bluuebunny/crossref_metadata_2025 huggingface dataset:
Vibrio cholerae LeuO Links the ToxR Regulon to Expression of Lipid A Remodeling Genes
Authors: Bina X. Renee , Howard Mondraya F. , Ante Vanessa M. , Bina James E.
Published: August 2016

Vibrio cholerae
is an intestinal pathogen that causes the diarrheal disease cholera. Colonization of the intestine depends upon the expression of genes that allow
V. cholerae
to overcome host barriers, including low pH, bile acids, and the innate immune system. ToxR is a major contributor to this process. ToxR is a membrane-spanning transcription factor that coordinates gene expression in response to environmental cues. In previous work we showed that ToxR upregulated
leuO
expression in response to bile salts. LeuO is a LysR family transcription factor that contributes to acid tolerance, bile resistance, and biofilm formation in
V. cholerae
. Here, we investigated the function of ToxR and LeuO in cationic antimicrobial peptide (CAMP) resistance. We report that ToxR and LeuO contribute to CAMP resistance by regulating
carRS
transcription. CarRS is a two-component regulatory system that positively regulates
almEFG
expression. AlmEFG confers CAMP resistance by glycinylation of lipid A. We found that the expression of
carRS
and
almEFG
and the polymyxin B MIC increased in mutants lacking
toxRS
or
leuO
. Conversely,
leuO
overexpression decreased the polymyxin B MIC. Furthermore, we found that LeuO directly bound to the
carRS
promoter and that ToxR-dependent activation of
leuO
transcription regulated
carRS
transcription in response to bile salts. Our results suggest that LeuO functions downstream of ToxR to modulate
carRS
expression in response to environmental cues. This study extends the functional role of ToxR and LeuO in environmental adaptation to include cell surface remodeling and CAMP resistance.
Impact of LytR-CpsA-Psr Proteins on Cell Wall Biosynthesis in Corynebacterium glutamicum
Authors: Baumgart Meike , Schubert Karin , Bramkamp Marc , Frunzke Julia
Published: August 2016

Proteins of the LCP (LytR, CpsA, Psr) family have been shown to inherit important roles in bacterial cell wall biosynthesis. However, their exact function in the formation of the complex cell wall structures of theCorynebacteriales, including the prominent pathogensMycobacterium tuberculosisandCorynebacterium diphtheriae, remains unclear. Here, we analyzed the role of the LCP proteins LcpA and LcpB ofCorynebacterium glutamicum, both of which localize at regions of nascent cell wall biosynthesis. A strain lackinglcpBdid not show any growth-related or morphological phenotype under the tested conditions. In contrast, conditional silencing of the essentiallcpAgene resulted in severe growth defects and drastic morphological changes. Compared to the wild-type cell wall, the cell wall of this mutant contained significantly less mycolic acids and a reduced amount of arabinogalactan. In particular, rhamnose, a specific sugar component of the linker that connects arabinogalactan and peptidoglycan, was decreased. Complementation studies of thelcpA-silencing strain with several mutated and truncated LcpA variants suggested that both periplasmic domains are essential for function whereas the cytoplasmic N-terminal part is dispensable. Successful complementation experiments with proteins ofM. tuberculosisandC. diphtheriaerevealed a conserved function of LCP proteins in these species. Finally, pyrophosphatase activity of LcpA was shown in anin vitroassay. Taken together, our results suggest that LCP proteins are responsible for the transfer of arabinogalactan onto peptidoglycan in actinobacterial species and support a crucial function of a so-far-uncharacterized C-terminal domain (LytR_C domain) which is frequently found at the C terminus of the LCP domain in this prokaryotic phylum.

