bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome characterization and high throughput SSRs and SNPs discovery in Cucurbita pepo (Cucurbitaceae)
Authors: Blanca José , Cañizares Joaquín , Roig Cristina , Ziarsolo Pello , Nuez Fernando , Picó Belén
Published: February 2011

Background

Cucurbita pepo belongs to the Cucurbitaceae family. The "Zucchini" types rank among the highest-valued vegetables worldwide, and other C. pepo and related Cucurbita spp., are food staples and rich sources of fat and vitamins. A broad range of genomic tools are today available for other cucurbits that have become models for the study of different metabolic processes. However, these tools are still lacking in the Cucurbita genus, thus limiting gene discovery and the process of breeding.

Results

We report the generation of a total of 512,751 C. pepo EST sequences, using 454 GS FLX Titanium technology. ESTs were obtained from normalized cDNA libraries (root, leaves, and flower tissue) prepared using two varieties with contrasting phenotypes for plant, flowering and fruit traits, representing the two C. pepo subspecies: subsp. pepo cv. Zucchini and subsp. ovifera cv Scallop. De novo assembling was performed to generate a collection of 49,610 Cucurbita unigenes (average length of 626 bp) that represent the first transcriptome of the species. Over 60% of the unigenes were functionally annotated and assigned to one or more Gene Ontology terms. The distributions of Cucurbita unigenes followed similar tendencies than that reported for Arabidopsis or melon, suggesting that the dataset may represent the whole Cucurbita transcriptome. About 34% unigenes were detected to have known orthologs of Arabidopsis or melon, including genes potentially involved in disease resistance, flowering and fruit quality. Furthermore, a set of 1,882 unigenes with SSR motifs and 9,043 high confidence SNPs between Zucchini and Scallop were identified, of which 3,538 SNPs met criteria for use with high throughput genotyping platforms, and 144 could be detected as CAPS. A set of markers were validated, being 80% of them polymorphic in a set of variable C. pepo and C. moschata accessions.

Conclusion

We present the first broad survey of gene sequences and allelic variation in C. pepo, where limited prior genomic information existed. The transcriptome provides an invaluable new tool for biological research. The developed molecular markers are the basis for future genetic linkage and quantitative trait loci analysis, and will be essential to speed up the process of breeding new and better adapted squash varieties.
Genetic predisposition to fracture non-union: a case control study of a preliminary single nucleotide polymorphisms analysis of the BMP pathway
Authors: Dimitriou Rozalia , Carr Ian M , West Robert M , Markham Alexander F , Giannoudis Peter V
Published: February 2011

Background

Despite the known multi-factorial nature of atrophic fracture non-unions, a possible genetic predisposition for the development of this complication after long bone fractures remains unknown. This pilot study aimed to address this issue by performing a preliminary SNP analysis of specific genes known to regulate fracture healing.

Methods

A total of fifteen SNPs within four genes of the Bone Morphogenetic Protein (BMP) pathway (BMP-2, BMP-7, NOGGIN and SMAD6) were examined, in 109 randomly selected patients with long bone fractures as a result of motor vehicle accident, fall or direct blow. There were sixty-two patients with atrophic non-union and forty-seven patients (54 fractures) with uneventful fracture union. Overall SNPs frequencies were computed with respect to patient's age, gender, smoking habits, fracture-associated parameters and the use of nonsteroidal anti-inflammatory drugs (NSAIDs), and tested for their association to the impaired bone healing process, using binary logistic regression (STATA 11.1; StataCorp, Texas USA).

Results

Statistical analysis revealed age to be an important covariate in the development of atrophic non-union (p = 0.01, OR 1.05 [per year]), and two specific genotypes (G/G genotype of the rs1372857 SNP, located on NOGGIN and T/T genotype of the rs2053423 SNP, located on SMAD6) to be associated with a greater risk of fracture non-union (p = 0.02, OR 4.56 and p = 0.04, OR 10.27, respectively, after adjustment for age).

Conclusions

This is the first clinical study to investigate the potential existence of genetic susceptibility to fracture non-union. Even though no concrete conclusions can be obtained from this pilot study, our results indicate the existence of a potential genetically predetermined impairment within the BMP signalling cascade, initiated after a fracture and when combined with other risk factors could synergistically increase the susceptibility of a patient to develop non-union. Further research is desirable in order to clarify the genetic component and its role and interaction with other risk factors in the development of atrophic long bone non-union, as simple genetic testing may contribute to the early identification of patients at risk in the future and the on-time intervention at the biologic aspects of bone healing.
Modulation of small leucine-rich proteoglycans (SLRPs) expression in the mouse uterus by estradiol and progesterone
Authors: Salgado Renato M , Favaro Rodolfo R , Zorn Telma MT
Published: February 2011

Background

We have previously demonstrated that four members of the family of small leucine-rich-proteoglycans (SLRPs) of the extracellular matrix (ECM), named decorin, biglycan, lumican and fibromodulin, are deeply remodeled in mouse uterine tissues along the estrous cycle and early pregnancy. It is known that the combined action of estrogen (E2) and progesterone (P4) orchestrates the estrous cycle and prepares the endometrium for pregnancy, modulating synthesis, deposition and degradation of various molecules. Indeed, we showed that versican, another proteoglycan of the ECM, is under hormonal control in the uterine tissues.

