bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV-1 Induces Telomerase Activity in Monocyte-Derived Macrophages, Possibly Safeguarding One of Its Reservoirs
Authors: Reynoso Rita , Wieser Matthias , Ojeda Diego , Bönisch Maximilian , Kühnel Harald , Bolcic Federico , Quendler Heribert , Grillari Johannes , Grillari-Voglauer Regina , Quarleri Jorge 
Published: July 2012

ABSTRACTMonocyte-derived macrophages (MDM) are widely distributed in all tissues and organs, including the central nervous system, where they represent the main part of HIV-infected cells. In contrast to activated CD4+T lymphocytes, MDM are resistant to cytopathic effects and survive HIV infection for a long period of time. The molecular mechanisms of how HIV is able to persist in macrophages are not fully elucidated yet. In this context, we have studied the effect ofin vitroHIV-1 infection on telomerase activity (TA), telomere length, and DNA damage. Infection resulted in a significant induction of TA. This increase was directly proportional to the efficacy of HIV infection and was found in both nuclear and cytoplasmic extracts, while neither UV light-inactivated HIV nor exogenous addition of the viral protein Tat or gp120 affected TA. Furthermore, TA was not modified during monocyte-macrophage differentiation, MDM activation, or infection with vaccinia virus. HIV infection did not affect telomere length. However, HIV-infected MDM showed less DNA damage after oxidative stress than noninfected MDM, and this resistance was also increased by overexpressing telomerase alone. Taken together, our results suggest that HIV induces TA in MDM and that this induction might contribute to cellular protection against oxidative stress, which could be considered a viral strategy to make macrophages better suited as longer-lived, more resistant viral reservoirs. In the light of the clinical development of telomerase inhibitors as anticancer therapeutics, inhibition of TA in HIV-infected macrophages might also represent a novel therapeutic target against viral reservoirs.
ORF45 of Kaposi's Sarcoma-Associated Herpesvirus Inhibits Phosphorylation of Interferon Regulatory Factor 7 by IKKε and TBK1 as an Alternative Substrate
Authors: Liang Qiming , Fu Bishi , Wu Fayi , Li Xiaojuan , Yuan Yan , Zhu Fanxiu 
Published: July 2012

ABSTRACT
Open reading frame 45 (ORF45) of Kaposi's sarcoma-associated herpesvirus (KSHV) is an immediate-early and tegument protein that plays critical roles in antagonizing host antiviral responses. We have previously shown (Zhu et al, Proc. Natl. Acad. Sci. U. S. A., 99:5573–5578, 2002) that ORF45 suppresses activation of interferon regulatory factor 7 (IRF7), a crucial regulator of type I interferon gene expression, by blocking its virus-induced phosphorylation and nuclear accumulation. We report here further characterization of the mechanisms by which ORF45 inhibits IRF7 phosphorylation. In most cell types, IRF7 is phosphorylated and activated by IKKε and TBK1 after viral infection. We found that phosphorylation of IRF7 on Ser477 and Ser479 by IKKε or TBK1 is inhibited by ORF45. The inhibition is specific to IRF7 because phosphorylation of its close relative IRF3 is not affected by ORF45, implying that ORF45 does not inactivate the kinases directly. In fact, we found that ORF45 is phosphorylated efficiently on Ser41 and Ser162 by IKKε and TBK1. We demonstrated that ORF45 competes with the associated IRF7 and inhibits its phosphorylation by IKKε or TBK1 by acting as an alternative substrate.
Signatures of Host mRNA 5′ Terminus for Efficient Hantavirus Cap Snatching
Authors: Cheng Erdong , Mir Mohammad A. 
Published: July 2012

