bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics and outcomes of transjugular intrahepatic portosystemic shunt recipients in the VA Healthcare System
Authors: Lerrigo Robert , Beste Lauren A. , Leipertz Steven L. , Green Pamela K. , Lok Anna S.F. , Kogut Matthew J. , Ioannou George N. 
Published: February 2016

Background and Aims
Transjugular intrahepatic portosystemic shunt (TIPS) placement is an effective treatment for complications of portal hypertension. We aimed to describe post-TIPS mortality and its predictors in the modern era of covered stents.

Patients and methods
We identified patients with cirrhosis who underwent TIPS insertion at Veterans Affairs Healthcare facilities nationally from 2004 to 2014 (n=703), most of which (95%) were performed as elective procedures. We followed patients until the date of death, transplantation, or the end of the observation period.

Results
TIPS recipients had a mean age of 59.3 years (SD 8) and 97% were men. The mean Model for End Stage Liver Disease (MELD) score was 13 (SD 4.8); 47% had hepatitis C virus (HCV) infection, 48% had variceal hemorrhage, and 40% had ascites. During a mean follow-up of 1.72 years (SD 1.9), 57.5% of TIPS recipients died (n=404) and only 5.3% underwent liver transplantation (n=37). The median survival after TIPS was 1.74 years (interquartile range 0.3–4.7). Thirty-day mortality after TIPS was 11.6% [95% confidence interval (CI) 9.4–14.2], 1-year mortality was 40.3% (95% CI 36.7–44.2), and 3-year mortality was 61.9% (95% CI 57.9–66.0). Independent predictors of post-TIPS mortality included medical comorbidity burden, low albumin, HCV infection, and high MELD score (or high international normalized ratio and bilirubin when the components of the MELD score were analyzed individually). TIPS revision was performed at least once in 27.3% of TIPS recipients.

Conclusion
TIPS should not be considered simply as a bridge to transplantation. Burden of extra-hepatic comorbidities, HCV infection, and low serum albumin strongly predict post-TIPS mortality in addition to the MELD score.
Myoepithelial Carcinoma: The Role of Radiation Therapy. A Case Report and Analysis of Data From the Surveillance, Epidemiology, and End Results (SEER) Registry
Authors: Miccio Joseph A. , Oladeru Oluwadamilola T. , Yang Jie , Xue Yaqi , Hoda Syed T. , Ryu Samuel , Stessin Alexander M. , Parker Robert I. 
Published: February 2016

Purpose/Objective:
The role of radiation therapy in the treatment of myoepithelial carcinoma (MC) is unknown. We present a case of a high-grade soft-tissue MC in a pediatric patient and retrospectively examine the effect of postoperative radiation on survival in patients with MC.

Materials and Methods:
Our patient was treated with 4 cycles of ifosfamide, cisplatin, and etoposide followed by 3 cycles of ifosfamide vincristine and etoposide. Radiation was delivered to a total dose of 5580 cGy in 180 cGy/fraction to the surgical bed with a 2 cm margin starting after the third cycle of chemotherapy. The Surveillance, Epidemiology, and End Results (SEER) registry database was queried for cases of surgically resected MC. Retrospective analysis was performed with the endpoint of overall survival (OS).

Results:
Two hundred thirty-four cases of MC were identified; for 62 of these cases, the grade of the tumor wasidentified. Of these 62 patients, 27 received postoperative radiation. OS was improved with adjuvant radiation therapy in patients with grade III or IV MC (P<0.01) as determined by the log-rank test.

Conclusions:
This analysis of SEER data showed an OS benefit with adjuvant radiation therapy in the treatment of high-grade MC. Physicians should report all cases of MC to improve clinical decision making in the treatment of this rare disease.
Which Factors Are Associated with Open Reduction of Adult Mandibular Condylar Injuries?
Authors: Wang Howard D. , Susarla Srinivas M. , Mundinger Gerhard S. , Schultz Benjamin D. , Yang Robin , Bojovic Branko , Christy Michael R. , Manson Paul N. , Rodriguez Eduardo D. , Dorafshar Amir H. 
Published: February 2016

Background:
The purpose of this study was to identify factors associated with the decision to perform open reduction and internal fixation of mandibular condylar fractures.

