bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of life among the family caregivers of patients with terminal cancer at home in Japan
Authors: Ito Eriko , Tadaka Etsuko
Published: February 2017

Aim

To identify the associated factors of quality of life (QOL) among the family caregivers of patients with terminal cancer at home.

Methods

The design was an epidemiological study with self‐administered questionnaires by mail. Date collection was carried out in the Tokyo Metropolitan, Tochigi, Ibaraki, Saitama, Chiba, Kanagawa, Nara, Hyogo, Kagawa, Ehime, and Saga prefectures in Japan. The participants who met the criteria for the present study were 262 family caregivers. Their QOL was assessed by the Japanese version of the Caregiver Quality of Life Index‐Cancer. The potential factors that are associated with family caregivers' QOL included three factors: patient factors, including demographic characteristics and disease‐related factors, family caregiver factors, including demographic characteristics, health conditions, and self‐efficacy of family caregiving, and environmental factors, including instrumental, emotional, informational support, and satisfaction with the home care service. A multiple regression analysis was conducted in order to identify the associated factors with family caregivers' QOL.

Results

A total of 74 family caregivers participated in this study (response rate: 33.2%). The mean age of the family caregivers was 63.6 years and 79.7% was female. The multiple regression analysis indicated that depression, self‐efficacy of family caregiving, the subcaregiver, and satisfaction with the home care service were associated with family caregivers' QOL.

Conclusion

It is recommended that health practitioners should develop interventions for family caregivers in order to enhance the competence of the individual and home care system in order to achieve the sustainability of high‐quality home care for patients with terminal cancer and the family caregivers' QOL.
Counter‐intuitive moral judgement following traumatic brain injury
Authors: Rowley Dane A. , Rogish Miles , Alexander Timothy , Riggs Kevin J.
Published: February 2017

Several neurological patient populations, including traumatic brain injury (TBI), appear to produce an abnormally ‘utilitarian’ pattern of judgements to moral dilemmas; they tend to make judgements that maximize the welfare of the majority, rather than deontological judgements based on the following of moral rules (e.g., do not harm others). However, this patient research has always used extreme dilemmas with highly valued moral rules (e.g., do not kill). Data from healthy participants, however, suggest that when a wider range of dilemmas are employed, involving less valued moral rules (e.g., do not lie), moral judgements demonstrate sensitivity to the psychological intuitiveness of the judgements, rather than their deontological or utilitarian content (Kahane et al., Social Cognitive and Affective Neuroscience, 7, 2011, 393). We sought the moral judgements of 30 TBI participants and 30 controls on moral dilemmas where content (utilitarian/deontological) and intuition (intuitive/counter‐intuitive) were measured concurrently. Overall TBI participants made utilitarian judgements in equal proportions to controls; disproportionately favouring utilitarian judgements only when they were counter‐intuitive, and deontological judgements only when they were counter‐intuitive. These results speak against the view that TBI causes a specific utilitarian bias, suggesting instead that moral intuition is broadly disrupted following TBI.
Biochemical analysis of intraplacental choriocarcinoma and fetomaternal transfusion
Authors: Ishiguro Tatsuya , Suda Kazuaki , Enomoto Takayuki
Published: February 2017

Intraplacental choriocarcinoma is one of the rarest forms of gestational tumors and is believed to be one of the causes of fetomaternal transfusion (FMT). A 35‐year‐old woman, gravida 2, para 2, with a history of two vaginal deliveries, was incidentally diagnosed as having stage I gestational intraplacental choriocarcinoma with a FIGO/World Health Organization 2000 risk score of 2 after term delivery. This disease caused neonatal anemia but did not metastasize to either the mother or infant. Short tandem repeat analysis with laser microdissection revealed that the tumor had originated from the current pregnancy. Serological test and immunohistochemical analysis revealed that the patient and her baby suffered from FMT. She has been free from disease without any medical intervention for the last 1 year. A combination of multiple biochemical analyses might help us diagnose the precursor pregnancy of a gestational choriocarcinoma and FMT.
Cesarean myomectomy in modern obstetrics: More light and fewer shadows
Authors: Sparić Radmila , Kadija Saša , Stefanović Aleksandar , Spremović Radjenović Svetlana , Likić Ladjević Ivana , Popović Jela , Tinelli Andrea
Published: February 2017

The study aim was to evaluate management of myomas during cesarean section, the pro and cons and the outcomes of cesarean myomectomy. Moreover, we tried to investigate the long‐term outcomes of cesarean myomectomy. The authors conducted a literature review using scientific databases, focusing on the benefits and outcomes of cesarean myomectomy and the recent trends regarding this topic, and identified relevant articles, related references and other papers citing them. Despite the demonstrated advantages of cesarean myomectomy, postponed myomectomy after cesarean section was recommended in some instances. Apart from recent reports on the safety and feasibility of cesarean myomectomy, the current literature also describes serious complications of cesarean myomectomy, including even maternal death. This poses a question about the reported rate of complications: whether it is underestimated in common practice. Although some studies strongly suggest the safety of cesarean myomectomy, data on the long‐term outcomes of cesarean myomectomy in women are lacking. The risk–benefit ratio of cesarean myomectomy should be re‐evaluated in the new century, given the increasing patient age, incidence of myoma in pregnancy, and the wide use of assisted reproductive techniques.
Clinical and psychological effects of excessive screen time on children
Authors: Domingues‐Montanari Sophie
Published: February 2017