IMPORTANCEAbout one-third of the world's population is infected withMycobacterium tuberculosis, and multiple-antibiotic resistance provokes the demand for novel antibiotics. The special cell wall architecture ofCorynebacterialesis critical for treatments because it is either a direct target or a barrier that the drug has to cross. Here, we present the analysis of LcpA and LcpB of the closely relatedCorynebacterium glutamicum, the first of which is an essential protein involved in cell wall biogenesis. Our work provides a comprehensive characterization of the impact of LCP proteins on cell wall biogenesis in this medically and biotechnologically important class of bacteria. Special focus is set on the two periplasmic LcpA domains and their contributions to physiological function.
Circuitry Linking the Catabolite Repression and Csr Global Regulatory Systems of Escherichia coli
Authors: Pannuri Archana , Vakulskas Christopher A. , Zere Tesfalem , McGibbon Louise C. , Edwards Adrianne N. , Georgellis Dimitris , Babitzke Paul , Romeo Tony
Published: August 2016

Cyclic AMP (cAMP) and the cAMP receptor protein (cAMP-CRP) and CsrA are the principal regulators of the catabolite repression and carbon storage global regulatory systems, respectively. cAMP-CRP controls the transcription of genes for carbohydrate metabolism and other processes in response to carbon nutritional status, while CsrA binds to diverse mRNAs and regulates translation, RNA stability, and/or transcription elongation. CsrA also binds to the regulatory small RNAs (sRNAs) CsrB and CsrC, which antagonize its activity. The BarA-UvrY two-component signal transduction system (TCS) directly activates
csrB
and
csrC
(
csrB
/
C
) transcription, while CsrA does so indirectly. We show that cAMP-CRP inhibits
csrB
/
C
transcription without negatively regulating phosphorylated UvrY (P-UvrY) or CsrA levels. A
crp
deletion caused an elevation in CsrB/C levels in the stationary phase of growth and increased the expression of
csrB-lacZ
and
csrC-lacZ
transcriptional fusions, although modest stimulation of CsrB/C turnover by the
crp
deletion partially masked the former effects. DNase I footprinting and other studies demonstrated that cAMP-CRP bound specifically to three sites located upstream from the
csrC
promoter, two of which overlapped the P-UvrY binding site. These two proteins competed for binding at the overlapping sites.
In vitro
transcription-translation experiments confirmed direct repression of
csrC-lacZ
expression by cAMP-CRP. In contrast, cAMP-CRP effects on
csrB
transcription may be mediated indirectly, as it bound nonspecifically to
csrB
DNA. In the reciprocal direction, CsrA bound to
crp
mRNA with high affinity and specificity and yet exhibited only modest, conditional effects on expression. Our findings are incorporated into an emerging model for the response of Csr circuitry to carbon nutritional status.

IMPORTANCE
Csr (Rsm) noncoding small RNAs (sRNAs) CsrB and CsrC of
Escherichia coli
use molecular mimicry to sequester the RNA binding protein CsrA (RsmA) away from lower-affinity mRNA targets, thus eliciting major shifts in the bacterial lifestyle. CsrB/C transcription and turnover are activated by carbon metabolism products (e.g., formate and acetate) and by a preferred carbon source (glucose), respectively. We show that cAMP-CRP, a mediator of classical catabolite repression, inhibits
csrC
transcription by binding to the upstream region of this gene and also inhibits
csrB
transcription, apparently indirectly. We propose that glucose availability activates pathways for both synthesis and turnover of CsrB/C, thus shaping the dynamics of global signaling in response to the nutritional environment by poising CsrB/C sRNA levels for rapid response.
Carotenoid Biosynthetic Pathways Are Regulated by a Network of Multiple Cascades of Alternative Sigma Factors in Azospirillum brasilense Sp7
Authors: Rai Ashutosh Kumar , Dubey Ashutosh Prakash , Kumar Santosh , Dutta Debashis , Mishra Mukti Nath , Singh Bhupendra Narain , Tripathi Anil Kumar
Published: August 2016

Carotenoids constitute an important component of the defense system against photooxidative stress in bacteria. In
Azospirillum brasilense
Sp7, a nonphotosynthetic rhizobacterium, carotenoid synthesis is controlled by a pair of extracytoplasmic function sigma factors (RpoEs) and their cognate zinc-binding anti-sigma factors (ChrRs). Its genome harbors two copies of the gene encoding geranylgeranyl pyrophosphate synthase (CrtE), the first critical step in the carotenoid biosynthetic pathway in bacteria. Inactivation of each of two
crtE
paralogs found in
A. brasilense
caused reduction in carotenoid content, suggesting their involvement in carotenoid synthesis. However, the effect of
crtE1
deletion was more pronounced than that of
crtE2
deletion. Out of the five paralogs of
rpoH
in
A. brasilense
, overexpression of
rpoH1
and
rpoH2
enhanced carotenoid synthesis. Promoters of
crtE2
and
rpoH2
were found to be dependent on RpoH2 and RpoE1, respectively. Using a two-plasmid system in
Escherichia coli
, we have shown that the
crtE2
gene of
A. brasilense
Sp7 is regulated by two cascades of sigma factors: one consisting of RpoE1and RpoH2 and the other consisting of RpoE2 and RpoH1. In addition, expression of
crtE1
was upregulated indirectly by RpoE1 and RpoE2. This study shows, for the first time in any carotenoid-producing bacterium, that the regulation of carotenoid biosynthetic pathway involves a network of multiple cascades of alternative sigma factors.

