian controls yielding 38 females and 29 males per group. Factors tested for an association with EARR included the following: 1) treatment duration, 2) extraction of maxillary premolars, 3) numerous cephalometric measurements, and 4) DNA polymorphisms within/near candidate genes in a pathway previously implicated in EARR such as the purinergic‐receptor‐P2X, ligand‐gated ion channel 7 (P2RX7; rs208294, rs1718119, and rs2230912), caspase‐1 (CASP1; rs530537, rs580253, and rs554344), interleukin‐1 beta (IL1B; rs1143634), interleukin‐1 alpha (IL1A; rs1800587), and interleukin‐1 receptor antagonist (IL1RA; rs419598) genes. Stepwise logistic regression was utilized to identify the factors significantly associated (significance taken at or less than the layered Bonferroni correction alpha) with the occurrence of EARR.

Results

A long length of treatment and the presence of specific genotypes for P2RX7 SNP rs208294 were significantly associated with EARR.

Conclusion

EARR occurrence was associated with both genetic and treatment‐related variables, which together explained 25% of the total variation associated with EARR in the sample tested.
Ideal orthodontic alignment load relationships based on periodontal ligament stress
Authors: Viecilli R. F. , Burstone C. J.
Published: April 2015

Structured Abstract

Objectives

To test the hypothesis that periodontal ligament (PDL) stress relationships that yield resistance numbers representing load proportions between different teeth depend on alignment load type.

Materials and Methods

Finite element models of all teeth, except the third molars, were produced. Four different types of loads were applied, and the third principal stresses of different teeth in standardized areas of most compression were calculated. Based on these results, resistance numbers, representing the load proportions for each tooth derived from PDL stress, were determined.

Results

The third principal stress values for typical alignment loads in the areas of most stress were very different for different load types for each tooth. Differences in resistance numbers between teeth also varied with different loads.

Conclusion

Resistance numbers, that is, load proportion numbers between teeth to achieve similar stress at the compressive PDL zone, depend on the type of applied load.
The effects of tissue‐non‐specific alkaline phosphatase gene therapy on craniosynostosis and craniofacial morphology in the FGFR2C342Y/+ mouse model of Crouzon craniosynostosis
Authors: Wang E. , Nam H. K. , Liu J. , Hatch N. E.
Published: April 2015

Structured Abstract

Objectives

Craniosynostosis, the premature fusion of cranial bones, has traditionally been described as a disease of increased bone mineralization. However, multiple mouse models of craniosynostosis display craniosynostosis simultaneously with diminished cranial bone volume and/or density. We propose an alternative hypothesis that craniosynostosis results from abnormal tissue mineralization through the downregulation of tissue‐non‐specific alkaline phosphatase (TNAP) enzyme downstream of activating mutations in FGFRs.

Material and Methods

Neonatal Crouzon (FGFRC342Y/+) and wild‐type (FGFR+/+) mice were injected with lentivirus to deliver a recombinant form of TNAP. Mice were sacrificed at 4 weeks postnatal. Serum was collected to test for alkaline phosphatase (AP), phosphorus, and calcium levels. Craniofacial bone fusion and morphology were assessed by micro‐computed tomography.

Results

Injection with the TNAP lentivirus significantly increased serum AP levels (increased serum AP levels are indicative of efficient transduction and production of the recombinant protein), but results were variable and dependent upon viral lot and the litter of mice injected. Morphological analysis revealed craniofacial form differences for inferior surface (p = 0.023) and cranial height (p = 0.014) regions between TNAP lentivirus‐injected and vehicle‐injected Crouzon mice. With each unit increase in AP level, the odds of lambdoid suture fusion decreased by 84.2% and these results came close to statistical significance (p = 0.068).

Conclusion

These results suggest that TNAP deficiency may mediate FGFR2‐associated craniosynostosis. Future studies should incorporate injection of recombinant TNAP protein, to avoid potential side effects and variable efficacy of lentiviral gene delivery.
Visible red and infrared light alters gene expression in human marrow stromal fibroblast cells
Authors: Guo J. , Wang Q. , Wai D. , Zhang Q. Z. , Shi S. H. , Le A. D. , Shi S. T. , Yen S. L.‐K.
Published: April 2015

Structured Abstract

Objectives

This study tested whether or not gene expression in human marrow stromal fibroblast (MSF) cells depends on light wavelength and energy density.