Over recent years, screen time has become a more complicated concept, with an ever‐expanding variety of electronic media devices available throughout the world. Television remains the predominant type of screen‐based activity among children. However, computer use, video games and ownership of devices, such as tablets and smart phones, are occurring from an increasingly young age. Screen time, in particular, television viewing, has been negatively associated with the development of physical and cognitive abilities, and positively associated with obesity, sleep problems, depression and anxiety. The physiological mechanisms that underlie the adverse health outcomes related to screen time and the relative contributions of different types of screen and media content to specific health outcomes are unclear. This review discusses the positive and negative effects of screen time on the physiological and psychological development of children. Furthermore, recommendations are offered to parents and clinicians.
Job creators, job creation, and the tax code
Authors: Masters Adrian
Published: February 2017

This paper considers the role of the tax code in determining income dispersion and vacancy creation. A “span‐of‐control” model is embedded into a search and matching environment. A cut to the tax on profits in isolation improves job creation and reduces before‐tax income inequality. The impact of a budget‐balancing increase in the wage tax depends on the bargaining power of firms. When it is high, firms pick up the lion's share of the tax burden. The tax acts like a barrier to entry: it benefits large firms at the expense of marginal ones. Net effects are an increase in unemployment and before‐tax income dispersion. Low firm bargaining power means workers pick up more of the tax burden. It acts like a subsidy to entrepreneurship reinforcing the impact of the profit tax reduction. Taxes on the returns to capital leave everyone worse off.
Fairness in tax compliance: A political competition model
Authors: Solano‐Garcia Ángel
Published: February 2017

This paper analyzes the political economy of income redistribution when voters are concerned about fairness in tax compliance. We consider a two‐stage model where there is a two‐party competition over the tax rate and over the intensity of the tax enforcement policy in the first stage, and voters decide about their level of tax compliance in the second stage. We find that if the concern about fairness in tax compliance is high enough, a liberal middle‐income majority of voters may block any income redistribution policy. Alternatively, we find an equilibrium in which the preferences of the median voter are ignored in favor of a coalition formed by a group of relatively poor voters and the richest voters. In this equilibrium income redistribution prevails with no tax enforcement.
Complex crater formation: Insights from combining observations of shock pressure distribution with numerical models at the West Clearwater Lake impact structure
Authors: Rae A. S. P. , Collins G. S. , Grieve R. A. F. , Osinski G. R. , Morgan J. V.
Published: February 2017

Large impact structures have complex morphologies, with zones of structural uplift that can be expressed topographically as central peaks and/or peak rings internal to the crater rim. The formation of these structures requires transient strength reduction in the target material and one of the proposed mechanisms to explain this behavior is acoustic fluidization. Here, samples of shock‐metamorphosed quartz‐bearing lithologies at the West Clearwater Lake impact structure, Canada, are used to estimate the maximum recorded shock pressures in three dimensions across the crater. These measurements demonstrate that the currently observed distribution of shock metamorphism is strongly controlled by the formation of the structural uplift. The distribution of peak shock pressures, together with apparent crater morphology and geological observations, is compared with numerical impact simulations to constrain parameters used in the block‐model implementation of acoustic fluidization. The numerical simulations produce craters that are consistent with morphological and geological observations. The results show that the regeneration of acoustic energy must be an important feature of acoustic fluidization in crater collapse, and should be included in future implementations. Based on the comparison between observational data and impact simulations, we conclude that the West Clearwater Lake structure had an original rim (final crater) diameter of 35–40 km and has since experienced up to ~2 km of differential erosion.
Knowing the Meaning of a Word: Shared Psychological States and the Determination of Extensions
Authors: Pritchard Timothy
Published: February 2017

What is it to know the meaning of a word? The traditional view is that it involves the possession of a concept that determines the extension of a word, with the concept corresponding to a single psychological state. Millikan criticizes this view, denying not only that concepts determine extensions but also that sharing a concept means sharing a psychological state. The purpose of this article is to defend a modified version of the traditional view. I argue that Millikan's claims do not translate directly into a thesis about word meaning. Her arguments relate to an extra‐linguistic approach to extension, which we can distinguish from a linguistically oriented notion of extension.
Comparison of AT8 immunoreactivity in the locus ceruleus and hippocampus of 154 brains from routine autopsies
Authors: Okamoto Koichi , Amari Masakuni , Fukuda Toshio , Suzuki Keiji , Takatama Masamitsu
Published: February 2017

We compared semiquantitatively AT8 immunoreactivity in the locus ceruleus (LC) and hippocampus of 154 brains from routine autopsies to investigate the initial sites of phosphorylated tau (phospho‐tau) development. The numbers of AT8‐positive neurons and the severity of AT8‐positive neuropil threads (NTs) in the LC were strongly associated: there were no cases with AT8‐positive neurons that lacked NTs and 20 cases (13%) had only NTs in the LC. Phospho‐tau pathologies in the LC were almost equally on both sides, although some cases (7.8%) showed unilateral predominance. The numbers of AT8‐positive neurons in the LC and the numbers of AT8‐positive neurons and NTs in the hippocampus were also strongly associated. There were only two cases with AT8‐positive neurons in the LC that lacked phospho‐tau pathology in the hippocampus, and 21 cases (13.6%) with phospho‐tau pathology in the hippocampus that lacked AT8‐positive neurons in the LC. The numbers of AT8‐positive NTs in the LC and AT8‐positive neurons and NTs in the hippocampus were also strongly associated. There were seven cases (4.5%) with AT8‐positive NTs in the LC that lacked phospho‐tau pathology in the hippocampus, and five cases (3.2 %) with phospho‐tau pathologies in the hippocampus that lacked AT8‐positive NTs in the LC. In this study, we could not confirm that phospho‐tau pathologies begin in the LC. We suspect their simultaneous occurrences in both hippocampal regions and in LC.
Conditioned inhibitory and excitatory gain modulations of visual cortex in fear conditioning: Effects of analysis strategies of magnetocortical responses
Authors: Moratti Stephan , Giménez‐Fernández Tamara , Méndez‐Bértolo Constantino , de Vicente‐Pérez Francisco
Published: February 2017

