bluuebunny/crossref_metadata_2025_split huggingface dataset:
Type IV Pili in Gram-Positive Bacteria
Authors: Melville Stephen , Craig Lisa 
Published: September 2013

SUMMARY
Type IV pili (T4P) are surface-exposed fibers that mediate many functions in bacteria, including locomotion, adherence to host cells, DNA uptake (competence), and protein secretion and that can act as nanowires carrying electric current. T4P are composed of a polymerized protein, pilin, and their assembly apparatuses share protein homologs with type II secretion systems in eubacteria and the flagella of archaea. T4P are found throughout Gram-negative bacterial families and have been studied most extensively in certain model Gram-negative species. Recently, it was discovered that T4P systems are also widespread among Gram-positive species, in particular the clostridia. Since Gram-positive and Gram-negative bacteria have many differences in cell wall architecture and other features, it is remarkable how similar the T4P core proteins are between these organisms, yet there are many key and interesting differences to be found as well. In this review, we compare the two T4P systems and identify and discuss the features they have in common and where they differ to provide a very broad-based view of T4P systems across all eubacterial species.
Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines
Authors: Liévin-Le Moal Vanessa , Servin Alain L. 
Published: September 2013

SUMMARYHosts are protected from attack by potentially harmful enteric microorganisms, viruses, and parasites by the polarized fully differentiated epithelial cells that make up the epithelium, providing a physical and functional barrier. Enterovirulent bacteria interact with the epithelial polarized cells lining the intestinal barrier, and some invade the cells. A better understanding of the cross talk between enterovirulent bacteria and the polarized intestinal cells has resulted in the identification of essential enterovirulent bacterial structures and virulence gene products playing pivotal roles in pathogenesis. Cultured animal cell lines and cultured human nonintestinal, undifferentiated epithelial cells have been extensively used for understanding the mechanisms by which some human enterovirulent bacteria induce intestinal disorders. Human colon carcinoma cell lines which are able to express in culture the functional and structural characteristics of mature enterocytes and goblet cells have been established, mimicking structurally and functionally an intestinal epithelial barrier. Moreover, Caco-2-derived M-like cells have been established, mimicking the bacterial capture property of M cells of Peyer's patches. This review intends to analyze the cellular and molecular mechanisms of pathogenesis of human enterovirulent bacteria observed in infected cultured human colon carcinoma enterocyte-like HT-29 subpopulations, enterocyte-like Caco-2 and clone cells, the colonic T84 cell line, HT-29 mucus-secreting cell subpopulations, and Caco-2-derived M-like cells, including cell association, cell entry, intracellular lifestyle, structural lesions at the brush border, functional lesions in enterocytes and goblet cells, functional and structural lesions at the junctional domain, and host cellular defense responses.
Long-term benefit of hepatitis C therapy in a safety net hospital system: a cross-sectional study with median 5-year follow-up
Authors: Singal Amit G , Dharia Tushar D , Malet Peter F , Alqahtani Saleh , Zhang Song , Cuthbert Jennifer A 
Published: September 2013

ObjectivesTo demonstrate the survival benefit from sustained virological response (SVR) in a safety net hospital population with limited resources for hepatitis C virus (HCV) therapy.Design and settingWe conducted a retrospective study at an urban safety net hospital in the USA.Participants and intervention242 patients receiving standard HCV therapy between 2001 and 2006.Primary and secondary outcome measuresResponse rates, including SVR, were recorded for each patient. Univariate and multivariate analyses were performed to identify predictors of SVR and 5-year survival.ResultsA total of 242 eligible patients were treated. Treatment was completed in 197 (81%) patients, with 43 patients discontinuing therapy early—32 due to adverse events and 11 due to non-compliance. Complications on treatment were frequent, including three deaths. SVR was achieved in 83 patients (34%). On multivariate analysis, independent predictors of adecreasedlikelihood of achieving SVR included African–American race (OR 0.20, 95% CI 0.07 to 0.54), genotype 1 HCV infection (OR 0.25, 95% CI 0.13 to 0.50) and the presence of cirrhosis (OR 0.26, 95% CI 0.12 to 0.58). Survival was 98% in those achieving SVR (median follow-up 72 months) and 71% in non-responders and those discontinuing therapy (n=91, median known follow-up 65 and 36 months, respectively). On multivariate analysis, the only independent predictor of improved survival was SVR (HR 0.12, 95% CI 0.03 to 0.52). Both cirrhosis and hypoalbuminaemia were independent predictors of increased mortality.ConclusionsTreatment before histological cirrhosis develops, in combination with careful selection, may improve long-term outcomes without compromising other healthcare endeavours in safety net hospitals and areas with financial limitations.
Outcomes of transplantation of livers from donation after circulatory death donors in the UK: a cohort study
Authors: Callaghan Christopher J , Charman Susan C , Muiesan Paolo , Powell James J , Gimson Alexander E , van der Meulen Jan H P ,   on behalf of the UK Liver Transplant Audit
Published: September 2013

