bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coevolution of the Hepatitis C Virus Polyprotein Sites in Patients on Combined Pegylated Interferon and Ribavirin Therapy
Authors: Lara James , Xia Guoliang , Purdy Mike , Khudyakov Yury 
Published: January 2011

ABSTRACTGenotype-specific sensitivity of the hepatitis C virus (HCV) to interferon-ribavirin (IFN-RBV) combination therapy and reduced HCV response to IFN-RBV as infection progresses from acute to chronic infection suggest that HCV genetic factors and intrahost HCV evolution play important roles in therapy outcomes. HCV polyprotein sequences (n= 40) from 10 patients with unsustainable response (UR) (breakthrough and relapse) and 10 patients with no response (NR) following therapy were identified through the Virahep-C study. Bayesian networks (BNs) were constructed to relate interrelationships among HCV polymorphic sites to UR/NR outcomes. All models showed an extensive interdependence of HCV sites and strong connections (P≤ 0.003) to therapy response. Although all HCV proteins contributed to the networks, the topological properties of sites differed among proteins. E2 and NS5A together contributed ∼40% of all sites and ∼62% of all links to the polyprotein BN. The NS5A BN and E2 BN predicted UR/NR outcomes with 85% and 97.5% accuracy, respectively, in 10-fold cross-validation experiments. The NS5A model constructed using physicochemical properties of only five sites was shown to predict the UR/NR outcomes with 83.3% accuracy for 6 UR and 12 NR cases of the HALT-C study. Thus, HCV adaptation to IFN-RBV is a complex trait encoded in the interrelationships among many sites along the entire HCV polyprotein. E2 and NS5A generate broad epistatic connectivity across the HCV polyprotein and essentially shape intrahost HCV evolution toward the IFN-RBV resistance. Both proteins can be used to accurately predict the outcomes of IFN-RBV therapy.
Rotavirus VP2 Core Shell Regions Critical for Viral Polymerase Activation
Authors: McDonald Sarah M. , Patton John T. 
Published: January 2011

ABSTRACT

The innermost VP2 core shell of the triple-layered, icosahedral rotavirus particle surrounds the viral genome and RNA processing enzymes, including the RNA-dependent RNA polymerase (VP1). In addition to anchoring VP1 within the core, VP2 is also an essential cofactor that triggers the polymerase to initiate double-stranded RNA (dsRNA) synthesis using packaged plus-strand RNA templates. The VP2 requirement effectively couples packaging with genome replication and ensures that VP1 makes dsRNA only within an assembling previrion particle. However, the mechanism by which the rotavirus core shell protein activates the viral polymerase remains very poorly understood. In the current study, we sought to elucidate VP2 regions critical for VP1-mediated
in vitro
dsRNA synthesis. By comparing the functions of proteins from several different rotaviruses, we found that polymerase activation by the core shell protein is specific. Through truncation and chimera mutagenesis, we demonstrate that the VP2 amino terminus, which forms a decameric, internal hub underneath each 5-fold axis, plays an important but nonspecific role in VP1 activation. Our results indicate that the VP2 residues correlating with polymerase activation specificity are located on the inner face of the core shell, distinct from the amino terminus. Based on these findings, we predict that several regions of VP2 engage the polymerase during the concerted processes of rotavirus core assembly and genome replication.
Cellular SNF2H Chromatin-Remodeling Factor Promotes Herpes Simplex Virus 1 Immediate-Early Gene Expression and Replication
Authors: Bryant Kevin F. , Colgrove Robert C. , Knipe David M. 
Published: January 2011