ABSTRACT
Hantaviruses, similarly to other negative-strand segmented RNA viruses, initiate the synthesis of translation-competent capped mRNAs by a unique cap-snatching mechanism. Hantavirus nucleocapsid protein (N) binds to host mRNA caps and requires four nucleotides adjacent to the 5′ cap for high-affinity binding. N protects the 5′ caps of cellular transcripts from degradation by the cellular decapping machinery. The rescued 5′ capped mRNA fragments are stored in cellular P bodies by N, which are later efficiently used as primers by the hantaviral RNA-dependent RNA polymerase (RdRp) for transcription initiation. We showed that N also protects the host mRNA caps in P-body-deficient cells. However, the rescued caps were not effectively used by the hantavirus RdRp during transcription initiation, suggesting that caps stored in cellular P bodies by N are preferred for cap snatching. We examined the characteristics of the 5′ terminus of a capped test mRNA to delineate the minimum requirements for a capped transcript to serve as an efficient cap donor during hantavirus cap snatching. We showed that hantavirus RdRp preferentially snatches caps from the nonsense mRNAs compared to mRNAs engaged in translation. Hantavirus RdRp preferentially cleaves the cap donor mRNA at a G residue located 14 nucleotides downstream of the 5′ cap. The sequence complementarity between the 3′ terminus of viral genomic RNA and the nucleotides located in the vicinity of the cleavage site of the cap donor mRNA favors cap snatching. Our results show that hantavirus RdRp snatches caps from viral mRNAs. However, the negligible cap-donating efficiency of wild-type mRNAs in comparison to nonsense mRNAs suggests that viral mRNAs will not be efficiently used for cap snatching during viral infection due to their continuous engagement in protein synthesis. Our results suggest that efficiency of an mRNA to donate caps for viral mRNA synthesis is primarily regulated at the translational level.
Novel Cell Culture-Adapted Genotype 2a Hepatitis C Virus Infectious Clone
Authors: Date Tomoko , Kato Takanobu , Kato Junko , Takahashi Hitoshi , Morikawa Kenichi , Akazawa Daisuke , Murayama Asako , Tanaka-Kaneko Keiko , Sata Tetsutaro , Tanaka Yasuhito , Mizokami Masashi , Wakita Takaji 
Published: July 2012

ABSTRACT

Although the recently developed infectious hepatitis C virus system that uses the JFH-1 clone enables the study of whole HCV viral life cycles, limited particular HCV strains have been available with the system. In this study, we isolated another genotype 2a HCV cDNA, the JFH-2 strain, from a patient with fulminant hepatitis. JFH-2 subgenomic replicons were constructed. HuH-7 cells transfected with
in vitro
transcribed replicon RNAs were cultured with G418, and selected colonies were isolated and expanded. From sequencing analysis of the replicon genome, several mutations were found. Some of the mutations enhanced JFH-2 replication; the 2217AS mutation in the NS5A interferon sensitivity-determining region exhibited the strongest adaptive effect. Interestingly, a full-length chimeric or wild-type JFH-2 genome with the adaptive mutation could replicate in Huh-7.5.1 cells and produce infectious virus after extensive passages of the virus genome-replicating cells. Virus infection efficiency was sufficient for autonomous virus propagation in cultured cells. Additional mutations were identified in the infectious virus genome. Interestingly, full-length viral RNA synthesized from the cDNA clone with these adaptive mutations was infectious for cultured cells. This approach may be applicable for the establishment of new infectious HCV clones.
The short Synacthen test: a questionnaire survey of current usage
Authors: Elder Charlotte Jane , Sachdev Pooja , Wright Neil Peter 
Published: July 2012

BackgroundSupported by meta-analyses, the low-dose Synacthen test (LDST) has gained in popularity, with many believing it to be more sensitive than the supraphysiological standard (250 µg) short ST (SSST), particularly when assessing children prescribed high-dose inhaled corticosteroids (HDICS). However, consensus is lacking about its specific clinical application, what is considered ‘low dose’ and how that dose is made up.MethodsTo ascertain current use of the short Synacthen test (SST), a questionnaire was emailed to members of the British Society of Paediatric Endocrinology and Diabetes in the UK and Ireland (N=257), requesting a response from each department (N=92). A reminder was sent a month later to members of departments which had not responded.ResultsThe authors received 39 replies, giving a response rate of 42%. All departments use the SST: 82% use an LDST, 87% use the SSST and 69% use both. The 1 µg dose was used by 44% of hospitals, with the other 56% using seven different doses based on age, weight and body surface area. There were 14 different methods of preparing the low dose test. Additionally, variations in the timings of cortisol sampling and the diagnostic cut-offs for adrenal insufficiency were found. Increased requests for SSTs in children with asthma prescribed HDICS were noted by 44% of respondents, with 67% reporting the detection of adrenal suppression in this group.ConclusionStandardisation of the SST is required to address the considerable variation in the methodology and application of this test in the UK and Ireland.
Long-term prophylaxis in hereditary angio-oedema: a systematic review
Authors: Costantino Giorgio , Casazza Giovanni , Bossi Ilaria , Duca Piergiorgio , Cicardi Marco 
Published: July 2012