Methods

E2 and/or medroxiprogesterone acetate (MPA) were used to demonstrate, by real time PCR and immunoperoxidase staining, respectively, their effects on mRNA expression and protein deposition of these SLRPs, in the uterine tissues.

Results

Decorin and lumican were constitutively expressed and deposited in the ECM in the absence of the ovarian hormones, whereas deposition of biglycan and fibromodulin were abolished from the uterine ECM in the non-treated group. Interestingly, ovariectomy promoted an increase in decorin, lumican and fibromodulin mRNA levels, while biglycan mRNA conspicuously decreased. Hormone replacement with E2 and/or MPA differentially modulates their expression and deposition.

Conclusions

The patterns of expression of these SLRPs in the uterine tissues were found to be hormone-dependent and uterine compartment-related. These results reinforce the existence of subpopulations of endometrial fibroblasts, localized into distinct functional uterine compartments, resembling the organization into basal and functional layers of the human endometrium.
The origin of the red emission in n-ZnO nanotubes/p-GaN white light emitting diodes
Authors: Alvi N H , ul Hasan Kamran , Nur Omer , Willander Magnus
Published: February 2011

In this article, the electroluminescence (EL) spectra of zinc oxide (ZnO) nanotubes/p-GaN light emitting diodes (LEDs) annealed in different ambients (argon, air, oxygen, and nitrogen) have been investigated. The ZnO nanotubes by aqueous chemical growth (ACG) technique on p-GaN substrates were obtained. The as-grown ZnO nanotubes were annealed in different ambients at 600°C for 30 min. The EL investigations showed that air, oxygen, and nitrogen annealing ambients have strongly affected the deep level emission bands in ZnO. It was concluded from the EL investigation that more than one deep level defect is involved in the red emission appearing between 620 and 750 nm and that the red emission in ZnO can be attributed to oxygen interstitials (Oi) appearing in the range from 620 nm (1.99 eV) to 690 nm (1.79 eV), and to oxygen vacancies (Vo) appearing in the range from 690 nm (1.79 eV) to 750 nm (1.65 eV). The annealing ambients, especially the nitrogen ambient, were also found to greatly influence the color-rendering properties and increase the CRI of the as - grown LEDs from 87 to 96.
Evidence for regulatory diversity and auto-regulation at the TAC1 locus in sensory neurones
Authors: Shanley Lynne , Lear Marissa , Davidson Scott , Ross Ruth , MacKenzie Alasdair
Published: February 2011

The neuropeptide substance-P (SP) is expressed from the TAC1 gene in sensory neurones where it acts as a key modulator of neurogenic inflammation. The promoter of TAC1 (TAC1prom) plays a central role in the regulation of the TAC1 gene but requires the presence of a second regulatory element; ECR2, to support TAC1 expression in sensory neurones and to respond appropriately to signalling pathways such as MAPkinases and noxious induction by capsaicin. We examined whether the effect of capsaicin on ECR2-TAC1prom activity in larger diameter neurones was cell autonomous or non- cell autonomous. We demonstrate that TRPV1 is not expressed in all the same cells as SP following capsaicin induction suggesting the presence of a non-cell autonomous mechanism for TAC1 up-regulation following capsaicin induction. In addition, we demonstrate that induction of SP and ECR1-TAC1prom activity in these larger diameter neurones can be induced by potassium depolarisation suggesting that, in addition to capsaicin induction, transgene activity may be modulated by voltage gated calcium channels. Furthermore, we show that NK1 is expressed in all SP- expressing cells after capsaicin induction and that an agonist of NK1 can activate both SP and the transgene in larger diameter neurones. These observations suggest the presence of an autocrine loop that controls the expression of the TAC1 promoter in sensory neurones. In contrast, induction of the TAC1 promoter by LPS was not dependent on ECR2 and did not occur in large diameter neurones. These studies demonstrate the diversity of mechanisms modulating the activity of the TAC1 promoter and provide novel directions for the development of new anti-inflammatory therapies.
Enterovirus 71 induces degradation of TRIM38, a potential E3 ubiquitin ligase
Authors: Liu Xinlei , Lei Xiaobo , Zhou Zhuo , Sun Zhenmin , Xue Qinghua , Wang Jianwei , Hung Tao
Published: February 2011

Background

The tripartite motif (TRIM) proteins are a family of more than 70 members in human. However, only a few of them have been well studied. The TRIM proteins contain the conserved RING, B-box, coiled-coil, and SPRY domains, most of which are involved in protein ubiquitination. TRIM38 is a member of the TRIM protein family, which we studied in more detail here as its functions are largely unknown.

Results

Our study shows that, similar to other TRIM family members, TRIM38 is localized in the cytoplasm. TRIM38 increases ubiquitination of other cellular proteins and catalyzes self-ubiquitination. TRIM38 also promotes K63- and K48-linked ubiquitination of cellular proteins. An intact RING domain is important for the functions of TRIM38. In addition, enterovirus 71 infection induces TRIM38 degradation.

Conclusions

Our observations demonstrate that TRIM38 has E3 ubiquitin ligase activity and can be degraded during virus infection. These findings may provide insight into innate immune signaling pathways.
Relationship between static foot posture and foot mobility
Authors: Cornwall Mark W , McPoil Thomas G
Published: February 2011

Background

It is not uncommon for a person's foot posture and/or mobility to be assessed during a clinical examination. The exact relationship, however, between static posture and mobility is not known.

