bluuebunny/crossref_metadata_2025 huggingface dataset:
Companion forms in parallel weight one
Authors: Gee Toby , Kassaei Payman
Published: May 2013

Let $p\gt 2$ be prime, and let $F$ be a totally real field in which $p$ is unramified. We give a sufficient criterion for a $\mathrm{mod} \hspace{0.167em} p$ Galois representation to arise from a $\mathrm{mod} \hspace{0.167em} p$ Hilbert modular form of parallel weight one, by proving a ‘companion forms’ theorem in this case. The techniques used are a mixture of modularity lifting theorems and geometric methods. As an application, we show that Serre’s conjecture for $F$ implies Artin’s conjecture for totally odd two-dimensional representations over $F$.
MBE growth optimization of InAs (001) homoepitaxy
Authors: Ye Hao , Li Lu , Hinkey Robert T. , Yang Rui Q. , Mishima Tetsuya D. , Keay Joel C. , Santos Michael B. , Johnson Matthew B.
Published: May 2013

The optimal conditions for growth of homoepitaxial InAs layers by molecular beam epitaxy were investigated over a wide range of substrate temperatures and As2/In flux ratios at a growth rate of 0.66 monolayer/s. Material quality was investigated using a variety of techniques: differential interference contrast microscopy, scanning electron microscopy, and atomic force microscopy. The results indicated that the InAs layer grown at a temperature between 430 and 450 °C with an As2/In flux ratio of about 15:1 yielded the highest quality, with a defect density of 2 × 104 cm−2 and a root mean square roughness of 0.19 nm. The quality can be further improved by growth at a lower growth rate of 0.22 monolayer/s. The morphology of large oval hillock defects on the InAs layers suggested that these defects originated at the substrate surface.
Hydrogen Isotopes in Lunar Volcanic Glasses and Melt Inclusions Reveal a Carbonaceous Chondrite Heritage
Authors: Saal Alberto E. , Hauri Erik H. , Van Orman James A. , Rutherford Malcolm J.
Published: May 2013

Common Water

The Moon has been traditionally considered bone-dry, but in recent years a number of studies have shown that during mantle melting, the lunar mantle had as much water as Earth's upper mantle.

Saal
et al.

(p.
1317
, published online 9 May; see the cover) measured the isotopic composition of hydrogen dissolved in volcanic glass and olivine-hosted melt inclusions recovered from the Moon by the Apollo 15 and 17 missions. Lunar magmatic water was indistinguishable from the bulk water in carbonaceous chondrites and similar to terrestrial water, implying a common origin for the water contained in the interiors of Earth and the Moon.
Complete Genome Sequences of Four Virulent Rabies Virus Strains Isolated from Rabid Animals in Russia
Authors: Poleshchuk E. M. , Deviatkin A. A. , Dedkov V. G. , Sidorov G. N. , Ochkasova J. V. , Hodjakova I. A. , Schukina I. A. , Savel'ev S. I. , Golenskih A. G. , Shipulin G. A.
Published: May 2013

Rabies virus (RABV) strains Rus(Lipetsk)-8052f, Rus(Lipetsk)-8053c, Rus(Lipetsk)-8054f, and Rus(Lipetsk)-8057f were isolated from foxes (
Vulpes vulpes
) and a cat (
Felis catus
) in the Lipetsk region of Russia in 2011. Close relationships between these strains and the members of the “Cosmopolitan” group from Russia (98% homology) and from Europe (95% homology) were estimated.
Complete Genome Sequence of a Newly Emerging Newcastle Disease Virus Isolated in China
Authors: Sun Minhua , Dong Jiawen , Wang Zhaoxiong , Li Linlin , Yuan Jianfeng , Jiao Peirong , Hu Qilin , Ren Tao
Published: May 2013

Goose/GD/2010 is a newly emerging Newcastle disease virus (NDV) isolated from a sick goose flock in southern China. Here, we report the complete genome sequence of this isolate, which belongs to NDV subgenotype VIIb. This is the first report about the complete genome information of an isolate of subgenotype VIIb in China.
Genome Sequence of Klebsiella pneumoniae HSL4, a New Strain Isolated from Mangrove Sediment for Biosynthesis of 1,3-Propanediol
Authors: Zhou Sheng , Li Lili , Wei Jingguang , Qin Qiwei
Published: May 2013

Klebsiella pneumoniae
HSL4 is a 1,3-propanediol-producing bacterium strain isolated from mangrove sediment. We present here a 5,221,448-bp assembly of its genome sequence. Genome analysis revealed that it contains 10 coding sequences (CDSs) responsible for glycerol fermentation to 1,3-propanediol, 19 CDSs encoding glycerol utilization, and 140 CDSs related to its virulence.
Draft Genome Sequence of Lactobacillus pobuzihii E100301
T
Authors: Chiu Chi-ming , Chang Chi-huan , Pan Shwu-fen , Wu Hui-chung , Li Shiao-wen , Chang Chuan-hsiung , Lee Yun-shien , Chiang Chih-ming , Chen Yi-sheng
Published: May 2013

Lactobacillus pobuzihii
E100301
T
is a novel
Lactobacillus
species previously isolated from pobuzihi (fermented cummingcordia) in Taiwan. Phylogenetically, this strain is closest to
Lactobacillus acidipiscis
, but its phenotypic characteristics can be clearly distinguished from those of
L. acidipiscis
. We present the draft genome sequence of strain
L. pobuzihii
E100301
T
.
Complete Genome Sequence of a Newly Emerging Newcastle Disease Virus
Authors: Wang Jing-Yu , Liu Wan-Hua , Ren Juan-Juan , Tang Pan , Wu Ning , Liu Hung-Jen
Published: May 2013