Methods:
This was a retrospective cohort study of patients with mandibular condylar fractures managed by the plastic and reconstructive surgery, oral and maxillofacial surgery, and otorhinolaryngology services over a 15-year period. Bivariate associations and a multiple logistic regression model were computed for injury characteristics that were associated with open reduction and internal fixation. For all analyses, a value of p ≤ 0.05 was considered significant.

Results:
Six hundred fifty-four condylar injuries were identified in 547 patients. The sample’s mean age was 36.0 ± 16.5 years, 20.5 percent were women, and 63 percent were Caucasian. The most common mechanisms of injury were motor vehicle collisions (49 percent), 53.4 percent involved the subcondylar region and 20 percent were bilateral injuries. Associated noncondylar mandibular fractures were present in 60 percent of cases; 20.7 percent were managed with open reduction and internal fixation. The overall complication rate was 21.6 percent. In a multiple logistic regression model, factors associated with an increased likelihood of open reduction and internal fixation were the presence of extracondylar mandibular injuries, condylar neck or subcondylar region injuries, increasing dislocation, and treatment by plastic and reconstructive surgery/oral and maxillofacial surgery (p ≤ 0.04).

Conclusions:
Increasing severity of mandibular injury, lower level of fracture, joint dislocation, and treatment by plastic and reconstructive surgery/oral and maxillofacial surgery are associated with open reduction and internal fixation of mandibular condylar injuries.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, III.
Recovery after work experiences, employee well-being and intent to quit
Authors: Singh Parbudyal , Burke Ronald J. , Boekhorst Janet 
Published: February 2016

Purpose– A growing body of research suggests that psychological experiences related to recovery after work may reduce employee fatigue and exhaustion and improve well-being. The purpose of this paper is to extend this literature by examining several correlates and consequences of four recovery experiences: psychological detachment, relaxation, mastery, and control.Design/methodology/approach– Data were collected from 290 nursing staff working in hospitals using a questionnaire study and well-established measures. Hierarchical regression analyses were used to test the hypotheses.Findings– The results suggest that the four recovery experiences were, with one exception, positively and significantly correlated. Personal demographic variables (e.g. work status and level of education) had relationships with the use of particular recovery experiences. Passion was positively related to the use of mastery and control, while work intensity was negatively associated with the use of psychological detachment and relaxation. The use of particular recovery experiences was generally associated with lower intentions to quit and positive indicators of psychological well-being.Research limitations/implications– There are several implications for research and practice. Scholars can use the results to extend the theories such as the job demands-resources model, including the role of work intensity as job demands. At the organizational level, managers and leaders should consider supporting strategies that help employees recover after work.Originality/value– This study extends the empirical research on recovery after work using some variables not previously used. The theory on recovery after work is also extended.
Identification of Synthetic and Natural Host Defense Peptides with Leishmanicidal Activity
Authors: Marr A. K. , Cen S. , Hancock R. E. W. , McMaster W. R. 
Published: February 2016

ABSTRACT

Leishmania
parasites are a major public health problem worldwide. Effective treatment of leishmaniasis is hampered by the high incidence of adverse effects to traditional drug therapy and the emergence of resistance to current therapeutics. A vaccine is currently not available. Host defense peptides have been investigated as novel therapeutic agents against a wide range of pathogens. Here we demonstrate that the antimicrobial peptide LL-37 and the three synthetic peptides E6, L-1018, and RI-1018 exhibit leishmanicidal activity against promastigotes and intramacrophage amastigotes of
Leishmania donovani
and
Leishmania major
. We also report that the
Leishmania
protease/virulence factor GP63 confers protection to
Leishmania
from the cytolytic properties of all
l
-form peptides (E6, L-1018, and LL-37) but not the
d
-form peptide RI-1018. The results suggest that RI-1018, E6, and LL-37 are promising peptides to develop further into components for antileishmanial therapy.
Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study
Authors: Davanço Marcelo Gomes , Campos Michel Leandro , Rosa Talita Atanazio , Padilha Elias Carvalho , Alzate Alejandro Henao , Rolim Larissa Araújo , Rolim-Neto Pedro José , Peccinini Rosângela Gonçalves 
Published: February 2016