Objective

The purpose of this study was to determine the degree of association between static foot posture and mobility.

Method

The static foot posture and foot mobility of 203 healthy individuals was assessed and then analyzed to determine if low arched or “pronated” feet are more mobile than high arched or “supinated” feet.

Results

The study demonstrated that those individuals with a lower standing dorsal arch height and/or a wider standing midfoot width had greater mobility in their foot. In addition, those individuals with higher Foot Posture Index (FPI) values demonstrated greater mobility and those with lower FPI values demonstrated less mobility. Finally, the amount of foot mobility that an individual has can be predicted reasonably well using either a 3 or 4 variable linear regression model.

Conclusions

Because of the relationship between static foot posture and mobility, it is recommended that both be assessed as part of a comprehensive evaluation of a individual with foot problems.
Multiple developmental programs are altered by loss ofZic1andZic4to cause Dandy-Walker malformation cerebellar pathogenesis
Authors: Blank Marissa C. , Grinberg Inessa , Aryee Emmanuel , Laliberte Christine , Chizhikov Victor V. , Henkelman R. Mark , Millen Kathleen J.
Published: February 2011

Heterozygous deletions encompassing the ZIC1;ZIC4 locus have been identified in a subset of individuals with the common cerebellar birth defect Dandy-Walker malformation (DWM). Deletion of Zic1 and Zic4 in mice produces both cerebellar size and foliation defects similar to human DWM, confirming a requirement for these genes in cerebellar development and providing a model to delineate the developmental basis of this clinically important congenital malformation. Here, we show that reduced cerebellar size in Zic1 and Zic4 mutants results from decreased postnatal granule cell progenitor proliferation. Through genetic and molecular analyses, we show that Zic1 and Zic4 have Shh-dependent function promoting proliferation of granule cell progenitors. Expression of the Shh-downstream genes Ptch1, Gli1 and Mycn was downregulated in Zic1/4 mutants, although Shh production and Purkinje cell gene expression were normal. Reduction of Shh dose on the Zic1+/−;Zic4+/− background also resulted in cerebellar size reductions and gene expression changes comparable with those observed in Zic1−/−;Zic4−/− mice. Zic1 and Zic4 are additionally required to pattern anterior vermis foliation. Zic mutant folial patterning abnormalities correlated with disrupted cerebellar anlage gene expression and Purkinje cell topography during late embryonic stages; however, this phenotype was Shh independent. In Zic1+/−;Zic4+/−;Shh+/−, we observed normal cerebellar anlage patterning and foliation. Furthermore, cerebellar patterning was normal in both Gli2-cko and Smo-cko mutant mice, where all Shh function was removed from the developing cerebellum. Thus, our data demonstrate that Zic1 and Zic4 have both Shh-dependent and -independent roles during cerebellar development and that multiple developmental disruptions underlie Zic1/4-related DWM.
Pkd1l1 establishes left-right asymmetry and physically interacts with Pkd2
Authors: Field Sarah , Riley Kerry-Lyn , Grimes Daniel T. , Hilton Helen , Simon Michelle , Powles-Glover Nicola , Siggers Pam , Bogani Debora , Greenfield Andy , Norris Dominic P.
Published: February 2011

In mammals, left-right (L-R) asymmetry is established by posteriorly oriented cilia driving a leftwards laminar flow in the embryonic node, thereby activating asymmetric gene expression. The two-cilia hypothesis argues that immotile cilia detect and respond to this flow through a Pkd2-mediated mechanism; a putative sensory partner protein has, however, remained unidentified. We have identified the Pkd1-related locus Pkd1l1 as a crucial component of L-R patterning in mouse. Systematic comparison of Pkd1l1 and Pkd2 point mutants reveals strong phenocopying, evidenced by both morphological and molecular markers of sidedness; both mutants fail to activate asymmetric gene expression at the node or in the lateral plate and exhibit right isomerism of the lungs. Node and cilia morphology were normal in mutants and cilia demonstrated typical motility, consistent with Pkd1l1 and Pkd2 activity downstream of nodal flow. Cell biological analysis reveals that Pkd1l1 and Pkd2 localise to the cilium and biochemical experiments demonstrate that they can physically interact. Together with co-expression in the node, these data argue that Pkd1l1 is the elusive Pkd2 binding partner required for L-R patterning and support the two-cilia hypothesis.
TheC. elegansSoxC protein SEM-2 opposes differentiation factors to promote a proliferative blast cell fate in the postembryonic mesoderm
Authors: Tian Chenxi , Shi Herong , Colledge Clark , Stern Michael , Waterston Robert , Liu Jun
Published: February 2011

The proper development of multicellular organisms requires precise regulation and coordination of cell fate specification, cell proliferation and differentiation. Abnormal regulation and coordination of these processes could lead to disease, including cancer. We have examined the function of the sole C. elegans SoxC protein, SEM-2, in the M lineage, which produces the postembryonic mesoderm. We found that SEM-2/SoxC is both necessary and sufficient to promote a proliferating blast cell fate, the sex myoblast fate, over a differentiated striated bodywall muscle fate. A number of factors control the specific expression of sem-2 in the sex myoblast precursors and their descendants. This includes direct control of sem-2 expression by a Hox-PBC complex. The crucial nature of the HOX/PBC factors in directly enhancing expression of this proliferative factor in the C. elegans M lineage suggests a possible more general link between Hox-PBC factors and SoxC proteins in regulating cell proliferation.
Role of Relative Transition Energy Level in Regioselective Chlorinations on Bithiophenes: Ab Initio Study
Authors: Yoon Yong-Jin , Koo In Sun , Park Jong Keun
Published: February 2011

