bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unusual accelerated rate of deletions and insertions in toxin genes in the venom glands of the pygmy copperhead (Austrelaps labialis) from kangaroo island
Authors: Doley Robin , Tram Nguyen Ngoc Bao , Reza Md Abu , Kini R Manjunatha 
Published: February 2008

Abstract

Background
Toxin profiling helps in cataloguing the toxin present in the venom as well as in searching for novel toxins. The former helps in understanding potential pharmacological profile of the venom and evolution of toxins, while the latter contributes to understanding of novel mechanisms of toxicity and provide new research tools or prototypes of therapeutic agents.

Results
The pygmy copperhead (Austrelaps labialis) is one of the less studied species. In this present study, an attempt has been made to describe the toxin profile of A. labialis from Kangaroo Island using the cDNA library of its venom glands. We sequenced 658 clones which represent the common families of toxin genes present in snake venom. They include (a) putative long-chain and short-chain neurotoxins, (b) phospholipase A2, (c) Kunitz-type protease inhibitor, (d) CRISPs, (e) C-type lectins and (f) Metalloproteases. In addition, we have also identified a novel protein with two Kunitz-type domains in tandem similar to bikunin.

Conclusion
Interestingly, the cDNA library reveals that most of the toxin families (17 out of 43 toxin genes; ~40%) have truncated transcripts due to insertion or deletion of nucleotides. These truncated products might not be functionally active proteins. However, cellular trancripts from the same venom glands are not affected. This unusual higher rate of deletion and insertion of nucleotide in toxin genes may be responsible for the lower toxicity of A. labialis venom of Kangroo Island and have significant effect on evolution of toxin genes.
Molecular evolution and functional divergence of the bestrophin protein family
Authors: Milenkovic Vladimir M , Langmann Thomas , Schreiber Rainer , Kunzelmann Karl , Weber Bernhard HF 
Published: February 2008

Abstract

Background
Mutations in human bestrophin 1 are associated with at least three autosomal-dominant macular dystrophies including Best disease, adult onset vitelliform macular dystrophy and autosomal dominant vitreo-retinochoroidopathy. The protein is integral to the membrane and is likely involved in Ca2+-dependent transport of chloride ions across cellular membranes. Bestrophin 1 together with its three homologues forms a phylogenetically highly conserved family of proteins.

Results
A bioinformatics study was performed to investigate the phylogenetic relationship among the bestrophin family members and to statistically evaluate sequence conservation and functional divergence. Phylogenetic tree assembly with all available eukaryotic bestrophin sequences suggests gene duplication events in the lineage leading to the vertebrates. A common N-terminal topology which includes four highly conserved transmembrane domains is shared by the members of the four paralogous groups of vertebrate bestrophins and has been constrained by purifying selection. Pairwise comparison shows that altered functional constraints have occurred at specific amino acid positions after phylogenetic diversification of the paralogues. Most notably, significant functional divergence was found between bestrophin 4 and the other family members, as well as between bestrophin 2 and bestrophin 3. Site-specific profiles were established by posterior probability analysis revealing significantly divergent clusters mainly in two hydrophilic loops and a region immediately adjacent to the last predicted transmembrane domain. Strikingly, codons 279 and 347 of human bestrophin 4 reveal high divergence when compared to the paralogous positions strongly indicating the functional importance of these residues for the bestrophin 4 protein. None of the functionally divergent amino acids were found to reside within obvious sequences patterns or motifs.

Conclusion
Our study highlights the molecular evolution of the bestrophin family of transmembrane proteins and indicates amino acid residues likely relevant for distinct functional properties of the paralogues. These findings may provide a starting point for further experimental verifications.
Annotation and analysis of a large cuticular protein family with the R&R Consensus in Anopheles gambiae
Authors: Cornman R Scott , Togawa Toru , Dunn W Augustine , He Ningjia , Emmons Aaron C , Willis Judith H 
Published: February 2008

Abstract

Background
The most abundant family of insect cuticular proteins, the CPR family, is recognized by the R&R Consensus, a domain of about 64 amino acids that binds to chitin and is present throughout arthropods. Several species have now been shown to have more than 100 CPR genes, inviting speculation as to the functional importance of this large number and diversity.