ABSTRACT
Like other DNA viruses that replicate in the nucleus, herpes simplex virus 1 (HSV-1) regulates the association of histones with its genome to promote viral replication and gene expression. We previously demonstrated that SNF2H, a member of the ISWI family of chromatin-remodeling factors, is concentrated in HSV-1 replication compartments in the nuclei of infected cells, suggesting that this cellular enzyme plays a role in viral replication. We show here that small interfering RNA (siRNA)-mediated knockdown of SNF2H in HEp-2 cells resulted in an approximately 20-fold decrease in HSV-1 replication, arguing that SNF2H promotes efficient HSV-1 replication. Decreases in HSV-1 replication were observed with multiple SNF2H-specific siRNAs, and the extent of the replication decrease correlated with the amount of SNF2H knockdown, indicating that the phenotype resulted from decreased SNF2H levels rather than off-target effects of the siRNAs. We also observed a decrease in the accumulation of immediate-early (IE) gene products in HSV-1-infected cells in which SNF2H was knocked down. Histone H3 occupancy on viral promoters was increased in HSV-1-infected cells that were transfected with SNF2H-specific siRNAs, suggesting that SNF2H promotes removal of histones from viral promoters during infection. Furthermore, chromatin immunoprecipitation (ChIP) studies showed that SNF2H associated with the HSV-1 genome during infection, which suggests that SNF2H may directly remodel viral chromatin. We hypothesize that SNF2H is recruited to viral promoters during HSV-1 infection, where it can remodel the chromatin state of the viral genome, facilitate the transcription of immediate-early genes, and enhance viral replication.

IMPORTANCE
It is becoming increasingly appreciated that regulation of the state of chromatin is a major determinant in control of gene expression. It has also become clear that the state of chromatin of the herpes simplex virus 1 (HSV-1) genome is dynamically regulated during both productive and latent stages of infection. In addition, multiple viral gene products have been reported to play roles in regulating the viral chromatin state. However, the cellular chromatin-remodeling factors involved in altering nucleosome occupancy at viral genes remain largely unknown. The results in this report represent the first evidence that cellular chromatin-remodeling proteins, and SNF2H in particular, can play important roles in regulating the chromatin state of the HSV-1 genome during infection. This work also further establishes HSV-1 infection as a useful model to study chromatin control of gene expression and suggests that disrupting the regulation of viral chromatin states can possibly be exploited as a novel antiviral therapeutic target.
Establishing practical guidelines for exercise in insulin treated diabetics
Authors: Redgrave Ann , Gallen Ian , Hudson Zoe 
Published: January 2011

AbstractPractical guidelines for exercise in insulin treated diabetics – a prospective cohort series of insulin treated diabetics using a simple questionnaire and continuous glucose monitoring to assess the influence of specific guidelines on blood sugar levels before, during and after exercise.BackgroundScientific literature suggests that if a diabetic on insulin can achieve euglycaemia during exercise the metabolic response to exercise is normalised. Problems occur both during and post exercise due to swings in blood sugar that are aggravated by the diabetic’s response to these swings.ObjectivesThe principle objective was to establish practical exercise guidelines for insulin treated diabetics that could be used as a safe reference by diabetics themselves and sports physicians/general practitioners. The guidelines were set to minimise the swings into hyperglycaemia and hypoglycaemia commonly seen in diabetics during exercise. A secondary objective was to assess whether use of the guidelines could approximate the blood sugar of the diabetic during exercise to that of the non-diabetic during exercise.DesignUsing a cohort of insulin treated diabetics the efficacy of practical exercise guidelines were assessed before, during and after exercise using a simple questionnaire and continuous interstitial glucose monitoring.SubjectsNine insulin treated diabetics were recruited from a diabetic sports clinic in the Buckinghamshire Hospitals NHS Trust, which took referrals from anywhere in England. Two non-diabetic, elite athletes were recruited for comparison.ResultsOn questioning 86% of subjects reported a reduction in exercise associated hypoglycaemia and 28% reported an improvement in exercise performance when using the guidelines. There was a narrowing of the glucose oscillations in 85% of the subjects studied however the difference in the recording of interstitial glucose outside the range of 4–10 mmol/l before and after using the exercise guidelines was statistically not significant p>0.05 (p=0.058).ConclusionsThe outcomes of this study suggest that these guidelines are effective clinically in reducing blood sugar oscillations during exercise in insulin treated diabetics; however the outcomes were not statistically significant probably as a result of the small sample size. Further study with a larger sample size is merited to validate these guidelines further.
Physiology of cold water immersion: a comparison of cold water acclimatised and non-cold water acclimatised participants during static and dynamic immersions
Authors: Hingley Elizabeth , Morrissey Dylan , Tipton Michael , House Jim , Lunt Heather 
Published: January 2011