The equilibrium and transition geometric structures from bithiophene to hexachlorobithiophene derivatives and relative energies of bithiophene derivatives in electrophilic chlorination were fully optimized using the ab initio Hartree–Fock and second-order Møller–Plesset perturbation method with a 6-311+G** basis set. The regioselectivity of the electrophilic chlorination of bithiophene derivatives was determined primarily by the gaps (ΔE1, ΔE2, ΔE3, … ) of the relative transition energy levels in the transition π-complexes. The gaps of the relative transition energy level were correlated with both the chlorinated positions and atomic charges of the carbon atoms on the bithiophene ring, the HOMO–LUMO gaps of the transition π-complexes due to the (Cl+···Cδ−) interaction, the geometric structures of the neutral and transition derivatives, and the π-conjugation effect (delocalization energy) originating from the π-orbitals. The order of relative stability in the transition π-complexes was found to be 5,5′-dichlorinated > 3,3′-dichlorinated > 4,4′-dichlorinated derivatives. Particularly, with increasing the relative transition energy gaps (ΔE2, ΔE3, ΔE8, ΔE9, … ) in the transition π-complexes, the regioselective chlorinations from BT to 6Cl-BT occurred at specific position of bithiophenes.
A Two-Dimensional Zinc(II)–Schiff Base Coordination Polymer Formed by Six-Membered Metallacyclic Repeating Motif: Structural Aspects, Thermal and Photophysical Properties
Authors: Sadhukhan Dipali , Ray Aurkie , Rosair Georgina , Charbonnière Loïc , Mitra Samiran
Published: February 2011

A dicyanoamide-bridged 2D polynuclear zinc(II) complex having formula [Zn2(L)(μ-dca-κN1κN5)2]n, 1 has been synthesized using the Schiff base ligand N,N′-bis(salicylidene)-1,3-diaminopentane, (H2L) and sodium dicyanoamide [Na(dca)]. The complex presents a 2D hexagonal structure formed by 1,5-dca singly bridged helical chains connected through double 1,5-dca bridges. The ligand and the complex are well characterized by elemental analyses, IR and UV–vis spectroscopy. Thermogravimetric analysis is performed to investigate the thermal stability of the metal–organic framework. Photoluminescence studies of the Schiff base ligand in methanol and of the zinc(II) complex 1 in solid state show the presence of blue emission. The emission of the ligand occurs from an excited state involving an intramolecular proton-transfer process as a result of keto–enol tautomerisation and the zinc(II) complex emits from a ligand-centered excited state.
A role for tRNAHisguanylyltransferase (Thg1)-like proteins fromDictyostelium discoideumin mitochondrial 5′-tRNA editing
Authors: Abad Maria G. , Long Yicheng , Willcox Allison , Gott Jonatha M. , Gray Michael W. , Jackman Jane E.
Published: February 2011

Genes with sequence similarity to the yeast tRNAHisguanylyltransferase (Thg1) gene have been identified in all three domains of life, and Thg1 family enzymes are implicated in diverse processes, ranging from tRNAHismaturation to 5′-end repair of tRNAs. All of these activities take advantage of the ability of Thg1 family enzymes to catalyze 3′-5′ nucleotide addition reactions. Although many Thg1-containing organisms have a single Thg1-related gene, certain eukaryotic microbes possess multiple genes with sequence similarity to Thg1. Here we investigate the activities of four Thg1-like proteins (TLPs) encoded by the genome of the slime mold,Dictyostelium discoideum(a member of the eukaryotic supergroup Amoebozoa). We show that one of the four TLPs is a bona fide Thg1 ortholog, a cytoplasmic G−1addition enzyme likely to be responsible for tRNAHismaturation inD. discoideum. Two otherD. discoideumTLPs exhibit biochemical activities consistent with a role for these enzymes in mitochondrial 5′-tRNA editing, based on their ability to efficiently repair the 5′ ends of mitochondrial tRNA editing substrates. Although 5′-tRNA editing was discovered nearly two decades ago, the identity of the protein(s) that catalyze this activity has remained elusive. This article provides the first identification of any purified protein that appears to play a role in the 5′-tRNA editing reaction. Moreover, the presence of multiple Thg1 family members inD. discoideumsuggests that gene duplication and divergence during evolution has resulted in paralogous proteins that use 3′-5′ nucleotide addition reactions for diverse biological functions in the same organism.
New Drugs Approved by the FDA; New Dosage Forms and Indications Approved by the FDA; Agents Pending FDA Approval; Significant Labeling Changes or “Dear Health Professional” Letters Related to Safety
Authors: Baker Danial E.
Published: February 2011

This monthly feature will help readers keep current on new drugs, new indications, dosage forms, and safety-related changes in labeling or use. Efforts have been made to ensure the accuracy of this information; however, if there are any questions, please let me know at bakerdan@wsu.edu .
Creating Next Level Patient Safety in a Fully Digital System
Authors: Felkey Bill G. , Fox Brent I.
Published: February 2011

