bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of Fluoroquinolone Resistance in Gram-Negative Bacteria Causing Bloodstream Infections
Authors: Dan Seejil , Shah Ansal , Justo Julie Ann , Bookstaver P. Brandon , Kohn Joseph , Albrecht Helmut , Al-Hasan Majdi N.
Published: February 2016

Increasing rates of fluoroquinolone resistance (FQ-R) have limited empirical treatment options for Gram-negative infections, particularly in patients with severe beta-lactam allergy. This case-control study aims to develop a clinical risk score to predict the probability of FQ-R in Gram-negative bloodstream isolates. Adult patients with Gram-negative bloodstream infections (BSI) hospitalized at Palmetto Health System in Columbia, South Carolina, from 2010 to 2013 were identified. Multivariate logistic regression was used to identify independent risk factors for FQ-R. Point allocation in the fluoroquinolone resistance score (FQRS) was based on regression coefficients. Model discrimination was assessed by the area under receiver operating characteristic curve (AUC). Among 824 patients with Gram-negative BSI, 143 (17%) had BSI due to fluoroquinolone-nonsusceptible Gram-negative bacilli. Independent risk factors for FQ-R and point allocation in FQRS included male sex (adjusted odds ratio [aOR], 1.97; 95% confidence intervals [CI], 1.36 to 2.98; 1 point), diabetes mellitus (aOR, 1.54; 95% CI, 1.03 to 2.28; 1 point), residence at a skilled nursing facility (aOR, 2.28; 95% CI, 1.42 to 3.63; 2 points), outpatient procedure within 30 days (aOR, 3.68; 95% CI, 1.96 to 6.78; 3 points), prior fluoroquinolone use within 90 days (aOR, 7.87; 95% CI, 4.53 to 13.74; 5 points), or prior fluoroquinolone use within 91 to 180 days of BSI (aOR, 2.77; 95% CI, 1.17 to 6.16; 3 points). The AUC for both final logistic regression and FQRS models was 0.73. Patients with an FQRS of 0, 3, 5, or 8 had predicted probabilities of FQ-R of 6%, 22%, 39%, or 69%, respectively. The estimation of patient-specific risk of antimicrobial resistance using FQRS may improve empirical antimicrobial therapy and fluoroquinolone utilization in Gram-negative BSI.
Whole-Genome Sequence of a
bla
OXA-48
-Harboring Raoultella ornithinolytica Clinical Isolate from Lebanon
Authors: Al-Bayssari Charbel , Olaitan Abiola Olumuyiwa , Leangapichart Thongpan , Okdah Liliane , Dabboussi Fouad , Hamze Monzer , Rolain Jean-Marc
Published: February 2016

We analyzed the whole-genome sequence of a
bla
OXA-48
-harboring
Raoultella ornithinolytica
clinical isolate from a patient in Lebanon. The size of the
Raoultella ornithinolytica
CMUL058 genome was 5,622,862 bp, with a G+C content of 55.7%. We deciphered all the molecular mechanisms of antibiotic resistance, and we compared our genome to other available
R. ornithinolytica
genomes in GenBank. The resistome consisted of 9 antibiotic resistance genes, including a plasmidic
bla
OXA-48
gene whose genetic organization is also described.
Linezolid Surveillance Results for the United States (LEADER Surveillance Program 2014)
Authors: Flamm Robert K. , Mendes Rodrigo E. , Hogan Patricia A. , Streit Jennifer M. , Ross James E. , Jones Ronald N.
Published: February 2016

The
l
inezolid
e
xperience and
a
ccurate
d
etermination of
r
esistance (LEADER) surveillance program has monitored linezolid activity, spectrum, and resistance since 2004. In 2014, a total of 6,865 Gram-positive pathogens from 60 medical centers from 36 states were submitted. The organism groups evaluated were
Staphylococcus aureus
(3,106), coagulase-negative staphylococci (CoNS; 797), enterococci (855),
Streptococcus pneumoniae
(874), viridans group streptococci (359), and beta-hemolytic streptococci (874). Susceptibility testing was performed by reference broth microdilution at the monitoring laboratory. Linezolid-resistant isolates were confirmed by repeat testing. PCR and sequencing were performed to detect mutations in 23S rRNA, L3, L4, and L22 proteins and acquired genes (
cfr
and
optrA
). The MIC
50/90
for
Staphylococcus aureus
was 1/1 μg/ml, with 47.2% of isolates being methicillin-resistant
Staphylococcus aureus
. Linezolid was active against all
Streptococcus pneumoniae
strains and beta-hemolytic streptococci with a MIC
50/90
of 1/1 μg/ml and against viridans group streptococci with a MIC
50/90
of 0.5/1 μg/ml. Among the linezolid-nonsusceptible MRSA strains, one strain harbored
cfr
only (MIC, 4 μg/ml), one harbored G2576T (MIC, 8 μg/ml), and one contained
cfr
and G2576T with L3 changes (MIC, ≥8 μg/ml). Among CoNS, 0.75% (six isolates) of all strains demonstrated linezolid MIC results of ≥4 μg/ml. Five of these were identified as
Staphylococcus epidermidis
, four of which contained
cfr
in addition to the presence of mutations in the ribosomal proteins L3 and L4, alone or in combination with 23S rRNA (G2576T) mutations. Six enterococci (0.7%) were linezolid nonsusceptible (≥4 μg/ml; five with G2576T mutations, including one with an additional
cfr
gene, and one strain with
optrA
only). Linezolid demonstrated excellent activity and a sustained susceptibility rate of 99.78% overall.
Oritavancin Combinations with β-Lactams against Multidrug-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci
Authors: Smith Jordan R. , Yim Juwon , Raut Animesh , Rybak Michael J.
Published: February 2016

