bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the Regulated Transcriptome of Neisseria meningitidis in Human Blood Using a Tiling Array
Authors: Del Tordello Elena , Bottini Silvia , Muzzi Alessandro , Serruto Davide 
Published: September 2012

ABSTRACTNeisseria meningitidisis the major cause of septicemia and meningococcal meningitis. During the course of infection, the bacterium must adapt to different host environments as a crucial factor for survival and dissemination; in particular, one of the crucial factors inN. meningitidispathogenesis is the ability to grow and survive in human blood. We recently showed thatN. meningitidisalters the expression of 30% of the open reading frames (ORFs) of the genome during incubation in human whole blood and suggested the presence of fine regulation at the gene expression level in order to control this step of pathogenesis. In this work, we used a customized tiling oligonucleotide microarray to define the changes in the whole transcriptional profile ofN. meningitidisin a time course experiment ofex vivobacteremia by incubating bacteria in human whole blood and then recovering RNA at different time points. The application of a newly developed bioinformatic tool to the tiling array data set allowed the identification of new transcripts—small intergenic RNAs,cis-encoded antisense RNAs, mRNAs with extended 5′ and 3′ untranslated regions (UTRs), and operons—differentially expressed in human blood. Here, we report a panel of expressed small RNAs, some of which can potentially regulate genes involved in bacterial metabolism, and we show, for the first time inN. meningitidis, extensive antisense transcription activity. This analysis suggests the presence of a circuit of regulatory RNA elements used byN. meningitidisto adapt to proliferate in human blood that is worthy of further investigation.
Novel High-Molecular-Weight, R-Type Bacteriocins of Clostridium difficile
Authors: Gebhart Dana , Williams Steven R. , Bishop-Lilly Kimberly A. , Govoni Gregory R. , Willner Kristin M. , Butani Amy , Sozhamannan Shanmuga , Martin David , Fortier Louis-Charles , Scholl Dean 
Published: September 2012

ABSTRACT

Clostridium difficile
causes one of the leading nosocomial infections in developed countries, and therapeutic choices are limited. Some strains of
C. difficile
produce phage tail-like particles upon induction of the SOS response. These particles have bactericidal activity against other
C. difficile
strains and can therefore be classified as bacteriocins, similar to the R-type pyocins of
Pseudomonas aeruginosa
. These R-type bacteriocin particles, which have been purified from different strains, each have a different
C. difficile
-killing spectrum, with no one bacteriocin killing all
C. difficile
isolates tested. We have identified the genetic locus of these “diffocins” (open reading frames 1359 to 1376) and have found them to be common among the species. The entire diffocin genetic locus of more than 20 kb was cloned and expressed in
Bacillus subtilis
, and this resulted in production of bactericidal particles. One of the interesting features of these particles is a very large structural protein of ∼200 kDa, the product of gene 1374. This large protein determines the killing spectrum of the particles and is likely the receptor-binding protein. Diffocins may provide an alternate bactericidal agent to prevent or treat infections and to decolonize individuals who are asymptomatic carriers.
Streptococcus pneumoniae Uses Glutathione To Defend against Oxidative Stress and Metal Ion Toxicity
Authors: Potter Adam J. , Trappetti Claudia , Paton James C. 
Published: September 2012

ABSTRACT

The thiol-containing tripeptide glutathione is an important cellular constituent of many eukaryotic and prokaryotic cells. In addition to its disulfide reductase activity, glutathione is known to protect cells from many forms of physiological stress. This report represents the first investigation into the role of glutathione in the Gram-positive pathogen
Streptococcus pneumoniae
. We demonstrate that pneumococci import extracellular glutathione using the ABC transporter substrate binding protein GshT. Mutation of
gshT
and the gene encoding glutathione reductase (
gor
) increases pneumococcal sensitivity to the superoxide generating compound paraquat, illustrating the importance of glutathione utilization in pneumococcal oxidative stress resistance. In addition, the
gshT
and
gor
mutant strains are hypersensitive to challenge with the divalent metal ions copper, cadmium, and zinc. The importance of glutathione utilization in pneumococcal colonization and invasion of the host is demonstrated by the attenuated phenotype of the
gshT
mutant strain in a mouse model of infection.
Greater trochanteric pain syndrome: defining the clinical syndrome
Authors: Fearon Angela M , Scarvell Jennie M , Neeman Terry , Cook Jill L , Cormick Wes , Smith Paul N 
Published: September 2012