The complete genome sequence of a newly emerging Newcastle disease virus, isolated in China, was determined. A phylogenetic analysis based on the F gene revealed that the isolate is phylogenetically related to Newcastle disease virus genotype VIId. Sequence analysis indicated that amino acid residue substitutions occur at neutralizing epitopes on the hemagglutinin-neuraminidase (HN) protein.
Draft Genome Sequence of Methylophaga lonarensis MPL
T
, a Haloalkaliphilic (Non-Methane-Utilizing) Methylotroph
Authors: Shetty Sudarshan A. , Marathe Nachiket P. , Munot Hitendra , Antony Chakkiath Paul , Dhotre Dhiraj P. , Murrell J. Colin , Shouche Yogesh S.
Published: May 2013

Methylophaga lonarensis
strain MPL
T
is a haloalkaliphilic methylotroph isolated from Lonar Lake, a saline and alkaline lake in Maharashtra, India. Strain MPL
T
utilizes methanol as its sole carbon and energy source. Here, we present the draft genome sequence of
M. lonarensis
MPL
T
(VKM B-2684
T
= MCC 1002
T
).
Genome Sequences of
Pseudomonas
spp. Isolated from Cereal Crops
Authors: Gardiner Donald M. , Stiller Jiri , Covarelli Lorenzo , Lindeberg Magdalen , Shivas Roger G. , Manners John M.
Published: May 2013

Compared to those of dicot-infecting bacteria, the available genome sequences of bacteria that infect wheat and barley are limited. Herein, we report the draft genome sequences of four pseudomonads originally isolated from these cereals. These genome sequences provide a useful resource for comparative analyses within the genus and for cross-kingdom analyses of plant pathogenesis.
Whole-Genome Sequences of Four Salmonella enterica Serotype Newport Strains from Humans
Authors: Zhang Jianmin , Cao Guojie , Xu Xuebin , Jin Huiming , Zhang Qiong , Chen Jianwei , Yang Xiaowei , Pan Haijian , Zhang Xiuli , Allard Marc , Brown Eric , Meng Jianghong
Published: May 2013

Salmonellosis contributes significantly to the public health burden globally.
Salmonella enterica
serotype Newport is among
Salmonella
serotypes most associated with food-borne illness in the United States and China. It was thought to be polyphyletic and to contain different lineages. We report draft genomes of four
S
. Newport strains isolated from humans in China.
Draft Genome Sequence of Myxococcus xanthus Wild-Type Strain DZ2, a Model Organism for Predation and Development
Authors: Müller Susanne , Willett Jonathan W. , Bahr Sarah M. , Darnell Cynthia L. , Hummels Katherine R. , Dong Carolyn K. , Vlamakis Hera C. , Kirby John R.
Published: May 2013

Myxococcus xanthus
is a member of the
Myxococcales
order within the
Deltaproteobacteria
subdivision. The myxobacteria reside in soil, have relatively large genomes, and display complex life cycles. Here, we report the whole-genome shotgun sequence of strain DZ2, which includes unique genes not found previously in strain DK1622.
Complete Genome Sequences of Two Sweet Potato Chlorotic Stunt Virus Isolates from China
Authors: Qin Yanhong , Zhang Zhenchen , Qiao Qi , Zhang Desheng , Tian Yuting , Wang Yongjiang , Wang Shuang
Published: May 2013

Sweet potato chlorotic stunt virus (SPCSV) was first detected in China in 2010, and several partial sequences have been determined for Chinese SPCSV isolates. This report describes the complete genome sequences of two SPCSV isolates from the Guangdong and Jiangsu provinces and will be valuable for understanding the characteristics of SPCSVs in China.
Genome Sequence of Hydrothermal Arsenic-Respiring Bacterium Marinobacter santoriniensis NKSG1
T
Authors: Handley Kim M. , Upton Mathew , Beatson Scott A. , Héry Marina , Lloyd Jonathan R.
Published: May 2013

Marinobacter santoriniensis
NKSG1
T
originates from metalliferous marine sediment. It can respire and redox cycle arsenic species and perform mixotrophic, nitrate-dependent Fe(II) oxidation. The genome sequence, reported here, will help further elucidate the genetic mechanisms underlying these and other potential biogeochemically relevant functions, such as arsenic and mercury resistance and hydrocarbon degradation.
Lactococcus lactis cremorisinfection: not rare anymore?
Authors: Hadjisymeou Simone , Loizou Peter , Kothari Prasad
Published: May 2013

A middle-aged female patient with diabetes was admitted with a right neck abscess. Ultrasound scan revealed a necrotic abscess suspicious of malignancy and biopsy showed evidence of chronic inflammation. In order to isolate the primary source of malignancy, we performed MRI and positron emission tomography scans but neither had conclusive results. Subsequently, we performed an incision and drainage of the mass in order to alleviate pressure symptoms. The ensuing histological examination revealed that the mass was caused byLactococcus lactis cremoris. As such, the patient was treated with antibiotics and made a complete recovery. This report reinforces the scarce existing evidence thatL lactis cremorisis a potential pathogen in adults. The case shows that atypical organisms should always be considered in the working diagnosis of an atypical neck abscess especially due to the rise in popularity of organic farming.
The dental management of troublesome twos: renal tubular acidosis and rampant caries
Authors: B Sandhyarani , Huddar Dayanand , Patil Anil , Sankeshwari Banashree
Published: May 2013

