bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimicrobial cathelicidin peptide LL-37 inhibits the pyroptosis of macrophages and improves the survival of polybacterial septic mice
Authors: Hu Zhongshuang , Murakami Taisuke , Suzuki Kaori , Tamura Hiroshi , Reich Johannes , Kuwahara-Arai Kyoko , Iba Toshiaki , Nagaoka Isao 
Published: January 2016

AbstractLL-37 is the only known member of the cathelicidin family of antimicrobial peptides in humans. In addition to its broad spectrum of antimicrobial activities, LL-37 can modulate various inflammatory reactions. We previously revealed that LL-37 suppresses the LPS/ATP-induced pyroptosis of macrophages in vitro by both neutralizing the action of LPS and inhibiting the response of P2X7 (a nucleotide receptor) to ATP. Thus, in this study, we further evaluated the effect of LL-37 on pyroptosis in vivo using a cecal ligation and puncture (CLP) sepsis model. As a result, the intravenous administration of LL-37 improved the survival of the CLP septic mice. Interestingly, LL-37 inhibited the CLP-induced caspase-1 activation and pyroptosis of peritoneal macrophages. Moreover, LL-37 modulated the levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α) in both peritoneal fluids and sera, and suppressed the activation of peritoneal macrophages (as evidenced by the increase in the intracellular levels of IL-1β, IL-6 and TNF-α). Finally, LL-37 reduced the bacterial burdens in both peritoneal fluids and blood samples. Together, these observations suggest that LL-37 improves the survival of CLP septic mice by possibly suppressing the pyroptosis of macrophages, and inflammatory cytokine production by activated macrophages and bacterial growth. Thus, the present findings imply that LL-37 can be a promising candidate for sepsis because of its many functions, such as the inhibition of pyroptosis, modulation of inflammatory cytokine production and antimicrobial activity.
Quantifying usability: an evaluation of a diabetes mHealth system on effectiveness, efficiency, and satisfaction metrics with associated user characteristics
Authors: Georgsson Mattias , Staggers Nancy 
Published: January 2016

Abstract
Objective Mobile health (mHealth) systems are becoming more common for chronic disease management, but usability studies are still needed on patients’ perspectives and mHealth interaction performance. This deficiency is addressed by our quantitative usability study of a mHealth diabetes system evaluating patients’ task performance, satisfaction, and the relationship of these measures to user characteristics.
Materials and Methods We used metrics in the International Organization for Standardization (ISO) 9241-11 standard. After standardized training, 10 patients performed representative tasks and were assessed on individual task success, errors, efficiency (time on task), satisfaction (System Usability Scale [SUS]) and user characteristics.
Results Tasks of exporting and correcting values proved the most difficult, had the most errors, the lowest task success rates, and consumed the longest times on task. The average SUS satisfaction score was 80.5, indicating good but not excellent system usability. Data trends showed males were more successful in task completion, and younger participants had higher performance scores. Educational level did not influence performance, but a more recent diabetes diagnosis did. Patients with more experience in information technology (IT) also had higher performance rates.
Discussion Difficult task performance indicated areas for redesign. Our methods can assist others in identifying areas in need of improvement. Data about user background and IT skills also showed how user characteristics influence performance and can provide future considerations for targeted mHealth designs.
Conclusion Using the ISO 9241-11 usability standard, the SUS instrument for satisfaction and measuring user characteristics provided objective measures of patients’ experienced usability. These could serve as an exemplar for standardized, quantitative methods for usability studies on mHealth systems.
Beneficial Properties of Argon After Experimental Subarachnoid Hemorrhage: Early Treatment Reduces Mortality and Influences Hippocampal Protein Expression*
Authors: Höllig Anke , Weinandy Agnieszka , Liu Jingjin , Clusmann Hans , Rossaint Rolf , Coburn Mark 
Published: January 2016

Objectives:
Until now, treatment ameliorating early brain injury following subarachnoid hemorrhage has been nonexistent. Here, we evaluate the neuroprotective properties of argon after experimental subarachnoid hemorrhage with mortality as the primary endpoint and functional outcome, as well as hippocampal cellular and molecular stress response as secondary endpoints.

Design:
Randomized controlled animal study.

Setting:
University research laboratory.

Subjects:
Ninety-eight male Sprague-Dawley rats.