BackgroundEffective treatment of hip pain improves population health and quality of life. Accurate differential diagnosis is fundamental to effective treatment. The diagnostic criteria for one common hip problem, greater trochanteric pain syndrome (GTPS) have not been well defined.PurposeTo define the clinical presentation of GTPS.MethodsForty-one people with GTPS, 20 with hip osteoarthritis (OA), and 23 age-matched and sex-matched asymptomatic participants (ASC) were recruited. Inclusion and exclusion criteria ensured mutually exclusive groups. Assessment: the Harris hip score (HHS), a battery of clinical tests, and single leg stance (SLS). Participants identified the site of reproduced pain. Analysis: Fisher's exact test, analysis of variance (ANOVA) informed recursive partitioning to develop two classification trees.ResultsMaximum walking distance and the ability to manipulate shoes and socks were the only HHS domains to differentiate GTPS from OA (ANOVA: p=0.010 and <0.001); OR (95% CI) of 3.47 (1.09 to 10.93) and 0.06 (0.00 to 0.26), respectively. The lateral hip pain (LHP) classification tree: (dichotomous LHP associated with a flexion abduction external rotation (FABER) test) had a mean (SE) sensitivity and specificity of 0.81 (0.019) and 0.82 (0.044), respectively. A non-specific hip pain classification tree had a mean (SE) sensitivity and specificity of 0.78 (0.058) and 0.28 (0.080).ConclusionsPatients with LHP in the absence of difficulty with manipulating shoes and socks, together with pain on palpation of the greater trochanter and LHP with a FABER test are likely to have GTPS.
Musculoskeletal disorders among municipal solid waste collectors in Mansoura, Egypt: a cross-sectional study
Authors: Abou-ElWafa Hala Samir , El-Bestar Sohair Fouad , El-Gilany Abdel-Hady , Awad Ehab El-Sayed 
Published: September 2012

ObjectiveTo assess the percentage of musculoskeletal complaints and their possible risk factors among municipal solid waste (MSW) collectors.DesignA descriptive cross-sectional study with a comparison group.SettingPrimary level of care, at the Western Municipality of Mansoura City, Egypt.ParticipantsA total of 160 male MSW collectors fulfilled the eligibility criteria and 120 of them participated in the study (response rate of 75%). The inclusion criteria were permanent or temporary solid waste collectors employed for 1 year or more. A comparison group of 110 male service workers at the Faculty of Medicine, Mansoura University, comparable to MSW collectors in most of the variables.OutcomeThe percentage of musculoskeletal disorders (MSDs) among collectors, their risk factors (socio-demographic, psychosocial, physical), and the independent risk factors for having the disorders.ResultsThe percentage of musculoskeletal complaints during the past 12 months was higher among MSW collectors (60.8%) than the comparison group (43.6%). Low back was the most frequently affected body region among MSW collectors. The differences in the distribution of musculoskeletal complaints between the two groups were statistically significant for the neck and hip/thigh regions. Logistic regression analysis revealed that the independent risk factors for musculoskeletal symptoms among MSW collectors were the longer duration of employment (OR=0.4, 95% CI=0.1 to 0.9); low decision latitude (OR=0.3, 95% CI=0.1 to 0.7); lifting, pulling; pushing/carrying loads >20 kg (OR=5.5, 95% CI=1.8 to 17.0) and walking for long periods of time (OR=2.6, 95% CI=1.1 to 6.6).ConclusionsMusculoskeletal complaints are highly prevalent among MSW collectors which require engineering, medical and legislative measures. We suggest further research in the interventions that could reduce the high percentage among collectors.
Reducing postnatal depression, anxiety and stress using an infant sleep intervention
Authors: Symon Brian , Bammann Michael , Crichton Georgina , Lowings Chris , Tucsok James 
Published: September 2012