IntroductionDrowning is the third leading cause of accidental death worldwide. Many deaths from immersion in cold water are wrongly attributed to hypothermia. Humans can survive numerous hours in cold water, as seen in open water swimmers who complete endurance swims for many hours at low water temperatures. Previous studies performed on cold-water swimmers have shown distinct physiological differences in those regularly exposed to cold water compared to controls. The aim of this study was to identify whether regular cold water swimmers exhibit physiological adaptation to cold water immersion in static and dynamic conditions.MethodA prospective case-control study, where participants were immersed in cold water (12°C); once during a static immersion and once during a swimming (dynamic) immersion. Six cold water acclimatised (CWAI) participants were matched to six non-cold water acclimatised participants for body fat percentage and gender for both the static and dynamic immersions and mean changed between the two groups compared.ResultsCWAI participants show a decreased metabolic rate leading to fall in core temperature during static immersion. In dynamic immersion, deep body temperature is maintained with little increase in metabolic heat production.DiscussionCWAI participants show a hypothermic-type adaptation during static immersion in cold water. In contrast, an insulative-type adaptation is seen during dynamic immersion in the CWAI participants. The onset of shivering is delayed by adaptation to cold water. Insulative adaptation benefits the cold water swimmer as there is little or no increase in metabolic heat production. The swimmer can maintain their core temperature without wasting vital energy.ConclusionCWAI participants exhibit different types of adaptation depending on the type of immersion experienced.
Clinical decison making and knee arthroscopy
Authors: Derrett Sarah , Walley Gayle , Bridgman Stephen , Richards Paula , Maffulli Nicola 
Published: January 2011

ObjectivesThis study aimed to identify decisions made by orthopaedic surgeons about whether patients on a waiting list should proceed to arthroscopy, and to describe surgeons' decisions.MethodsSurgeons were asked to think aloud as they made their decisions as the clinical management for patients from a previous randomised controlled trial (RCT) looking at the use of MRI for patients on a waiting list for knee arthroscopy. Audiotapes of the decision making were transcribed for analysis.ResultsSurgeons agreed about proceeding with arthroscopy for five patients, although reasoning differed. In no cases did surgeons agree about not proceeding to arthroscopy. However, more súrgenos decided not to proceed to arthroscopy than to proceed. Patients with clinically diagnosed with osteoartritis were less likely to be cosen to have arhtroscopy than those with meniscal abnormalities for which the general consensus was to proceed with arthroscopy..ConclusionsThere tended to be disagreement between súrgeons about proceeding with arthorscopy when osteoarthritis was diagnosed clinically. Surgeons decisions did not reflect the decision making as reflected in the original RCT. Surgeons' decisions were influenced by patient wishes. For some patients, the decision to proceed with arthroscopy was based solely on clinical diagnosis; MRI may not be advantageous in these instances. This study has implications for decision making in the current NHS patient choice environment. Patients may choose a treatment provider from a list of available providers at time of original clinical assessment and diagnosis. However, the treating surgeon does not necessarily re-examine the patient until the day of surgery. Given the variation between surgeons about the merits of proceeding with arthroscopy, surgeons may end up in the invidious position of providing surgery to patients whom they do not believe will benefit from arthroscopy.
The use of epcs (endothelial progenitor cells) for the regeneration of the musculoskeletal system and the spine
Authors: Keramaris N C , Tsiridis E , Malliaropoulos N , Kostakos A , Topkas A , Pnevmatikos S , Papagellopoulos P J , Sapkas G 
Published: January 2011