ObjectivesOutcomes of liver transplantations from donation after circulatory death (DCD) donors may be inferior to those achieved with donation after brain death (DBD) donors. The impact of using DCD donors is likely to depend on specific national practices. We compared risk-adjusted graft loss and recipient mortality after transplantation of DCD and DBD livers in the UK.DesignProspective cohort study. Multivariable Cox regression and propensity score matching were used to estimate risk-adjusted HR.Setting7 liver transplant centres in the National Health Service (NHS) hospitals in England and Scotland.ParticipantsAdults who received a first elective liver transplant between January 2005 and December 2010 who were identified in the UK Liver Transplant Audit.InterventionsTransplantation of DCD and DBD livers.OutcomesGraft loss and recipient mortality.ResultsIn total, 2572 liver transplants were identified with 352 (14%) from DCD donors. 3-year graft loss (95% CI) was higher with DCD livers (27.3%, 21.8% to 33.9%) than with DBD livers (18.2%, 16.4% to 20.2%). After adjustment with regression, HR for graft loss was 2.3 (1.7 to 3.0). Similarly, 3-year mortality was higher with DCD livers (19.4%, 14.5% to 25.6%) than with DBD livers (14.1%, 12.5% to 16.0%) with an adjusted HR of 2.0 (1.4 to 2.8). Propensity score matching gave similar results. Centre-specific adjusted HRs for graft loss and recipient mortality seemed to differ among transplant centres, although statistical evidence is weak (p value for interaction 0.08 and 0.24, respectively).ConclusionsGraft loss and recipient mortality were about twice as high with DCD livers as with DBD livers in the UK. Outcomes after DCD liver transplantation may vary between centres. These results should inform policies for the use of DCD livers.
The mortality and cancer experience of New Zealand Vietnam war veterans: a cohort study
Authors: McBride David , Cox Brian , Broughton John , Tong Darryl 
Published: September 2013

ObjectivesThe aim was to observe the patterns of mortality and cancer incidence in New Zealand Vietnam veterans. The objectives were to assess whether the patterns of disease observed were consistent with those associated with military service in Vietnam, and similar to the patterns identified in other groups of Vietnam veterans.DesignA historical cohort study.SettingVeterans, identified from service records, with Vietnam service between 1964 and 1972.ParticipantsOf the 3322 survivors of Vietnam service, we followed up 2783 (84%).Outcome measuresStandardised mortality and incidence ratios (SMRs and SIRs, respectively) were calculated based on the number of deaths and cancer registrations observed, those expected being based on New Zealand national rates.ResultsAll cause mortality was significantly reduced (SMR 0.85, 95% CI 0.77 to 0.94) and cancer incidence non-significantly increased (SIR 1.06, 95% CI 0.97 to 1.16). The risk of mortality from cancers of the head and neck (SMR 2.20, 95% CI 1.09 to 3.93); oral cavity pharynx and larynx (SMR 2.13, 95% CI 1.06 to 3.81) and the incidence of chronic lymphatic leukaemia (CLL) (SIR 1.91, 95% CI 1.04 to 3.20) were, however, significantly increased. Other lymphohaematopoietic disorders, specifically multiple myeloma and Hodgkin disease, showed non-significant mortality excesses, reflected by a similar increase in incidence.ConclusionsService in the Vietnam war was associated with defoliant herbicide exposure, including 2,4,5-trichlorophenoxyacetic acid, 2,4-dichlorophenoxyacetic acid, picloram and cacodylic acid. Subsequent reviews of mechanistic, animal and epidemiological evidence led to certain conditions being deemed compensable. The pattern of mortality and cancer incidence is not at odds with the list of compensable conditions and consistent with that found in Australian veterans serving in the same area of Vietnam, but also consistent with smoking and the healthy soldier effect. In common with the Australian experience, this is the only veterans group to show a significant excess of CLL.
Improving outcomes for patients with type 2 diabetes using general practice networks: a quality improvement project in east London
Authors: Hull Sally , Chowdhury Tahseen A , Mathur Rohini , Robson John 
Published: September 2013