Renal tubular acidosis is a group of disorders in which there is metabolic acidosis due to defect in renal tubular acidification mechanism to maintain normal plasma bicarbonate and blood pH. Irrespective of organ system involved, oral cavity often reflects the disease occurring anywhere in the body. Thus congenital chronic renal diseases, causing acid–base disturbances affects development and structure of the teeth. Chronic renal tubular acidosis causes enamel defects, dental caries, oral candidiasis, angular cheilitis, etc. We hereby present an unusual case report of a 4-year-old boy suffering from renal tubular acidosis associated with rampant caries, whose full mouth rehabilitation has been done.
Panic-related hyperventilation resulting in hypophosphataemia and a high lactate
Authors: Suarez Nicolas , Conway Nerys , Pickett Tom
Published: May 2013

A 22-year-old lady presented to the emergency department with dyspnoea and pleuritic chest pain. Life-threatening asthma, pulmonary embolus and pneumothorax were all excluded. However, investigations did show an unexplained hypophosphataemia and raised lactate, both of which were subsequently attributed to hyperventilation with a component of panic. Here we explore the mechanism of these findings and the management of hypophosphataemia.
Bilateral lateral periodontal cyst
Authors: Govil Somya , Gupta Vishesh , Misra Neeta , Misra Pradyumna
Published: May 2013

The bilateral lateral periodontal cyst is a rare nasological entity, which despite clinical and radiological presentation is being diagnosed by histological characteristics. It is asymptomatic in nature and is observed in routine radiography. The aim and objective of this article is to present a rare case of bilateral lateral periodontal cyst in a 14-year-old child. The clinical and radiographical findings, along with its management have been discussed. Enucleation of bilateral cyst without extraction of the adjacent tooth was performed. Lesion samples were sent for histopathological analysis. The histopathological analysis revealed a thin, non keratinised stratified squamous epithelium resembling reduced enamel epithelium. Epithelial plaques were also seen. A clinicopathological correlation incorporating the surgical, radiographical and gold standard histopathological findings was obtained to suggest the final diagnosis of the bilateral lateral periodontal cyst.
Triceps tendon avulsion and associated injuries of the elbow
Authors: Canbora Kerem , Ozyurek Selahattin , Gumussuyu Gurkan , Kose Ozkan
Published: May 2013

A rupture or avulsion of the triceps tendon is very rare but concomitant elbow injuries with avulsion of the triceps tendon are even rarer. In this study, an extraordinary and unusual injury combination (radial head and trochlear fracture associated with triceps tendon avulsion), which happened during a fall onto the elbow with outstretched hand, was identified and has been discussed in the literature.
Dementia complicated with Takotsubo cardiomyopathy associated with unconsciousness induced by Wernicke's encephalopathy
Authors: Yanagawa Youichi , Mikasa Michita , Nishioka Kenya , Hirano Keiko
Published: May 2013

An 85-year-old woman who had been living alone and eating an unbalanced diet suddenly entered a neighbour's house. Her house was hot and humid due to lack of air conditioning caused by a loss of electrical power. After arrival, the patient exhibited disorientation, paresis of the right upper extremity, a tendency towards right conjugated deviation and perseveration. Electrocardiogram showed ST segment elevation and prolongation of the QT interval. Echocardiography suggested Takotsubo cardiomyopathy. The cardiac wall motion and neurological abnormalities improved after admission. The serum thiamine level was found to be low, which was compatible with a diagnosis of Wernicke's encephalopathy. Hasegawa dementia score was 10 points and the patient was suspected to have frontotemporal dementia. She was transferred to a nursing home with continuing dementia. In this case, psychological stress trigged by poor living circumstances induced by dementia and Wernicke's encephalopathy may result in the occurrence of Takotsubo cardiomyopathy.
Dangers of neglect: partially embedded ring upon a finger
Authors: Kumar Anand , Edwards Huw , Lidder Surjit , Mestha Prabhakar
Published: May 2013

Digital swelling is a common presentation in clinical practice. Patients presenting with swollen fingers to the emergency department will often have rings on their finger, which can be removed using a variety of simple non-operative techniques or by cutting the ring off and thus avoiding any long-term consequences. Very rarely, when there is a delay in presentation of these patients, serious consequences may proceed, including finger ischaemia, infection, tendon attrition or ultimately the need for surgical amputation. We present an unusual case of patient with psychiatric illness who presented late with a ring that had embedded upon the volar aspect of the index finger. The difficulties faced by the emergency care practitioners in such circumstances, the consequences of rings acting as a tourniquet and strategies for removal of rings on swollen fingers are highlighted.
Indacaterol-induced severe constipation and abdominal pain: is there a role for colonic β3-adrenoceptors?
Authors: Carrascosa Miguel F , Lucena M Isabel , Bellido Inmaculada , Salcines-Caviedes José Ramón
Published: May 2013

Indacaterol is an ultra-long-acting β2-adrenoceptor agonist that is indicated for the maintenance treatment of chronic obstructive pulmonary disease. We present a patient with severe chronic constipation and abdominal pain most probably induced by this medicament. Symptoms rapidly disappeared within 2 days after the drug withdrawal. As far as we know, no reports describing severe chronic constipation associated with indacaterol have been published. The Naranjo algorithm score and the Edwards and Aronson scale for causality assessment of suspected adverse drug reactions indicated a probable relationship between indacaterol use and constipation. Indacaterol-induced constipation is an unusual event that could be accounted for the high intrinsic activity of the drug on colonic β3-adrenoreceptors, resulting in an inhibitory control of smooth muscle function and intestinal secretion. Clinicians should monitor such a possibility when prescribing this drug and maybe avoid its use in patients with a history of difficult bowel evacuation.
Epidermoid cyst of the spleen
Authors: Vo Quoc Duy , Monnard Etienne , Hoogewoud Henri Marcel
Published: May 2013