Materials and Methods

Primary cultures of isolated human bone marrow stem cells (hBMSC) were exposed to visible red (VR, 633 nm) and infrared (IR, 830 nm) radiation wavelengths from a light emitting diode (LED) over a range of energy densities (0.5, 1.0, 1.5, and 2.0 Joules/cm2) Cultured cells were assayed for cell proliferation, osteogenic potential, adipogenesis, mRNA and protein content. mRNA was analyzed by microarray and compared among different wavelengths and energy densities. Mesenchymal and epithelial cell responses were compared to determine whether responses were cell type specific. Protein array analysis was used to further analyze key pathways identified by microarrays.

Result

Different wavelengths and energy densities produced unique sets of genes identified by microarray analysis. Pathway analysis pointed to TGF‐beta 1 in the visible red and Akt 1 in the infrared wavelengths as key pathways to study. TGF‐beta protein arrays suggested switching from canonical to non‐canonical TGF‐beta pathways with increases to longer IR wavelengths. Microarrays suggest RANKL and MMP 10 followed IR energy density dose–response curves. Epithelial and mesenchymal cells respond differently to stimulation by light suggesting cell type‐specific response is possible.

Conclusions

These studies demonstrate differential gene expression with different wavelengths, energy densities and cell types. These differences in gene expression have the potential to be exploited for therapeutic purposes and can help explain contradictory results in the literature when wavelengths, energy densities and cell types differ.
Locally limited inhibition of bone resorption and orthodontic relapse by recombinant osteoprotegerin protein
Authors: Schneider D. A. , Smith S. M. , Campbell C. , Hayami T. , Kapila S. , Hatch N. E.
Published: April 2015

Structured Abstract

Objectives

To determine minimal dose levels required for local inhibition of orthodontic relapse by recombinant OPG protein (OPG‐Fc), while also determining effects of injected OPG‐Fc on alveolar bone and long bone.

Setting and Sample Population

The Department of Orthodontics and Pediatric Dentistry at the University of Michigan. Eighteen male Sprague Dawley rats.

Materials & Methods

Maxillary molars were moved with nickel–titanium springs and then allowed to relapse in Sprague Dawley rats. Upon appliance removal, animals were injected with a single dose of 1.0 mg/kg OPG‐Fc, 0.1 mg/kg OPG‐Fc, or phosphate‐buffered saline (vehicle) just distal to the molar teeth. Tooth movement measurements were made from stone casts, which were scanned and digitally measured. Alveolar tissues were examined by histology. Micro‐computed tomography was used to quantify changes in alveolar and femur bone.

Results

Local injection of OPG‐Fc inhibited molar but not incisor relapse, when compared to vehicle‐injected animals. No significant differences in alveolar or femur bone were seen between the three treatment groups after 24 days of relapse.

Conclusions

Our results demonstrate that a single local injection of OPG‐Fc effectively inhibits orthodontic relapse, with minimal systemic bone metabolic effects. Our results also show that a single injection of OPG‐Fc will influence tooth movement only in teeth close to the injection site. These findings indicate that OPG‐Fc has potential as a safe and effective pharmacological means to locally control osteoclasts, for uses such as maintaining anchorage during orthodontic tooth movement and preventing orthodontic relapse in humans.
A Subgroup Analysis Found no Diminished Response to Buprenorphine Transdermal System Treatment for Chronic Low Back Pain Patients Classified with Depression
Authors: Yarlas Aaron , Miller Kate , Wen Warren , Lynch Shau Yu , Munera Catherine , Dain Bradley , Pergolizzi Joseph V. , Raffa Robert , Ripa Steven R.
Published: April 2015

Background

Chronic pain (CP) patients with depression typically exhibit worse post‐treatment outcomes than nondepressed CP patients. The cause is often assumed to reflect a differential response to treatment, neglecting other potential explanations, such as the continuation of differences in pretreatment outcomes. This post hoc analysis examines whether worse post‐treatment outcomes for depressed patients with chronic low back pain (CLBP) are driven by reduced treatment efficacy.