Results
We have identified 156 genes in Anopheles gambiae that code for putative cuticular proteins in this CPR family, over 1% of the total number of predicted genes in this species. Annotation was verified using several criteria including identification of TATA boxes, INRs, and DPEs plus support from proteomic and gene expression analyses. Two previously recognized CPR classes, RR-1 and RR-2, form separate, well-supported clades with the exception of a small set of genes with long branches whose relationships are poorly resolved. Several of these outliers have clear orthologs in other species. Although both clades are under purifying selection, the RR-1 variant of the R&R Consensus is evolving at twice the rate of the RR-2 variant and is structurally more labile. In contrast, the regions flanking the R&R Consensus have diversified in amino-acid composition to a much greater extent in RR-2 genes compared with RR-1 genes. Many genes are found in compact tandem arrays that may include similar or dissimilar genes but always include just one of the two classes. Tandem arrays of RR-2 genes frequently contain subsets of genes coding for highly similar proteins (sequence clusters). Properties of the proteins indicated that each cluster may serve a distinct function in the cuticle.

Conclusion
The complete annotation of this large gene family provides insight on the mechanisms of gene family evolution and clues about the need for so many CPR genes. These data also should assist annotation of other Anopheles genes.
The United States and Canada as a coupled epidemiological system: An example from hepatitis A
Authors: Amariei Raluca , Willms Allan R , Bauch Chris T 
Published: February 2008

AbstractBackgroundHepatitis A (HA) is a low-incidence, non-endemic disease in Canada and the United States (US). However, a large difference in HA incidence between Canada and HA-endemic countries has made travel an important contributor to hepatitis A prevalence in Canada. There is also a (smaller) incidence differential between Canada and the US. Although the US has only moderately higher HA incidence, the volume of travel by Canadians to the US is many times higher than travel volume to endemic countries. Hence, travel to the US may constitute a source of low to moderate risk for Canadian travelers. To our knowledge, travel to the US has never been included as a potential risk factor for HA infection in Canadian epidemiologic analyses. The objective of this study was to use dynamic models to investigate the possible effects on hepatitis A incidence in Canada due to (1) implementing vaccination in the US, and (2) varying the volume of travel by Canadians to the US.MethodsWe developed and analyzed age-structured compartmental models for the transmission and vaccination of hepatitis A, for both Canada and the US. Models were parameterized using data on seroprevalence, case reporting, and travel patterns. The potential effect of hepatitis A prevalence in the US on hepatitis A prevalence in Canada was captured through a term representing infection of Canadians due to travel in the US.ResultsThe model suggests that approximately 22% of HA cases in Canada in the mid 1990s may have been attributable to travel to the US. A universal vaccination programme that attained 70% coverage in young children in the US in the mid 1990s could have reduced Canadian incidence by 21% within 5 years.ConclusionSince not all necessary data were available to parameterize the model, the results should be considered exploratory. However, the analysis shows that, under plausible assumptions, the US may be more important for determining HA prevalence in Canada than is currently supposed. As international travel continues to grow, making vaccination policies ever more relevant to populations beyond a country's borders, such multi-country models will most likely come into wider use as predictive aids for policy development.
A role for subchondral bone changes in the process of osteoarthritis; a micro-CT study of two canine models
Authors: Sniekers Yvonne H , Intema Femke , Lafeber Floris PJG , van Osch Gerjo JVM , van Leeuwen Johannes PTM , Weinans Harrie , Mastbergen Simon C 
Published: February 2008

Abstract

Background
This study evaluates changes in peri-articular bone in two canine models for osteoarthritis: the groove model and the anterior cruciate ligament transection (ACLT) model.

Methods
Evaluation was performed at 10 and 20 weeks post-surgery and in addition a 3-weeks time point was studied for the groove model. Cartilage was analysed, and architecture of the subchondral plate and trabecular bone of epiphyses was quantified using micro-CT.