We report the case of a patient with a palpable mass and abdominal pain in the left upper quadrant. A physical examination revealed tenderness in this region. An ultrasound performed initially showed a large cystic structure. A CT examination revealed a large cyst originating in the spleen with loculations in its upper part and focal calcification in the wall. On MRI, the cystic mass showed high signal on T1-weighted and T2-weighted images. The carbohydrate antigen 19-9 (CA 19-9) was measured at 88 U/ml (standard <37.1 mUI/l). According to the imaging examinations and laboratory tests performed, it was impossible to determine if the splenic cyst was parasitic or non-parasitic. Given the most important risks of complications encountered in parasitic cysts, it was decided to treat this splenic cyst as a parasitic cyst. For this reason, an elective laparoscopic splenectomy with preoperative embolisation of the splenic artery was performed. The histological diagnosis was a primary epidermoid splenic cyst with inner lining epithelial cells.
Acute encephalomyelitis with multiple herpes viral reactivations during abatacept therapy
Authors: Nakajima Hideto , Takayama Ayami , Ito Takumi , Yoshikawa Tetsushi
Published: May 2013

To describe the case of a patient who had been receiving abatacept, a T-cell costimulatory molecule blocker for rheumatoid arthritis, and developed an acute encephalomyelitis associated with reactivation of the varicella zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). A 61-year-old woman receiving abatacept therapy for rheumatoid arthritis developed a disturbance of consciousness. MRI indicated multifocal parenchymal lesions in the brainstem, supratentorial areas and cervical spinal cord. Although steroid therapy significantly improved the neurological symptoms and MRI findings, the patient died of sepsis aggravated by coinfection with a fungal infection. Retrospectively, a PCR assay revealed continued systemic reactivation of VZV, EBV and CMV. Acute encephalomyelitis may be associated with VZV EBV and CMV reactivation during abatacept therapy. Clinicians must be aware of the possibility of acute encephalomyelitis associated with herpes virus reactivation during abatacept therapy for rheumatoid arthritis.
The genetic basis for elite running performance
Authors: Tucker Ross , Santos-Concejero Jordan , Collins Malcolm
Published: May 2013

The dominance of East African distance runners and sprinters of West African origin invites discussion around the contribution of genetic and lifestyle factors to performance. In this review, we focus on the genetic basis for performance. Previous research associating candidate genes such asACEandACTN3to endurance and sprint performance in Caucasian populations has not been replicated in African populations. This may be influenced by numerous factors, including small sample sizes, comparisons across different ethnic populations and problems identifying appropriate control groups. Conceptually, these failures reveal the complex polygenic nature of physiology and performance, and the erroneous application of a candidate gene approach to more genetically diverse African populations. We argue that research has in fact established a role for genes in performance, and that the frequency, rather than the prevalence, of favourable genetic variants within certain populations may account for the performance dominance in these populations.
MECHANICAL LOADING MODULATES ANGIOGENIC FACTORS IN TENDON CELLS
Authors: Mousavizadeh R , Duronio V , McCormack B , Khosravi S , Scott A
Published: May 2013

Introduction

Tendon disorders are a significant cause of pain and morbidity amongst athletes, workers and the general public.1 2 Tendinopathy is often viewed as the result of failed or inadequate healing response through repetitive overuse.3 The clinical symptoms of tendinopathy are activity–related pain, focal tenderness, and intratendinous imaging changes. Previous authors have suggested there may be an association between pain and neurovascular changes resulting from tendon overuse in tendinopathy patients.4 5 In order to examine the effects of repetitive overuse on the expression of angiogenic genes which regulate neovascularization in tendinopathy, primary human tendon cells were subjected to cyclic strain.

Methods

By using Flexcell Tension Systems, the isolated tendon cells from human hamstring tendons (excess ACL autograft material) were exposed to cyclic tension (1 Hz frequency and 10% strain). RNA samples were isolated at different time points and gene expression was evaluated by qPCR and qPCR array. Zymography assay was also conducted in order to measure the activity of MMP-2 in the supernatant of tendon cell culture.

Results

Initial experiments show that cyclic strain of two-dimensional primary tenocyte cell cultures (1 Hz) promotes increased expression of VEGF, bFGF, Cox-2 and IL-6 genes, and increased activity of MMP-2. But, by increasing the time course (∼after 4 h), bFGF, Cox-2 and VEGF are progressively downregulated. Our preliminary results of qPCR array for angiogenic profiling of tendon cells also led to the discovery of other genes (ANGPTL4, FGF-1, TGFα, VEGF-C, PROK2 and SPHK1) that may respond to tensile loading following a similar pattern.

Conclusion

It seems that the early response of the tendon cell to overuse tensile loading leads to upregulation of some angiogenic factors which may play an important role in tissue homeostasis following periods of overuse.
AGING UNIQUELY INFLUENCES TISSUE INHIBITOR OF METALLOPROTEINASE-2 (TIMP-2) EXPRESSION IN NORMAL TENDON
Authors: Thornton G M , Reno C R , Lo I K Y , Hart D A
Published: May 2013

Introduction

The incidence of tendinopathy increases with aging. Alterations to the balance between matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) may play a role in the degenerative changes seen in tendinopathy.1 In addition, aging may have an effect on the expression of these molecules in tendon, as was found in skin.2 Our purpose in this study was to examine the effect of aging on patellar tendons from 1-year-old and 3-year-old rabbits comparing molecular expression of MMPs and TIMPs. Our hypothesis was that patellar tendons from 3-year-old rabbits would have increased MMP expression and decreased TIMP expression compared to patellar tendons from 1-year-old rabbits.