ObjectiveTo examine the psychological well-being of mothers following participation in a behavioural modification programme previously shown to improve infant sleep.Design, setting and participantsA 45 min consultation with either a general practitioner (GP) or trained nurse providing verbal and written information describing sleep physiology in infants and strategies to improve infant sleep. Eighty mothers of infants 6−12 months of age with established infant sleep problems at a single general practice, Adelaide, South Australia.Main outcome measuresThe Depression Anxiety Stress Scale 21 (DASS21) immediately prior to the first consultation and again at follow-up approximately 3 weeks later. The number of infant nocturnal awakenings requiring parental support was also reported by mothers on both occasions.ResultsAll measures of maternal well-being and infant nocturnal awakenings improved significantly. The mean number of maximum nocturnal awakenings decreased from 5.0 to 0.5 (mean difference 4.4, 95% CI 3.4 to 5.5). All measures of DASS21 improved significantly. The mean total DASS21 decreased from 29.1 to 14.9 (mean decrease 14.2, 95% CI 10.2 to 18.2); mean depression decreased from 7.9 to 2.8 (mean difference 5.2, 95% CI 3.7 to 6.7); mean anxiety decreased from 4.6 to 2.6 (mean difference 2.0, 95% CI 0.7 to 3.2); mean stress decreased from 16.6 to 9.5 (mean difference 7.0, 95% CI 5.1 to 9.0). The proportion of mothers assessed as having any degree of depression decreased by 85% from 26/80 (32.5%) to 4/80 (5%).ConclusionsThe number of nocturnal awakenings requiring parental support among infants aged 6−12 months significantly decreased following a single consultation on infant sleep physiology and teaching behavioural strategies to improve sleep. Significant improvements in maternal stress, anxiety and depression were also observed.
Early rehabilitation in critical care (eRiCC): functional electrical stimulation with cycling protocol for a randomised controlled trial
Authors: Parry Selina M , Berney Sue , Koopman René , Bryant Adam , El-Ansary Doa , Puthucheary Zudin , Hart Nicholas , Warrillow Stephen , Denehy Linda 
Published: September 2012

IntroductionIntensive care-acquired weakness is a common problem, leads to significant impairment in physical functioning and muscle strength, and is prevalent in individuals with sepsis. Early rehabilitation has been shown to be safe and feasible; however, commencement is often delayed due to a patient's inability to co-operate. An intervention that begins early in an intensive care unit (ICU) admission without the need for patient volition may be beneficial in attenuating muscle wasting. The eRiCC (early rehabilitation in critical care) trial will investigate the effectiveness of functional electrical stimulation-assisted cycling and cycling alone, compared to standard care, in individuals with sepsis.Methods and analysisThis is a single centre randomised controlled trial. Participants (n=80) aged ≥18 years, with a diagnosis of sepsis or severe sepsis, who are expected to be mechanically ventilated for ≥48 h and remain in the intensive care ≥4 days will be randomised within 72 h of admission to (1) standard care or (2) intervention where participants will receive functional electrical muscle stimulation-assisted supine cycling on one leg while the other leg undergoes cycling alone. Primary outcome measures include: muscle mass (quadriceps ultrasonography; bioelectrical impedance spectroscopy); muscle strength (Medical Research Council Scale; hand-held dynamometry) and physical function (Physical Function in Intensive Care Test; Functional Status Score in intensive care; 6 min walk test). Blinded outcome assessors will assess measures at baseline, weekly, at ICU discharge and acute hospital discharge. Secondary measures will be evaluated in a nested subgroup (n=20) and will consist of biochemical/histological analyses of collected muscle, urine and blood samples at baseline and at ICU discharge.Ethics and disseminationEthics approval has been obtained from the relevant institution, and results will be published to inform clinical practice in the care of patients with sepsis to optimise rehabilitation and physical function outcomes.Trial registrationAustralian and New Zealand Clinical Trials Registry ACTRN12612000528853.
Using Healthcare Failure Mode and Effect Analysis to reduce medication errors in the process of drug prescription, validation and dispensing in hospitalised patients
Authors: Vélez-Díaz-Pallarés Manuel , Delgado-Silveira Eva , Carretero-Accame María Emilia , Bermejo-Vicedo Teresa 
Published: September 2012