Oritavancin possesses activity against vancomycin-resistant enterococci (VRE) and methicillin-resistant
Staphylococcus aureus
(MRSA).
In vitro
data suggest synergy between beta-lactams (BLs) and vancomycin or daptomycin, agents similar to oritavancin. We evaluated the activities of BLs combined with oritavancin against MRSA and VRE. Oritavancin MICs were determined for 30 strains, 5 each of MRSA, daptomycin-nonsusceptible (DNS) MRSA, vancomycin-intermediate MRSA (VISA), heteroresistant VISA (hVISA), vancomycin-resistant
Enterococcus faecalis
, and vancomycin-resistant
Enterococcus faecium
. Oritavancin MICs were determined in the presence of subinhibitory concentrations of BLs. Oritavancin combined with ceftaroline, cefazolin, or nafcillin was evaluated for lethal synergy against MRSA, and oritavancin combined with ceftaroline, ampicillin, or ertapenem was evaluated for lethal synergy against VRE in 24-h time-kill assays. Oritavancin at 0.5× the MIC was combined with BLs at 0.5× the MIC or the biological free peak concentration, whichever one was lower. Synergy was defined as a ≥2-log
10
-CFU/ml difference between the killing achieved with the combination and that achieved with the most active single agent at 24 h. Oritavancin MICs were ≤0.125 μg/ml for all MRSA isolates except three VISA isolates with MICs of 0.25 μg/ml. Oritavancin MICs for VRE ranged from 0.03 to 0.125 μg/ml. Oritavancin in combination with ceftaroline was synergistic against all MRSA phenotypes and statistically superior to all other combinations against DNS MRSA, hVISA, and MRSA isolates (
P
< 0.02). Oritavancin in combination with cefazolin and oritavancin in combination with nafcillin were also synergistic against all MRSA strains. Synergy between oritavancin and all BLs was revealed against VRE strain 8019, while synergy between oritavancin and ampicillin or ertapenem but not ceftaroline was demonstrated against VRE strain R7164. The data support the potential use of oritavancin in combination with BLs, especially oritavancin in combination with ceftaroline, for the treatment of infections caused by MRSA. The data from the present study are not as strong for oritavancin in combination with BLs for VRE. Further study of both MRSA and VRE in more complex models is warranted.
Pharmacodynamics of Voriconazole in Children: Further Steps along the Path to True Individualized Therapy
Authors: Huurneman Luc J. , Neely Michael , Veringa Anette , Docobo Pérez Fernando , Ramos-Martin Virginia , Tissing Wim J. , Alffenaar Jan-Willem C. , Hope William
Published: February 2016

Voriconazole is the agent of choice for the treatment of invasive aspergillosis in children at least 2 years of age. The galactomannan index is a routinely used diagnostic marker for invasive aspergillosis and can be useful for following the clinical response to antifungal treatment. The aim of this study was to develop a pharmacokinetic-pharmacodynamic (PK-PD) mathematical model that links the pharmacokinetics of voriconazole with the galactomannan readout in children. Twelve children receiving voriconazole for treatment of proven, probable, and possible invasive fungal infections were studied. A previously published population PK model was used as the Bayesian prior. The PK-PD model was used to estimate the average area under the concentration-time curve (AUC) in each patient and the resultant galactomannan-time profile. The relationship between the ratio of the AUC to the concentration of voriconazole that induced half maximal killing (AUC/EC
50
) and the terminal galactomannan level was determined. The voriconazole concentration-time and galactomannan-time profiles were both highly variable. Despite this variability, the fit of the PK-PD model was good, enabling both the pharmacokinetics and pharmacodynamics to be described in individual children. (AUC/EC
50
)/15.4 predicted terminal galactomannan (
P
= 0.003), and a ratio of >6 suggested a lower terminal galactomannan level (
P
= 0.07). The construction of linked PK-PD models is the first step in developing control software that enables not only individualized voriconazole dosages but also individualized concentration targets to achieve suppression of galactomannan levels in a timely and optimally precise manner. Controlling galactomannan levels is a first critical step to maximizing clinical response and survival.
Evaluation of the Efficacy of ME1111 in the Topical Treatment of Dermatophytosis in a Guinea Pig Model
Authors: Long L. , Hager C. , Ghannoum M.
Published: February 2016

The treatment of dermatophytoses, including onychomycosis, has come a long way over the past few decades with the introduction of oral antifungals (e.g., terbinafine and itraconazole). However, with these advancements in oral therapies come several undesirable effects, such as kidney and liver toxicity, along with drug-drug interactions. Consequently, there is a need for new topical agents that are effective against dermatophytosis. ME1111 is a topical antifungal under development. In this study, the
in vivo
efficacy of ME1111 was compared to that of ciclopirox in the topical treatment of dermatophytosis caused by
Trichophyton mentagrophytes
using a guinea pig model. Animals were treated with the topical antifungals starting at 3 days postinfection, with each agent being applied once daily for seven consecutive days. After the treatment period, the clinical and mycological efficacies were evaluated. The data showed that both antifungals demonstrated significant clinical and mycological efficacies; however, ME1111 showed clinical efficacy superior to that of ciclopirox (46.9% and 25.0%, respectively, with a
P
value of <0.001). The potent efficacy of ME1111 could be attributed to its properties, such as low keratin binding.
Perforin-2 Protects Host Cells and Mice by Restricting the Vacuole to Cytosol Transitioning of a Bacterial Pathogen
Authors: McCormack Ryan , Bahnan Wael , Shrestha Niraj , Boucher Justin , Barreto Marcella , Barrera Carlos M. , Dauer Edward A. , Freitag Nancy E. , Khan Wasif N. , Podack Eckhard R. , Schesser Kurt
Published: February 2016

