bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coping and disability: evidence from a developing country
Authors: SLIM Zeinab N. , DOWLI Alexander , CHAAYA Monique , MAHFOUD Ziyad , UTHMAN Imad 
Published: January 2011

AbstractAim:  In view of the increasing burden of musculoskeletal‐related disability, the growing number of older persons and the scarcity of research on musculoskeletal conditions in the Eastern Mediterranean region, coping with musculoskeletal problems deserves special attention. This paper examines how good coping links to musculoskeletal‐related disability among Lebanese citizens aged 15 years and older.Methods:  The sample included 200 people living in southern Lebanon and who participated in the Community Oriented Program for Control of Rheumatic Diseases (COPCORD) survey. Disability and coping were assessed using self‐reported questions. Covariates included demographics, musculoskeletal pain variables, and body mass index (BMI).Results:  Around one‐third of the sample had lifetime functional disability due to musculoskeletal problems and 62% were coping well with their problems. Adjusted data showed that the odds of musculoskeletal‐related disability among individuals who were not coping well was 2.35 times the odds of disability among individuals who were coping well with 95% CI = 1.10–5.02.Conclusion:  This study provides evidence of the importance of complementing pharmacological treatment with a cognitive‐behavioral approach for management of musculoskeletal problems.
Rheumatic‐musculoskeletal manifestations in type 2 diabetes mellitus patients in south India
Authors: MATHEW Ashish J. , NAIR Jayakumar B. , PILLAI Saran S. 
Published: January 2011

AbstractAim:  To determine the prevalence of rheumatic musculoskeletal disorders (RMSD) in type 2 diabetes mellitus (T2DM) and study their risk factors.Methods:  Diagnosed patients of T2DM attending the diabetic clinic in a premier teaching institution in south India were interviewed and requested to mark their RMS pain sites on a mannequin and intensity of pain on a visual analogue scale (VAS). A complete RMS examination was done and diagnoses were noted. These RMSDs were compared with those in age‐ and sex‐matched, non‐diabetic individuals from the general population. Association of RMSD with variables was determined using Chi‐square test and multiple logistic regression models for risk factors were created using SPSS 17.0 software.Results:  Prevalence of RMSD in 310 cases and controls was 42.58%; 95% CI: 37.08–48.08 and 31.61%; 95% CI: 26.43–36.79, respectively. RMS pain was marked by 194 individuals. Knee was the most common site of pain (33.4%). Prevalence of common RMSD was osteoarthritis knee (20.64%; 95% CI 16.14–25.16), frozen shoulder (16.45%; 95% CI: 12.32–20.58), diffuse idiopathic skeletal hyperostosis (14.52%; 95% CI: 10.6–18.44) and limited joint mobility (8.06%; 95% CI: 5.03–11.09). Age (P = 0.046), duration of T2DM (P < 0.001) and glycosylated hemoglobin (P < 0.001) were found to have significant associations with RMSD. In logistic regression analysis, duration (OR: 1.467; 95% CI: 1.210–1.779) and severity (OR: 1.354; 95% CI: 1.169–1.569) of T2DM were identified as the risk factors.Conclusion:  Thorough RMS examination should be included as an integral part of care in T2DM patients.
A qualitative investigation into the effects of brief training in solution‐focused therapy in a social work team
Authors: Smith Ian C. 
Published: January 2011

Objectives.  Previous research into the effectiveness of brief training in psychological therapies for non‐therapist health and social services workers has found mixed results regarding transferring learning into practice. Very few published studies have assessed the impact of such training in Solution‐Focused Brief Therapy (SFBT), despite such training being popular. This study explored the impact of brief SFBT training for a group of community‐based social workers. Design.  A qualitative interview‐based design was used, with the researcher adopting an ethnographic stance to obtain a rich, detailed and focused account of events. Methods.  Six social workers working with adults with intellectual disabilities took part in the study. All had attended a 2‐day workshop in SFBT 9 months previously. The interviews were transcribed and subjected to thematic analysis. Results and Conclusions.  Factors affecting skill transfer included being able to practise, peer and organizational support, and perceived conflicts between SFBT and work role. Whilst specific trained techniques were not consistently adopted, most workers changed the style of their interaction with clients in simple ways which they reported resulted in benefits including improved communication, collaboration, and increased feelings of control and self‐efficacy for clients and workers. The findings suggest that in addition to peer and organizational support, trainees’ perceptions of the fit of the training with their work role may be a key factor in determining transfer. Recommendations are made for developing training for non‐therapists that focuses on helping change the style of their interactions rather than on learning to implement specific psychological therapy techniques.
Pharmacodynamics of Razupenem (PZ601) Studied in an
In Vitro
Pharmacokinetic Model of Infection
Authors: MacGowan Alasdair P. , Noel Alan , Tomaselli Sharon , Elliott Heather , Bowker Karen 
Published: January 2011