Financial and quality pressures continue to be placed on health systems as the country struggles with the clearly visible challenge of improving care outcomes while decreasing the costs of care delivery. We believe that your institution should already be (and is likely) engaged in discussions about this issue. In this installment, we describe what we believe should be a component of your dialogue: how to leverage digital information technology to address these pressures.
Cannabis-Induced Acute Pancreatitis; Bleomycin-Induced Flagellate Hyperpigmentation; Risperidone-Associated Hypocalcemia; Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome Associated with Clindamycin; New-Onset Psychosis in Depressed Patient Treated with Aripiprazole; Emergency Re-admissions to Hospital Due to Adverse Drug Reactions within 1 Year of Index Admission; Inhaled Corticosteroids and the Risks of Diabetes Onset and Progression; Angiotensin-Converting Enzyme Inhibitors and Associated Cough
Authors: Shuster Joel
Published: February 2011

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers.
Novel Immunohistochemical Techniques Using Discrete Signal Amplification Systems for Human Cutaneous Peripheral Nerve Fiber Imaging
Authors: Wang Ningshan , Gibbons Christopher H. , Freeman Roy
Published: February 2011

Confocal imaging uses immunohistochemical binding of specific antibodies to visualize tissues, but technical obstacles limit more widespread use of this technique in the imaging of peripheral nerve tissue. These obstacles include same-species antibody cross-reactivity and weak fluorescent signals of individual and co-localized antigens. The aims of this study were to develop new immunohistochemical techniques for imaging of peripheral nerve fibers. Three-millimeter punch skin biopsies of healthy individuals were fixed, frozen, and cut into 50-µm sections. Tissues were stained with a variety of antibody combinations with two signal amplification systems, streptavidin-biotin-fluorochrome (sABC) and tyramide-horseradish peroxidase-fluorochrome (TSA), used simultaneously to augment immunohistochemical signals. The combination of the TSA and sABC amplification systems provided the first successful co-localization of sympathetic adrenergic and sympathetic cholinergic nerve fibers in cutaneous human sweat glands and vasomotor and pilomotor systems. Primary antibodies from the same species were amplified individually without cross-reactivity or elevated background interference. The confocal fluorescent signal-to-noise ratio increased, and image clarity improved. These modifications to signal amplification systems have the potential for widespread use in the study of human neural tissues.
Stressing zebrafish for behavioral genetics
Authors: Clark Karl J. , Boczek Nicole J. , Ekker Stephen C.
Published: February 2011

The stress response is a normal reaction to a real or perceived threat. However, stress response systems that are overwhelmed or out of balance can increase both the incidence and severity of diseases including addiction and mood and anxiety disorders. Using an animal model with both genetic diversity and large family size can help discover the specific genetic and environmental contributions to these behavioral diseases. The stress response has been studied extensively in teleosts because of their importance in food production. The zebrafish (Danio rerio) is a major model organism with a strong record for use in developmental biology, genetic screening, and genomic studies. More recently, the stress response of larval and adult zebrafish has been documented. High-throughput automated tracking systems make possible behavioral readouts of the stress response in zebrafish. This non-invasive measure of the stress response can be combined with mutagenesis methods to dissect the genes involved in complex stress response behaviors in vertebrates. Understanding the genetic and epigenetic basis for the stress response in vertebrates will help to develop advanced screening and therapies for stress-aggravated diseases such as addiction and mood and anxiety disorders.
Zebrafish models to study drug abuse-related phenotypes
Authors: Stewart Adam , Wong Keith , Cachat Jonathan , Gaikwad Siddharth , Kyzar Evan , Wu Nadine , Hart Peter , Piet Valerie , Utterback Eli , Elegante Marco , Tien David , Kalueff Allan V.
Published: February 2011

Mounting evidence implicates the zebrafish (Danio rerio) as a promising model species for reward and addiction research. Modeling drug abuse-related behavior in both adult and larval zebrafish produced a wealth of clinically translatable data, also demonstrating their sensitivity to various drugs of abuse and the ability to develop tolerance. Several studies have also applied withdrawal paradigms to model the adverse effects of drug abuse in zebrafish. In this review, we summarize recent findings of a wide spectrum of zebrafish drug abuse-related behavioral and physiological phenotypes, discuss the existing challenges, and outline potential future directions of research in this field.
Time Truncated Group Acceptance Sampling Plans for Generalized Exponential Distribution
Authors: Aslam Muhammad , Kundu Debasis , Jun Chi- Hyuck , Ahmad Munir
Published: February 2011

Two group acceptance sampling plans are considered for a two-parameter generalized exponential distribution when the life-test is truncated at a pre-specified time. It is assumed that the shape parameter of the generalized exponential distribution is known. The design parameters such as the number of groups and the acceptance number are obtained by satisfying the producer’s and consumer’s risks at the specified quality levels in terms of medians, under the assumption that the termination time and the number of items in each group are pre-fixed. Examples are provided for illustrative purposes.
Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor
Authors: Kim Soo-Hyun , Turnbull Jeremy , Guimond Scott
Published: February 2011