ABSTRACT

Benznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentration
in vivo
, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease.
Preventing Implant-Associated Infections by Silver Coating
Authors: Kuehl Richard , Brunetto Priscilla S. , Woischnig Anne-Kathrin , Varisco Massimo , Rajacic Zarko , Vosbeck Juerg , Terracciano Luigi , Fromm Katharina M. , Khanna Nina 
Published: February 2016

ABSTRACT

Implant-associated infections (IAIs) are a dreaded complication mainly caused by biofilm-forming staphylococci. Implant surfaces preventing microbial colonization would be desirable. We examined the preventive effect of a silver-coated titanium-aluminum-niobium (TiAlNb) alloy. The surface elicited a strong, inoculum-dependent activity against
Staphylococcus epidermidis
and
Staphylococcus aureus
in an agar inhibition assay. Gamma sterilization and alcohol disinfection did not alter the effect. In a tissue cage mouse model, silver coating of TiAlNb cages prevented perioperative infections in an inoculum-dependent manner and led to a 100% prevention rate after challenge with 2 × 10
6
CFU of
S. epidermidis
per cage. In
S. aureus
infections, silver coating had only limited effect. Similarly, daptomycin or vancomycin prophylaxis alone did not prevent
S. aureus
infections. However, silver coating combined with daptomycin or vancomycin prophylaxis thwarted methicillin-resistant
S. aureus
infections at a prevention rate of 100% or 33%, respectively. Moreover, silver release from the surface was independent of infection and occurred rapidly after implantation. On day 2, a peak of 82 μg Ag/ml was reached in the cage fluid, corresponding to almost 6× the MIC of the staphylococci. Cytotoxicity toward leukocytes in the cage was low and temporary. Surrounding tissue did not reveal histological signs of silver toxicity.
In vitro
, no emergence of silver resistance was observed in several clinical strains of staphylococci upon serial subinhibitory silver exposures. In conclusion, our data demonstrate that silver-coated TiAlNb is potent for prevention of IAIs and thus can be considered for clinical application.
Susceptibility of Multidrug-Resistant Gram-Negative Urine Isolates to Oral Antibiotics
Authors: Hirsch Elizabeth B. , Zucchi Paola C. , Chen Alice , Raux Brian R. , Kirby James E. , McCoy Christopher , Eliopoulos George M. 
Published: February 2016

ABSTRACT
Increasing resistance among Gram-negative uropathogens limits treatment options, and susceptibility data for multidrug-resistant isolates are limited. We assessed the activity of five oral agents against 91 multidrug-resistant Gram-negative urine isolates that were collected from emergency department/hospitalized patients. Fosfomycin and nitrofurantoin were most active (>75% susceptibility). Susceptibilities to sulfamethoxazole-trimethoprim, ciprofloxacin, and ampicillin were ≤40%; empirical use of these agents likely provides inadequate coverage in areas with a high prevalence of multidrug-resistant uropathogens.
Daptomycin Tolerance in the Staphylococcus aureus pitA6 Mutant Is Due to Upregulation of the
dlt
Operon
Authors: Mechler Lukas , Bonetti Eve-Julie , Reichert Sebastian , Flötenmeyer Matthias , Schrenzel Jacques , Bertram Ralph , François Patrice , Götz Friedrich 
Published: February 2016