ABSTRACT

Simulations of administration of razupenem at 1 g every 12 h by 1-h intravenous (i.v.) infusion were performed in an
in vitro
pharmacokinetic model of infection. The antibacterial effect of this razupenem dosing regimen against six strains of
Staphylococcus aureus
(one methicillin-sensitive
S. aureus
[MSSA] strain [MIC, 0.015 μg/ml] and five methicillin-resistant
S. aureus
[MRSA] strains [MIC range, 0.09 to 3 μg/ml]) and five strains of
Enterobacteriaceae
(three
Escherichia coli
strains [two containing extended-spectrum β-lactamases {ESBLs}] and two
Enterobacter
sp. strains [one with an AmpC enzyme and the other with a raised razupenem MIC; MIC range, 0.09 to 6 μg/ml]) was assessed. Against the MSSA and MRSA strains, razupenem produced a >3.5-log-unit reduction in viable count after 24 h. There were no changes in population profiles. In a second series of experiments, over 5 days there was rapid initial clearance of MRSA from the model followed by regrowth after 48 h. MRSA colonies appeared on 2× MIC recovery medium after 72 h with strain 33820 (MIC, 3.0 μg/ml) and at 120 h with strain 27706 (MIC, 1.5 μg/ml). Against
E. coli
and
Enterobacter
spp., razupenem produced a >3.5-log-unit reduction in bacterial counts for all strains except that with an MIC of 6 μg/ml, where razupenem had a notably poorer antibacterial effect. Population profiles were unchanged after 48 h of exposure to razupenem except for
Enterobacter
strain 34425 (MIC, 6.0 μg/ml), where colonies were recovered from media containing 2×, 4×, and 8× MIC. In dose-ranging studies with MRSA strains, the percentage of the dosing interval that the free drug concentration remained higher than the pathogen MIC (
fT
>MIC) for a 24-h bacteriostatic effect was 5.0% ± 1.4%, and that for a 1-log-unit reduction in count was 12.5% ± 5.8%. Population profiles indicated growth on 2× MIC recovery medium at
fT
>MIC values of 1 to 35% but not at a value of >35%. In a similar set of experiments with
Enterobacteriaceae
, the
fT
>MIC for a 24-h bacteriostatic effect was 34.2% ± 7.6% and that for a 1-log-unit reduction in count was 42.5% ± 7.8%. Population analysis profiles indicated growth on recovery media with 2×, 4×, and 8× MIC at
fT
>MICs in the range of 1 to 69% but rarely at values of ≥70%. In conclusion, razupenem at simulated human doses of 1 g i.v. every 12 h has a marked antibacterial effect on MSSA and MRSA strains with MICs of ≤3.0 μg/ml and
Enterobacteriaceae
with MICs of ≤0.4 μg/ml.
fT
>MIC targets of ≥35% for MRSA and ≥70% for
Enterobacteriaceae
should provide significant antibacterial effects combined with low risks of changing pathogen antibiotic population profiles.
Comparison of the Antibacterial Properties of Phage Endolysins SAL-1 and LysK
Authors: Jun Soo Youn , Jung Gi Mo , Son Jee-Soo , Yoon Seong Jun , Choi Yun-Jaie , Kang Sang Hyeon 
Published: January 2011

ABSTRACT

In spite of the high degree of amino acid sequence similarity between the newly discovered phage endolysin SAL-1 and the phage endolysin LysK, SAL-1 has an approximately 2-fold-lower MIC against several
Staphylococcus aureus
strains and higher bacterial cell-wall-hydrolyzing activity than LysK. The amino acid residue change contributing the most to this enhanced enzymatic activity is a change from glutamic acid to glutamine at the 114th residue.
Penetration of Topically Administered 0.5-Percent Caspofungin Eye Drops into Human Aqueous Humor
Authors: Neoh Chin Fen , Leung Lok , Misra Anant , Vajpayee Rasik B. , Davies Geoffrey E. , Fullinfaw Robert O. , Stewart Kay , Kong David C. M. 
Published: January 2011