Methods

Data were from opioid‐naïve adult patients with moderate‐to‐severe CLBP who participated in a randomized, placebo‐controlled, double‐blind clinical trial of Butrans® (buprenorphine) Transdermal System (BTDS) for pain relief. Depression screening was based on baseline SF‐36v2 Mental Health subscale scores. Patient‐reported measures of pain severity, pain interference, quality of life, sleep problems, and functional disability were administered at screening and during the study. Differential treatment efficacy for each outcome was examined using analysis of covariance models that included interaction terms between treatment arm and depression status.

Results

At baseline, patients classified as depressed showed greater pain interference, lower quality of life, more sleep problems, and greater functional disability than nondepressed patients; the two groups did not differ in pain severity. No statistically significant interactions between treatment arm and depression status were observed. The direction of improvement post‐treatment favored the depressed group on nine of seventeen outcomes.

Conclusions

Results do not support a differential response to BTDS treatment between depressed and nondepressed CLBP patients across a variety of patient‐reported outcomes. These findings raise the question of whether depressed mood actually moderates the effectiveness of treatment in CP patients.
Occipital Nerve Stimulation for Migraine: A Systematic Review
Authors: Yang Yuecheng , Song Mingmin , Fan Yinghui , Ma Ke
Published: April 2015

Patients who suffer from migraines often report impaired quality of life. Occipital nerve stimulation (ONS) is a novel treatment modality for migraines, although few systematic reviews have evaluated whether this therapy is efficacious. The objective of this study was to evaluate the clinical efficacy and safety of ONS for treating migraine through a literature review. We performed a literature search to identify studies that investigated ONS for migraine treatment. Evidence levels of these studies were assessed by recommendations set by the University of Oxford Centre for Evidence‐Based Medicine. Five randomized controlled trials, 4 retrospective studies, and one prospective study met the inclusion criteria. Results from the retrospective studies and case series indicated that ONS significantly reduced the pain intensity and the number of days with headache in patients with migraine. However, the evidence of ONS efficacy established by randomized controlled trials was limited. Improvement in the migraine disability assessment (MIDAS) score was more dramatic than improvement in the SF‐36 score at follow‐up. The mean complication incidence of ONS was 66% for the reviewed studies. Future clinical studies should optimize and standardize the ONS intervention process and identify the relationship among the surgical process, efficacy, and complications resulting from the procedure.
Prevalence of ADHD in primary school children in Vinh Long, Vietnam
Authors: Pham Hoai Danh , Nguyen Huu Bao Han , Tran Diep Tuan
Published: April 2015

Background

Attention‐deficit hyperactivity disorder (ADHD) is the most common behavioral disorder in children. It affects not only the subjects but also their families and society. The purpose of this study was to determine the prevalence of ADHD in primary school children in South Vietnam, especially Vinh Long province.

Method

Children were chosen randomly from primary schools in Vinh Long from February to March in 2009 in a cross‐sectional study to determine the prevalence of ADHD using the ADHD Rating Scale‐IV for parents/caregivers and teachers. ADHD Rating Scale‐IV was based on DSM‐IV for diagnosis of ADHD.

Results

A total of 600 children were chosen and 1200 reports were collected from parents/caregivers and teachers. The prevalence rate of ADHD was 7.7%. The rates of the predominantly inattentive type, predominantly hyperactive type and combined type were 1.7%, 5% and 1%, respectively. The difference in sex was not significant across all subtypes. The prevalence of ADHD in urban children was 2.2‐fold that in rural children.

Conclusion

The prevalence of ADHD in primary school children in Vinh Long, southern Vietnam, is in the same range as other regions in the world. Therefore, awareness of ADHD needs to be raised, to ensure suitable psychiatric care for children.
Physiological adjustment to salt stress in Jatropha curcas is associated with accumulation of salt ions, transport and selectivity of K+, osmotic adjustment and K+/Na+ homeostasis
Authors: Silva E. N. , Silveira J. A. G. , Rodrigues C. R. F. , Viégas R. A.
Published: April 2015