BackgroundStructured diabetes care can improve outcomes and reduce risk of complications, but improving care in a deprived, ethnically diverse area can prove challenging. This report evaluates a system change to enhance diabetes care delivery in a primary care setting.MethodsAll 35 practices in one inner London Primary Care Trust were geographically grouped into eight networks of four to five practices, each supported by a network manager, clerical staff and an educational budget. A multidisciplinary team developed a ‘care package’ for type 2 diabetes management, with financial incentives based on network achievement of targets. Monthly electronic performance dashboards enabled networks to track and improve performance. Network multidisciplinary team meetings including the diabetic specialist team supported case management and education. Key measures for improvement included the number of diabetes care plans completed, proportion of patients attending for digital retinal screen and proportions of patients achieving a number of biomedical indices (blood pressure, cholesterol, glycated haemoglobin).ResultsBetween 2009 and 2012, completed care plans rose from 10% to 88%. The proportion of patients attending for digital retinal screen rose from 72% to 82.8%. The proportion of patients achieving a combination of blood pressure ≤140/80 mm Hg and cholesterol ≤4 mmol/L rose from 35.3% to 46.1%. Mean glycated haemoglobin dropped from 7.80% to 7.66% (62–60 mmol/mol).ConclusionsInvestment of financial, organisational and education resources into primary care practice networks can achieve clinically important improvements in diabetes care in deprived, ethnically diverse communities. This success is predicated on collaborative working between practices, purposively designed high-quality information on network performance and engagement between primary and secondary care clinicians.
Exploring the experiences of bereaved families involved in assisted suicide in Southern Switzerland: a qualitative study
Authors: Gamondi Claudia , Pott Murielle , Forbes Karen , Payne Sheila 
Published: September 2013

BackgroundIn Switzerland, helping with assisted suicide under certain conditions is not prosecuted. With approximately 300 cases annually, this leaves behind a large group of bereaved people where its consequences are mostly unknown. The study aimed to explore family involvement in decision making prior to assisted suicide, and to examine their ways of coping during the bereavement period.MethodsA qualitative interview study used the principles of Grounded Theory analysis. Eleven relatives of eight patients, who died in Southern Switzerland after assisted suicide, participated in semistructured interviews.ResultsThe large majority of family members faced moral dilemmas during the decision-making phase. Their respect for patient's autonomy was a key justification to resolve dilemmas. Two types of involvement were identified: categorised as ‘passive’ when the decision making was located with the patient, and ‘active’ when assisted suicide was proposed by the family member and/or the relative was involved in some way. The relatives reported feelings of isolation during and after assisted suicide. Family members reported fear of social stigma and did not openly disclose assisted suicide as the cause of death. None of those interviewed received formal psychological support.ConclusionsBereaved families express moral dilemmas, feelings of isolation and secrecy in the management of assisted suicide in Southern Switzerland. These features seem underestimated and not sufficiently recognised by the healthcare professionals. Management of assisted suicide requests should include consideration of family members’ needs, in addition to those of the patient.
The role of near-patient coeliac serology testing in the follow-up of patients with coeliac disease
Authors: George D A , Hui L L , Rattehalli D , Lovatt T , Perry I , Green M , Robinson K , Walters J R F , Brookes M J 
Published: September 2013

ObjectiveThis pilot study was undertaken to assess the validity and effectiveness of near-patient coeliac immunological testing, compared to standard laboratory immunological techniques, used in the context of dietician-led coeliac disease follow-up clinics.DesignThe study was designed in two phases, each assessing the near-patient test and standard laboratory immunological techniques. Phase 1 analysed stored serum samples; Phase 2 analysed whole blood from patients attending the dietician-led coeliac disease clinics.SettingPatients were recruited from New Cross Hospital, Wolverhampton (n=50), and Imperial College London (n=30), between March 2010 and February 2011.PatientsThose with a diagnosis of coeliac disease for greater than 12 months attending dietician-led coeliac disease clinics.InterventionsIn addition to whole blood taken for routine analysis, patients required a capillary finger-prick blood sample.Main outcome measureTo determine if the whole blood and serum near-patient test results were in correlation with outcomes of standard laboratory evaluation.ResultsPhase 1 demonstrated that the near-patient serum test had a sensitivity of 93.5% (95% CI 0.79% to 0.98%), specificity of 94.9% (0.83% to 0.99%), when compared to standard laboratory ELISA. Phase 2, involving patients whole blood, had a sensitivity of 77.8% (0.45% to 0.93%), and specificity of 100% (0.94% to 1%).ConclusionsThis pilot study has demonstrated that there appears to be a role for near-patient testing in coeliac disease, but further studies are recommended.
Ultrasensitive Detection of Unknown Colon Cancer-Initiating Mutations Using the Example of the Adenomatous Polyposis Coli Gene
Authors: Gerecke Christian , Mascher Conny , Gottschalk Uwe , Kleuser Burkhard , Scholtka Bettina 
Published: September 2013