The host-encoded Perforin-2 (encoded by the macrophage-expressed gene 1,
Mpeg1
), which possesses a pore-forming MACPF domain, reduces the viability of bacterial pathogens that reside within membrane-bound compartments. Here, it is shown that Perforin-2 also restricts the proliferation of the intracytosolic pathogen
Listeria monocytogenes
. Within a few hours of systemic infection, the massive proliferation of
L. monocytogenes
in
Perforin
-2
−/−
mice leads to a rapid appearance of acute disease symptoms. We go on to show in cultured
Perforin
-2
−/−
cells that the vacuole-to-cytosol transitioning of
L. monocytogenes
is greatly accelerated. Unexpectedly, we found that in
Perforin
-2
−/−
macrophages,
Listeria
-containing vacuoles quickly (≤15 min) acidify, and that this was coincident with greater virulence gene expression, likely accounting for the more rapid translocation of
L. monocytogenes
to its replicative niche in the cytosol. This hypothesis was supported by our finding that a
L. monocytogenes
strain expressing virulence factors at a constitutively high level replicated equally well in
Perforin
-2
+/+
and
Perforin
-2
−/−
macrophages. Our findings suggest that the protective role of Perforin-2 against listeriosis is based on it limiting the intracellular replication of the pathogen. This cellular activity of Perforin-2 may derive from it regulating the acidification of
Listeria
-containing vacuoles, thereby depriving the pathogen of favorable intracellular conditions that promote its virulence gene activity.
Minicells, Back in Fashion
Authors: Farley Madeline M. , Hu Bo , Margolin William , Liu Jun
Published: February 2016

Cryo-electron tomography (cryo-ET) has emerged as a leading technique for three-dimensional visualization of large macromolecular complexes and their conformational changes in their native cellular environment. However, the resolution and potential applications of cryo-ET are fundamentally limited by specimen thickness, preventing high-resolution
in situ
visualization of macromolecular structures in many bacteria (such as
Escherichia coli
and
Salmonella enterica
). Minicells, which were discovered nearly 50 years ago, have recently been exploited as model systems to visualize molecular machines
in situ
, due to their smaller size and other unique properties. In this review, we discuss strategies for producing minicells and highlight their use in the study of chemotactic signaling, protein secretion, and DNA translocation. In combination with powerful genetic tools and advanced imaging techniques, minicells provide a springboard for in-depth structural studies of bacterial macromolecular complexes
in situ
and therefore offer a unique approach for gaining novel structural insights into many important processes in microbiology.
Sulfide Consumption in Sulfurimonas denitrificans and Heterologous Expression of Its Three Sulfide-Quinone Reductase Homologs
Authors: Han Yuchen , Perner Mirjam
Published: February 2016

Sulfurimonas denitrificansis a sulfur-oxidizing epsilonproteobacterium. It has been reported to grow with sulfide and to harbor genes that encode sulfide-quinone reductases (SQRs) (catalyze sulfide oxidation). However, the actual sulfide concentrations at whichS. denitrificansgrows and whether its SQRs are functional remain enigmatic. Here, we illustrate the sulfide concentrations at whichS. denitrificansexhibits good growth, namely, 0.18 mM to roughly 1.7 mM. Around 2.23 mM, sulfide appears to inhibit growth.S. denitrificansharbors three SQR homolog genes on its genome (Suden_2082 for type II SQR, Suden_1879 for type III SQR, and Suden_619 for type IV SQR). They are all transcribed inS. denitrificans. According to our experiments, they appear to be loosely bound to the membrane. Each individualS. denitrificansSQR was heterologously expressed in theRhodobacter capsulatusSB1003sqrdeletion mutant, and all exhibited SQR activities individually. This suggests that all of these three genes encode functional SQRs. This study also provides the first experimental evidence of a functional bacterial type III SQR.

IMPORTANCEAlthough the epsilonproteobacteriumSulfurimonas denitrificanshas been described as using many reduced sulfur compounds as electron donors, there is little knowledge about its growth with sulfide. In many bacteria, the sulfide-quinone reductase (SQR) is responsible for catalyzing sulfide oxidation.S. denitrificanshas an array of different types ofsqrgenes on its genome and so do several other sulfur-oxidizingEpsilonproteobacteria. However, whether these SQRs are functional has remained unknown. Here, we shed light on sulfide metabolism inS. denitrificans. Our study provides the first experimental evidence of active epsilonproteobacterial SQRs and also gives the first report of a functional bacterial type III SQR.
Different Functions of Phylogenetically Distinct Bacterial Complex I Isozymes
Authors: Spero Melanie A. , Brickner Joshua R. , Mollet Jordan T. , Pisithkul Tippapha , Amador-Noguez Daniel , Donohue Timothy J.
Published: February 2016

NADH:quinone oxidoreductase (complex I) is a bioenergetic enzyme that transfers electrons from NADH to quinone, conserving the energy of this reaction by contributing to the proton motive force. While the importance of NADH oxidation to mitochondrial aerobic respiration is well documented, the contribution of complex I to bacterial electron transport chains has been tested in only a few species. Here, we analyze the function of two phylogenetically distinct complex I isozymes in
Rhodobacter sphaeroides
, an alphaproteobacterium that contains well-characterized electron transport chains. We found that
R. sphaeroides
complex I activity is important for aerobic respiration and required for anaerobic dimethyl sulfoxide (DMSO) respiration (in the absence of light), photoautotrophic growth, and photoheterotrophic growth (in the absence of an external electron acceptor). Our data also provide insight into the functions of the phylogenetically distinct
R. sphaeroides
complex I enzymes (complex I
A
and complex I
E
) in maintaining a cellular redox state during photoheterotrophic growth. We propose that the function of each isozyme during photoheterotrophic growth is either NADH synthesis (complex I
A
) or NADH oxidation (complex I
E
). The canonical alphaproteobacterial complex I isozyme (complex I
A
) was also shown to be important for routing electrons to nitrogenase-mediated H
2
production, while the horizontally acquired enzyme (complex I
E
) was dispensable in this process. Unlike the singular role of complex I in mitochondria, we predict that the phylogenetically distinct complex I enzymes found across bacterial species have evolved to enhance the functions of their respective electron transport chains.