IMPORTANCE
Carotenoids play a very important role in coping with photooxidative stress in prokaryotes and eukaryotes. Although extracytoplasmic function (ECF) sigma factors are known to directly regulate the expression of carotenoid biosynthetic genes in bacteria, regulation of carotenoid biosynthesis by one or multiple cascades of sigma factors had not been reported. This study provides the first evidence of the involvement of multiple cascades of sigma factors in the regulation of carotenoid synthesis in any bacterium by showing the regulation of a gene encoding geranylgeranyl pyrophosphate synthase (
crtE2
) by RpoE1→RpoH2→CrtE2 and RpoE2→RpoH1→CrtE2 cascades in
A. brasilense
. It also provides an insight into existence of an additional cascade or cascades regulating expression of another paralog of
crtE
.
Predictors of fever-related admissions to a paediatric assessment unit, ward and reattendances in a South London emergency department: the CABIN 2 study
Authors: Bustinduy Amaya L , Chis Ster Irina , Shaw Rebecca , Irwin Adam , Thiagarajan Jaiganesh , Beynon Rhys , Ladhani Shamez , Sharland Mike
Published: August 2016

Objective

To explore the risk factors for ward and paediatric assessment unit (PAU) admissions from the emergency department (ED).

Design

Prospective observational study.

Setting and patients

Febrile children attending a large tertiary care ED during the winter of 2014–2015.

Main outcome measures

Ward and PAU admissions, National Institute for Health and Care Excellence (NICE) guidelines classification, reattendance to the ED within 28 days and antibiotic use.

Results

A total of 1097 children attending the children's ED with fever were analysed. Risk factors for PAU admission were tachycardia (RR=1.1, 95% CI (1 to 1.1)), ill-appearance (RR=2.2, 95% CI (1.2 to 4.2)), abnormal chest findings (RR=2.1, 95% CI (1.2 to 4.3)), categorised as NICE amber (RR 1.7 95% CI (1.2 to 2.5)). There was a 30% discordance between NICE categorisation at triage and statistical internal validation. Predictors of ward admission were a systemic (RR=6.9, 95% CI (2.4 to 19.8)) or gastrointestinal illness (RR=3.8, 95% (1.4 to 10.4)) and categorised as NICE Red (RR=5.9, 95% CI (2.2 to 15.3)). Only 51 children had probable bacterial pneumonia (4.6%), 52 children had a proven urinary tract infection (4.2%), with just 2 (0.2%) positive blood cultures out of 485 (44%) children who received an antibiotic. 15% of all children reattended by 28 days and were more likely to have been categorised as Amber and had investigations on initial visit.

Conclusions

Risk factors for PAU and ward admissions are different in this setting with high reattendance rates and very low proportion of confirmed/probable serious bacterial infections. Future studies need to focus on reducing avoidable admissions and antibiotic treatment.
Reconstruction of a large upper arm defect with muscle sparing latissimus dorsi
Authors: Cadenelli Pierfrancesco , Bordoni Daniele , Ornelli Matteo , Radaelli Stefano
Published: August 2016

Reconstruction of large soft tissue defects in the upper arm represents a challenge for the reconstructive surgeon. The latissimus dorsi flap is widely used and preferred for this latter type of reconstruction due to its reliability and versatility, although sacrificing the entire muscle can lead to higher incidences of postoperative seroma and functional disability. The recent introduction of the perforator-based flap concept has led to an evolution in upper extremity reconstruction by significantly reducing donor-site morbidity and simultaneously ensuring optimal soft tissues coverage. We report a case of a large soft tissue defect of the posterolateral part of the upper arm, consequent to a sarcoma resection, in which a muscle-sparing latissimus dorsi technique was used to obtain total soft tissue coverage. A 2-year follow-up showed a satisfactory functional result and no evidence of recurrence.
Aberrant migration ofDirofilaria immitisin the peritoneum of a dog
Authors: Brines Courtenay , Agbedanu Prince , Juelsgaard Rachel , Carlson Steve , Brewer Matthew
Published: August 2016