In unpredictable environments, stimuli that predict potential danger or its absence can change rapidly. Therefore, it is highly adaptive to prioritize incoming sensory information flexibly as a function of prior experience. Previously, these changes have only been conceptualized as excitatory gain increases in sensory cortices for acquired fear‐relevant stimuli during associative learning. However, formal descriptions of associative processes by Rescorla and Wagner predict both conditioned excitatory and inhibitory processes in response systems for fear and safety cues, respectively. Magnetocortical steady‐state visual evoked fields (ssVEFs) have been shown to vary in amplitude as a function of associative strength. Therefore, we wondered why previous studies reporting ssVEF modulations by fear learning did not observe conditioned inhibition of ssVEF responses for the safety cue. Three analysis strategies were applied: (1) traditional analysis of ssVEF amplitude at occipital MEG sensors, (2) applying a general linear model (GLM) at each sensor, and (3) fitting the same GLM to cortically localized ssVEF responses. First, we replicated previous findings of increased ssVEFs for acquired fear‐relevant stimuli using all three analysis strategies. Critically, we demonstrated conditioned inhibition of ssVEF responses for fear‐irrelevant cues for specific gradiometer sensor types using the traditional analysis technique and for all sensor types when applying a GLM to the sensor space. However, sensor space effects were rather small. In stark contrast, cortical source space effect sizes were most pronounced. The results of opposing CS+ and CS‐ modulations in sensory cortex reflect predictions of the Rescorla‐Wagner model and current neurobiological findings.
Oral administration of Saccharomyces cerevisiaeUFMG A‐905 prevents allergic asthma in mice
Authors: Fonseca Vanessa M.B. , Milani Thamires M.S. , Prado Rafael , Bonato Vania L.D. , Ramos Simone G. , Martins Flaviano S. , Vianna Elcio O. , Borges Marcos de C.
Published: February 2017

ABSTRACT

Background and objective

The prevalence of asthma has increased in communities that adopt a Western lifestyle and become more urbanized. Probiotics may be effective in the prevention of allergic diseases, such as asthma. The aim of the current study was to examine the effects of Saccharomyces cerevisiae UFMG A‐905 in an allergic model of asthma.

Methods

Balb/c mice were sensitized twice with ovalbumin (OVA) intraperitoneally, 1 week apart and challenged with OVA intranasally for 3 days. Mice were daily treated with S. cerevisiae UFMG A‐905 via gavaging needle 10 days before OVA sensitization and during challenges. After challenge, in vivo lung function was measured, and bronchoalveolar lavage (BAL) and lung inflammation were assessed.

Results

Oral treatment with S. cerevisiae UFMG A‐905 significantly decreased airway hyperresponsiveness, total cell number and the influx of eosinophils to the airway, inflammatory cell in the lung, mucus expression in epithelial cells and the levels of IL‐4, IL‐5 and IL‐13. Additionally, S. cerevisiae UFMG A‐905 restored the levels of IL‐10 and interferon (IFN)‐gamma, and increased the levels of IL‐17A.

Conclusion

Oral administration of S. cerevisiae UFMG A‐905 prevented the development of major asthma‐like characteristics in a mouse model.
Having it both ways: White denial of racial salience while claiming oppression
Authors: Kolber Jesse
Published: February 2017

This work will examine literature on white ideologies concerning the denial of the significance of race, the denial of white privilege, and increasingly popular claims of ‘anti‐white bias’ and white victimhood. Variant literatures on white attitudes and interracial practices recently emerged regarding racism; this review will examine how they are inextricably linked to one another. In reviewing the recent literature on colorblindness, the denial of white privilege, and white victimhood, I will show how these (sometimes contradictory) beliefs work in concert to perpetuate racial inequalities. I argue that volatile racist tactics obscure accountability, sustain denial, and ultimately create a protective barrier to directly addressing white supremacy in the United States.
Water-modulated oxidation in the growth of m-ZnO epitaxial thin film by atomic layer deposition
Authors: Hsieh Wan-Chen , Wadekar Paritosh Vilas , Liu Hua-Huei , Lee Chiao-Han , Chang Chun-Fu , Tu Li-Wei , You Shou-Ting , Chen Quark Yungsung , Huang Hui-Chun , Ho New-Jin , Seo Hye-Won , Chu Wei-Kan
Published: February 2017

The effects of extra H2O-modulated oxidation are reported on the structural, optical, and electrical properties of nonpolar m-plane ZnO thin films grown on m-plane Al2O3 substrates by atomic layer deposition. Films without modulation, one modulated layer, and two modulated layers are compared. Structural properties studied using x-ray reflectivity, x-ray diffraction, and transmission electron microscopy show that all the films have a largely similar thickness and epitaxial relations with their substrates, but the rocking curves grow broader as the number of modulations increases. However, the extra layer of water modulation reduces the surface roughness drastically and also improves the electrical properties as compared to the unmodulated ZnO films. Water modulation is believed to serve as a source of atomic oxygen that promotes compensation of the pre-existing oxygen vacancies. The films tend to exhibit larger mosaicity around the a-axis as compared to that around the c-axis.
Preliminary Investigation of Executive Functions in Elite Ice Hockey Players
Authors: Lundgren Tobias , Högman Lennart , Näslund Markus , Parling Thomas
Published: February 2017