ObjectiveTo systematically review the evidence regarding long-term prophylaxis in the prevention or reduction of attacks in hereditary angio-oedema (HAE).DesignSystematic review and meta-analysis.Data sourcesElectronic databases were searched up to April 2011. Two reviewers selected the studies and extracted the study data, patient characteristics and outcomes of interest.Eligibility criteria for selected studiesControlled trials for HAE prophylaxis.Results7 studies were included, for a total of 73 patients and 587 HAE attacks. Due to the paucity of studies, a meta-analysis was not possible. Since two studies did not report the number of HAE attacks, five studies (52 patients) were finally included in the summary analysis. Four classes of drugs with at least one controlled trial have been proposed for HAE prophylaxis. All those drugs, except heparin, were found to be more effective than placebo. In the absence of direct comparisons, the relative efficacies of these drugs were determined by calculating a RR of attacks (drug vs placebo). The results were as follows: danazol (RR=0.023, 95% CI 0.003 to 0.162), methyltestosterone (RR=0.054, 95% CI 0.013 to 0.163), ɛ-aminocaproic acid (RR=0.095, 95% CI 0.025 to 0.356), tranexamic acid (RR=0.308, 95% CI 0.195 to 0.479) and C1-INH 0.491 (95% CI 0.395 to 0.607).ConclusionsFew trials have evaluated the benefits of HAE prophylaxis, and all drugs but heparin seem to be effective in this setting. Since there are no direct comparisons of HAE drugs, it was not possible to draw definitive conclusions on the most effective one. Thus, to accumulate evidence for HAE prophylaxis, further studies are needed that consider the dose–efficacy relationship and include a head-to-head comparison between drugs, with the active group, rather than placebo, as the control.
Variation in physical development in schoolboy rugby players: can maturity testing reduce mismatch?
Authors: Nutton Richard W , Hamilton David F , Hutchison James D , Mitchell Martin J , Simpson A Hamish RW , MacLean James G B 
Published: July 2012

ObjectivesThis study set out to pursue means of reducing mismatch in schoolboy rugby players. The primary objective was to determine whether application of previously reported thresholds of height and grip strength could be used to distinguish those 15-year-old boys appropriate to play under-18 school rugby from their peers. A secondary objective was to obtain normative data for height, weight and grip strength and to assess the variation within that data of current schoolboy rugby players.DesignCross-sectional cohort study.Setting3 Scottish schools and ‘Regional Assessment Centres’ organised by the Scottish Rugby Union.Participants472 rugby playing youths aged 15 years (Regional Assessment Centres) and 382 schoolboys aged between 12 and 18 years (three schools).Outcome measuresHeight, weight and grip strength.Results97% of 15-year-olds achieved the height and grip strength thresholds based on previous reported values. Larger mean values and wide variation of height, weight and grip strength were recorded in the schoolboy cohort. However, using the mean values of the cohort of 17-year-olds as a new threshold, only 7.7% of 15-year-olds would pass these thresholds.ConclusionsLarge morphological variation was observed in schoolboy rugby players of the same age. Physical maturity tests described in earlier literature as pre-participation screening for contact sports were not applicable to current day 15-year-old rugby players. New criteria were measured and found to be better at identifying those 15-year-old players who had sufficient physical development to play senior school rugby.
Continuous palliative sedation until death: practice after introduction of the Dutch national guideline
Authors: Swart Siebe J , van der Heide Agnes , Brinkkemper Tijn , van Zuylen Lia , Perez Roberto , Rietjens Judith 
Published: July 2012