Interventions:
One hour after subarachnoid hemorrhage induction via endovascular perforation technique or sham surgery, a breathing gas mixture containing 50 vol% argon/50 vol% oxygen (argon group) or 50 vol% nitrogen/50 vol% oxygen (control group) was applied for 1 hour.

Measurements and Main Results:
The primary objective was mortality after subarachnoid hemorrhage. Additionally, outcome was assessed via 1) neurologic testing and 2) an open-field test 24 hours after subarachnoid hemorrhage, 3) protein analysis of hippocampal samples for hypoxia-inducible factor 1α and heme oxygenase 1, and 4) immunohistochemistry of hippocampal slices to quantify vital neurons. Animals were euthanized 6, 24, or 72 hours after subarachnoid hemorrhage or sham surgery. Occurrence of premature death (death prior to scheduled euthanasia) was assessed. Postconditioning with argon resulted in a reduction of risk with respect to premature death to 20.6% compared with the control group (95% CI, 4.39–96.7). Body weight was higher in the argon group over the entire observation period (p < 0.05). There was no difference in the neuroscore (p = 0.550). Expression of hypoxia-inducible factor 1α and heme oxygenase 1 in the hippocampus was increased in the argon group. Higher quantity of vital neurons in the hippocampal samples of the argon group was discovered 24 hours after subarachnoid hemorrhage.

Conclusions:
Argon application after experimental subarachnoid hemorrhage met the primary endpoint of reducing the risk of mortality. In addition, higher body weight indicating good overall condition was observed in the argon group over the entire observation period. Regarding the mechanism of action, hypoxia-inducible factor 1α–induced heme oxygenase 1 expression resulting in improved survival of neurons may contribute to the beneficial effect of argon application after subarachnoid hemorrhage.
Microvesicle Tissue Factor Activity and Interleukin-8 Levels are Associated with Mortality in Patients with Influenza A/H1N1 Infection
Authors: Rondina Matthew T. , Tatsumi Kohei , Bastarache Julie A. , Mackman Nigel 
Published: January 2016

Objectives:
To identify plasma biomarkers that can be early predictors of mortality in critically ill patients with primary influenza A/H1N1.

Design:
A prospective, multicenter, case-cohort pilot study.
Setting: Three academic ICUs.

Patients:
Fifteen patients with primary influenza A/H1N1 that included seven survivors and eight nonsurvivors. For comparison, age- and gender-matched healthy controls (n = 27) were also studied.

Interventions:
Plasma was prepared from whole blood drawn on ICU admission in patients with influenza (ICU day 1). Microvesicle tissue factor activity, thrombin-antithrombin complexes, and D-dimers were measured as procoagulant markers and markers of activation of coagulation. Plasma cytokine levels were measured on the same blood samples in a subset of 12 patients with influenza using the Luminex Multi-Analyte Profiling system (Luminex Corporation, DeSoto, TX). Patients were followed up for the primary outcome of 28-day mortality.

Measurements and Main Results:
The average admission Acute Physiology and Chronic Health Evaluation II score of the patients was 25.5 ± 9.3, 60% of patients had shock, and the 28-day mortality rate was 53.3% (n = 8/15). Patients with influenza had dysregulated indices of coagulation and inflammation compared with controls. Among the markers of activation of coagulation measured on ICU day 1, only increased microvesicle tissue factor activity was significantly associated with subsequent influenza-related mortality (5.6 ± 1.2 pg/mL in nonsurvivors vs 1.8 ± 0.8 pg/mL in survivors; p < 0.05). Interleukin-8 was significantly higher in nonsurvivors compared with survivors (71.8 ± 29.1 pg/mL, n = 5 vs 17.3 ± 3.7 pg/mL, n = 7; p < 0.05). In addition, microvesicle tissue factor activity and interleukin-8 levels were significantly and positively correlated (r
2 = 0.60; p = 0.003). Other cytokines, thrombin-antithrombin complexes, and D-dimer were not different between nonsurvivors and survivors and did not correlate with illness severity or mortality.

Conclusions:
This study identifies an association between plasma interleukin-8 and microvesicle tissue factor activity measured on admission in patients with severe, primary influenza A/H1N1 infection and subsequent mortality. Thus, these biomarkers may serve as very early prognostic markers for patients with influenza A/H1N1.
Treatment of Slow Transit Constipation With Fecal Microbiota Transplantation
Authors: Tian Hongliang , Ding Chao , Gong Jianfeng , Ge Xiaolong , McFarland Lynne V. , Gu Lili , Wei Yao , Chen Qiyi , Zhu Weiming , Li Jieshou , Li Ning 
Published: January 2016

Background:
Fecal microbiota transplantation (FMT) has been proposed as a therapeutic approach for functional gastrointestinal disease. We launched a clinical study to examine the safety and efficacy of FMT for slow transit constipation (STC).