IntroductionEndothelial progenitor cells (EPCs) are cells that can differentiate into endothelial cells in vitro. Their importance lies on the fact that vasculature has a cornerstone role in the healing process after injury of the musculoskeletal system and of the spine. The main target of this review is to clarify whether EPCs could be a viable alternative of mesenchymal stem cells for musculoskeletal regeneration.MethodsThe literature search was performed via the internet using the Medline, Scopus and Cochrane database. The key words which were searched in the abstracts were the terms ‘EPCs’, ‘bone’, ‘spine cord’, ‘cartilage’, ‘menisci’, ‘ligament’, ‘tendon’ and ‘healing’.ResultsThree papers reported that EPCs can differentiate into osteoblasts in vitro. In a fourth paper, EPCs were used in an in vivo model in order to enhance the fracture healing in a non-union animal model. A fifth paper implies that fracture may induce mobilisation of EPCs and recruitment of the mobilised EPCs into fracture sites. Another two papers showed that local transplantation of EPCs with atelocollagen scaffold is a feasible strategy for therapeutic vasculogenesis and osteogenesis needed for fracture and ligament healing. Another paper suggested that co-transplantation of hematopoietic and mesenchymal stem/progenitor cells may improve the regeneration of vascular dependent tissues such as bone, adipose, muscle and dermal grafts. Two papers reported stimulating results for the use of EPCs for spine cord regeneration.DiscussionThe importance of EPCs for the healing of both musculoskeletal tissue and spine is based on the advantages of this cell population for regeneration purposes: (1) relative abundance, (2) isolation by the circulation, (3) new insight revealing new mechanisms
Small leucine rich proteoglycans (SLRP's) expression in skin, tendons and capsules of athletic population after shoulder dislocation and ACL injuries
Authors: Akhtar M A , Ingman T G , Robinson C M , Keating J F , Muir A Y , Simpson H , Salter D 
Published: January 2011

IntroductionCruciate ligament ruptures and shoulder dislocations are often caused by trauma, but predisposing intrinsic factors might also influence the risk. Decorin and biglycan are members of the small leucine rich proteoglycans (SLRP's) family which are important constituents of interstitial extracellular matrices (ECM) and play important roles in the regulation of collagen fibrillogenesis. Their deficiency could influence wound healing and integrity of skin and muscle. The aim of this study was to localise Decorin and Biglycan in skin, hamstring tendons and shoulder capsules.Patients and methodsLocalisation of decorin and biglycan was studied by immunohistochemical staining of paraffin embedded sections of skin, tendons and capsules of the patients attending for shoulder stabilisation or anterior cruciate ligament (ACL) reconstruction between November 2008 and July 2009.Results40 patients were studied, 25 undergoing primary ACL reconstruction and 15 undergoing shoulder stabilisation. The mean age of patients was 26 years. 34 patients (85%) were male and 6 female (15%). Most common sport played was football in 13 patients (32%) followed by rugby in 10 (25%) and skiing in 5 (12%).Skin epidermis, blood vessels, sweat glands, sebaceous glands and arrector pilli stained negative but dermis stained positive to varying degrees for decorin. Synovial surface of the capsule, blood vessels and skeletal muscles stained negative but ECM was positive to varying degrees for decorin. Tendon sheath and collagen fibres in ECM stained positive to varying degrees but skeletal muscle stained negative for decorin.Skin epidermis, blood vessels, sweat glands, sebaceous glands and arrector pilli and dermis stained positive for biglycan to varying degrees. Synovial surface of the capsule, blood vessels and ECM stained positive for biglycan to varying degrees. Tendon sheath stained negative but collagen fibres, blood vessels and skeletal muscles stained positive for biglycan to varying degrees.DiscussionWe looked at the expression and distribution of decorin and biglycan in skin, tendons and capsules of patients undergoing shoulder stabilisation or ACL reconstruction following sports injuries. There may be a link in the distribution of these SLRP's and strength of tissues, which can predispose individuals to injuries while playing sports and can also affect healing process. Further studies are needed to study this link.
Physiotherapy for prevention of lower back injuries in wrestling
Authors: Dimitrova E , Stanev S 
Published: January 2011