BackgroundIn 2005, a national palliative guideline was launched in The Netherlands. The authors describe the practice of continuous palliative sedation until death (CPS) after the introduction of this guideline.MethodsIn 2008, a random sample of physicians (n=1580) were asked to fill out a questionnaire regarding the last patient in whom they had provided CPS until death.ResultsThe response was 38%. In all, 82% of the respondents were aware of the existence of the national guideline. Dyspnoea, pain and physical exhaustion were most often mentioned as decisive indications for continuous sedation. The decision to use sedation was discussed with all competent patients, but in 18% this merely involved informing the patient. Life expectancy at the start of continuous sedation was estimated to be less than 2 weeks in 97% of the cases. In 14%, the physicians had felt pressure to start the sedation, predominantly from patients and relatives. Physicians were present at the start of the sedation in 81% of the cases. Midazolam was used to induce the sedation in 92%. Overall, 41% of the physicians estimated that continuous sedation had hastened death to some extent. Most physicians thought that patients' complaints were adequately relieved by continuous sedation, that relatives were satisfied and that a good quality of dying was achieved.InterpretationContinuous palliative sedation practice in The Netherlands largely reflects the recommendations from the national guideline. Issues needing further attention are the pressure felt by physicians to start continuous sedation and the potential life-shortening effect as mentioned by the physicians.
Spiritual care: how to do it
Authors: Sinclair Shane , Bouchal Shelley Raffin , Chochinov Harvey , Hagen Neil , McClement Susan 
Published: July 2012

ObjectiveThis study explores the provision of spiritual care by healthcare professionals working at the end of life.DesignQualitative–ethnographic inquiry.SettingPhase 1: five Canadian sites; phase 2: a residential hospice in Alberta, Canada.ParticipantsPhase 1: six palliative care leaders; phase 2: 24 frontline palliative care clinicians.ResultsData were collected over a 12-month period with analysis of findings occurring concurrently. Using semistructured interviews and participant observation, 11 themes, organised under five overarching categories, emerged from the data. Five bedside skills were identified as essential to spiritual care: hearing, sight, speech, touch and presence. The integration of these bedside skills with the intrinsic qualities of healthcare professionals, including their values and spiritual beliefs, appeared to be essential to their application in spiritual care. Spiritual care primarily involved the tacit qualities of healthcare professionals and their effect on patient's spiritual well-being, rather than their explicit technical skill set or expert knowledge base.ConclusionParticipants identified spiritual care as both a specialised care domain and as a philosophy of care that informs and is embedded within physical and psychosocial care. Hearing, sight, speech, touch and presence were identified as the means by which healthcare professionals impacted patients' spiritual well-being regardless of clinician's awareness or intent. An empirical framework is presented providing clinicians with a pragmatic way of incorporating spiritual care into clinical practice.
Associations between childhood obesity and upper and lower extremity injuries
Authors: Adams Annette L , Kessler Jeffrey I , Deramerian Krikor , Smith Ning , Black Mary Helen , Porter Amy H , Jacobsen Steven J , Koebnick Corinna 
Published: July 2012

ObjectivesTo estimate the overall and age-specific associations between obesity and extremity musculoskeletal injuries and pain in children.MethodsThis cross-sectional study used information from electronic medical records of 913 178 patients aged 2–19 years enrolled in an integrated health plan in the period 2007–2009. Children were classified as underweight, normal weight, overweight, or moderately/extremely obese and, using multivariable logistic regression methods, the associations between weight class and diagnosis of upper or lower extremity fractures, sprains, dislocations and pain were calculated.ResultsOverweight (OR 1.18, 95% CI 1.15 to 1.20), moderately obese (OR 1.24, 95% CI 1.20 to 1.27) and extremely obese (OR 1.34, 95% CI 1.30 to 1.39) children had statistically significantly higher odds of lower extremity injuries/pain compared to normal weight, adjusted for sex, age, race/ethnicity and insurance status. Age-stratified analyses yielded similar results. No consistent association was observed between body mass index and injuries/pain of the upper extremities.ConclusionsGreater body mass index is associated with increased odds of lower extremity injuries and pain issues. Because the benefits of physical activity may still outweigh the risk of injury, attention should be paid to injury prevention strategies for these children at greater risk for lower extremity injuries.
AngioSuite: an accurate method to calculate aneurysm volumes and packing densities
Authors: Woodward Keith , Forsberg David A 
Published: July 2012