IMPORTANCE
Cells use a proton motive force (PMF), NADH, and ATP to support numerous processes. In mitochondria, complex I uses NADH oxidation to generate a PMF, which can drive ATP synthesis. This study analyzed the function of complex I in bacteria, which contain more-diverse and more-flexible electron transport chains than mitochondria. We tested complex I function in
Rhodobacter sphaeroides
, a bacterium predicted to encode two phylogenetically distinct complex I isozymes.
R. sphaeroides
cells lacking both isozymes had growth defects during all tested modes of growth, illustrating the important function of this enzyme under diverse conditions. We conclude that the two isozymes are not functionally redundant and predict that phylogenetically distinct complex I enzymes have evolved to support the diverse lifestyles of bacteria.
Nocturnal seizure and simultaneous bilateral shoulder fracture-dislocation
Authors: Sahbudin Ilfita , Filer Andrew
Published: February 2016

An otherwise fit and well 27-year-old man presented with acute onset unexplained bilateral shoulder pain, and was found to have bilateral shoulder fractures and dislocations on imaging. Although features were atypical, a nocturnal seizure causing the bilateral shoulder fractures was suspected and EEG showed features compatible with epilepsy.
Urothelial carcinoma presenting with distant metastasis to the rectum
Authors: Esfandiari Alireza , Speakman Chris
Published: February 2016

Urothelial carcinomas (UC) arise from transitional cells in the urothelial tract. Advanced cases can spread locally to invade surrounding organs, or metastasise distantly to the lungs, bone or liver. We describe a case of an elderly woman with no previous cancer history, presenting with symptoms of an unusual distant metastasis.
Hidden acral lentiginous melanoma with cutaneous metastases masquerading as Kaposi's sarcoma in an HIV-positive Indian man
Authors: Gupta Vishal , Patra Suman , Arava Sudheer , Sethuraman Gomathy
Published: February 2016

A 33-year-old HIV-positive Indian man presented with multiple bluish and erythematous papulo-nodules on his right leg and foot. A diagnosis of Kaposi's sarcoma was suspected clinically. Biopsy of the cutaneous lesions showed features of melanoma. On careful re-examination, an irregular brown-black macule, of which the patient was unaware, was noted on the ipsilateral sole. Histological examination of the sole lesion also showed features of melanoma. Systemic evaluation revealed extensive nodal and visceral metastases.
Recovery from delirium and psychotic manifestations following treatment of anaemia with off-label rituximab in active cold haemagglutinin disease
Authors: Kaklamanos Michail , Regmi Sadie , Wrench David , Kinirons Mark
Published: February 2016

Anaemia is an independent, commonly under-recognised risk factor for delirium. Prompt management of anaemia and its underlying aetiology could result in recovery from delirium and associated psychotic manifestations. We report this unprecedented case of complete recovery from delirium and challenging behaviour, following treatment of autoimmune haemolytic anaemia with rituximab.
Acute EBV masquerading as peripheral T-cell lymphoma
Authors: Zhang Xiao-Yin , Collins Graham P , Soilleux Elizabeth , Eyre Toby Andrew
Published: February 2016

Histological features of Epstein-Barr virus (EBV) can rarely mimic lymphoma. A 25-year-old presented with a spontaneous splenic rupture following a short illness. Histopathology assessment of the splenic and marrow tissue was highly suggestive of peripheral T-cell lymphoma not-otherwise-specified (PTCL-NOS). T-cell receptor (TCR) PCR clonality studies revealed a monoclonal T-cell population expressing for both TCRβ and γ, strongly suggestive of a T-cell clonal disease. EBV IgM was positive and IgG negative. EBV PCR was positive (7.02 ×104/mL). Despite the strong suggestion of PTCL-NOS from histopathology and clonality studies, the decision was made to observe the patient and not start multiagent chemotherapy. The patient remained well, with no signs of PTCL and subsequently seroconverted to IgG+ EBV. We highlight the potential pitfall of acute EBV masquerading as PTCL and show the critical role of the multidisciplinary integration of histopathological, serology, molecular and clinical features to avoid misdiagnosis.
Randomised controlled trial of topical kanuka honey for the treatment of acne
Authors: Semprini Alex , Braithwaite Irene , Corin Andrew , Sheahan Davitt , Tofield Christopher , Helm Colin , Montgomery Barney , Fingleton James , Weatherall Mark , Beasley Richard
Published: February 2016

Objective

To investigate the efficacy of Honevo, a topical 90% medical-grade kanuka honey, and 10% glycerine (honey product) as a treatment for facial acne.

Design

Randomised controlled trial with single blind assessment of primary outcome variable.

Setting

Outpatient primary care from 3 New Zealand localities.

Participants

Of 136 participants aged between 16 and 40 years with a diagnosis of acne and baseline Investigator's Global Assessment (IGA) for acne score of ≥2.68, participants were randomised to each treatment arm.

Interventions

All participants applied Protex, a triclocarban-based antibacterial soap twice daily for 12 weeks. Participants randomised to the honey product treatment arm applied this directly after washing off the antibacterial soap, twice daily for 12 weeks.