Methods

Patellar tendons from 1-year-old (n=8) and 3-year-old (n=6) female New Zealand White rabbits underwent RT-qPCR using rabbit specific primers for MMPs (MMP-1, MMP-3, MMP-13) and TIMPs (TIMP-1, TIMP-2, TIMP-3), and the housekeeping gene 18S. Data were compared using Mann Whitney U tests.

Results

Comparing patellar tendons from 3-year-old to 1-year-old rabbits, the expression of MMP-1, MMP-3 and MMP-13 did not change with aging. The expression of TIMP-2 was decreased comparing patellar tendons from 3-year-old to 1-year-old rabbits (p=0.02; figure 1). TIMP-1 and TIMP-3 expression were not affected by aging.

Figure 1.

MMP and TIMP Expression in Patellar Tendons from 1-year-old and 3-year-old rabbits. Expression of TIMP-2 was decreased comparing patellar tendons from 3-year-old to 1-year-old rabbits (p=0.02).

Discussion

Aging significantly decreased TIMP-2 expression in patellar tendon with no changes in the other TIMPs and MMPs investigated. This suggests a change in the balance of MMP/TIMP expression towards degradation in tendon with aging, or a significant shift in the MMP-independent activities of TIMP-2.3 In human skin, TIMP-2 expression was decreased with aging.2 Despite no change in TIMP-2 expression in degenerated human patellar4 and Achilles1 tendons compared to normal tendons, TIMP-2 expression was decreased in ruptured human Achilles1 and rotator cuff5 tendons compared to normal tendons.
MOLECULAR GENETICS AN IMPORTANT TOOL IN ELUCIDATING THE MOLECULAR MECHANISMS UNDERLYING TENDINOPATHIES
Authors: Collins M
Published: May 2013

The causation of tendinopathy is multifactorial and there is increasing evidence that genetic factors play an important role in its aetiology. Some of the genes implicated encode: (i) structural components of connective tissue (collagens and glycoproteins); (ii) extracellular matrix (ECM) proteinases (MMPs); and (iii) cytokines and growth factors.1 2 Although several genes have been implicated to date, variants within the 3′-untranslated region (UTR) ofCOL5A1were shown to associate with chronic Achilles tendinopathy3 4 and lower limb range of motion measurements,5 6 an additional intrinsic risk factor for chronic Achilles tendinopathy.COL5A1encodes the α1 chain of type V collagen, a quantitatively minor fibrillar collagen that regulates type I fibrillogenesis.

We have recently described two major functional forms of theCOL5A13′-UTR, namely the C- and T-forms, which contained a set of seven strongly linked sequence variants that showed significant differences in mRNA stability.7 Four of theseCOL5A1variants are associated with Achilles tendinopathy and appear to alter the predicted mRNA secondary structure of the 3′-UTR. We propose that this change in secondary structure causes the alteredCOL5A1mRNA stability and, by implication, type V collagen production.

In addition theCOL5A13′-UTR contains several putative cis-acting elements including a functional microRNA binding site for Hsa-miR-608.7 Two forms of the mature Hsa-miR-608, which are produced by the polymorphicMIR608gene, can potentially bind this miRNA binding site (http://www.ncbi.nlm.nih.gov). This variant within theMIR608gene is also independently associated with chronic Achilles tendinopathy. These genetic association studies of theCOL5A1andMIR608genes, together with the functional studies of theCOL5A13′-UTR, suggest that type V collagen synthesis is involved in the molecular mechanisms of, at least, chronic Achilles tendinopathy.

We hypothesise that the T-functional form of theCOL5A13′-UTR, which is associated with chronic Achilles tendinopathy, results in increased type V collagen production, decreased mean fibril diameter, and increased fibril density. These structural changes in the fibril result in changes to the mechanical properties of tendons. More specifically, we hypothesise that the changes in mechanical properties associated with the T-functional form result in (i) a reduced tensile strength and (ii) increased creep inhibition and/or stiffness. However, future work is required to test this hypothesis.8
AN ASSOCIATION BETWEEN COMPONENTS OF THE APOPTOSIS PATHWAY AND THE GENETIC PREDISPOSITION TO ACHILLES TENDINOPATHY
Authors: Nell E , van der Merwe L , Cook J , Handley C J , Collins M , September A V
Published: May 2013

Introduction

Achilles tendinopathy is a degenerative condition for which several risk factors have been implicated including components of the inflammatory pathway. The aims of this study was to evaluate (i) several functional variants within genes encoding components of the apoptosis signalling cascade and (ii) the effectiveness of a polygenic apoptosis profile to capture Achilles tendinopathy (TEN) risk.

Methods

A total of 358 unaffected control (CON) participants (159 South Africa (SA CON) and 199 Australia (AUS CON)) and 166 affected TEN participants (87 SA TEN and 79 AUS TEN) were genotyped for four variants (CASP8(rs384129),CASP8(rs1045485), NOS3(rs1799983) andNOS2(rs2779249)). Logistic regression was used to derive risk models for TEN and a receiver operator characteristic (ROC) curve was plotted to determine the effectiveness of the models to capture TEN risk.

Results

An independent association ofCASP8_rs1045485 andCASP8_rs3834129, together with their haplotype was observed with TEN risk. The optimal risk model identified from the study included the two CASP8 genetic loci investigated (CASP8_rs384129 andCASP8_rs1045485) together with sex to capture TEN risk in both SA and AUS participants collectively.

Conclusions

These findings further implicate the apoptosis signalling cascade as one of the important biological pathways involved in the development of Achilles tendinopathy.
TENDINOPATHY: MORE QUESTIONS THAN ANSWERS
Authors: Langberg H
Published: May 2013

Tendinopathy is a big problem for athletes, ordinary people and clinicians. At present neither the aetiology and pathology, nor the rehabilitations is well understood, and good evidence is lacking within all these areas.