This study assessed the capacity of Jatropha curcas to physiologically adjust to salinity. Seedlings were exposed to increasing NaCl concentrations (25, 50, 75 and 100 mm) for 15 days. Treatment without NaCl was adopted as control. Shoot dry weight was strongly reduced by NaCl, reaching values of 35% to 65% with 25 to 100 mm NaCl. The shoot/root ratio was only affected with 100 mm NaCl. Relative water content (RWC) increased only with 100 mm NaCl, while electrolyte leakage (EL) was much enhanced with 50 mm NaCl. The Na+ transport rate to the shoot was more affected with 50 and 100 mm NaCl. In parallel, Cl− transport rate increased with 75 and 100 mm NaCl, while K+ transport rate fell from 50 mm to 100 mm NaCl. In roots, Na+ and Cl− transport rates fell slightly only in 50 mm (to Na+) and 50 and 100 mm (to Cl−) NaCl, while K+ transport rate fell significantly with increasing NaCl. In general, our data demonstrate that J. curcas seedlings present changes in key physiological processes that allow this species to adjust to salinity. These responses are related to accumulation of Na+ and Cl− in leaves and roots, K+/Na+ homeostasis, transport of K+ and selectivity (K–Na) in roots, and accumulation of organic solutes contributing to osmotic adjustment of the species.
An adaptive filtered back‐projection for photoacoustic image reconstruction
Authors: Huang He , Bustamante Gilbert , Peterson Ralph , Ye Jing Yong
Published: April 2015

Purpose:

The purpose of this study is to develop an improved filtered‐back‐projection (FBP) algorithm for photoacoustic tomography (PAT), which allows image reconstruction with higher quality compared to images reconstructed through traditional algorithms.

Methods:

A rigorous expression of a weighting function has been derived directly from a photoacoustic wave equation and used as a ramp filter in Fourier domain. The authors’ new algorithm utilizes this weighting function to precisely calculate each photoacoustic signal's contribution and then reconstructs the image based on the retarded potential generated from the photoacoustic sources. In addition, an adaptive criterion has been derived for selecting the cutoff frequency of a low pass filter. Two computational phantoms were created to test the algorithm. The first phantom contained five spheres with each sphere having different absorbances. The phantom was used to test the capability for correctly representing both the geometry and the relative absorbed energy in a planar measurement system. The authors also used another phantom containing absorbers of different sizes with overlapping geometry to evaluate the performance of the new method for complicated geometry. In addition, random noise background was added to the simulated data, which were obtained by using an arc‐shaped array of 50 evenly distributed transducers that spanned 160° over a circle with a radius of 65 mm. A normalized factor between the neighbored transducers was applied for correcting measurement signals in PAT simulations. The authors assumed that the scanned object was mounted on a holder that rotated over the full 360° and the scans were set to a sampling rate of 20.48 MHz.

Results:

The authors have obtained reconstructed images of the computerized phantoms by utilizing the new FBP algorithm. From the reconstructed image of the first phantom, one can see that this new approach allows not only obtaining a sharp image but also showing the correct signal strength of the absorbers. The reconstructed image of the second phantom further demonstrates the capability to form clear images of the spheres with sharp borders in the overlapping geometry. The smallest sphere is clearly visible and distinguishable, even though it is surrounded by two big spheres. In addition, image reconstructions were conducted with randomized noise added to the observed signals to mimic realistic experimental conditions.

Conclusions:

The authors have developed a new FBP algorithm that is capable for reconstructing high quality images with correct relative intensities and sharp borders for PAT. The results demonstrate that the weighting function serves as a precise ramp filter for processing the observed signals in the Fourier domain. In addition, this algorithm allows an adaptive determination of the cutoff frequency for the applied low pass filter.
Proton beam deflection in MRI fields: Implications for MRI‐guided proton therapy
Authors: Oborn B. M. , Dowdell S. , Metcalfe P. E. , Crozier S. , Mohan R. , Keall P. J.
Published: April 2015

Purpose:

This paper investigates, via magnetic modeling and Monte Carlo simulation, the ability to deliver proton beams to the treatment zone inside a split‐bore MRI‐guided proton therapy system.

Methods:

Field maps from a split‐bore 1 T MRI‐Linac system are used as input to geant4 Monte Carlo simulations which model the trajectory of proton beams during their paths to the isocenter of the treatment area. Both inline (along the MRI bore) and perpendicular (through the split‐bore gap) orientations are simulated. Monoenergetic parallel and diverging beams of energy 90, 195, and 300 MeV starting from 1.5 and 5 m above isocenter are modeled. A phase space file detailing a 2D calibration pattern is used to set the particle starting positions, and their spatial location as they cross isocenter is recorded. No beam scattering, collimation, or modulation of the proton beams is modeled.