Outcome measures

The primary outcome was ≥2 point decrease in IGA score from baseline at 12 weeks. Secondary outcomes included mean lesion counts and changes in subject-rated acne improvement and severity at weeks 4 and 12, and withdrawals for worsening acne.

Results

4/53 (7.6%) participants in the honey product group and 1/53 (1.9%) of participants in the control group had a ≥ 2 improvement in IGA score at week 12, compared with baseline, OR (95% CI) for improvement 4.2 (0.5 to 39.3), p=0.17. There were 15 and 14 participants who withdrew from the honey product group and control group, respectively.

Conclusions

This randomised controlled trial did not find evidence that addition of medical-grade kanuka honey in combination with 10% glycerine to standard antibacterial soap treatment is more effective than the use of antibacterial soap alone in the treatment of acne.

Trial registration number

ACTRN12614000003673; Results.
Secular trends in smoking during pregnancy according to income and ethnic group: four population-based perinatal surveys in a Brazilian city
Authors: Silveira Mariangela F , Matijasevich Alicia , Menezes Ana Maria B , Horta Bernardo L , Santos Ina S , Barros Aluisio J D , Barros Fernando C , Victora Cesar G
Published: February 2016

Objectives

To assess socioeconomic and ethnic inequalities in smoking during pregnancy over three decades (1982–2011).

Setting

Population-based study in Pelotas City, Brazil.

Participants

All urban women giving birth in the city hospitals in 1982 (5909), 1993 (5223) and 2004 (4201), plus all urban and rural women delivering from January 2011 to April 2012 (6275).

Primary outcome

Self-reported smoking during pregnancy.

Results

The prevalence of smoking during pregnancy fell from 35.7% in 1982 to 21.0% in 2011. In each survey, prevalence decreased with increasing income (p<0.001). In the poorest quintile, smoking fell by 27.4% in the period studied compared to 67.1% in the wealthiest quintile. In all surveys, prevalence was lower among white women than among those who classified themselves as black or brown (p<0.001). Over time, smoking declined by 50.0% among the former and 30.7% among the latter. Absolute and relative inequalities both increased over time.

Conclusions

The reduction in smoking during pregnancy was primarily due to a decline among white, high-income women. Further efforts are needed to reduce smoking among all population groups.
Does T wave inversion in lead aVL predict mid-segment left anterior descending lesions in acute coronary syndrome? A retrospective study
Authors: Nakanishi Nobuto , Goto Tadahiro , Ikeda Tomoya , Kasai Atsunobu
Published: February 2016

Objectives

Limited data are available regarding the predictive value of electrocardiographic T wave inversion in lead aVL for mid-segment left anterior descending (MLAD) lesions among patients with acute coronary syndrome (ACS).

Setting

Retrospective single-centre study, using a prospectively-collected coronary angiography database from January 2012 to December 2013.

Participants

We included consecutive adult patients with ACS who underwent urgent percutaneous coronary intervention (PCI) within 24 h after arriving at the hospital. We excluded patients who did not undergo an ECG before PCI, patients with proximal MLAD occlusion and patients diagnosed with vasospastic angina.

Primary and secondary outcome measures

The primary outcome was MLAD lesion >50%. The other outcome of interest was MLAD lesion as a cause of ACS. First, we evaluated the diagnostic values of T wave inversion in lead aVL regardless of other T wave changes for each outcome. Second, we evaluated the diagnostic values of isolated T wave inversion in lead aVL.

Results

Overall, 219 patients were eligible for the analysis. T wave inversion in lead aVL regardless of other T wave changes had a sensitivity of 32.9%, specificity of 48.2%, positive predictive value of 27.6% and negative predictive value of 54.5% for predicting MLAD lesions. Isolated T wave inversion in lead aVL had a sensitivity of 9.8%, specificity of 86.9%, positive predictive value of 30.8% and negative predictive value of 61.7% for predicting MLAD lesions. These diagnostic values did not change materially when focusing on patients with MLAD lesion as the cause.

Conclusions

While T wave inversion in lead aVL regardless of other T wave changes had low diagnostic values for predicting MLAD lesions, isolated T wave inversion in lead aVL had a high specificity. Our inferences underscore the importance of a cautious interpretation of T wave inversion in lead aVL among patients with ACS.
Palliative care reimagined: a needed shift
Authors: Abel Julian , Kellehear Allan
Published: February 2016

Palliative care, since its inception over 60 years ago, has set the standard of how to care for people who are dying. Key features among these standards have been the professional development of clinical specialisms such as palliative medicine and palliative nursing; the essential addition of the multidisciplinary team to these two new specialisms that included social, spiritual and allied health workers—an outgrowth of the recognition that routine work with the dying, their carers, and the bereaved required more than solely clinical skills; and the unique partnership with communities that yielded the volunteer movement within palliative care. Professional, evidence-based symptom management and the importance of supportive care in its widest possible sense were and remain the cornerstones of the modern palliative care approach. However, the majority of people with terminal illnesses do not have access to palliative care teams, whose main focus of care remains patients with cancer. In the context outlined above this paper therefore poses two key questions: how can we provide an equitable level of care for all people irrespective of diagnosis and how can we increase the range and quality of non-medical/nursing supportive care in a context of diminishing resources? We argue that an important opportunity and solution can be found by adopting the principles of a public health approach to end-of-life care.
Compression-only cardiopulmonary resuscitation in improving bystanders’ cardiopulmonary resuscitation performance: a literature review
Authors: Min Ko Rachel Jia , Wu Vivien Xi , Lim Swee Han , San Tam Wilson Wai , Liaw Sok Ying
Published: February 2016

Background

Compression-only cardiopulmonary resuscitation (CPR) has been advocated as a preferable approach for bystanders in an out-of-hospital cardiac arrest (OHCA) event as it has been associated with an increased chance of survival. The elimination of mouth-to-mouth ventilation also addresses some of the barriers to performing CPR. The aim of this study is to undertake a literature review investigating the effectiveness of compression-only CPR in improving rescuers’ CPR performance when compared with standard CPR.