During the last 10 years substantial research has been performed. New data indicate that in the chronic state, tendinopathy in humans is characterised by focal changes in the expression of matrix proteins, increased collagen turnover, smaller collagen fibrils and increased microvascular volume. These changes are attenuated with increased loading as during running. Despite this new knowledge, models for investigating the development of tendinopathy are still lacking and the complex nature of tendinopathy is still a great challenge. However, by developing novel human and animal models, hopefully a thorough understanding of human tendinopathy will be possible within the near future.

In relation to treatment, new methods such as injection of platelet rich plasma (PRP) and large quantities of isotonic saline (HVI) have been developed based on sound rationales, but with only minor scientific evidence. More research is needed in this area too.
MATRIX THERAPY IN REGENERATIVE MEDICINE EVIDENCE IN TENDINITIS
Authors: Barritault D , Denoix J M , Dupays A G , Maertens C , Coudry V , Carciner D , Jaquet S , Auigié F , Kichenin K , Filipe S , Denoix-Crevier N
Published: May 2013

Heparan sulfates (HS) are key elements of the extracellular matrix (ECM), which store and protect various cell communication peptides (CCP). HS play a central role in tissue homeostasis, by modulating the bioavailability of CCP. As such, they control the cell migration and differentiation required for wound healing processes. Tissue injury will lead to destruction of cells and surrounding ECM is destroyed. CCPs synthesised by inflammatory and circulating cells can then promote tissue repair, but with a loss of tissue quality, leaving traces, scars or fibroses. We have engineered biodegradable nano-polymers mimicking the HS. They bind to the structure proteins of the damaged ECM, and to the CCP produced by healthy neighbouring cells, thereby restoring the ECM microenvironment and tissue homeostasis. This matrix therapy approach has considerably improved the quality of wound healing in various animal models. Our HS mimetics have therefore been named RGTA, for ReGeneraTing Agents. The RGTA technology has been validated in over 80 published preclinical studies and is now available as a wound healing agent both for corneal (CACICOL20) and skin ulcers (CACIPLIQ20)-see www.OTR3.com. Few thousand patients in therapeutic failure with non-healing ulcers have been successfully treated in Europe and the Middle East, suggesting great safety and efficacy with respect to both speed and quality. More controlled randomised clinical trials are ongoing. Concerning tendonitis, a dedicated injectable RGTA, namely EQUITEND, was developed and a first study measured the healing capacity on the injured tendon after unique and echo guided intra-lesion injection in 137 horses over 2 years. A controlled randomised study was performed on 32 trotters with SDFT injury and another randomised study on mechanically injured SDFT tendons in 12 laboratory horses was also documented. Altogether, these studies indicate that RGTA accelerates both speed and quality of tendon healing. RGTA treated injured racing horses had improvements on earlier echography images, returned to races 2.4 months earlier than control, their breakage recurrence was twice as low, and their gains were as high as before injury versus half in control horses. This underlines the potential of RGTA as a new therapeutic class in the field of regenerative medicine, simple safe and exploiting our natural potential without need for exogenous cells supply.
A KNOWLEDGE TRANSLATION INITIATIVE TO ENHANCE EVIDENCE-INFORMED CLINICAL MANAGEMENT OF ACHILLES TENDINOPATHY: THE PURPOSE, PROCESS AND OUTCOMES OF THE BC TENDINOPATHY TOOLKIT
Authors: Hoens A M , Ezzat A , Anthony J , Scott A , Yates M , Justesen J R , Hughes D
Published: May 2013

Introduction

Translation of knowledge to practice in health care is a significant challenge.1–3 This presentation describes the purpose, process and preliminary outcomes of a knowledge translation (KT) initiative undertaken by a unique partnership of physical therapy researchers, educators and expert clinicians to address the gap between evidence and practice in the management of Achilles tendinopathy.

Methods

Physiotherapy clinicians in British Columbia requested evidence-informed guidance on the management of tendinopathy. To address this need, the provincial Physical Therapy Knowledge Broker assembled a team of researchers, educators and expert clinicians with the mandate to develop, disseminate and implement a toolkit of decision aids to guide clinical decision-making for Achilles Tendinopathy.

The process to develop the toolkit involved the following components: (1) identification of the purpose and scope of the project (2) agreement on the processes for selection of content and format (3) creation of a mechanism for resolution of conflicting opinion (4) an iterative feedback process with stakeholders and (4) the incorporation of concepts and strategies from the knowledge translation and implementation science literature to support the stages of knowledge synthesis, dissemination and implementation.1–4

Results

The ‘Tendinopathy Toolkit’ included: (1) a tabulated summary of the evidence for manual therapy, exercise, low level laser therapy, ultrasound, extracorporeal shock wave therapy, iontophoresis using dexamethasone, taping, orthotics, night splints and braces, heel raise inserts, needling techniques, and the appropriate outcome measures for this population (targeted ‘take home messages’ and clinical implications for each were also included); (2) an algorithm to guide the sequence of interventions; (3) and appendices including (a) exercise programmes (b) low level laser dosage calculation (c) tabulated details for each article reviewed and (d) a review of common medical interventions.

The second phase of the initiative—utilization of strategies to enhance implementation and uptake of the toolkit—is currently being undertaken.