Elite level ice hockey places high demands on player’s physical and technical attributes as well as on cognitive and executive functions. There is, however, a notable lack of research on these attributes and functions. The present study investigated executive function with selected tests from the D-KEFS test battery among 48 ice hockey players and compared them to a standardized sample. Results show that ice hockey players’ scores were significantly higher on Design Fluency (DF) compared with the standardized sample score. Elite players’ scores were not significantly higher than those of lower-league hockey players. A significant correlation was found between on-ice performance and Trail Making Test (TMT) scores. Exploratory analysis showed that elite-level center forwards scored significantly higher on DF than did players in other positions. Future research should investigate whether assessment of executive function should be taken into account, in addition to physical and technical skills, when scouting for the next ice hockey star.
Physical Activity Throughout Adolescence and Hba1c in Early Adulthood: Birth Cohort Study
Authors: Nakamura Priscila M. , Mielke Grégore I. , Horta Bernardo L. , Assunção Maria Cecília , Gonçalves Helen , Menezes Ana M.B. , Barros Fernando C. , Ekelund Ulf , Brage Soren , Wehrmeister Fernando C. , Oliveira Isabel O. , Hallal Pedro C.
Published: February 2017

Background:

Physical inactivity is responsible for 7% of diabetes deaths worldwide, but little is known whether low levels of physical activity (PA) during adolescence increase the risk of diabetes in early adulthood. We evaluated the cross-sectional and longitudinal associations between PA throughout adolescence and HbA1c concentration in early adulthood.

Methods:

HbA1c was measured by high performance liquid chromatography. PA was assessed by self-report at the ages of 11, 15, and 18 years and by accelerometry at the ages of 13 (subsample) and 18 years. The loss percentages of follow up were 12.5% at 11 years, 14.4% at 15 years, and 18.7% at 18 years.

Results:

At 18 years, boys showed higher HbA1c than girls. At age 18 years, accelerometrybased PA at 18 years was inversely related to HbA1c levels in boys. Self-reported leisure-time PA at ages 11, 15, and 18 were unrelated to HbA1c in both genders. PA at 13 years of age was unrelated to HbA1c among both genders. In trajectory analysis, PA and accelerometer PA trajectories were not associated with later HbA1c.

Conclusions:

Objectively measured PA at 18 years was cross-sectionally inversely associated with HbA1c in boys only. No prospective associations were identified.
New Polymyxin B Dosing Strategies To Fortify Old Allies in the War against KPC-2-Producing Klebsiella pneumoniae
Authors: Bulman Zackery P. , Satlin Michael J. , Chen Liang , Kreiswirth Barry N. , Shin Beom Soo , Walsh Thomas J. , Holden Patricia N. , Forrest Alan , Nation Roger L. , Li Jian , Tsuji Brian T.
Published: February 2017

Pharmacodynamics of a polymyxin B, meropenem, and rifampin triple combination were examined against
Klebsiella pneumoniae
carbapenemase-producing
Klebsiella pneumoniae
(KPC-Kp) ST258. In time-kill experiments against three KPC-Kp isolates, triple combination generated 8.14, 8.19, and 8.29 log
10
CFU/ml reductions within 24 h. In the hollow-fiber infection model, the triple combination caused maximal killing of 5.16 log
10
CFU/ml at 78 h and the time required for regrowth was more than doubled versus the 2-drug combinations. Remarkably, combinations with a high single-dose polymyxin B burst plus rifampin preserved KPC-Kp polymyxin susceptibility (MIC
240 h
= 0.5 mg/liter) versus the same combination with traditionally dosed polymyxin B, where resistance was amplified (MIC
240 h
= 32 mg/liter).
Can Ceftazidime-Avibactam and Aztreonam Overcome β-Lactam Resistance Conferred by Metallo-β-Lactamases in Enterobacteriaceae?
Authors: Marshall Steven , Hujer Andrea M. , Rojas Laura J. , Papp-Wallace Krisztina M. , Humphries Romney M. , Spellberg Brad , Hujer Kristine M. , Marshall Emma K. , Rudin Susan D. , Perez Federico , Wilson Brigid M. , Wasserman Ronald B. , Chikowski Linda , Paterson David L. , Vila Alejandro J. , van Duin David , Kreiswirth Barry N. , Chambers Henry F. , Fowler Vance G. , Jacobs Michael R. , Pulse Mark E. , Weiss William J. , Bonomo Robert A.
Published: February 2017