ABSTRACTTen participants attending elective anterior segment eye surgery received 0.5% caspofungin eye drops either 1 drop hourly for 4 h or 1 drop an hour before surgery. The eye drops were generally well tolerated. In the absence of inflammation or corneal abrasion, topical caspofungin does not achieve clinically relevant concentrations.
Emergence of Linezolid-Resistant
Staphylococcus aureus
after Prolonged Treatment of Cystic Fibrosis Patients in Cleveland, Ohio
Authors: Endimiani Andrea , Blackford Martha , Dasenbrook Elliot C. , Reed Michael D. , Bajaksouszian Saralee , Hujer Andrea M. , Rudin Susan D. , Hujer Kristine M. , Perreten Vincent , Rice Louis B. , Jacobs Michael R. , Konstan Michael W. , Bonomo Robert A. 
Published: January 2011

ABSTRACT

Linezolid (LZD)-resistant
Staphylococcus aureus
(LRSA) isolates were monitored from 2000 to 2009 in Cleveland, OH. LRSA first emerged in 2004 only in cystic fibrosis (CF) patients, with 11 LRSA-infected CF patients being identified by 2009. LRSA was isolated from 8 of 77 CF patients with
S. aureus
respiratory tract infection treated with LZD from 2000 to 2006. Analysis of clinical data showed that the 8 CF patients with LRSA received more LZD courses (18.8 versus 5.9;
P
= 0.001) for a longer duration (546.5 versus 211.9 days;
P
< 0.001) and had extended periods of exposure to LZD (83.1 versus 30.1 days/year;
P
< 0.001) than the 69 with LZD-susceptible isolates. Five LRSA isolates included in the clinical analysis (2000 to 2006) and three collected in 2009 were available for molecular studies. Genotyping by repetitive extrapalindromic PCR and pulsed-field gel electrophoresis revealed that seven of these eight LRSA strains from unique patients were genetically similar. By multilocus sequence typing, all LRSA isolates were included in clonal complex 5 (seven of sequence type 5 [ST5] and one of ST1788, a new single-locus variant of ST5). However, seven different variants were identified by
spa
typing. According to the
Escherichia coli
numbering system, seven LRSA isolates contained a G2576T mutation (G2603T,
S. aureus
numbering) in one to four of the five copies of domain V of the 23S rRNA genes. One strain also contained a mutation (C2461T,
E. coli
numbering) not previously reported. Two strains, including one without domain V mutations, possessed single amino acid substitutions (Gly152Asp or Gly139Arg) in the ribosomal protein L3 of the peptidyltransferase center, substitutions not previously reported in clinical isolates. Emergence of LRSA is a serious concern for CF patients who undergo prolonged courses of LZD therapy.
Mutational Analysis of the Thienamycin Biosynthetic Gene Cluster from
Streptomyces cattleya
Authors: Rodríguez Miriam , Núñez Luz Elena , Braña Alfredo F. , Méndez Carmen , Salas José A. , Blanco Gloria 
Published: January 2011

ABSTRACT

The generation of non-thienamycin-producing mutants with mutations in the
thnL
,
thnN
,
thnO
, and
thnI
genes within the
thn
gene cluster from
Streptomyces cattleya
and their involvement in thienamycin biosynthesis and regulation were previously reported. Four additional mutations were independently generated in the
thnP
,
thnG
,
thnR
, and
thnT
genes by insertional inactivation. Only the first two genes were found to play a role in thienamycin biosynthesis, since these mutations negatively or positively affect antibiotic production. A mutation of
thnP
results in the absence of thienamycin production, whereas a 2- to 3-fold increase in thienamycin production was observed for the
thnG
mutant. On the other hand, mutations in
thnR
and
thnT
showed that although these genes were previously reported to participate in this pathway, they seem to be nonessential for thienamycin biosynthesis, as thienamycin production was not affected in these mutants. High-performance liquid chromatography (HPLC)-mass spectrometry (MS) analysis of all available mutants revealed some putative intermediates in the thienamycin biosynthetic pathway. A compound with a mass corresponding to carbapenam-3-carboxylic acid was detected in some of the mutants, suggesting that the assembly of the bicyclic nucleus of thienamycin might proceed in a way analogous to that of the simplest natural carbapenem, 1-carbapen-2-em-3-carboxylic acid biosynthesis. The accumulation of a compound with a mass corresponding to 2,3-dihydrothienamycin in the
thnG
mutant suggests that it might be the last intermediate in the biosynthetic pathway. These data, together with the establishment of cross-feeding relationships by the cosynthesis analysis of the non-thienamycin-producing mutants, lead to a proposal for some enzymatic steps during thienamycin assembly.
Combination Therapy of Murine Mucormycosis or Aspergillosis with Iron Chelation, Polyenes, and Echinocandins
Authors: Ibrahim Ashraf S. , Gebremariam Teclegiorgis , Luo Guanpingsheng , Fu Yue , French Samuel W. , Edwards John E. , Spellberg Brad 
Published: January 2011