Discussion

Clinicians want to provide evidence-informed management of tendinopathy but many struggle with accessing, appraising and synthesising the vast array of literature available on this topic. This KT initiative highlights the need for, challenges associated with, evidence-informed process for and positive response to the development of decision aids synthesising the current evidence to guide clinical management of this patient population.
JUMPING ABILITY AND CHANGE OF JUMPING ABILITY AS RISK FACTORS FOR DEVELOPING JUMPER'S KNEE
Authors: Visnes H , Aandahl H , Bahr R
Published: May 2013

Introduction

The ‘jumper's knee paradox’, where symptomatic athletes appear to perform better in a counter movement jump (CMJ) compared to asymptomatic controls in previous case-control studies, is not fully understood. The aim was to examine the relationship between jumping ability and change of jumping ability as potential risk factors for developing jumper's knee.

Methods

A 5-year prospective cohort study among elite volleyball players, aged 16–18 was performed. Jump tests were done on a portable force plate at the time of inclusion and semi-annually. Jumper's knee was diagnosed based on a standardised clinical examination.

Results

150 students (68 males and 82 females) were included and 28 developed jumper's knee (22 males and 6 females). At the time of inclusion, male athletes who went on to develop jumper's knee had significantly better results in CMJ (38.0±5.8 cm) compared to asymptomatic males(34.6±5.5 cm, p=0.03), while no difference was detected in standing jump (SJ: jumper's knee: 30.3±7.4 cm, asymptomatic: 28.1±6.1 cm, p=0.23). In a multivariate logistic regression analysis corrected for gender and previous volleyball training, the OR was 2.09 (1.03–4.25) per cm difference in CMJ at the time of inclusion. Our results did not reveal any significant differences in the change in jumping ability between the groups, although both groups improved their jump performance.

Conclusion

Volleyball players with a natural ability for jumping high are at an increased risk for developing jumper's knee.
NEW BIOMECHANICAL MODEL TO EXPLAIN THE INJURY SITE OF PATELLAR TENDINOPATHY: AN ULTRASONOGRAPHY STUDY
Authors: Jaén T F , Rey G A , Vicente I G , García P G
Published: May 2013

Introduction

The deep and proximal face of the patellar tendon is the most frequently injured site. Up to now, we have been thinking that this could be a result of two factors: mechanism of compression (impingement) produced by inferior patellar pole, and a hypovascularized site. We have elaborated a new biomechanical model to show that this pathology may be caused by a traction mechanism and not by compression. The insertion area of tendon on patella is a weak transition site between tendon and bone; while the anatomical tendon-to-bone insertion in the proximal end shows a perpendicular angle, at the distal end at the tibial level, it shows an oblique angle.

Methods

With ultrasound, we have measured the maximum length of the superficial and deep faces, bone to bone. These measurements were done in two positions: in maximal extension and 90° flexion. All samples were right knees, and there were 10 patients. Measurements were taken by the same technician (figure 1).

Figure 1.

Sagittal knee view.

Results

Measurements were as follows: in maximal extension for the deep face, the mean value was 4.15cm (range 3.40–5.05) and for the superficial face, the mean value was 4.857cm (range 4.57–5.20). Alternatively, in 90° flexion, the deep face showed a mean value of 3.938 cm (range 2.77–4.64) while for the superficial face it was 4.916 (range 4.27–5.11). Variations in face lengths when we changed the knee position were 1.21% for the superficial face and 5.38% for deep face.

Discussion

These results have demonstrated that the deep face had a greater percent increase in length than the superficial face when the knee changed position from extension to flexion. This study has some limitations- it was performed at only 90° flexion because the longitudinal probe is limited, and there are a low number of subjects. In conclusion, traction forces are probably more intense in the deep face than in the superficial face.
PROTEASE-ACTIVATED RECEPTORS ARE EXPRESSED IN HUMAN TENDON TISSUE AND MAY EXPLAIN EXCESSIVE PAIN-SIGNALLING IN TENDINOPATHY
Authors: Andersson G , Alfredson H
Published: May 2013

Introduction

Several painful conditions throughout the human body—such as interstitial cystitis, Dupuytren's contracture, and complex regional pain syndrome—have been shown to exhibit tissues with an increase in mast cell population. One such painful condition—where the pain is not considered proportionate to the tissue changes—is tendinopathy. One study has shown that activation via protease-activated receptor 4 (PAR4) can lead to an increased nociception in joints, and similar mechanisms may be at play in tendinopathy, where substances released by mast cells may activate the PARs. Mast cells are also known mediators of inflammatory responses to injury, but have also been found to regulate cell proliferation and vasodilation in certain tissues via PARs, and tendinopathies are known to exhibit tissue characteristics involving hypercellularity and vascular changes.

The aim of this study was to determine whether tissues surrounding the Achilles tendon exhibit PAR4, as a basis for further studies on interactions between the tendon, vascularity and nerves, and the mast cell population found in tendinopathy tendons.

Methods

Biopsies of about 5×5 mm were taken from the ventral part of the Achilles tendon and the paratendinous tissues of this area, from two groups. One group consisted of patients suffering from mid-portion tendinopathy with tendinosis (n=8). Normal controls (n=2) donated biopsies from the same area. Both procedures were guided by ultrasound and performed through a minimal skin incision. These biopsies were later sectioned and immunocytochemistry was used to study the expression patterns of PAR4.

Double-staining with PAR4and substance P (SP) was performed.

Results

The sections showed strong reactivity for PAR4in the blood vessels both in the tendon tissue proper as well as in the more abundant vascular areas ventral to the tendon in biopsies from both normal tendons and those from patients diagnosed with tendinosis. Tenocytes expressed PAR4to a varying degree (figure 1), with it being expressed more in cells with a rounded nuclei, primarily in tendons from the tendinosis group. PAR4was expressed on SP-positive nerve fibres in the paratendinous tissue (figure 2).