Methods

A literature search was conducted in the following databases: Cumulative Index to Nursing and Allied Health Literature, Science Direct, Scopus and PubMed from January 2003 to January 2014, to include research studies that compared compression-only CPR with standard CPR on participants above the age of 21, and reported quality of CPR performance as the primary outcome.

Findings

Of the 3004 articles retrieved, 16 met the inclusion criteria. The reviewed studies revealed that compression-only CPR requires a shorter time to initiate CPR and delivers a higher number of total compressions. The depth of compressions in compression-only CPR performed may be shallower than that of standard CPR due to greater rescuer fatigue. It therefore remains inconclusive if compression-only CPR can deliver a higher number of adequate compressions over extended periods of time. It is also unclear if simplified CPR can improve skill retention level in the long run.

Conclusions

More studies are needed to determine whether compression-only CPR can indeed help improve rescuers’ CPR performance. Future research efforts, together with resuscitation policy and practice implications, are needed to further improve rescuers’ CPR performance with the ultimate goal to enhance OHCA survival rates.
Axillary temperature measurement: a less stressful alternative for hospitalised cats?
Authors: Girod M. , Vandenheede M. , Farnir F. , Gommeren K.
Published: February 2016

Rectal temperature measurement (RTM) can promote stress and defensive behaviour in hospitalised cats. The aim of this study was to assess if axillary temperature measurement (ATM) could be a reliable and less stressful alternative for these animals. In this prospective study, paired rectal and axillary temperatures were measured in 42 cats, either by a veterinarian or a student. To assess the impact of these procedures on the cat's stress state, their heart rate was checked and a cat stress score (CSS) was defined and graded from 1 (relaxed) to 5 (terrified). A moderate correlation was found between RTM and ATM (r=0.52; P<0.0001). RTM was on average 0.9°C (1.6°F) higher than ATM (P<0.0001), although a wide variation was found in the difference between these two measurements (−2.1°C to 3.6°C (−3.8°F to 6.5°F)). ATM failed to identify hypothermia in 25 per cent of the cases and hyperthermia in 19 per cent of the cases but may be considered less stressful than RTM. Indeed, RTM induced a mildly greater increase in heart rate (+6 bpm; P=0.01) and in CSS (+0.2; P=0.001) than ATM. The results were not affected by operator type. In conclusion, RTM should remain the standard method to obtain accurate temperatures in cats.
Genome scan for nonadditive heterotic trait loci reveals mainly underdominant effects inSaccharomyces cerevisiae
Authors: Laiba Efrat , Glikaite Ilana , Levy Yael , Pasternak Zohar , Fridman Eyal
Published: February 2016

The overdominant model of heterosis explains the superior phenotype of hybrids by synergistic allelic interaction within heterozygous loci. To map such genetic variation in yeast, we used a population doubling time dataset of Saccharomyces cerevisiae 16 × 16 diallel and searched for major contributing heterotic trait loci (HTL). Heterosis was observed for the majority of hybrids, as they surpassed their best parent growth rate. However, most of the local heterozygous loci identified by genome scan were surprisingly underdominant, i.e., reduced growth. We speculated that in these loci adverse effects on growth resulted from incompatible allelic interactions. To test this assumption, we eliminated these allelic interactions by creating hybrids with local hemizygosity for the underdominant HTLs, as well as for control random loci. Growth of hybrids was indeed elevated for most hemizygous to HTL genes but not for control genes, hence validating the results of our genome scan. Assessing the consequences of local heterozygosity by reciprocal hemizygosity and allele replacement assays revealed the influence of genetic background on the underdominant effects of HTLs. Overall, this genome-wide study on a multi-parental hybrid population provides a strong argument against single gene overdominance as a major contributor to heterosis, and favors the dominance complementation model.
Characterization and abiotic stress-responsive expression analysis ofSGT1genes inBrassica oleracea
Authors: Shanmugam Ashokraj , Thamilarasan Senthil Kumar , Park Jong-In , Jung Mi Young , Nou Ill-Sup
Published: February 2016

SGT1 genes are involved in enhancing plant responses to various biotic and abiotic stresses. Brassica oleracea is known to contain two types of SGT1 genes, namely suppressor of G2 allele of SKP1 and suppressor of GCR2. In this study, through systematic analysis, four putative SGT1 genes were identified and characterized in B. oleracea. In phylogenetic analysis, the genes clearly formed separate groups, namely BolSGT1a, BolSGT1b (both suppressor of G2 allele of SKP1 types), and BolSGT1 (suppressor of GCR2). Functional domain analysis and organ-specific expression patterns suggested possible roles for BolSGT1 genes during stress conditions. BolSGT1 genes showed significant changes in expression in response to heat, cold, drought, salt, or ABA treatment. Interaction network analysis supported the expression analysis, and showed that the BolSGT1a and BolSGT1b genes are strongly associated with co-regulators during stress conditions. However, the BolSGT1 gene did not show any strong association. Hence, BolSGT1 might be a stress resistance-related gene that functions without a co-regulator. Our results show that BolSGT1 genes are potential target genes to improve B. oleracea resistance to abiotic stresses such as heat, cold, and salt.
Characterization of wheat – Psathyrostachys huashanica small segment translocation line with enhanced kernels per spike and stripe rust resistance
Authors: Kang Hou-Yang , Zhang Zhi-Juan , Xu Li-Li , Qi Wei-Liang , Tang Yao , Wang Hao , Zhu Wei , Li Dai-Yan , Zeng Jian , Wang Yi , Fan Xing , Sha Li-Na , Zhang Hai-Qin , Zhou Yong-Hong
Published: February 2016