Results
At 10 and 20 weeks cartilage histology and biochemistry demonstrated characteristic features of osteoarthritis in both models (very mild changes at 3 weeks). The groove model presented osteophytes only at 20 weeks, whereas the ACLT model showed osteophytes already at 10 weeks. Trabecular bone changes in the groove model were small and not consistent. This contrasts the ACLT model in which bone volume fraction was clearly reduced at 10 and 20 weeks (15–20%). However, changes in metaphyseal bone indicate unloading in the ACLT model, not in the groove model. For both models the subchondral plate thickness was strongly reduced (25–40%) and plate porosity was strongly increased (25–85%) at all time points studied.

Conclusion
These findings show differential regulation of subchondral trabecular bone in the groove and ACLT model, with mild changes in the groove model and more severe changes in the ACLT model. In the ACLT model, part of these changes may be explained by unloading of the treated leg. In contrast, subchondral plate thinning and increased porosity were very consistent in both models, independent of loading conditions, indicating that this thinning is an early response in the osteoarthritis process.
Immunologic activation of human syncytiotrophoblast by Plasmodium falciparum
Authors: Lucchi Naomi W , Peterson David S , Moore Julie M 
Published: February 2008

AbstractBackgroundMalaria during pregnancy is characterized by the sequestration of malaria-infected red blood cells (iRBC) in the intervillous spaces of the placenta, often accompanied by the infiltration of maternal mononuclear cells, causing substantial maternal and foetal/infant morbidity. The iRBC bind to receptors expressed by the syncytiotrophoblast (ST). How ST responds to this interaction remains poorly understood. Because it is known that ST is immunoactive and can respond to infectious agents, the consequences of this ST-iRBC interaction should be investigated.MethodsAn in vitro system was used to assess the biochemical and immunological changes induced in ST by ST-adherent iRBCs. Changes in ST mitogen-activated protein kinase (MAPK) activation were assessed by immunoblotting and mRNA expression levels of selected cytokine and chemokines in primary ST bound by iRBC were determined using real-time, reverse transcription PCR. In addition, secreted cytokine and chemokine proteins were assayed by standard ELISA, and chemotaxis of PBMC was assessed using a two-chamber assay system.ResultsFollowing iRBC/ST interaction, ST C-Jun N-terminal kinase 1 (JNK1) was activated and modest increases in the mRNA expression of TGF-β and IL-8/CXCL8 were observed. In addition, this interaction increased secretion of MIF and MIP-1α/CCL3 by ST and induced migration of PBMC towards iRBC-stimulated ST.ConclusionResults from this study provide the first evidence that ST participates in shaping the local immunological milieu and in the recruitment of maternal immune cells to the maternal blood space during placental malaria infection.
Post-traumatic soft tissue tumors: Case report and review of the literature a propos a Post-traumatic paraspinal desmoid tumor
Authors: Cohen Sarit , Ad-El Dean , Benjaminov Ofer , Gutman Haim 
Published: February 2008

AbstractBackgroundAntecedent trauma has been implicated in the causation of soft tissue tumors. Several criteria have been established to define a cause-and-effect relationship. We postulate possible mechanisms in the genesis of soft tissue tumors following antecedent traumatic injury.Case presentationWe present a 27-year-old woman with a paraspinal desmoid tumor, diagnosed 3-years following a motor vehicle accident. Literature is reviewed.ConclusionSoft tissue tumors arising at the site of previous trauma may be desmoids, pseudolipomas or rarely, other soft tissue growths. The cause-and-effect issue of desmoid or other soft tissue tumors goes beyond their diagnosis and treatment. Surgeons should be acquainted with this diagnostic entity as it may also involve questions of longer follow-up and compensation and disability privileges.
A study to assess changes in myocardial perfusion after treatment with spinal cord stimulation and percutaneous myocardial laser revascularisation; data from a randomised trial
Authors: Khan Sadia N , McNab Duncan C , Sharples Linda D , Freeman Carol J , Hardy Ian , Stone David L , Schofield Peter M 
Published: February 2008

Abstract

Background
Spinal cord stimulation (SCS) and percutaneous myocardial laser revascularisation (PMR) are treatment modalities used to treat refractory angina pectoris, with the major aim of such treatment being the relief of disabling symptoms. This study compared the change in myocardial perfusion following SCS and PMR treatment.