Based upon knowledge of the hydrolytic profile of major β-lactamases found in Gram-negative bacteria, we tested the efficacy of the combination of ceftazidime-avibactam (CAZ-AVI) with aztreonam (ATM) against carbapenem-resistant enteric bacteria possessing metallo-β-lactamases (MBLs). Disk diffusion and agar-based antimicrobial susceptibility testing were initially performed to determine the
in vitro
efficacy of a unique combination of CAZ-AVI and ATM against 21 representative
Enterobacteriaceae
isolates with a complex molecular background that included
bla
IMP
,
bla
NDM
,
bla
OXA-48
,
bla
CTX-M
,
bla
AmpC
, and combinations thereof. Time-kill assays were conducted, and the
in vivo
efficacy of this combination was assessed in a murine neutropenic thigh infection model. By disk diffusion assay, all 21 isolates were resistant to CAZ-AVI alone, and 19/21 were resistant to ATM. The
in vitro
activity of CAZ-AVI in combination with ATM against diverse
Enterobacteriaceae
possessing MBLs was demonstrated in 17/21 isolates, where the zone of inhibition was ≥21 mm. All isolates demonstrated a reduction in CAZ-AVI agar dilution MICs with the addition of ATM. At 2 h, time-kill assays demonstrated a ≥4-log
10
-CFU decrease for all groups that had CAZ-AVI with ATM (8 μg/ml) added, compared to the group treated with CAZ-AVI alone. In the murine neutropenic thigh infection model, an almost 4-log
10
-CFU reduction was noted at 24 h for CAZ-AVI (32 mg/kg every 8 h [q8h]) plus ATM (32 mg/kg q8h) versus CAZ-AVI (32 mg/kg q8h) alone. The data presented herein require us to carefully consider this new therapeutic combination to treat infections caused by MBL-producing
Enterobacteriaceae
.
Nanoliposomal Buparvaquone Immunomodulates Leishmania infantum-Infected Macrophages and Is Highly Effective in a Murine Model
Authors: da Costa-Silva Thais Alves , Galisteo Andrés Jimenez , Lindoso José Angelo Lauletta , Barbosa Leandro R. S. , Tempone Andre Gustavo
Published: February 2017

Visceral leishmaniasis is a fatal parasitic neglected disease affecting 1.5 million people worldwide. Based on a drug repositioning approach, the aim of this work was to investigate thein vitroimmunomodulatory potential of buparvaquone (BPQ) and to establish a safe regimen to evaluate thein vivoefficacy of BPQ entrapped by negatively charged nanoliposomes (BPQ-LP) inLeishmania infantum-infected hamsters. Small-angle X-ray scattering, dynamic light scattering, and the ζ-potential were applied in order to study the influence of BPQ on the liposome structure. Our data revealed that BPQ was located in the polar-apolar interface, snorkeling the polar region, and protected against aggregation inside the lipophilic region. The presence of BPQ also decreased the Z-average hydrodynamic diameter and increased the surface charge. Compared to intravenous and intramuscular administration, a subcutaneous route was a more effective route for BPQ-LP; at 0.4 mg/kg, BPQ-LP reduced infection in the spleen and liver by 98 and 96%, respectively. Treatment for 5 days resulted in limited efficacy, but 10 days of treatment resulted in an efficacy similar to that of a 15-day regimen. The nanoliposomal drug was highly effective, with a mean 50% effective dose of 0.25 mg/kg, reducing the parasite load in bone marrow by 80%, as detected using quantitative PCR analysis. In addition, flow cytometry studies showed that BPQ upregulated cytokines as tumor necrosis factor, monocyte chemoattractant protein 1, interleukin-10 (IL-10), and IL-6 inLeishmania-infected macrophages, eliminating the parasites via a nitric oxide-independent mechanism. This new formulation proved to be a safe and effective treatment for murine leishmaniasis that could be a useful candidate against visceral leishmaniasis.
Nephrotoxicity in Patients with or without Cystic Fibrosis Treated with Polymyxin B Compared to Colistin
Authors: Crass Ryan L. , Rutter W. Cliff , Burgess Donna R. , Martin Craig A. , Burgess David S.
Published: February 2017

Nephrotoxicity is the primary adverse effect of the polymyxins. The relative rates of toxicity of polymyxin B and colistin have not been fully elucidated, especially in patients with cystic fibrosis (CF). A retrospective cohort study of adults treated with polymyxin B or colistin for at least 48 h was conducted. The primary endpoint was the incidence of kidney injury assessed by RIFLE (i.e.,
r
isk,
i
njury,
f
ailure,
l
oss,
e
nd-stage renal disease) criteria. Risk factors for kidney injury were evaluated using multivariate Cox regression. A total of 414 patients were evaluated, 220 of whom had CF. In patients without CF, there was no difference in kidney injury with polymyxin B and colistin (42.9% versus 50.3%,
P
= 0.46). Loop diuretic exposure was a risk factor for kidney injury (adjusted hazard ratio [aHR], 1.82; 95% confidence interval [CI], 1.16 to 2.83) in this population. In patients with CF, polymyxin B and colistin were associated with similar rates of kidney injury (34.5% versus 29.8%,
P
= 0.77). Diabetes (aHR, 2.68; 95% CI, 1.01 to 7.11), loop diuretics (aHR, 3.02; 95% CI, 1.36 to 6.73), and progressive care unit admission (aHR, 8.21; 95% CI, 2.55 to 26.46) were risk factors for kidney injury, while higher baseline serum creatinine levels (per 1 mg/dl) were protective (aHR, 0.08; 95% CI, 0.01 to 0.48). Total unadjusted kidney injury in polymyxin-treated patients was less frequent in those who had CF (30.5% versus 48.5%,
P
< 0.001). Polymyxin B and colistin are associated with a high incidence of kidney injury; cystic fibrosis may be protective against polymyxin nephrotoxicity, but further investigation is needed to confirm this conjecture.
Intracellular Targeting Mechanisms by Antimicrobial Peptides
Authors: Le Cheng-Foh , Fang Chee-Mun , Sekaran Shamala Devi
Published: February 2017