Figure 1.

(a) Tenocytes show reactions for PAR4(in red). Counterstained with DAPI. (b) Vessels positive for PAR4.

Figure 2.

(a) A nerve fibre and vessel positive for PAR4. In b the nerve fibre shows reactivity for substance P.

Discussion

These findings give basis for further studies into the interactions of SP-positive nerves and mast cells in tendon pathology. Earlier studies have shown regulation of vascular permeability and dilation, as well as fibroblast proliferation through activation of PARs. The PAR4may, through activation of proteases released from mast cells, to some extent be responsible not only for tenocyte proliferation and vascular regulation, but also for an enhanced pain signalling in tendinopathy through SP-positive afferents.
TENDON RESPONSE IN ACHILLES TENDON OF AUSTRALIAN FOOTBALL PLAYERS USING ULTRASOUND TISSUE CHARACTERISATION
Authors: Rosengarten S , Docking S I , van Schie J T M , Daffy J , Cook J L
Published: May 2013

Introduction

The Achilles tendon is an elastic storage tendon that converts kinetic energy into mechanical energy and reduces the metabolic cost of high-speed locomotion. Numerous studies have shown that the tendon is responsive to mechanical stimuli with changes in CSA and collagen synthesis both in the short- and long-term.1 2 This mechano-responsiveness of the tendon has been implicated in the development of tendinopathy and detecting early and/or short-term changes may have a role in managing tendinopathy. Ultrasound tissue characterisation (UTC) uses contiguous ultrasound images to render a 3-dimensional image that allows semi-quantitative analysis of tendon structure. This novel ultrasound technique has been used to show short-term changes in tendon structure in response to maximal exercise in thoroughbred horses.3 This study aims to investigate short-term changes in the Achilles tendon in Australian football players in response to loading during competitive games.

Methods

22 elite male Australian football players, some with history of tendinopathy (six and three players with a history of patellar and Achilles tendinopathy, respectively) were recruited. Players were scanned prior to the game and days 1, 2 and 4 post-game using UTC. A 1cm region at the midsubstance of the tendon was selected and the ultra-structure quantified into four echo-types based on the stability of the echopattern. Changes in the echopattern were compared over the 4 days using a related samples Friedmans two-way analysis of variance. If a significant difference in the median was observed, post-hoc (Wilcoxon signed rank test) analysis was performed to identify the differences between days 1, 2 and 4 and day 0.

Results

Preliminary data analysis showed differences in baseline tendon structure in players with and without a history of lower limb tendinopathy. Further analysis will examine differences between groups in change over the 4 days, and examine intrinsic (age, mass) and extrinsic factors (game load, GPS data) that are associated with change in UTC parameters.

Conclusions

This study demonstrated the changes seen in the Achilles tendons of athletes after intense loading. The factors that affect the magnitude of the response were elucidated.
GREATER TROCHANTERIC PAIN SYNDROME: DEFINING THE SYNDROME
Authors: Fearon A M , Scarvell J M , Cook J L , Neeman T , Cormick W , Smith P N
Published: May 2013

Introduction

Effective treatment of hip pain leads to improved quality of life and population health. This is dependent on accurate differential diagnosis. While hip osteoarthritis (OA) diagnosis is well defined,1 the diagnosis of greater trochanteric pain syndrome (GTPS) is not. The aim of this study was to clinically define GTPS.

Methods

Forty one people with GTPS, ranging from mild to severe (11 not seeking treatment and 10 awaiting surgery), 20 with severe hip OA, and 23 age and sex matched asymptomatic participants (ASC) were recruited from public and private hospitals, and the community. Inclusion and exclusion criteria assured mutually exclusive groups. Assessment included the Harris Hip Score (HHS), a battery of passive and resisted tests (recording reproduction and location of pain), and the single leg stance test. Statistical analyses used include Fisher exact test, ANOVA, and recursive partitioning to develop two classification trees. The first classification tree was based on an undifferentiated hip pain response and the second was based on a clearly identified lateral hip pain response.

Results

The HHS domains of maximum walking distance and the ability to manipulate shoes and socks were the only domains to differentiate between the two symptomatic groups, (ANOVA: p=0.010 and p<0.001 respectively). Dichotomising these data resulted in OR (95% CI) of 3.47 (1.09 to 10.93)—for the ability to walk >30/60; and of 0.06 (0.00 to 0.26)—for the ability to manipulate shoes and socks, of having GTPS versus hip OA. The first classification tree resulted in a four branch tree for diagnosing GTPS, with a mean (se) sensitivity and specificity of 0.78 (0.058) and 0.28 (0.080) respectively. These branches included a positive Ober and passive to active medial rotation ratios. The second tree resulted in one branch, FABER, for diagnosing GTPS with a mean (se) sensitivity and specificity of 0.81 (0.019) and 0.82 (0.044) respectively. The single leg stance test did not differentiate between the two symptomatic groups.

Discussion

Three features differentiated people with GTPS from those with hip OA without reference to our inclusion criteria. These results provide clinicians with markers to aid with the sometimes difficult diagnosis of GTPS.2 When combined with greater trochanter palpation, this combination of features is likely to be more sensitive and specific than the FABER test result. We recommend that the clinical syndrome of GTPS be defined as a history of lateral hip pain in the absence of difficulty with manipulating shoes and socks, together with an examination of findings of pain reproduction on palpation of the greater trochanter (a previously recognised sign) and lateral hip pain with a FABER test. In patients who cannot differentiate the site of their pain, multiple pathologies should be considered. For research purposes or in cases of poor response to treatment, multiple pathologies should be considered and a hip x-ray should be undertaken to exclude joint pathology.