Results:

In the inline orientation, the radial symmetry of the solenoidal style fringe field acts to rotate the protons around the beam's central axis. For protons starting at 1.5 m from isocenter, this rotation is 19° (90 MeV) and 9.8° (300 MeV). A minor focusing toward the beam's central axis is also seen, but only significant, i.e., 2 mm shift at 150 mm off‐axis, for 90 MeV protons. For the perpendicular orientation, the main MRI field and near fringe field act as the strongest to deflect the protons in a consistent direction. When starting from 1.5 m above isocenter shifts of 135 mm (90 MeV) and 65 mm (300 MeV) were observed. Further to this, off‐axis protons are slightly deflected toward or away from the central axis in the direction perpendicular to the main deflection direction. This leads to a distortion of the phase space pattern, not just a shift. This distortion increases from zero at the central axis to 10 mm (90 MeV) and 5 mm (300 MeV) for a proton 150 mm off‐axis. In both orientations, there is a small but subtle difference in the deflection and distortion pattern between protons fired parallel to the beam axis and those fired from a point source. This is indicative of the 3D spatially variant nature of the MRI fringe field.

Conclusions:

For the first time, accurate magnetic and Monte Carlo modeling have been used to assess the transport of generic proton beams toward a 1 T split‐bore MRI. Significant rotation is observed in the inline orientation, while more complex deflection and distortion are seen in the perpendicular orientation. The results of this study suggest that due to the complexity and energy‐dependent nature of the magnetic deflection and distortion, the pencil beam scanning method will be the only choice for delivering a therapeutic proton beam inside a potential MRI‐guided proton therapy system in either the inline or perpendicular orientation. Further to this, significant correction strategies will be required to account for the MRI fringe fields.
Dosimetric characterization of two radium sources for retrospective dosimetry studies
Authors: Candela‐Juan C. , Karlsson M. , Lundell M. , Ballester F. , Tedgren Å. Carlsson
Published: April 2015

Purpose:

During the first part of the 20th century, 226Ra was the most used radionuclide for brachytherapy. Retrospective accurate dosimetry, coupled with patient follow up, is important for advancing knowledge on long‐term radiation effects. The purpose of this work was to dosimetrically characterize two 226Ra sources, commonly used in Sweden during the first half of the 20th century, for retrospective dose–effect studies.

Methods:

An 8 mg 226Ra tube and a 10 mg 226Ra needle, used at Radiumhemmet (Karolinska University Hospital, Stockholm, Sweden), from 1925 to the 1960s, were modeled in two independent Monte Carlo (MC) radiation transport codes: geant4 and mcnp5. Absorbed dose and collision kerma around the two sources were obtained, from which the TG‐43 parameters were derived for the secular equilibrium state. Furthermore, results from this dosimetric formalism were compared with results from a MC simulation with a superficial mould constituted by five needles inside a glass casing, placed over a water phantom, trying to mimic a typical clinical setup. Calculated absorbed doses using the TG‐43 formalism were also compared with previously reported measurements and calculations based on the Sievert integral. Finally, the dose rate at large distances from a 226Ra point‐like‐source placed in the center of 1 m radius water sphere was calculated with geant4.

Results:

TG‐43 parameters [including gL(r), F(r, θ), Λ, and sK] have been uploaded in spreadsheets as additional material, and the fitting parameters of a mathematical curve that provides the dose rate between 10 and 60 cm from the source have been provided. Results from TG‐43 formalism are consistent within the treatment volume with those of a MC simulation of a typical clinical scenario. Comparisons with reported measurements made with thermoluminescent dosimeters show differences up to 13% along the transverse axis of the radium needle. It has been estimated that the uncertainty associated to the absorbed dose within the treatment volume is 10%–15%, whereas uncertainty of absorbed dose to distant organs is roughly 20%–25%.

Conclusions:

The results provided here facilitate retrospective dosimetry studies of 226Ra using modern treatment planning systems, which may be used to improve knowledge on long term radiation effects. It is surely important for the epidemiologic studies to be aware of the estimated uncertainty provided here before extracting their conclusions.