Psathyrostachys huashanica Keng (2n = 2x = 14, NsNs), a distant wild relative of common wheat, possesses rich potentially valuable traits, such as disease resistance and more spikelets and kernels per spike, that could be useful for wheat genetic improvement. Development of wheat – P. huashanica translocation lines will facilitate its practical utilization in wheat breeding. In the present study, a wheat – P. huashanica small segmental translocation line, K-13-835-3, was isolated and characterized from the BC1F5 population of a cross between wheat – P. huashanica amphiploid PHW-SA and wheat cultivar CN16. Cytological studies showed that the mean chromosome configuration of K-13-835-3 at meiosis was 2n = 42 = 0.10 I + 19.43 II (ring) + 1.52 II (rod). GISH analyses indicated that chromosome composition of K-13-835-3 included 40 wheat chromosomes and a pair of wheat – P. huashanica translocation chromosomes. FISH results demonstrated that the small segment from an unidentified P. huashanica chromosome was translocated into wheat chromosome arm 5DS, proximal to the centromere region of 5DS. Compared with the cultivar wheat parent CN16, K-13-835-3 was highly resistant to stripe rust pathogens prevalent in China. Furthermore, spikelets and kernels per spike in K-13-835-3 were significantly higher than those of CN16 in two growing seasons. These results suggest that the desirable genes from P. huashanica were successfully transferred into CN16 background. This translocation line could be used as novel germplasm for high-yield and, eventually, resistant cultivar breeding.
Successful Pregnancy Using the NxStage Home Hemodialysis System
Authors: Brahmbhatt Yasmin , Ikeme Arinze , Bhogal Navjyot , Berghella Vincenzo
Published: February 2016

Pregnancy in the setting of the uremic milieu of renal disease has a lower success rate than in the normal population and is a rare event. While intensified renal replacement therapy (RRT) during pregnancy can lead to improved outcomes, most studies have focused on nocturnal hemodialysis as the main RRT in pregnancy. Although thousands of patients use the home NxStage System One short daily hemodialysis (SDHD) machine in the United States, pregnancy outcomes with this therapy are unknown. The NxStage System One uses low-volume dialysate and hence small and middle molecule clearance may differ compared to conventional therapies and affect pregnancy outcomes. We report a case of a successful conception and pregnancy using the home NxStage system. The NxStage system may provide an alternative to the more routinely used NHD or standard SDHD therapies for women of childbearing age.
Haploidentical Hematopoietic Stem Cell Transplantation: Expanding the Horizon for Hematologic Disorders
Authors: Zahid Mohammad Faizan , Rizzieri David Alan
Published: February 2016

Despite the advent of targeted therapies and novel agents, allogeneic hematopoietic stem cell transplantation remains the only curative modality in the management of hematologic disorders. The necessity to find an HLA-matched related donor is a major obstacle that compromises the widespread application and development of this field. Matched unrelated donors and umbilical cord blood have emerged as alternative sources of donor stem cells; however, the cost of maintaining donor registries and cord blood banks is very high and even impractical in developing countries. Almost every patient has an HLA haploidentical relative in the family, meaning that haploidentical donors are potential sources of stem cells, especially in situations where cord blood or matched unrelated donors are not easily available. Due to the high rates of graft failure and graft-versus-host disease, haploidentical transplant was not considered a feasible option up until the late 20th century, when strategies such as “megadose stem cell infusions” and posttransplantation immunosuppression with cyclophosphamide showed the ability to overcome the HLA disparity barrier and significantly improve the rates of engraftment and reduce the incidence and severity of graft-versus-host disease. Newer technologies of graft manipulation have also yielded the same effects in addition to preserving the antileukemic cells in the donor graft.
Some Remarks on Nonlinear Electrodynamics
Authors: Gaete Patricio
Published: February 2016

By using the gauge-invariant, but path-dependent, variables formalism, we study both massive Euler-Heisenberg-like and Euler-Heisenberg-like electrodynamics in the approximation of the strong-field limit. It is shown that massive Euler-Heisenberg-type electrodynamics displays the vacuum birefringence phenomenon. Subsequently, we calculate the lowest-order modifications to the interaction energy for both classes of electrodynamics. As a result, for the case of massive Euler-Heisenbeg-like electrodynamics (Wichmann-Kroll), unexpected features are found. We obtain a new long-range (1/r3-type) correction, apart from a long-range(1/r5-type) correction to the Coulomb potential. Furthermore, Euler-Heisenberg-like electrodynamics in the approximation of the strong-field limit (to the leading logarithmic order) displays a long-range (1/r5-type) correction to the Coulomb potential. Besides, for their noncommutative versions, the interaction energy is ultraviolet finite.
Gun Access and Safety Practices among Older Adults
Authors: Lum Hillary D. , Flaten Hanna K. , Betz Marian E.
Published: February 2016