Antimicrobial peptides (AMPs) are expressed in various living organisms as first-line host defenses against potential harmful encounters in their surroundings. AMPs are short polycationic peptides exhibiting various antimicrobial activities. The principal antibacterial activity is attributed to the membrane-lytic mechanism which directly interferes with the integrity of the bacterial cell membrane and cell wall. In addition, a number of AMPs form a transmembrane channel in the membrane by self-aggregation or polymerization, leading to cytoplasm leakage and cell death. However, an increasing body of evidence has demonstrated that AMPs are able to exert intracellular inhibitory activities as the primary or supportive mechanisms to achieve efficient killing. In this review, we focus on the major intracellular targeting activities reported in AMPs, which include nucleic acids and protein biosynthesis and protein-folding, protease, cell division, cell wall biosynthesis, and lipopolysaccharide inhibition. These multifunctional AMPs could serve as the potential lead peptides for the future development of novel antibacterial agents with improved therapeutic profiles.
Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States
Authors: Satlin Michael J. , Chen Liang , Patel Gopi , Gomez-Simmonds Angela , Weston Gregory , Kim Angela C. , Seo Susan K. , Rosenthal Marnie E. , Sperber Steven J. , Jenkins Stephen G. , Hamula Camille L. , Uhlemann Anne-Catrin , Levi Michael H. , Fries Bettina C. , Tang Yi-Wei , Juretschko Stefan , Rojtman Albert D. , Hong Tao , Mathema Barun , Jacobs Michael R. , Walsh Thomas J. , Bonomo Robert A. , Kreiswirth Barry N.
Published: February 2017

Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant
Enterobacteriaceae
(CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among
Enterobacteriaceae
bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (
cps
), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance among
Klebsiella pneumoniae
,
Enterobacter
spp., and
Escherichia coli
bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were
K. pneumoniae
and 92% produced
K. pneumoniae
carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing
K. pneumoniae
(KPC-
Kp
). The
wzi154
allele, corresponding to
cps-2
, was present in 93% of KPC-3-
Kp
, whereas KPC-2-
Kp
had greater
cps
diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-
Kp
had an CAZ-AVI MIC of ≥4/4 μg/ml. There was a median of 47 h from bacteremia onset until active antimicrobial therapy, 38% of patients had septic shock, and 49% died within 30 days. KPC-3-
Kp
bacteremia (adjusted odds ratio [aOR], 2.58;
P
= 0.045), cancer (aOR, 3.61,
P
= 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79;
P
= 0.03) were independently associated with mortality. Active empirical therapy and combination therapy were not associated with survival. Despite a decade of experience with CRE, patients with CRE bacteremia have protracted delays in appropriate therapies and high mortality rates, highlighting the need for rapid diagnostics and evaluation of new therapeutics.
Phenotypic and Molecular Antimicrobial Susceptibility of Helicobacter pylori
Authors: Chen Derrick , Cunningham Scott A. , Cole Nicolynn C. , Kohner Peggy C. , Mandrekar Jayawant N. , Patel Robin
Published: February 2017

Failure to eradicate
Helicobacter pylori
infection is often a result of antimicrobial resistance, which for clarithromycin is typically mediated by specific point mutations in the 23S rRNA gene. The purpose of this study was to define current patterns of antimicrobial susceptibility in
H. pylori
isolates derived primarily from the United States and to survey them for the presence of point mutations in the 23S rRNA gene and assess the ability of these mutations to predict phenotypic clarithromycin susceptibility. Antimicrobial susceptibility testing was performed using agar dilution on 413
H. pylori
isolates submitted to Mayo Medical Laboratories for susceptibility testing. For a subset of these isolates, a 150-bp segment of the 23S rRNA gene was sequenced. A total of 1,970 MICs were reported over the 4-year study period. The rate of clarithromycin resistance was high (70.4%), and elevated MICs were frequently observed for metronidazole (82.4% of isolates had an MIC of >8 μg/ml) and ciprofloxacin (53.5% of isolates had an MIC of >1 μg/ml). A total of 111 archived
H. pylori
isolates underwent 23S rRNA gene sequencing; we found 95% concordance between genotypes and phenotypes (
P
= 0.9802). Resistance to clarithromycin was most commonly due to an A2143G mutation (82%), followed by A2142G (14%) and A2142C (4%) mutations. Clinical
H. pylori
isolates derived primarily from the United States demonstrated a high rate of clarithromycin resistance and elevated metronidazole and ciprofloxacin MICs. The relative distribution of point mutations at positions 2143 and 2142 in the 23S rRNA gene in clarithromycin-resistant
H. pylori
was similar to that reported from other parts of the world; these mutations predict phenotypic resistance to clarithromycin.
Global Molecular Epidemiology of IMP-Producing Enterobacteriaceae
Authors: Matsumura Yasufumi , Peirano Gisele , Motyl Mary R. , Adams Mark D. , Chen Liang , Kreiswirth Barry , DeVinney Rebekah , Pitout Johann D. D.
Published: February 2017