IntroductionAbout 10% of all sport injuries in wrestling occur in lower back area.1 The purpose of this report is to summarise the incidence of lower back injuries in wrestling and the mechanisms involved, and to represent our experience in physiotherapy (PT) for prevention of these injuries.MethodsFrom a sample of 95 wrestlers (males), 11 lower back injuries were found (11.6%). Problems such as muscle and joint injuries and dysfunctions occur quite frequently. Treatment of dysfunctions begins with PT program, that emphasises analytical stretching2 and strengthening of the back and abdominal musculature. We allow a return to sport when the athlete has regained at least 70% of his viability and pain-free full range of motion.ResultsLower back injureis can be due to numerous factors: extensions, combined with twisting in take-downs (5 out of 11 wrestlers −45.5 %), extensions against resistance as in lifting an opponent off the mat (6 out of 11 wrestlers −54.5 %). Reduction in low back injuries was found as a result of a physiotherapy program. 8 out of 11 wrestlers who were treated from low back injuries returned to high-level competitions. In three cases the condition was not treated on time and it became chronic. As a result of our study, many changes have been made to the strength and conditioning training.ConclusionIn cases of low back injuries an early diagnosis is essential, so that treatment can be commenced as soon as possible. Preventive physiotherapy program is essential and should be included in every training program as an integral part of the warm-up and recovery.
The effect of resveratrol on the inflammatory response and delayed onset muscle soreness after a marathon in male athletes: a randomised, double-blind, placebo-controlled pilot study
Authors: Laupheimer Markus W 
Published: January 2011

ObjectivesResveratrol, a natural polyphenolic flavonoid antioxidant is known to have numerous health benefits and to act as a potent anti-inflammatory substance. This study was undertaken to investigate the inflammatory responses and delayed onset of muscle soreness after the London Marathon, and whether it is altered by Resveratrol.Design and settingDouble placebo-controlled randomised trial conducted at the London Marathon, 2010.MethodsSeven healthy male athletes were recruited for the study. Participants were randomised to either Resveratrol or placebo. The Resveratrol group was treated with 600 mg Resveratrol daily for 7 days immediately before the marathon. Blood was taken 48 h before the marathon and 18–32 h after the marathon. Samples were analysed for white blood cell count (WBC) and C reactive protein (CRP). To assess delayed onset muscle soreness a visual analogue scale (VAS) score was taken at the same times as the blood samples. The prepost changes were compared between the groups using the Mann–Whitney U test.ResultsThere was no significant difference between the two groups in terms of changes occurring between pre and post-tests for WBC, CRP or VAS (p=0.857, 0.629 and 0.70 respectively).ConclusionThis pilot study could not find a difference in immune response or delayed onset of muscle soreness between Resveratrol and placebo after the London Marathon 2010. Further investigations are needed with longer treatment time and higher doses, analysing additional parameters like interleukins for a possible effect of Resveratrol on the inflammatory response due to extensive exercise.
Patient pain drawing in diagnosing the cause of exercise-induced leg pain
Authors: Rennerfelt K , Zhang Q , Hamilton L , Styf J 
Published: January 2011

IntroductionClassifying symptoms by patient pain drawing (PPD) may be helpful in diagnosing chronic anterior compartment syndrome (CACS). We have investigated the sensitivity and interobserver reliability of the PPD to diagnose CACS among patients with exercise-induced leg pain (EILP).MethodsThis study included 88 consecutive patients (48 men, 40 women; mean age 33, range 13–66, years). Two observers independently diagnosed the causes of leg pain based solely on PPD. The causes of leg pain in patients were diagnosed into seven categories (CACS, chronic lateral compartment syndrome, chronic posterior compartment syndrome, medial tibial syndrome, peroneal tunnel syndrome, muscle rupture and miscellaneous). The true diagnosis was based on a complete clinical examination including laboratory measurements of intramuscular pressure and intramuscular oxygenation by near-infrared spectroscopy during and after an exercise test that elicited the symptoms.ResultsThe sensitivity of PPD to diagnose CACS was 69%. The positive predictive value was 53%. The interobserver reliability based solely on PPD in diagnosis of CACS was 92% (κ=0.81). Based on PPD, the causes of EILP were correctly diagnosed into the seven categories in 69% of all cases. The interobserver reliability in diagnosis of EILP reached 88%. Multiple pain locations on PPD were observed in 4% of patients with CACS and 24% of patients without CACS. No patient had chronic compartment syndrome in the lateral or posterior compartments.ConclusionsThis study indicates that PPD is a reliable tool to make accurate predictions in diagnosing CACS and other causes of EILP. Patients with CACS reported significantly less co-morbidity compared to patients with other causes of EILP. PPD should be combined with patient's history, clinical findings during an exercise test that elicits the symptoms and signs, as well as with the results from laboratory tests.