ObjectivesTo identify actions to reduce medication errors in the process of drug prescription, validation and dispensing, and to evaluate the impact of their implementation.MethodsA Health Care Failure Mode and Effect Analysis (HFMEA) was supported by a before-and-after medication error study to measure the actual impact on error rate after the implementation of corrective actions in the process of drug prescription, validation and dispensing in wards equipped with computerised physician order entry (CPOE) and unit-dose distribution system (788 beds out of 1080) in a Spanish university hospital. The error study was carried out by two observers who reviewed medication orders on a daily basis to register prescription errors by physicians and validation errors by pharmacists. Drugs dispensed in the unit-dose trolleys were reviewed for dispensing errors. Error rates were expressed as the number of errors for each process divided by the total opportunities for error in that process times 100.ResultsA reduction in prescription errors was achieved by providing training for prescribers on CPOE, updating prescription procedures, improving clinical decision support and automating the software connection to the hospital census (relative risk reduction (RRR), 22.0%; 95% CI 12.1% to 31.8%). Validation errors were reduced after optimising time spent in educating pharmacy residents on patient safety, developing standardised validation procedures and improving aspects of the software's database (RRR, 19.4%; 95% CI 2.3% to 36.5%). Two actions reduced dispensing errors: reorganising the process of filling trolleys and drawing up a protocol for drug pharmacy checking before delivery (RRR, 38.5%; 95% CI 14.1% to 62.9%).ConclusionsHFMEA facilitated the identification of actions aimed at reducing medication errors in a healthcare setting, as the implementation of several of these led to a reduction in errors in the process of drug prescription, validation and dispensing.
Role of routine pelvic radiography in initial evaluation of stable, high-energy, blunt trauma patients
Authors: Paydar Shahram , Ghaffarpasand Fariborz , Foroughi Mehdi , Saberi Ali , Dehghankhalili Maryam , Abbasi Hamidreza , Malekpoor Babak , Bananzadeh Ali Mohammad , Vahid Hosseini Mohammad , Bolandparvaz Shahram 
Published: September 2012

BackgroundPelvic fractures are among the most devastating traumatic injuries accompanied by high morbidity and mortality rate leading to catastrophic outcomes and haemodynamic consequences. Although Advanced Trauma Life Support (ATLS) recommends performing pelvic radiography in all major blunt trauma patients, several lines of evidence recommend that it can be limited to those blunt trauma patients who are haemodynamically unstable or have positive pelvic physical examination. Thus, we performed this study in order to evaluate the efficacy of routine pelvic radiography in haemodynamically stable, high-energy, blunt trauma patients.MethodsThis was a prospective cross-sectional study including all the haemodynamically stable, high-energy, blunt trauma patients with negative pelvic physical examination referring to our trauma centre during a 5-month period (May–September 2010). Pelvic radiographies were performed and reviewed for abnormalities. In those who had negative pelvic physical examination and the radiography was not revealing enough, CT imaging was requested and reviewed.ResultsDuring the study period, 1679 high-energy blunt trauma patients referred to our centre out of which 389 were haemodynamically stable and had negative pelvic physical examination. Pelvic radiography was found to be normal in all the patients except one (0.25%) who had pelvic fracture. Only three patients required CT imaging out of which two (0.5%) were found to be normal.ConclusionsPelvic radiography could be eliminated from the primary survey protocol of the patients with high-energy blunt trauma who are haemodynamically stable and have negative pelvic physical examination.
Avoidable emergency admissions?
Authors: Lillebo Borge , Dyrstad Bodil , Grimsmo Anders 
Published: September 2012