International data on the molecular epidemiology of
Enterobacteriaceae
with IMP carbapenemases are lacking. We performed short-read (Illumina) whole-genome sequencing on a global collection of 38 IMP-producing clinical
Enterobacteriaceae
(2008 to 2014). IMP-producing
Enterobacteriaceae
(7 varieties within 11 class 1 integrons) were mainly present in the South Pacific and Asia. Specific
bla
IMP
-containing integrons (In809 with
bla
IMP-4
, In722 with
bla
IMP-6
, and In687 with
bla
IMP-14
) were circulating among different bacteria in countries such as Australia, Japan, and Thailand. In1312 with
bla
IMP-1
was present in
Klebsiella pneumoniae
from Japan and
Citrobacter freundii
from Brazil.
Klebsiella pneumoniae
(
n
= 22) was the most common species; clonal complex 14 (CC14) from Philippines and Japan was the most common clone and contained In1310 with
bla
IMP-26
and In1321 with
bla
IMP-6
. The
Enterobacter cloacae
complex (
n
= 9) consisted of
Enterobacter hormaechei
and
E. cloacae
cluster III. CC78 (from Taiwan) containing In73 with
bla
IMP-8
was the most common clone among the
E. cloacae
complex. This study highlights the importance of surveillance programs using the latest molecular techniques for providing insight into the characteristics and global distribution of
Enterobacteriaceae
with
bla
IMP
genes.
Pleiotropic Regulation of Virulence Genes in Streptococcus mutans by the Conserved Small Protein SprV
Authors: Shankar Manoharan , Hossain Mohammad S. , Biswas Indranil
Published: February 2017

Streptococcus mutans
, an oral pathogen associated with dental caries, colonizes tooth surfaces as polymicrobial biofilms known as dental plaque.
S. mutans
expresses several virulence factors that allow the organism to tolerate environmental fluctuations and compete with other microorganisms. We recently identified a small hypothetical protein (90 amino acids) essential for the normal growth of the bacterium. Inactivation of the gene, SMU.2137, encoding this protein caused a significant growth defect and loss of various virulence-associated functions. An
S. mutans
strain lacking this gene was more sensitive to acid, temperature, osmotic, oxidative, and DNA damage-inducing stresses. In addition, we observed an altered protein profile and defects in biofilm formation, bacteriocin production, and natural competence development, possibly due to the fitness defect associated with SMU.2137 deletion. Transcriptome sequencing revealed that nearly 20% of the
S. mutans
genes were differentially expressed upon SMU.2137 deletion, thereby suggesting a pleiotropic effect. Therefore, we have renamed this hitherto uncharacterized gene as
sprV
(
s
treptococcal
p
leiotropic
r
egulator of
v
irulence). The transcript levels of several relevant genes in the
sprV
mutant corroborated the phenotypes observed upon
sprV
deletion. Owing to its highly conserved nature, inactivation of the
sprV
ortholog in
Streptococcus gordonii
also resulted in poor growth and defective UV tolerance and competence development as in the case of
S. mutans
. Our experiments suggest that SprV is functionally distinct from its homologs identified by structure and sequence homology. Nonetheless, our current work is aimed at understanding the importance of SprV in the
S. mutans
biology.

IMPORTANCE
Streptococcus mutans
employs several virulence factors and stress resistance mechanisms to colonize tooth surfaces and cause dental caries. Bacterial pathogenesis is generally controlled by regulators of fitness that are critical for successful disease establishment. Sometimes these regulators, which are potential targets for antimicrobials, are lost in the genomic context due to the lack of annotated homologs. This work outlines the regulatory impact of a small, highly conserved hypothetical protein, SprV, encoded by
S. mutans
. We show that SprV affects the transcript levels of various virulence factors required for normal growth, biofilm formation, stress tolerance, genetic competence, and bacteriocin production.
Vibrio Phage KVP40 Encodes a Functional NAD
+
Salvage Pathway
Authors: Lee Jae Yun , Li Zhiqun , Miller Eric S.
Published: February 2017

The genome of T4-type
Vibrio
bacteriophage KVP40 has five genes predicted to encode proteins of pyridine nucleotide metabolism, of which two,
nadV
and
natV
, would suffice for an NAD
+
salvage pathway. NadV is an apparent nicotinamide phosphoribosyltransferase (NAmPRTase), and NatV is an apparent bifunctional nicotinamide mononucleotide adenylyltransferase (NMNATase) and nicotinamide-adenine dinucleotide pyrophosphatase (Nudix hydrolase). Genes encoding the predicted salvage pathway were cloned and expressed in
Escherichia coli
, the proteins were purified, and their enzymatic properties were examined. KVP40 NadV NAmPRTase is active
in vitro
, and a clone complements a
Salmonella
mutant defective in both the bacterial
de novo
and salvage pathways. Similar to other NAmPRTases, the KVP40 enzyme displayed ATPase activity indicative of energy coupling in the reaction mechanism. The NatV NMNATase activity was measured in a coupled reaction system demonstrating NAD
+
biosynthesis from nicotinamide, phosphoribosyl pyrophosphate, and ATP. The NatV Nudix hydrolase domain was also shown to be active, with preferred substrates of ADP-ribose, NAD
+
, and NADH. Expression analysis using reverse transcription-quantitative PCR (qRT-PCR) and enzyme assays of infected
Vibrio parahaemolyticus
cells demonstrated
nadV
and
natV
transcription during the early and delayed-early periods of infection when other KVP40 genes of nucleotide precursor metabolism are expressed. The distribution and phylogeny of NadV and NatV proteins among several large double-stranded DNA (dsDNA) myophages, and also those from some very large siphophages, suggest broad relevance of pyridine nucleotide scavenging in virus-infected cells. NAD
+
biosynthesis presents another important metabolic resource control point by large, rapidly replicating dsDNA bacteriophages.