ObjectiveAngioSuite was developed to allow the easy and accurate calculation of cerebral aneurysm volumes and packing densities. The present study was undertaken to validate its accuracy.MethodsMathematical models and software were created to facilitate more complex aneurysm volume calculations than previously described three-dimensional geometric models. 20 phantom aneurysm clay models were created and analyzed (length, width, depth and volume) using angiographic mathematical modeling (AngioSuite), geometric modeling (AngioCalc) and three-dimensional volume reconstructions from the vendor's Leonardo workstation (Siemens).ResultsThe mean volumes of all phantoms analyzed by the AngioSuite system differed from true volumes by an average of 2.2%. Mean volumes of all phantoms analyzed by the AngioCalc system differed from true volumes by an average of 11.3%. Mean volumes obtained from the Leonardo workstation windowed for best appearance differed by an average of 5.18%.ConclusionsThe AngioSuite software system provides an accurate means of calculating aneurysm volumes. Typical packing densities (40% or less) are thus accurate within ±1%. Angiographic mathematical modeling with AngioSuite is more accurate than geometric modeling and three-dimensional volume reconstructions windowed for best appearance (Leonardo).
Multimodal endovascular management of acute ischemic stroke in patients over 75 years old is safe and effective
Authors: Ghobrial George M , Chalouhi Nohra , Rivers Lana , Witte Samantha , Davanzo Justin , Dalyai Richard , Gardecki Michelle L , Jabbour Pascal , Gonzalez Fernando , Dumont Aaron S , Rosenwasser Robert H , Tjoumakaris Stavropoula 
Published: July 2012

IntroductionGreater attention has been directed to endovascular recanalization of acute ischemic stroke in septuagenarians and above.TechniqueA retrospective chart review was conducted to include patients treated for acute ischemic stroke from 2006 to 2012. All patients underwent initial neurological assessment and non-contrast head CT. Patients treated from 2009 to 2012 additionally received emergent CT angiogram and CT perfusion. 51 patients met the clinical and radiographic criteria and underwent multimodal endovascular revascularization for acute ischemic events.ResultsAll patients underwent cerebral angiography and met angiographic criteria for endovascular thrombolysis. 34 patients (67%) were older than 80 years of age. 23 patients (45%) received intravenous tissue plasminogen activator prior to admission. Eight (16%) patients underwent stent placement after intra-arterial thrombolysis, 10 (20%) underwent balloon angioplasty and seven (14%) underwent both angioplasty and stent placement. 21 (41%) required only intra-arterial thrombolytics. An improvement in Thrombolysis in Myocardial Infarction score was noted in 34 patients (67%). The average modified Rankin Scale score on discharge was 3.9. Symptomatic intracranial hemorrhage occurred in three patients (6%); none required surgery. One patient (1.9%) had a postoperative retroperitoneal hematoma, which was managed conservatively. Two fatalities resulted from intraoperative vessel rupture (3.9%), with a combined morbidity and mortality of 27.5%.ConclusionsMultimodal endovascular recanalization of acute ischemic stroke is a relatively safe treatment option in patients older than 75 years of age. Careful patient selection by clinical and radiographic inclusion criteria is necessary for the successful management of stroke in this age group.
Composite faecal egg count reduction test to detect resistance to triclabendazole in Fasciola hepatica
Authors: Daniel R. , van Dijk J. , Jenkins T. , Akca A. , Mearns R. , Williams D. J. L. 
Published: July 2012

A faecal egg count reduction test, using composite samples, was developed in order to assess the efficacy of the flukicide, triclabendazole (TCBZ) on commercial sheep farms in England and Wales. First, a comparison between individual counts and composite counts was conducted using sheep on two farms with different levels of infection. Faecal samples were collected from 50 sheep on each farm at the time of TCBZ treatment and 21 days later. The results showed that a composite fluke egg count (CFEC) was as sensitive as using individual samples, and the test was subsequently validated on an additional 18 sheep farms. The pre‐ and post‐treatment CFECs using five composite samples were subjected to bootstrap analysis. The variance in fluke egg counts of composite samples was high, but analyses indicated that 20 individual samples analysed as two composites was as sensitive as using five composites. The two‐composite assay was evaluated on another five farms. On seven out of 25 farms sampled, egg counts either did not decrease significantly or increased following treatment, suggesting TCBZ resistance on these farms. This assay represents a practical field test that can be used in the first instance to evaluate the efficacy of TCBZ on sheep farms where resistance is suspected.