Materials and Methods:
Twenty-four patients with STC, aged from 20 to 74 were enrolled in this prospective open-label study. Patients received FMT on 3 consecutive days through nasojejunal tubes and followed up for 12 weeks after treatment. Rate of clinical improvement and remission, Wexner constipation scale, Bowel movement per week, and gastrointestinal quality-of-life index were evaluated.

Results:
The rate of clinical improvement and remission based on clinical activity at week 12 was 50% (12/24) and 37.5% (9/24), respectively. The patient’s stool frequency increased from a mean of 1.8 (SD 1.3) per week pre-FMT to 4.1 (SD 2.6) at week 12 post-FMT without laxative usage (P<0.01). The stool consistency showed a tendency to improve after FMT administration. Comparison of pre-FMT and post-FMT Wexner constipation scores demonstrated a significant reduction between baseline (14.1±3.3) and the first week (9.8±4.9), which was maintained up to the following 12 weeks (7.5±3.2; P<0.01). Compared with baseline, significant overall improvements were also seen in gastrointestinal quality-of-life index score at week 1, week 2, week 4, week 8, and week 12 of follow-up (P<0.01). The improvements were accompanied by the decline of colonic transit time. No severe adverse events during the whole FMT procedure follow-up except for venting (6/24), abdominal pain (3/24), bloating (2/24), and diarrhea (7/24).

Conclusion:
This is a pilot study demonstrating that FMT was safe and may have the potential to improve symptoms in patients with STC.
Reasons for Drug Administration Problems and Perceived Needs for Assistance of Patients, Family Caregivers, and Nurses: A Qualitative Study
Authors: Lampert Anette , Haefeli Walter E. , Seidling Hanna M. 
Published: January 2016

Objective
Investigation of drug administration problems, respective causes, and needs for assistance.

Methods
Focus group discussions with patients, family caregivers, and nurses were conducted using a semi-structured interview guideline for a focused exploration of the participants’ drug administration experiences and perceived needs for assistance. All discussions were audio-recorded and video-recorded, verbatim transcribed, and analyzed according to Mayring’s qualitative content analysis.

Results
In total, 6 focus group discussions were conducted. The qualitative content analysis revealed that patients and family caregivers frequently trivialized drug administration, were unaware of errors, and primarily blamed the dosage form of causing administration problems. Nurses also considered health-care system–related conditions and patient factors as potential causes of administration problems.

Conclusions
The administration problems and perceived causes were multifaceted and often directed toward inappropriate dosage forms or health-care system–related conditions rather than critically questioning the medicine user’s administration skills. To increase medicine users’ motivation to scrutinize wrong administration practices, health-care professionals should consider individual perspectives on administration problems and perceived causes, assist medicine users’ to identify the true cause of a distinct problem, and provide individualized support.
Localization of Interictal Epileptic Spikes With MEG: Optimization of an Automated Beamformer Screening Method (SAMepi) in a Diverse Epilepsy Population
Authors: Scott Jonathan M. , Robinson Stephen E. , Holroyd Tom , Coppola Richard , Sato Susumu , Inati Sara K. 
Published: January 2016

Purpose:
To describe and optimize an automated beamforming technique followed by identification of locations with excess kurtosis (g2) for efficient detection and localization of interictal spikes in patients with medically refractory epilepsy.

Methods:
Synthetic aperture magnetometry with g2 averaged over a sliding time window (SAMepi) was performed in seven patients with focal epilepsy and five healthy volunteers. The effect of varied window lengths on detection of spiking activity was evaluated.

Results:
Sliding window lengths of 0.5 to 10 seconds performed similarly, with 0.5- and 1-second windows detecting spiking activity in 1 of the 3 virtual sensor locations with highest kurtosis. These locations were concordant with the region of eventual surgical resection in these seven patients who remained seizure-free at 1 year. Average g2 values increased with increasing sliding window length in all subjects. In healthy volunteers, kurtosis values stabilized in data sets longer than 2 minutes.