IMPORTANCE
T4-type bacteriophages enhance DNA precursor synthesis through reductive reactions that use NADH/NADPH as the electron donor and NAD
+
for ADP-ribosylation of proteins involved in transcribing and translating the phage genome. We show here that phage KVP40 encodes a functional pyridine nucleotide scavenging pathway that is expressed during the metabolic period of the infection cycle. The pathway is conserved in other large, dsDNA phages in which the two genes,
nadV
and
natV
, share an evolutionary history in their respective phage-host group.
A Cross-Sectional Survey of Pain Catastrophising and Acupuncture Use among Breast Cancer Survivors
Authors: Lee Iris , Garland Sheila N , DeMichele Angela , Farrar John T , Im Eun-Ok , Mao Jun J
Published: February 2017

Introduction

Treatment-related joint pain affects almost half of all women with breast cancer using aromatase inhibitors and is a major reason for terminating treatment. Although acupuncture is becoming an increasingly popular, evidence-based option for treating pain, little is known about the potential influence of psychological factors on acupuncture use.

Objective

We aimed to evaluate the association between pain catastrophising and use of acupuncture in breast cancer survivors experiencing arthralgia.

Methods

We conducted a cross-sectional survey of arthralgic breast cancer patients. Patients were asked if they had used acupuncture since their cancer diagnosis. The Pain Catastrophising Scale (PCS) was used to measure negative coping styles related to the experience of pain. We performed multiple logistic regression analysis to evaluate the relationship between pain catastrophising and acupuncture use, adjusting for covariates.

Results

Of the 424 participants, 69 (16%) reported use of acupuncture since their breast cancer diagnosis. In multivariate analyses, compared to those in the lowest PCS score tertile, patients with the highest PCS scores were more likely to have used acupuncture (p=0.03). In particular, patients with high levels of rumination (p=0.005) and magnification (p=0.008) were more likely to have used acupuncture. Helplessness was not associated with acupuncture use (p=0.23).

Conclusions

High levels of pain catastrophising, and specifically the processes of rumination and magnification, were associated with greater acupuncture use. We believe this could have important implications for understanding which population is more likely to seek acupuncture treatment and how this alternative therapy could be better targeted to these patients.
Multiple myeloma presenting with bilateral ankle pain (microangiopathy) and complicated by streptococcal meningitis andPneumocystis cariniipneumonia
Authors: Dunphy Louise , Singh Neeraj , Keating Elizabeth
Published: February 2017

Multiple myeloma is characterised by the neoplastic proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin. This clone of plasma cells proliferates in the bone marrow, resulting in extensive skeletal destruction with osteolytic lesions, osteopenia and pathological fractures. Additional disease-related complications include hypercalcaemia, renal insufficiency, anaemia and infection. We present the case of a 64-year-old woman presenting with rapid onset, painful distal symmetrical lower limb weakness and an acute kidney injury. Owing to her IgG κ paraprotein (kappa light chain 4620, kappa:lambda ratio 826), she was diagnosed with probable plasma cell myeloma. This diagnosis was confirmed following a trephine biopsy. She required renal replacement therapy, inotropic support and a percutaneous tracheostomy. She became acutely confused with a Glasgow Coma Scale score of 10/15 and a CT head showed no acute pathology. Further investigation with a lumbar puncture confirmed the diagnosis of streptococcal meningitis. She was treated with intravenous acyclovir, ceftriaxone and fluconazole. Her non-bronchoalveolar lavage revealed a diagnosis ofPneumocystis cariniipneumonia and she required treatment with co-trimoxazole. This case report discusses the clinical presentation, diagnostic algorithm and treatment of myeloma. This manuscript offers an important clinical reminder to consider myeloma in the differential diagnosis in patients presenting with bone pain and acute kidney injury.
Randomised controlled trial examining the effect of an outpatient exercise training programme on haemodynamics and cardiac MR parameters of right ventricular function in patients with pulmonary arterial hypertension: the ExPAH study protocol
Authors: Chia Karen S W , Faux Steven G , Wong Peter K K , Holloway Cameron , Assareh Hassan , McLachlan Craig S , Kotlyar Eugene
Published: February 2017

Introduction

Pulmonary hypertension (PH) is a potentially life-threatening condition characterised by elevated pulmonary artery pressure. Early stage PH patients are often asymptomatic. Disease progression is associated with impairment of right ventricular function and progressive dyspnoea. Current guidelines recommend exercise training (grade IIa, level B). However, many questions remain regarding the mechanisms of improvement, intensity of supervision and optimal frequency, duration and intensity of exercise. This study will assess the effect of an outpatient rehabilitation programme on haemodynamics and cardiac right ventricular function in patients with pulmonary arterial hypertension (PAH), a subgroup of PH.

Methods and analysis

This randomised controlled trial involves both a major urban tertiary and smaller regional hospital in New South Wales, Australia. The intervention will compare an outpatient rehabilitation programme with a control group (home exercise programme). Participants will be stable on oral PAH-specific therapy. The primary outcome measure will be right ventricular ejection fraction measured by cardiac MRI. Secondary outcomes will include haemodynamics measured by right heart catheterisation, endurance, functional capacity, health-related quality of life questionnaires and biomarkers of cardiac function and inflammation.

Ethics approval and dissemination

Ethical approval has been granted by St Vincent's Hospital, Sydney (HREC/14/SVH/341). Results of this study will be disseminated through presentation at scientific conferences and in scientific journals.

Trial registration number

ACTRN12615001041549; pre-results.