ABSTRACT

Understanding the mechanisms of how bacteria become tolerant toward antibiotics during clinical therapy is a very important object. In a previous study, we showed that increased daptomycin (DAP) tolerance of
Staphylococcus aureus
was due to a point mutation in
pitA
(inorganic phosphate transporter) that led to intracellular accumulation of both inorganic phosphate (P
i
) and polyphosphate (polyP). DAP tolerance in the
pitA6
mutant differs from classical resistance mechanisms since there is no increase in the MIC. In this follow-up study, we demonstrate that DAP tolerance in the
pitA6
mutant is not triggered by the accumulation of polyP. Transcriptome analysis revealed that 234 genes were at least 2.0-fold differentially expressed in the mutant. Particularly, genes involved in protein biosynthesis, carbohydrate and lipid metabolism, and replication and maintenance of DNA were downregulated. However, the most important change was the upregulation of the
dlt
operon, which is induced by the accumulation of intracellular P
i
. The GraXRS system, known as an activator of the
dlt
operon (
d
-alanylation of teichoic acids) and of the
mprF
gene (multiple peptide resistance factor), is not involved in DAP tolerance of the
pitA6
mutant. In conclusion, DAP tolerance of the
pitA6
mutant is due to an upregulation of the
dlt
operon, triggered directly or indirectly by the accumulation of P
i
.
Mutagenesis and Functional Analysis of the Bacterial Arginine Glycosyltransferase Effector NleB1 from Enteropathogenic Escherichia coli
Authors: Wong Fok Lung Tania , Giogha Cristina , Creuzburg Kristina , Ong Sze Ying , Pollock Georgina L. , Zhang Ying , Fung Ka Yee , Pearson Jaclyn S. , Hartland Elizabeth L. 
Published: February 2016

ABSTRACT

Enteropathogenic
Escherichia coli
(EPEC) interferes with host cell signaling by injecting virulence effector proteins into enterocytes via a type III secretion system (T3SS). NleB1 is a novel T3SS glycosyltransferase effector from EPEC that transfers a single
N
-acetylglucosamine (GlcNAc) moiety in an
N
-glycosidic linkage to Arg
117
of the Fas-associated death domain protein (FADD). GlcNAcylation of FADD prevents the assembly of the canonical death-inducing signaling complex and inhibits Fas ligand (FasL)-induced cell death. Apart from the DXD catalytic motif of NleB1, little is known about other functional sites in the enzyme. In the present study, members of a library of 22 random transposon-based, in-frame, linker insertion mutants of NleB1 were tested for their ability to block caspase-8 activation in response to FasL during EPEC infection. Immunoblot analysis of caspase-8 cleavage showed that 17 mutant derivatives of NleB1, including the catalytic DXD mutant, did not inhibit caspase-8 activation. Regions of interest around the insertion sites with multiple or single amino acid substitutions were examined further. Coimmunoprecipitation studies of 34 site-directed mutants showed that the NleB1 derivatives with the E253A, Y219A, and PILN
(63–66)AAAA
(in which the PILN motif from residues 63 to 66 was changed to AAAA) mutations bound to but did not GlcNAcylate FADD. A further mutant derivative, the PDG
(236–238)AAA
mutant, did not bind to or GlcNAcylate FADD. Infection of mice with the EPEC-like mouse pathogen
Citrobacter rodentium
expressing NleB
E253A
and NleB
Y219A
showed that these strains were attenuated, indicating the importance of residues E253 and Y219 in NleB1 virulence
in vivo
. In summary, we identified new amino acid residues critical for NleB1 activity and confirmed that these are required for the virulence function of NleB1.
Identification and Validation of
Loa loa
Microfilaria-Specific Biomarkers: a Rational Design Approach Using Proteomics and Novel Immunoassays
Authors: Drame Papa M. , Meng Zhaojing , Bennuru Sasisekhar , Herrick Jesica A. , Veenstra Timothy D. , Nutman Thomas B. 
Published: February 2016