ABSTRACT
Liposomal amphotericin B (LAmB) combined wither either micafungin or deferasirox was synergistic in previous murine studies with mucormycosis or aspergillosis. We hypothesized that triple therapy using LAmB, micafungin, and deferasirox could further improve outcomes of mucormycosis or aspergillosis. Triple therapy improved survival and reduced tissue fungal burden of mice with mucormycosis and to a lesser extent with aspergillosis. Continued investigation into the use of triple therapy against mucormycosis and aspergillosis is warranted.
Effect of Half-Life on the Pharmacodynamic Index of Zanamivir against Influenza Virus Delineated by a Mathematical Model
Authors: Brown Ashley N. , Bulitta Jürgen B. , McSharry James J. , Weng Qingmei , Adams Jonathan R. , Kulawy Robert , Drusano George L. 
Published: January 2011

ABSTRACT

Intravenous zanamivir is recommended for the treatment of hospitalized patients with complicated oseltamivir-resistant influenza virus infections. In a companion paper, we show that the time above the 50% effective concentration (time>EC
50
) is the pharmacodynamic (PD) index predicting the inhibition of viral replication by intravenous zanamivir. However, for other neuraminidase inhibitors, the ratio of the area under the concentration-time curve to the EC
50
(AUC/EC
50
) is the most predictive index. Our objectives are (i) to explain the dynamically linked variable of intravenous zanamivir by using different half-lives and (ii) to develop a new, mechanism-based population pharmacokinetic (PK)/PD model for the time course of viral load. We conducted dose fractionation studies in the hollow-fiber infection model (HFIM) system with zanamivir against an oseltamivir-resistant influenza virus. A clinical 2.5-h half-life and an artificially prolonged 8-h half-life were simulated for zanamivir. The values for the AUC from 0 to 24 h (AUC
0-24
) of zanamivir were equivalent for the two half-lives. Viral loads and zanamivir pharmacokinetics were comodeled using data from the present study and a previous dose range experiment via population PK/PD modeling in S-ADAPT. Dosing every 8 h (Q8h) suppressed the viral load better than dosing Q12h or Q24h at the 2.5-h half-life, whereas all regimens suppressed viral growth similarly at the 8-h half-life. The model provided unbiased and precise individual (Bayesian) (
r
2
, >0.96) and population (pre-Bayesian) (
r
2
, >0.87) fits for log
10
viral load. Zanamivir inhibited viral release (50% inhibitory concentration [IC
50
], 0.0168 mg/liter; maximum extent of inhibition, 0.990). We identified AUC/EC
50
as the pharmacodynamic index for zanamivir at the 8-h half-life, whereas time>EC
50
best predicted viral suppression at the 2.5-h half-life, since the trough concentrations approached the IC
50
for the 2.5-h but not for the 8-h half-life. The model explained data at both half-lives and holds promise for optimizing clinical zanamivir dosage regimens.
Dissemination of Persistent Intestinal Bacteria via the Mesenteric Lymph Nodes Causes Typhoid Relapse
Authors: Griffin Amanda J. , Li Lin-Xi , Voedisch Sabrina , Pabst Oliver , McSorley Stephen J. 
Published: January 2011

ABSTRACTEnteric pathogens can cause relapsing infections in a proportion of treated patients, but greater understanding of this phenomenon is hindered by the lack of appropriate animal models. We report here a robust animal model of relapsing primary typhoid that initiates after apparently successful antibiotic treatment of susceptible mice. Four days of enrofloxacin treatment were sufficient to reduce bacterial loads below detectable levels in all major organs, and mice appeared otherwise healthy. However, any interruption of further antibiotic therapy allowed renewed fecal shedding and renewed bacterial growth in systemic tissues to occur, and mice eventually succumbed to relapsing infection.In vivoimaging of luminescentSalmonellaidentified the mesenteric lymph nodes (MLNs) as a major reservoir of relapsing infection. A magnetic-bead enrichment strategy isolated MLN-resident CD11b+Gr-1−monocytes associated with low numbers of persistentSalmonella. However, the removal of MLNs increased the severity of typhoid relapse, demonstrating that this organ serves as a protective filter to restrain the dissemination of bacteria during antibiotic therapy. Together, these data describe a robust animal model of typhoid relapse and identify an important intestinal phagocyte subset involved in protection against the systemic spread of enteric infection.
Listeria monocytogenes
Infection Induces Prosurvival Metabolic Signaling in Macrophages
Authors: Zou Tie , Garifulin Oleg , Berland Robert , Boyartchuk Victor L. 
Published: January 2011