Extracellular matrices (ECM) are secreted molecules that constitute the cell microenvironment, composed of a dynamic and complex array of glycoproteins, collagens, glycosaminoglycans and proteoglycans. ECM provides the bulk, shape and strength of many tissues in vivo, such as basement membrane, bone and cartilage. In vitro, most animal cells can only grow when they are attached to surfaces through ECM. ECM is also the substrate for cell migration. However, ECM provides much more than just mechanical and structural support, with implications in developmental patterning, stem cell niches and cancer. ECM imparts spatial context for signalling events by various cell surface growth factor receptors and adhesion molecules such as integrins. The external physical properties of ECM may also have a role in the signalling process. ECM molecules can be flexible and extendable, and mechanical tension can expose cryptic sites, which could further interact with growth factors or their receptors. ECM proteins and structures can determine the cell behaviour, polarity, migration, differentiation, proliferation and survival by communicating with the intracellular cytoskeleton and transmission of growth factor signals. Integrins and proteoglycans are the major ECM adhesion receptors which cooperate in signalling events, determining the signalling outcomes, and thus the cell fate. This review focuses on the emerging concept of spatial cell biology of ECM, especially the current understanding of integrins and heparan sulphate proteoglycans as the essential cellular machineries that sense, integrate and respond to the physical and chemical environmental information either by directly connecting with the local adhesion sites or by regulating global cellular processes through growth factor receptor signalling pathways, leading to the integration of both external and internal signals in space and time.
Scorpion Sting Envenomation in Children in Southeast Turkey
Authors: Bosnak Mehmet , Ece Aydin , Yolbas Ilyas , Bosnak Vuslat , Kaplan Metin , Gurkan Fuat
Published: February 2011

Background

Scorpion sting envenomation is a life-threatening emergency and a common public health problem in many regions of the world, particularly in children. Children are at greater risk of developing severe cardiac, respiratory, and neurological complications.

Objectives

The aims of this study were to evaluate demographic, clinical, laboratory, treatment, and outcome characteristics for pediatric patients with scorpion sting envenomation in southeast Turkey and to describe features that may be predictive of the need for pediatric intensive care unit (PICU) care.

Methods

A total of 52 charts of children (mean age: 7.7 ± 2.8 years; age range: 1.5–15 years) presenting with scorpion sting envenomation to a single hospital in southeastern Turkey were investigated. General characteristics of the children, species of the scorpions, anatomic site of the sting, clinical and laboratory findings, treatment approaches, complications, and outcomes were recorded.

Results

Twenty-four stings (46.2%) were inflicted by Androctonus crassicauda, 1 (1.9%) by Leiurus quinquestriatus, and the sources of the other stings were not known. Thirty-one patients (59.6%) were admitted from rural areas. Admission from a rural area was a significant risk factor for severe envenomation. Foot-leg was the most frequently stung part of the body (48%). The greatest number of stings occurred in the summer (78.8%). Cold extremities and tachycardia were the most frequently seen clinical findings (38.4% for both). Twenty patients (38.5%) had signs of serious envenomation and required admission to the PICU. Hemoglobin, white blood cell count, activated prothrombin time, aspartate aminotransferase, alanine aminotransferase, and creatine phosphokinase levels were higher in severely envenomed children compared to levels in those with mild-moderate stings. Antivenom was given at a primary or secondary health center before arrival to our hospital in 44 (84.6%) patients, without any apparent difference in the number of patients presenting with mild-moderate and severe envenomed stings. All patients recovered after treatment except for 1 child who died with severe pulmonary edema.

Conclusions

We found no clinically useful demographic or epidemiological data to guide decision making regarding the need for PICU admission for pediatric victims of scorpion sting in our area. Decisions on transfer and admission to a PICU should be based on the development of systemic findings of envenomation.
Polygraphy of Sleep at Altitudes Between 5300 m and 7500 m During an Expedition to Mt. Everest (MedEx 2006)
Authors: Mees Klaus , de la Chaux Richard
Published: February 2011

Objectives

Sleep at extreme altitudes is characterized by the repetitive occurrence of central apneas that in some cases may lead to a marked decrease in arterial oxygen saturation. During the Ludwig Maximilians University Expedition to Mt. Everest (MedEx 2006), nocturnal polygraphic recordings were made at different altitudes and included the first recordings ever made at 7500 m, which were completed on 8 separate occasions during the expedition.

Methods

The study was performed on the author (K.M., 58 years, 181 cm, 75 kg), who is an experienced high-altitude mountaineer. The standard polygraphic parameters, such as nasal and oral airflow, thoracic and abdominal effort, oxygen saturation, heart rate, body position, movement, and snoring, were collected with a portable sleep recording device (AlphaScreen, SensorMedics, Germany, Hochberg) at different altitudes between 5300 m and 7500 m, and were compared with baseline assessments made in Munich, Germany (altitude 508 m). The daytime value of oxygen saturation at rest was measured at South Col (8000 m) and at the South Summit (8763 m) without breathing supplemental oxygen for at least 10 minutes.

Results

The number of apneas and hypopneas of central origin increased up to a maximum of 148/h with a minimal blood oxygen saturation of 48% at 7500 m, compared with <5/h at Munich. After 11 days of acclimatization, data recorded at 5300 m showed a marked reduction of disturbed sleep. The Apnea-Hypopnea-Index dropped from 138/h to 51/h, and the minimal blood oxygen saturation rose from 57% to 67%. At South Col (8000 m), the daytime value of oxygen saturation at rest ranged between 53% and 55%, and on South Summit (8673 m) without breathing supplemental oxygen for at least 10 minutes, it fluctuated around 50%.