ABSTRACT

Immunoassays are currently needed to quantify
Loa loa
microfilariae (mf)
.
To address this need, we have conducted proteomic and bioinformatic analyses of proteins present in the urine of a
Loa
mf-infected patient and used this information to identify putative biomarkers produced by
L. loa
mf. In total, 70 of the 15,444 described putative
L. loa
proteins were identified. Of these 70, 18 were
L. loa
mf specific, and 2 of these 18 (LOAG_16297 and LOAG_17808) were biologically immunogenic. We developed novel reverse luciferase immunoprecipitation system (LIPS) immunoassays to quantify these 2 proteins in individual plasma samples. Levels of these 2 proteins in microfilaremic
L. loa
-infected patients were positively correlated to mf densities in the corresponding blood samples (
r
= 0.71 and
P
< 0.0001 for LOAG_16297 and
r
= 0.61 and
P
= 0.0002 for LOAG_17808). For LOAG_16297, the levels in plasma were significantly higher in
Loa
-infected (geometric mean [GM], 0.045 µg/ml) than in uninfected (
P
< 0.0001),
Wuchereria bancrofti
-infected (
P
= 0.0005), and
Onchocerca volvulus
-infected (
P
< 0.0001) individuals, whereas for LOAG_17808 protein, they were not significantly different between
Loa
-infected (GM, 0.123 µg/ml) and uninfected (
P
= 0.06) and
W. bancrofti
-infected (
P
= 0.32) individuals. Moreover, only LOAG_16297 showed clear discriminative ability between
L. loa
and the other potentially coendemic filariae. Indeed, the specificity of the LOAG_16297 reverse LIPS assay was 96% (with a sensitivity of 77%). Thus, LOAG_16297 is a very promising biomarker that will be exploited in a quantitative point-of-care immunoassay for determination of
L. loa
mf densities.

IMPORTANCE
Loa loa
, the causative agent of loiasis, is a parasitic nematode transmitted to humans by the tabanid
Chrysops
fly. Some individuals infected with
L. loa
microfilariae (mf) in high densities are known to experience post-ivermectin severe adverse events (SAEs [encephalopathy, coma, or death]). Thus, ivermectin-based mass drug administration (MDA) programs for onchocerciasis and for lymphatic filariasis control have been interrupted in parts of Africa where these filarial infections coexist with
L. loa
. To allow for implementation of MDA for onchocerciasis and lymphatic filariasis, tools that can accurately identify people at risk of developing post-ivermectin SAEs are needed. Our study, using host-based proteomics in combination with novel immunoassays, identified a single
Loa
-specific antigen (LOAG_16297) that can be used as a biomarker for the prediction of
L. loa
mf levels in the blood of infected patients. Therefore, the use of such biomarker could be important in the point-of-care assessment of
L. loa
mf densities.
Good-quality social care for people with Parkinson’s disease: a qualitative study
Authors: Tod Angela Mary , Kennedy Fiona , Stocks Amanda-Jayne , McDonnell Ann , Ramaswamy Bhanu , Wood Brendan , Whitfield Malcolm 
Published: February 2016

ObjectivesThe study examines the meaning of good-quality social care for people with Parkinson's disease and their carers. It identifies, from their perspective, the impact of good-quality social care on health and well-being.DesignQualitative case study methodology, interview and framework analysis techniques were used. Setting: community locations in the north and midlands of England.ParticipantsData were collected from 43 participants including individual interviews with people with Parkinson's disease (n=4), formal and informal social care providers (n=13), 2 focus groups, 1 with people with Parkinson's disease and their carers (n=17), and 1 with professionals (n=8), plus a telephone interview with a former commissioner.FindingsGood-quality social care, delivered in a timely fashion, was reported to have a positive impact on health. Furthermore, there is an indication that good-quality social care can prevent untoward events, such as infections, symptom deterioration and deterioration in mental health. The concept of the ‘Impact Gap’ developed from the findings, illustrates how the costs of care may be reduced by delivering good-quality social care. Control, choice and maintaining independence emerged as indicators of good-quality social care, irrespective of clinical condition. Participants identified characteristics indicative of good-quality social care specific to Parkinson's disease, including understanding Parkinson's disease, appropriate administration of medication, timing of care and reassessment. ‘Parkinson's aware’ social care was seen to generate psychological, physical and social benefits that were inter-related.ConclusionsThe findings indicate how maximising quality in social care delivery for people with Parkinson's disease can impact on health and well-being. Long-term or short-term benefits may result in prevented events and reductions in health and social care resource. Health professionals can be instrumental in early detection of and signposting to social care.