BackgroundUse of specialist healthcare services is increasing.AimTo evaluate whether alternative healthcare services could reduce the need for admissions to specialist care hospitals.DesignProspective observational study of emergency referrals for admission to specialist care.SettingA single out-of-hours primary care centre (OPCC) in Norway.MethodOut-of-hours physicians registered their referrals for hospital admission and stated whether the admission could have been avoided given the availability of six other healthcare services.ResultsOf 1083 registered encounters at the OPCC, 152 (14%) were referred for specialist care hospital admission. According to the referring physician, 32 (21%) of these referrals could have been avoided. The most eligible alternatives to such referrals were next-day appointments at a specialist outpatient clinic (11 of 32 referrals), or admission to a community hospital (21 of 32 referrals), or a nursing home (nine of 32 referrals). Respiratory (eight of 32 referrals) and gastrointestinal problems (12 of 32 referrals) were the most common among avoidable admissions.ConclusionsThe use of specialist care hospital admission can be reduced if appropriate alternatives are available.
p21-Activated Kinase 1 Is Required for Efficient Tumor Formation and Progression in a Ras-Mediated Skin Cancer Model
Authors: Chow Hoi Yee , Jubb Adrian M. , Koch Jennifer N. , Jaffer Zahara M. , Stepanova Dina , Campbell David A. , Duron Sergio G. , O'Farrell Marie , Cai Kathy Q. , Klein-Szanto Andres J.P. , Gutkind J. Silvio , Hoeflich Klaus P. , Chernoff Jonathan 
Published: September 2012

Abstract
The RAS genes are the most commonly mutated oncogenes in human cancer and present a particular therapeutic dilemma, as direct targeting of Ras proteins by small molecules has proved difficult. Signaling pathways downstream of Ras, in particular Raf/Mek/Erk and PI3K/Akt/mTOR, are dominated by lipid and protein kinases that provide attractive alternate targets in Ras-driven tumors. As p21-activated kinase 1 (Pak1) has been shown to regulate both these signaling pathways and is itself upregulated in many human cancers, we assessed the role of Pak1 in Ras-driven skin cancer. In human squamous cell carcinoma (SCC), we found a strong positive correlation between advanced stage and grade and PAK1 expression. Using a mouse model of Kras-driven SCC, we showed that deletion of the mouse Pak1 gene led to markedly decreased tumorigenesis and progression, accompanied by near total loss of Erk and Akt activity. Treatment of KrasG12D mice with either of two distinct small molecule Pak inhibitors (PF3758309 and FRAX597) caused tumor regression and loss of Erk and Akt activity. Tumor regression was also seen in mice treated with a specific Mek inhibitor, but not with an Akt inhibitor. These findings establish Pak1 as a new target in KRAS-driven tumors and suggest a mechanism of action through the Erk, but not the Akt, signaling pathway. Cancer Res; 72(22); 5966–75. ©2012 AACR.
Regulation of Pattern Recognition Receptors by the Apolipoprotein A-I Mimetic Peptide 4F
Authors: White C. Roger , Smythies Lesley E. , Crossman David K. , Palgunachari Mayakonda N. , Anantharamaiah G.M. , Datta Geeta 
Published: September 2012

Objective—
The apolipoprotein A-I (apoA-I) mimetic peptide 4F favors the differentiation of human monocytes to an anti-inflammatory phenotype and attenuates lipopolysaccharide (LPS)-induced inflammatory responses. We investigated the effects of LPS on the Toll-like receptor (TLR) signaling pathway in 4F-differentiated monocyte-derived macrophages.

Methods and Results—
Monocyte-derived macrophages were pretreated with 4F or vehicle for 7 days. 4F downregulated cell-surface TLRs (4, 5, and 6) as determined by flow cytometry. 4F attenuated the LPS-dependent upregulation of genes encoding TLR1, 2, and 6 and genes of the MyD88-dependent (CD14, MyD88, TRAF6, interleukin-1 receptor–associated kinase 4, and inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta) and MyD88-independent (interferon regulatory factor 3, TANK-binding kinase 1, and Toll-interleukin 1 receptor domain–containing adaptor-inducing interferon-β) pathways as determined by microarray analysis and quantitative reverse transcriptase polymerase chain reaction. Functional analyses of monocyte-derived macrophages showed that 4F reduced LPS-dependent TLR4 recycling, phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, activation and translocation of nuclear factor-κB and inhibited the secretion of tumor necrosis factor-α and interleukin-6 induced by LPS or lipoteichoic acid. These changes were associated with depletion of cellular cholesterol and caveolin, components of membrane lipid rafts.

Conclusion—
These data suggest that disruption of rafts by 4F alters the assembly of TLR–ligand complexes in cell membranes and inhibits proinflammatory gene expression in monocyte-derived macrophages, thus attenuating the responsiveness of macrophages to LPS.