Conclusions:
SAMepi using g2 averaged over 1-second sliding time windows in data sets of at least 2 minutes of duration reliably identified interictal spiking and the presumed seizure focus in these seven patients. Screening the five locations with highest kurtosis values for spiking activity is an efficient and accurate technique for localizing interictal activity using magnetoencephalography.

Significance:
SAMepi should be applied using the parameter values and procedure described for optimal detection and localization of interictal spikes. Use of this screening procedure could significantly improve the efficiency of magnetoencephalography analysis if clinically validated.
Genome-Wide Characterization of Maize Small RNA Loci and Their Regulation in the required to maintain repression6-1 (rmr6-1) Mutant and Long-Term Abiotic Stresses
Authors: Lunardon Alice , Forestan Cristian , Farinati Silvia , Axtell Michael J. , Varotto Serena 
Published: January 2016

Abstract
Endogenous small RNAs (sRNAs) contribute to gene regulation and genome homeostasis, but their activities and functions are incompletely known. The maize genome has a high number of transposable elements (TEs; almost 85%), some of which spawn abundant sRNAs. We performed sRNA and total RNA sequencing from control and abiotically stressed B73 wild-type plants and rmr6-1 mutants. RMR6 encodes the largest subunit of the RNA polymerase IV complex and is responsible for accumulation of most 24-nucleotide (nt) small interfering RNAs (siRNAs). We identified novel MIRNA loci and verified miR399 target conservation in maize. RMR6-dependent 23-24 nt siRNA loci were specifically enriched in the upstream region of the most highly expressed genes. Most genes misregulated in rmr6-1 did not show a significant correlation with loss of flanking siRNAs, but we identified one gene supporting existing models of direct gene regulation by TE-derived siRNAs. Long-term drought correlated with changes of miRNA and sRNA accumulation, in particular inducing down-regulation of a set of sRNA loci in the wild-typeleaf.
Nuclear Function of Subclass I Actin-Depolymerizing Factor Contributes to Susceptibility in Arabidopsis to an Adapted Powdery Mildew Fungus
Authors: Inada Noriko , Higaki Takumi , Hasezawa Seiichiro 
Published: January 2016

Abstract
Actin-depolymerizing factors (ADFs) are conserved proteins that function in regulating the structure and dynamics of actin microfilaments in eukaryotes. In this study, we present evidence that Arabidopsis (Arabidopsis thaliana) subclass I ADFs, particularly ADF4, functions as a susceptibility factor for an adapted powdery mildew fungus. The null mutant of ADF4 significantly increased resistance against the adapted powdery mildew fungus Golovinomyces orontii. The degree of resistance was further enhanced in transgenic plants in which the expression of all subclass I ADFs (i.e. ADF1–ADF4) was suppressed. Microscopic observations revealed that the enhanced resistance of adf4 and ADF1-4 knockdown plants (ADF1-4Ri) was associated with the accumulation of hydrogen peroxide and cell death specific to G. orontii-infected cells. The increased resistance and accumulation of hydrogen peroxide in ADF1-4Ri were suppressed by the introduction of mutations in the salicylic acid- and jasmonic acid-signaling pathways but not by a mutation in the ethylene-signaling pathway. Quantification by microscopic images detected an increase in the level of actin microfilament bundling in ADF1-4Ri but not in adf4 at early G. orontii infection time points. Interestingly, complementation analysis revealed that nuclear localization of ADF4 was crucial for susceptibility to G. orontii. Based on its G. orontii-infected-cell-specific phenotype, we suggest that subclass I ADFs are susceptibility factors that function in a direct interaction between the host plant and the powdery mildew fungus.
Long-Term Colonization by
bla
CTX-M
-Harboring Escherichia coli in Healthy Japanese People Engaged in Food Handling
Authors: Nakane Kunihiko , Kawamura Kumiko , Goto Kensuke , Arakawa Yoshichika 
Published: January 2016