Methods
Subjects with Canadian Cardiovascular Society class 3/4 angina and reversible perfusion defects as assessed by single-photon emission computed tomographic myocardial perfusion scintigraphy were randomised to SCS (34) or PMR (34). 28 subjects in each group underwent repeat myocardial perfusion imaging 12 months post intervention. Visual scoring of perfusion images was performed using a 20-segment model and a scale of 0 to 4.

Results
The mean (standard deviation) baseline summed rest score (SRS) and stress scores (SSS) were 4.6 (5.7) and 13.6 (9.0) in the PMR group and 6.1 (7.4) and 16.8 (11.6) in the SCS group. At 12 months, SRS was 5.5 (6.0) and SSS 15.3 (11.3) in the PMR group and 6.9 (8.2) and 15.1 (10.9) in the SCS group. There was no significant difference between the two treatment groups adjusted for baseline (p = 1.0 for SRS, p = 0.29 for SSS).

Conclusion
There was no significant difference in myocardial perfusion one year post treatment with SCS or PMR.
Intensive insulin therapy and mortality in critically ill patients
Authors: Treggiari Miriam M , Karir Veena , Yanez N David , Weiss Noel S , Daniel Stephen , Deem Steven A 
Published: February 2008

Abstract
Introduction
Intensive insulin therapy (IIT) with tight glycemic control may reduce mortality and morbidity in critically ill patients and has been widely adopted in practice throughout the world. However, there is only one randomized controlled trial showing unequivocal benefit to this approach and that study population was dominated by post-cardiac surgery patients. We aimed to determine the association between IIT and mortality in a mixed population of critically ill patients.

Methods
We conducted a cohort study comparing three consecutive time periods before and after IIT protocol implementation in a Level 1 trauma center: period I (no protocol); period II, target glucose 80 to 130 mg/dL; and period III, target glucose 80 to 110 mg/dL. Subjects were 10,456 patients admitted to intensive care units (ICUs) between 1 March 2001 and 28 February 2005. The main study endpoints were ICU and hospital mortality, Sequential Organ Failure Assessment score, and occurrence of hypoglycemia. Multivariable regression analysis was used to evaluate mortality and organ dysfunction during periods II and III relative to period I.

Results
Insulin administration increased over time (9% period I, 25% period II, and 42% period III). Nonetheless, patients in period III had a tendency toward higher adjusted hospital mortality (odds ratio [OR] 1.15, 95% confidence interval [CI] 0.98, 1.35) than patients in period I. Excess hospital mortality in period III was present primarily in patients with an ICU length of stay of 3 days or less (OR 1.47, 95% CI 1.11, 1.93 There was an approximately fourfold increase in the incidence of hypoglycemia from periods I to III.

Conclusion
A policy of IIT in a group of ICUs from a single institution was not associated with a decrease in hospital mortality. These results, combined with the findings from several recent randomized trials, suggest that further study is needed prior to widespread implementation of IIT in critically ill patients.
Predictors of employment for people with severe mental illness: results of an international six-centre randomised controlled trial
Authors: Catty Jocelyn , Lissouba Pascale , White Sarah , Becker Thomas , Drake Robert E. , Fioritti Angelo , Knapp Martin , Lauber Christoph , Rössler Wulf , Tomov Toma , van Busschbach Jooske , Wiersma Durk , Burns Tom ,   EQOLISE Group
Published: February 2008