ABSTRACT

Host cells use metabolic signaling through the LXRα nuclear receptor to defend against
Listeria monocytogenes
infection. 25-Hydroxycholesterol is a natural ligand of LXRs that is produced by the enzyme cholesterol 25-hydroxylase (CH25H). We found that expression of
Ch25h
is upregulated following
L. monocytogenes
infection in a beta interferon (IFN-β)-dependent fashion. Moreover, increased
Ch25h
expression promotes survival of
L. monocytogenes
-infected cells and increases sensitivity of the host to infection. We determined that expression of
Cd5l
, a prosurvival gene, is controlled by CH25H. In addition, we found that CD5L inhibits activation of caspase-1, promoting survival of infected macrophages. Our results reveal a mechanism by which an intracellular pathogen can prolong survival of infected cells, thus providing itself with a protected environment in which to replicate.
HIV priorities and health distributions in a rural region in Tanzania: a qualitative study
Authors: Johansson Kjell Arne , Miljeteig Ingrid , Kigwangalla Hamisi , Norheim Ole Frithjof 
Published: January 2011

BackgroundInternational and national agencies play a major role in setting HIV care-and-treatment priorities in low-income-countries. Little is known about priority setting at lower health-system levels. The objective of this article is to explore experiences of HIV priority decisions, at what levels these decisions are made and how they might influence the distribution of health benefits in a high-endemic region in Tanzania.MethodsThis is a qualitative study using observations, key documents and semistructured focus-group and individual interviews (43) with health workers, patients and administrators at one regional and one district hospital. The analysis was based on an editing analysis style.ResultsHealth workers did not perceive themselves as bedside rationing agents and they reported following national recommendations and felt they have little impact on important priority decisions. Health benefit distributions were largely determined by priority decisions made at a national level. External factors, such as eligibility criteria, inadequate funding and barriers to access seemed to play a major role in the actual distribution of health services and benefits in the region. Patient groups who were actually given high priority were the sickest patients, those living near a facility and those who could afford long journeys and frequent visits. Low-priority groups were those experiencing other co-morbidities or treatment failure, children, asymptomatic patients and the poorest.Conclusions/significanceThe interaction of priority setting across health-system levels and their impact on distribution of health outcomes in the population has been underestimated. The distributional pattern of health outcomes calls for further normative assessment.
MYC Phosphorylation, Activation, and Tumorigenic Potential in Hepatocellular Carcinoma Are Regulated by HMG-CoA Reductase
Authors: Cao Zhongwei , Fan-Minogue Hua , Bellovin David I. , Yevtodiyenko Aleksey , Arzeno Julia , Yang Qiwei , Gambhir Sanjiv Sam , Felsher Dean W. 
Published: January 2011

Abstract
MYC is a potential target for many cancers but is not amenable to existing pharmacologic approaches. Inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) by statins has shown potential efficacy against a number of cancers. Here, we show that inhibition of HMG-CoA reductase by atorvastatin (AT) blocks both MYC phosphorylation and activation, suppressing tumor initiation and growth in vivo in a transgenic model of MYC-induced hepatocellular carcinoma (HCC) as well as in human HCC-derived cell lines. To confirm specificity, we show that the antitumor effects of AT are blocked by cotreatment with the HMG-CoA reductase product mevalonate. Moreover, by using a novel molecular imaging sensor, we confirm that inhibition of HMG-CoA reductase blocks MYC phosphorylation in vivo. Importantly, the introduction of phosphorylation mutants of MYC at Ser62 or Thr58 into tumors blocks their sensitivity to inhibition of HMG-CoA reductase. Finally, we show that inhibition of HMG-CoA reductase suppresses MYC phosphorylation through Rac GTPase. Therefore, HMG-CoA reductase is a critical regulator of MYC phosphorylation, activation, and tumorigenic properties. The inhibition of HMG-CoA reductase may be a useful target for the treatment of MYC-associated HCC as well as other tumors. Cancer Res; 71(6); 2286–97. ©2011 AACR.