Abstract
Detection of cancer precursors contributes to cancer prevention, for example, in the case of colorectal cancer. To record more patients early, ultrasensitive methods are required for the purpose of noninvasive precursor detection in body fluids. Our aim was to develop a method for enrichment and detection of known as well as unknown driver mutations in the Adenomatous polyposis coli (APC) gene. By coupled wild-type blocking (WTB) PCR and high-resolution melting (HRM), referred to as WTB-HRM, a minimum detection limit of 0.01% mutant in excess wild-type was achieved according to as little as 1 pg mutated DNA in the assay. The technique was applied to 80 tissue samples from patients with colorectal cancer (n = 17), adenomas (n = 50), serrated lesions (n = 8), and normal mucosa (n = 5). Any kind of known and unknown APC mutations (deletions, insertions, and base exchanges) being situated inside the mutation cluster region was distinguishable from wild-type DNA. Furthermore, by WTB-HRM, nearly twice as many carcinomas and 1.5 times more precursor lesions were identified to be mutated in APC, as compared with direct sequencing. By analyzing 31 associated stool DNA specimens all but one of the APC mutations could be recovered. Transferability of the WTB-HRM method to other genes was proven using the example of KRAS mutation analysis. In summary, WTB-HRM is a new approach for ultrasensitive detection of cancer-initiating mutations. In this sense, it appears especially applicable for noninvasive detection of colon cancer precursors in body fluids with excess wild-type DNA like stool. Cancer Prev Res; 6(9); 898–907. ©2013 AACR.
Therapeutic Synergy between microRNA and siRNA in Ovarian Cancer Treatment
Authors: Nishimura Masato , Jung Eun-Jung , Shah Maitri Y. , Lu Chunhua , Spizzo Riccardo , Shimizu Masayoshi , Han Hee Dong , Ivan Cristina , Rossi Simona , Zhang Xinna , Nicoloso Milena S. , Wu Sherry Y. , Almeida Maria Ines , Bottsford-Miller Justin , Pecot Chad V. , Zand Behrouz , Matsuo Koji , Shahzad Mian M. , Jennings Nicholas B. , Rodriguez-Aguayo Cristian , Lopez-Berestein Gabriel , Sood Anil K. , Calin George A. 
Published: September 2013

AbstractDevelopment of improved RNA interference–based strategies is of utmost clinical importance. Although siRNA-mediated silencing of EphA2, an ovarian cancer oncogene, results in reduction of tumor growth, we present evidence that additional inhibition of EphA2 by a microRNA (miRNA) further “boosts” its antitumor effects. We identified miR-520d-3p as a tumor suppressor upstream of EphA2, whose expression correlated with favorable outcomes in two independent patient cohorts comprising 647 patients. Restoration of miR-520d-3p prominently decreased EphA2 protein levels, and suppressed tumor growth and migration/invasion both in vitro and in vivo. Dual inhibition of EphA2 in vivo using 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) nanoliposomes loaded with miR-520d-3p and EphA2 siRNA showed synergistic antitumor efficiency and greater therapeutic efficacy than either monotherapy alone. This synergy is at least in part due to miR-520d-3p targeting EphB2, another Eph receptor. Our data emphasize the feasibility of combined miRNA–siRNA therapy, and will have broad implications for innovative gene silencing therapies for cancer and other diseases.Significance: This study addresses a new concept of RNA inhibition therapy by combining miRNA and siRNA in nanoliposomal particles to target oncogenic pathways altered in ovarian cancer. Combined targeting of the Eph pathway using EphA2-targeting siRNA and the tumor suppressor miR-520d-3p exhibits remarkable therapeutic synergy and enhanced tumor suppression in vitro and in vivo compared with either monotherapy alone. Cancer Discov; 3(11); 1302–15. ©2013 AACR.See related commentary by Kasinski and Slack, p. 1220This article is highlighted in the In This Issue feature, p. 1207
Cardiac Perforation From Implantable Cardioverter-Defibrillator Lead Placement
Authors: Hsu Jonathan C. , Varosy Paul D. , Bao Haikun , Dewland Thomas A. , Curtis Jeptha P. , Marcus Gregory M. 
Published: September 2013