BackgroundAn international six-centre randomised controlled trial comparing individual placement and support (IPS) with usual vocational rehabilitation for people with serious mental illness found IPS to be more effective for all vocational outcomes.AimsTo determine which patients with severe mental illness do well in vocational services and which process and service factors are associated with better outcomes.MethodPatient characteristics and early process variables were tested as predictors of employment outcomes. Service characteristics were explored as predictors of the effectiveness of IPS.ResultsPatients with previous work history, fewer met social needs and better relationships with their vocational workers were more likely to obtain employment and work for longer. Remission and swifter service uptake were associated with working more. Having an IPS service closer to the original IPS model was the only service characteristic associated with greater effectiveness.ConclusionsThe IPS service was found to be more effective for all vocational outcomes. In addition, maintaining high IPS fidelity and targeting relational skills would be a valuable focus for all vocational interventions, leading to improved employment outcomes. Motivation to find work may be decreased by satisfaction with current life circumstances.
Audit of advice on driving following hospitalisation for an acute psychotic episode
Authors: Orr Eilidh M. , Elworthy Timothy S. E. 
Published: February 2008

Aims and MethodPsychiatrists are expected to follow guidelines in relation to patients' responsibilities regarding driving. In this study we reviewed advice on driving recorded for patients discharged from hospital following an acute psychotic episode. Guidelines on appropriate advice were then sent to all medical staff looking after in-patients.ResultsThe first cycle of the audit included 48 patients. No advice was recorded. The second cycle included 70 patients. Advice was recorded for 8 patients. Six of these patients received a standard discharge letter with a prompt for ‘driving advice’.Clinical ImplicationsIn contrast to current guidelines, advice regarding driving is not routinely given to patients with an acute psychotic episode. A standard discharge letter with prompts on driving may improve adherence to guidelines.
Shared care for treatment of opioid dependence and the new General Medical Services contract
Authors: Felice Anna Marie , Kouimtsidis Christos 
Published: February 2008

Aims and MethodsAn audit of clients in specialist and shared care services was undertaken in 2003 and in 2005 to investigate the capacity, quality of prescribed medication and profile of clients, and to assess the impact of the new General Medical Services contract on drug misuse treatment.ResultsCapacity in specialist services increased by 55% from 2003 to 2005, but not in shared care, and type and dosage of prescribed medication improved for shared care. Profile of clients suggests that stable clients are treated within shared care.Clinical ImplicationsAttention should be given in training general practitioners to provide shared care treatment, increasing the number of clients accepted in shared care, and considering new treatment models.
Patient characteristics and clinical activities at a British military department of community mental health
Authors: Gould Matthew , Sharpley John , Greenberg Neil 
Published: February 2008

Aims and MethodTo describe patient characteristics and clinical activities at a British military department of community mental health (DCMH). Data were drawn from a clinical database over a 1-year period (n=409).ResultsMean age was 29 years, 50% were single and 76% were from the junior ranks. Women were over-represented compared with the wider military population. Mean length of service prior to presentation was 5 years. The main presenting problem was alcohol misuse (33%) followed by depression (19%). Twenty-five per cent were referred for psychotherapy and 68% returned to full employment after treatment.Clinical ImplicationsPatient characteristics of those treated at a DCMH differ from those in the wider military. An out-patient occupational mental health service returns a substantial number of patients to occupational fitness within the Armed Forces.
A survey of in-patient and out-patient antipsychotic prescriptions in Hong Kong
Authors: Hung Gabriel B. K. , Cheung H. K. 
Published: February 2008

Aims and MethodAntipsychotic prescriptions were analysed for a large sample of psychiatric in-patients and out-patients in Hong Kong. Case notes for patients receiving high doses were reviewed and compared with the most recent consensus statement issued by the Royal College of Psychiatrists.ResultsDemographic and prescription data were obtained from 1254 in-patients and 19 986 out-patients. Antipsychotic medications were prescribed to 1129 in-patients and 7520 out-patients, with 9.2% of in-patients and 1.8% of out-patients receiving a high dose. Almost all case notes failed to record the clinical indications for high-dose prescribing or that the patient had been informed. Electrocardiograms were performed in a very small proportion of patients receiving a high dose.Clinical ImplicationsLow levels of adherence to established guidelines for high-dose antipsychotic prescription were found in this study, with clinical and medico-legal implications. The results of this study highlight the need for staff education and regular audit of antipsychotic doses in the in-patient and out-patient setting.