Conclusions

These data correlate well compared with those obtained in hypobaric chamber studies and show that regardless of physiologic adjustment to low oxygen conditions at Base Camp altitude, during the final summit attempt oxygen saturation drops further to 55% and even less. Thus recordings of nocturnal oxygen saturation at Camp 3 (7500 m) on Everest, where the night is spent before the summit attempt, may help to show the actual efficiency of hypoxic ventilatory response and to detect the individual hypoxic tolerance to altitudes above 8000 m.
Field Management of Displaced Ankle Fractures: Techniques for Successful Reduction
Authors: Brian Dean D.
Published: February 2011

Ankle fracture/dislocations are generally low-energy injuries most commonly seen in older adults. Prompt reduction is indicated when evacuation to definitive care would be prolonged or neurovascular compromise to the foot is suspected. Reduction restores neurovascular integrity, realigns joint contact surfaces, reduces pain, and decreases soft-tissue edema. The hematoma block is a safe, easy, and effective method of obtaining adequate anesthesia to allow manipulation of displaced fractures. Although most commonly used for distal radius fractures, the hematoma block has been demonstrated to be as effective as conscious sedation for ankle reduction analgesia. Use of hematoma block is ideal for the wilderness setting because it requires few supplies, is easy to perform, and is effective. Quigley's traction consists of suspending the injured leg in a tubular fabric sling to allow gradual relaxation of deforming muscle forces and eventual reduction of a displaced ankle. For those displaced ankle fractures that are not amenable to reduction by direct manipulation, Quigley's traction applied after hematoma block may allow successful reduction. Improvised Quigley's traction can be built in a wilderness setting using available clothing. After successful reduction, fractured ankles should be adequately stabilized and the affected extremity should be kept nonweight bearing. The hematoma block and improvised Quigley's traction are valuable skills for the wilderness medical provider and may facilitate a successful and relatively pain-free reduction of dislocated ankle fractures in a wilderness setting.
A Prospective, Multi-Year Analysis of Illness and Injury During Summer Travel to Arid Environments
Authors: Tonna Joseph E. , Lewin Matthew R. , Hahn In-Hei , Platts-Mills Timothy F. , Norell Mark A.
Published: February 2011

Objective

There exist no prospectively generated analyses of the type and frequency of medical incidents in desert settings. We created a database of every illness and injury during 6 field seasons in the Gobi Desert in order to optimize expedition medical and safety planning.

Methods

Every incident presenting to the expeditions’ physicians, regardless of type, magnitude, treatment, or outcome, was recorded. Incidents ranged from headache, insomnia, and diarrhea to lacerations, infection, fights, psychosis, and foreign body extraction and were thus categorized, segregating urban travel-related complaints from illness and injury occurring in the desert setting. The chronology of incidents and illnesses was observed. The incidence of categorized illness and injury was analyzed using descriptive statistics and was presented in terms of person-days in the field.

Results

There were 412 incidents recorded during 2689 person-days from 6 field seasons in the Gobi Desert from 2003 through 2007. The expeditions’ physicians saw an average of 2.2 incidents·d−1 in the urban setting compared to 3.6 incidents·d−1 in the desert. Circadian rhythm disturbances, gastrointestinal illnesses, and musculoskeletal complaints predominated in the urban setting, while minor trauma, heat-related exposures, and gastrointestinal and orthopedic problems predominated in the desert setting. Our data show an absolute risk of illness or injury of 153.2 incidents per 1000 person-days and a risk of “gastrointestinal” and “trauma” complaints of 21.2 and 23.1 per 1000 person-days, respectively.

Conclusions

Herein we describe results from the first ever prospective study of the hazards of travel in an arid environment. We observed that there are patterns of injury and illness that are consistent across expeditions to the Gobi Desert. For example, while heat- and wind-exposure–related illness and injury in the desert are quite common, other aspects of the desert environment are very forgiving. Perhaps the most interesting finding in our cohort was the degree to which different problems occurred at different stages of the expeditions. Our data sets suggest several future studies to evaluate patterns of illness and injury and could be an asset to recreational travelers and religious pilgrims, as well as to those sending employees to extreme environments.
The Effect of Dynamic Intermittent Hypoxic Conditioning on Arterial Oxygen Saturation
Authors: Hetzler Ronald K. , Stickley Christopher D. , Kimura Iris F. , LaBotz Michelle , Nichols Andrew W. , Nakasone Kenneth T. , Sargent Ryan W. , Burgess Lawrence P.A.
Published: February 2011

Background

Increases in arterial oxygen saturation (SaO2) in response to intermittent hypoxic exposure (IHE) are well established. However, IHE protocols have historically involved static hypoxic environments. The effect of a dynamic hypoxic environment on SaO2 is not known.

Objective

The purpose of this study was to examine the effect of dynamic IHE conditioning on SaO2 using the Cyclical Variable Altitude Conditioning Unit.

Methods

Thirteen trained participants (9 males, age 30.1 ± 9.2 years; 4 females, age 30.3 ± 8.9 years) residing at or near sea level were exposed to a 7-week IHE conditioning protocol (mean total exposure time = 30.8 hours). Participants were exposed to a constantly varying series of hypobaric pressures simulating altitudes from sea level to 6858 m (22 500 feet) in progressive conditioning tiers, creating a dynamic hypoxic environment. SaO2 was evaluated using pulse oximetry (SpO2) 4 times: at 2740, 3360, and 4570 m, prior to and following the first 3 weeks of IHE, and at 4570, 5490, and 6400 m at the start and end of the final 4 weeks.