Background. Given high rates of gun ownership among older adults, geriatric providers can assess firearm safety practices using a “5 Ls” approach: Locked; Loaded; Little children; feeling Low; and Learned owner. This study describes gun access and the “5 Ls” among US older adults.Methods. Data on the “5 Ls” from the Second Injury Control and Risk Survey (ICARIS-2), a national telephone survey conducted by the Centers for Disease Control and Prevention, were analyzed. Weighted variables were used to generate national estimates regarding prevalence of gun ownership and associated gun safety among older adults (≥55 years).Results. Of 2939 older adults, 39% (95% CI 37%–42%) reported ≥1 gun stored at home. Among those with guns at home, 21% (95% CI 18–24%) stored guns loaded and unlocked; 9.2% (95% CI 6.6–12%) had ≥1 child in household; 5.1% (95% CI 3.5–6.8%) reported past-year suicidal ideation and 3.6% (95% CI 2.1–5.2%) reported history of a suicide attempt; and 55% (95% CI 51–59%) stated that ≥1 adult had attended firearm safety workshop.Conclusion. Some older adults may be at elevated risk of firearm injury because of storage practices, suicidal thoughts, or limited safety training. Future work should assess effective approaches to reduce the risk of gun-related injuries among older adults.
Evaluation of Hepatotoxicity with Treatment Doses of Flucytosine and Amphotericin B for Invasive Fungal Infections
Authors: Folk Alexandra , Cotoraci Coralia , Balta Cornel , Suciu Maria , Herman Hildegard , Boldura Oana Maria , Dinescu Sorina , Paiusan Lucian , Ardelean Aurel , Hermenean Anca
Published: February 2016

Invasive fungal infection is a well-known cause of morbidity and mortality in immunocompromised patients. In this study we aimed to evaluate the hepatotoxicity induced by combined therapy of flucytosine and amphotericin B, at three different doses administered to mice for 14 days: 50 mg/kg flucytosine and 300 μg/kg amphotericin B; 100 mg/kg flucytosine and 600 μg/kg amphotericin B; 150 mg/kg flucytosine and 900 μg/kg amphotericin B. Liver injuries were evaluated by analysis of optic and electron microscopy samples, changes in TNF-α, IL-6, and NF-κB inflammation markers levels of expression, and evaluation of mRNA profiles. Histological and ultrastructural analysis revealed an increase in parenchymal and portal inflammation in mice and Kupffer cells activation. Combined antifungal treatment stimulated activation of an inflammatory pathway, demonstrated by a significant dose-dependent increase of TNF-αand IL-6 immunoreactivity, together with mRNA upregulation. Also, NF-κB was activated, as suggested by the high levels found in hepatic tissue and upregulation of target genes. Our results suggest that antifungal combined therapy exerts a synergistic inflammatory activation in a dose-dependent manner, through NF-κB pathway, which promotes an inflammatory cascade during inflammation. The use of combined antifungal therapy needs to be dose limiting due to the associated risk of liver injury, especially for those patients with hepatic dysfunction.
Naoxintong Protects Primary Neurons from Oxygen‐Glucose Deprivation/Reoxygenation Induced Injury through PI3K‐Akt Signaling Pathway
Authors: Ma Yan , Zhao Pei , Zhu Jinqiang , Yan Chen , Li Lin , Zhang Han , Zhang Meng , Gao Xiumei , Fan Xiang
Published: February 2016

Naoxintong capsule (NXT), developed from Buyang Huanwu Decoction, has shown the neuroprotective effects in cerebrovascular diseases, but the neuroprotection mechanisms of NXT on ischemia/reperfusion injured neurons have not yet been well known. In this study, we established the oxygen‐glucose deprivation/reoxygenation (OGD/R) induced neurons injury model and treat the neurons with cerebrospinal fluid containing NXT (BNC) to investigate the effects of NXT on OGD/R induced neurons injury and potential mechanisms. BNC improved neuron viability and decreased apoptotic rate induced by OGD/R. BNC attenuated OGD/R induced cytosolic and mitochondrial Ca2+ overload, ROS generation, intracellular NO levels and nNOS mRNA increase, and cytochrome‐c release when compared with OGD/R group. BNC significantly inhibited both mPTP opening and ΔΨm depolarization. BNC increased Bcl‐2 expression and decreased Bax expression, upregulated the Bcl‐2/Bax ratio, downregulated caspase‐3 mRNA and caspase‐9 mRNA expression, and decreased cleaved caspase‐3 expression and caspase‐3 activity. BNC increased phosphorylation of Akt following OGD/R, while LY294002 attenuated BNC induced increase of phosphorylated Akt expression. Our study demonstrated that NXT protected primary neurons from OGD/R induced injury by inhibiting calcium overload and ROS generation, protecting mitochondria, and inhibiting mitochondrial apoptotic pathway which was mediated partially by PI3K‐Akt signaling pathway activation.
Predicting Renal Failure Progression in Chronic Kidney Disease Using Integrated Intelligent Fuzzy Expert System
Authors: Norouzi Jamshid , Yadollahpour Ali , Mirbagheri Seyed Ahmad , Mazdeh Mitra Mahdavi , Hosseini Seyed Ahmad
Published: February 2016

Background.Chronic kidney disease (CKD) is a covert disease. Accurate prediction of CKD progression over time is necessary for reducing its costs and mortality rates. The present study proposes an adaptive neurofuzzy inference system (ANFIS) for predicting the renal failure timeframe of CKD based on real clinical data.Methods.This study used 10-year clinical records of newly diagnosed CKD patients. The threshold value of 15 cc/kg/min/1.73 m2of glomerular filtration rate (GFR) was used as the marker of renal failure. A Takagi-Sugeno type ANFIS model was used to predict GFR values. Variables of age, sex, weight, underlying diseases, diastolic blood pressure, creatinine, calcium, phosphorus, uric acid, and GFR were initially selected for the predicting model.Results.Weight, diastolic blood pressure, diabetes mellitus as underlying disease, and currentGFR(t)showed significant correlation with GFRs and were selected as the inputs of model. The comparisons of the predicted values with the real data showed that the ANFIS model could accurately estimate GFR variations in all sequential periods (Normalized Mean Absolute Error lower than 5%).Conclusions.Despite the high uncertainties of human body and dynamic nature of CKD progression, our model can accurately predict the GFR variations at long future periods.