ABSTRACT

The actual state of intestinal long-term colonization by extended-spectrum β-lactamase (ESBL)-producing
Escherichia coli
in healthy Japanese people remains unclear. Therefore, a total of 4,314 fecal samples were collected from 2,563 food handlers from January 2010 to December 2011. Approximately 0.1 g of each fecal sample was inoculated onto a MacConkey agar plate containing cefotaxime (1 μg/ml). The bacterial colonies that grew on each plate were checked for ESBL production by the double-disk synergy test, as recommended by the Clinical and Laboratory Standards Institute. The bacterial serotype, antimicrobial susceptibility, pulsotype, sequence type (ST), and ESBL genotype were checked, and the replicon types of plasmids harboring the ESBL gene were also determined after conjugation experiments. ESBL producers were recovered from 70 (3.1%) of 2,230 participants who were checked only once. On the other hand, ESBL producers were isolated at least once from 52 (15.6%) of 333 participants who were checked more than twice, and 13 of the 52 participants carried ESBL producers for from more than 3 months to up to 2 years. Fluoroquinolone (FQ)-resistant
E. coli
strains harboring
bla
CTX-M
were repeatedly recovered from 11 of the 13 carriers of
bla
CTX-M
-harboring
E. coli
. A genetically related FQ-resistant
E. coli
O25b:H4-ST131 isolate harboring
bla
CTX-M-27
was recovered from 4 of the 13 carriers for more than 6 months. Three FQ-resistant
E. coli
O1:H6-ST648 isolates that harbored
bla
CTX-M-15
or
bla
CTX-M-14
were recovered from 3 carriers. Moreover, multiple CTX-M-14- or CTX-M-15-producing
E. coli
isolates with different serotypes were recovered from 2 respective carriers. These findings predict a provable further spread of ESBL producers in both community and clinical settings.
Evaluation of Ultrasound-Induced Damage to Escherichia coli and Staphylococcus aureus by Flow Cytometry and Transmission Electron Microscopy
Authors: Li Jiao , Ahn Juhee , Liu Donghong , Chen Shiguo , Ye Xingqian , Ding Tian 
Published: January 2016

ABSTRACT

As a nonthermal sterilization technique, ultrasound has attracted great interest in the field of food preservation. In this study, flow cytometry and transmission electron microscopy were employed to investigate ultrasound-induced damage to
Escherichia coli
and
Staphylococcus aureus
. For flow cytometry studies, single staining with propidium iodide (PI) or carboxyfluorescein diacetate (cFDA) revealed that ultrasound treatment caused cell death by compromising membrane integrity, inactivating intracellular esterases, and inhibiting metabolic performance. The results showed that ultrasound damage was independent of initial bacterial concentrations, while the mechanism of cellular damage differed according to the bacterial species. For the Gram-negative bacterium
E. coli
, ultrasound worked first on the outer membrane rather than the cytoplasmic membrane. Based on the double-staining results, we inferred that ultrasound treatment might be an all-or-nothing process: cells ruptured and disintegrated by ultrasound cannot be revived, which can be considered an advantage of ultrasound over other nonthermal techniques. Transmission electron microscopy studies revealed that the mechanism of ultrasound-induced damage was multitarget inactivation, involving the cell wall, cytoplasmic membrane, and inner structure. Understanding of the irreversible antibacterial action of ultrasound has great significance for its further utilization in the food industry.
Strong Seasonality of Marine Microbial Eukaryotes in a High-Arctic Fjord (Isfjorden, in West Spitsbergen, Norway)
Authors: Marquardt Miriam , Vader Anna , Stübner Eike I. , Reigstad Marit , Gabrielsen Tove M. 
Published: January 2016

ABSTRACT

The Adventfjorden time series station (IsA) in Isfjorden, West Spitsbergen, Norway, was sampled frequently from December 2011 to December 2012. The community composition of microbial eukaryotes (size, 0.45 to 10 μm) from a depth of 25 m was determined using 454 sequencing of the 18S V4 region amplified from both DNA and RNA. The compositional changes throughout the year were assessed in relation to
in situ
fjord environmental conditions. Size fractionation analyses of chlorophyll
a
showed that the photosynthetic biomass was dominated by small cells (<10 μm) most of the year but that larger cells dominated during the spring and summer. The winter and early-spring communities were more diverse than the spring and summer/autumn communities. Dinophyceae were predominant throughout the year. The Arctic
Micromonas
ecotype was abundant mostly in the early-bloom and fall periods, whereas heterotrophs, such as marine stramenopiles (MASTs), Picozoa, and the parasitoid marine alveolates (MALVs), displayed higher relative abundance in the winter than in other seasons. Our results emphasize the extreme seasonality of Arctic microbial eukaryotic communities driven by the light regime and nutrient availability but point to the necessity of a thorough knowledge of hydrography for full understanding of their succession and variability.