Background—
Cardiac perforation is a feared complication of implantable cardioverter-defibrillator (ICD) lead implantation because of the potential for significant morbidity and mortality. Predictors of perforation and the severity of associated adverse events have not been well studied. We sought to identify predictors of cardiac perforation from ICD lead implantation and subsequent outcomes.

Methods and Results—

We studied 440 251 first-time ICD recipients in the ICD Registry implanted between January 2006 and September 2011. Using hierarchical multivariable logistic regression adjusting for patient, implanting physician, and hospital characteristics, we examined the predictors of perforation and the association of perforation with other major complications, length of stay, and in-hospital mortality. Cardiac perforation occurred in 625 patients (0.14%). After multivariable adjustment, older age, female sex, left bundle branch block, worsened heart failure class, higher left ventricular ejection fraction, and non–single-chamber ICD implant were associated with a greater odds of perforation. Conversely, atrial fibrillation, diabetes mellitus, previous cardiac bypass surgery, and higher implanter procedural volume were associated with a lower odds of perforation (all
P
<0.05). After adjustment, ICD recipients with perforation had greater odds of other associated major complications (odds ratio, 27.5; 95% confidence interval, 19.9–38.0;
P
<0.0001), postprocedural hospital stays >3 days (odds ratio, 16.3; 95% confidence interval, 13.7–19.4;
P
<0.0001), and in-hospital death (odds ratio, 17.7; 95% confidence interval, 12.2–25.6;
P
<0.0001).

Conclusions—
In a large population of ICD recipients, specific patient and implanter characteristics predicted cardiac perforation risk. Cardiac perforation was associated with a substantially increased risk of other major complications, prolonged hospital stays, and death.
High-Density Lipoprotein Cholesterol, Size, Particle Number, and Residual Vascular Risk After Potent Statin Therapy
Authors: Mora Samia , Glynn Robert J. , Ridker Paul M 
Published: September 2013

Background—
Chemically measured high-density lipoprotein cholesterol (HDL-C) may not be the best clinical measure of HDL. Little is known about alternative HDL measures such as HDL size or particle number (HDL-P) as determinants of residual risk after potent statin therapy.

Methods and Results—

In Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), HDL size and HDL-P were measured by nuclear magnetic resonance spectroscopy, and HDL-C and apolipoprotein A-I (apoA-I) were chemically assayed in 10 886 participants without cardiovascular disease (CVD) before and after random allocation to rosuvastatin 20 mg/d or placebo. Levels were examined with first CVD (n=234). HDL-P correlated better with apoA-I (Spearman
r
=0.69,
P
<0.0001) than with HDL-C (
r
=0.55,
P
<0.0001). Rosuvastatin lowered low-density lipoprotein cholesterol (49%) and raised HDL-C (6.1%), apoA-I (2.1%), HDL-P (3.8%), and HDL size (1.2%); all
P
<0.0001. Among placebo-allocated individuals, on-treatment HDL-C, apoA-I, and HDL-P had similar inverse associations with CVD (risk factor–adjusted hazard ratio and 95% confidence interval per 1 standard deviation: 0.79 [0.63–0.98], 0.75 [0.62–0.92], and 0.81 [0.67–0.97], respectively). Among rosuvastatin-allocated individuals, on-treatment HDL-P had a statistically significant and somewhat stronger association with CVD (0.73, 0.57–0.93,
P
=0.01) than HDL-C (0.82, 0.63–1.08,
P
=0.16) or apoA-I (0.86, 0.67–1.10,
P
=0.22). Among rosuvastatin-allocated individuals, on-treatment HDL-P remained significant (0.72, 0.53–0.97,
P
=0.03) after additionally adjusting for HDL-C. In risk factor–adjusted models, HDL size showed no significant association with CVD.

Conclusions—
In the setting of potent statin therapy, HDL particle number may be a better marker of residual risk than chemically measured HDL-C or apoA-I. This has potential implications for evaluating novel therapies targeting HDL.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00239681.