Results

SpO2 improved 3.5%, 3.8%, and 4.1% at 2470, 3360, and 4570 m, respectively ( P < .05), and 3.3%, 3.4%, and 5.9% at 4570, 5490, and 6400 m, respectively ( P < .05). At 4570 m, SpO2 increased from 81.7% ± 6.5% to 89.1% ± 3.2% over the entire 7-week conditioning period.

Discussion

The dynamic intermittent hypoxic conditioning protocol used in the present study resulted in an acclimation response, such that SpO2 was significantly increased at all altitudes tested, with shorter exposure times than generally reported.
Prevalence of Airway Obstruction in Recreational SCUBA Divers
Authors: Weaver Lindell K. , Churchill Susan K. , Hegewald Matthew J. , Jensen Robert L. , Crapo Robert O.
Published: February 2011

Objective

The prevalence of airflow obstruction in recreational self-contained underwater breathing apparatus (SCUBA) divers is unknown. Since airflow obstruction is a relative contraindication for diving, we conducted a study to determine its prevalence and magnitude in a cohort of recreational divers in Saba, Netherlands Antilles.

Methods

Prior to diving, divers were asked to complete a diving/health questionnaire and then to perform spirometry administered by trained dive store personnel. Spirometry instrumentation provided immediate feedback regarding test quality.

Results

Of 8365 eligible divers during the study period (November 1997–March 1999), 668 enrolled and completed questionnaires. Of those completing questionnaires, 46% reported a history of smoking, 13% were current smokers, 15% wheezed, 6% had asthma, 4% used bronchodilators, and 3% took oral steroids. Of 654 completing spirometry, 231 had acceptable spirometry quality and complete questionnaires. By forced expiratory volume in 1 second/forced vital capacity, 10% had mild, 1.7% had moderate, and 0.4% had severe airflow obstruction.

Conclusions

The prevalence of airflow obstruction was 6% to 15% by report and 12% by spirometry, approximating the combined prevalence of asthma and chronic obstructive pulmonary disease in the general population. Study limitations include possible self-selection and low enrollment rate. Prospective lung function testing can be conducted at remote sites using nonmedical personnel as “testers.” This study could guide future investigations to determine if asthma is a risk factor for decompression illness.
Comparison of Commercially Available Disposable Chemical Hand and Foot Warmers
Authors: Sands William A. , Kimmel Wendy L. , Wurtz Brittany R. , Stone Michael H. , McNeal Jeni R.
Published: February 2011

Objective

Small chemical hand and foot warmers are used by many winter sport athletes and other outdoor enthusiasts. The purpose of this study was to characterize the thermal behaviors of 14 commercially available hand and foot warmers.

Methods

Both types of warmers were instrumented with a fast-responding thermistor. One of each pair of warmers was placed in a boot or glove. Temperature was recorded in a data logger for a period of hours to more than a day until the heat output of the devices ceased and returned to room temperature. Thermal behaviors were characterized and graphed, including peak temperature, time to peak temperature, and duration of temperature greater than 30°C. Reliability was determined by comparing thermal behavior of 2 hand or foot warmers of the same type and from the same manufacturer. Comparisons were also made between package claims and measured behaviors.

Results

Measured outcomes were most noteworthy in their variability within and between manufacturers and types of warmers. A strong correlation was found between the masses of the warmers and their duration of heat production.

Conclusions

Although there is a paucity of research information on these types of warmers, this experiment showed that some of the devices exceeded packaging claims while others fell short; that the thermal behavior over time of the devices was variable; and that there appears to be a simple but strong relationship between the mass of the devices and the duration of their heat production.
Can People with Raynaud's Phenomenon Travel to High Altitude?
Authors: Luks Andrew M. , Grissom Colin K. , Jean Dominique , Swenson Erik R.
Published: February 2011

Objective

To determine whether high altitude travel adversely affects mountain enthusiasts with Raynaud's phenomenon.

Methods

Volunteers with Raynaud's phenomenon were recruited using announcements disseminated by organizations dedicated to climbing or wilderness travel and Internet discussion boards dedicated to mountain activities to complete an online, anonymous survey. Survey questions addressed demographic variables, aspects of their Raynaud's phenomenon, and features of their mountain activities. Respondents compared experiences with Raynaud's phenomenon between high (>2440 m; 8000 feet) and low elevations and rated agreement with statements concerning their disease and the effects of high altitude.

Results

One hundred forty-two people, 98% of whom had primary Raynaud's phenomenon, completed the questionnaire. Respondents spent 5 to 7 days per month at elevations above 2440 m and engaged in 5.4 ± 2.0 different activities. Eighty-nine percent of respondents engaged in winter sports and only 22% reported changing their mountain activities because of Raynaud's phenomenon. Respondents reported a variety of tactics to prevent and treat Raynaud's attacks, but only 12% used prophylactic medications. Fifteen percent of respondents reported an episode of frostbite following a Raynaud's phenomenon attack at high altitude. There was considerable heterogeneity in participants’ perceptions of the frequency, duration, and severity of attacks at high altitude compared to their home elevation.

Conclusions

Motivated individuals with primary Raynaud's phenomenon, employing various prevention and treatment strategies, can engage in different activities, including winter sports, at altitudes above 2440 m. Frostbite may be common in this population at high altitude, and care must be taken to prevent its occurrence.