Dirofilaria immitisis the causative agent of heartworm disease in North America. The adult nematodes are typically found in the pulmonary arteries leading to respiratory, cardiac and systemic illness. In this report, the authors describe an aberrant migration of adultD immitisassociated with fibrinous lesions in the peritoneum of a dog. The nematode was recovered during routine ovariohysterectomy. Examination of the organism revealed that the anterior end of the nematode contained several insignificant cranial papillae and no lips while the caudal region contained two rows of papillae. Histological examination demonstrated coelomyarian musculature and prominent lateral internal cuticular ridges. Subsequent amplification of a region of the 16S rRNA gene confirmed the authors’ diagnosis ofD immitis.Diagnosis of nematode parasites often heavily relies on the location of the worm and the identity of the host. This case highlights the use of integrating morphological, histopathological and molecular data in order to identify an aberrantly migrating nematode which is important for diagnostic, public health and epidemiological purposes.
Belowground herbivory decreases shoot water content and biomass of Lolium perenne seedlings under nutrient-poor conditions
Authors: Tsunoda Tomonori , Kachi Naoki , Suzuki Jun-Ichirou
Published: August 2016

Belowground herbivory under nutrient-poor conditions is known to significantly decrease plant biomass and root:shoot ratios. However, the mechanisms behind the changes in belowground plant–herbivore interactions that occur under different nutrient conditions remain unclear. We performed a pot experiment using Lolium perenne L. and the third-instar larva of Popillia japonica Newman. The experiment used a three-way factorial randomized-block design; the three factors were nutrient amount (rich/poor), nutrient heterogeneity (homogeneous/heterogeneous), and belowground herbivore (present/absent). Relative water content (RWC) of shoots under nutrient-poor conditions was smaller than that under nutrient-rich conditions, and a single herbivory significantly reduced the RWC under the nutrient-poor conditions. Plant biomass was larger under nutrient-rich conditions than under nutrient-poor conditions. A herbivore decreased plant biomass more under nutrient-poor conditions than under nutrient-rich conditions. Nutrient heterogeneity had no effect on plant biomass, but herbivory and nutrient amount interactively affected root proliferations to nutrient patches. Plants were smaller under nutrient-poor conditions; thus, a larger proportion of the roots was removed by a belowground herbivore. A loss of a larger proportion of roots would cause the small RWC, which restricts compensatory growth. Consequently, growth of L. perenne is more severely limited by a belowground herbivore under nutrient-poor conditions.
First-principles study of zinc-blende BxAlyIn1−x−yN quaternary alloy: Alchemical mixing approximation approach
Authors: Bamgbose M. K. , Adebambo P. O. , Badmus B. S. , Dare E. O. , Akinlami J. O. , Adebayo G. A.
Published: August 2016

Detailed first-principle calculations of properties in zinc blende quaternary alloy [Formula: see text] at various concentrations are investigated using density functional theory (DFT) within virtual crystal approximation (VCA) implemented in alchemical mixing approximation. The calculated bandgaps show direct transitions at [Formula: see text]–[Formula: see text] and indirect transitions at [Formula: see text]–[Formula: see text], which are opened by increasing boron concentration. The density of state (DOS) revealed upper valence band (VB1) domination by [Formula: see text]-states atoms, while [Formula: see text]-states dominate the lower valence band (VB2); also, the DOS shows the contribution of [Formula: see text]-states to the conduction band. The first critical point in the dielectric constant ranges between 0.07–4.47 eV and is due to the first threshold optical transitions in the energy bandgap. Calculated static dielectric function (DF) [Formula: see text] is between 5.15 and 10.35, an indication that small energy bandgaps yield large static DFs. The present results indicate [Formula: see text]-[Formula: see text] alloys are suitable candidates of deep ultraviolet light emitting diodes (LEDs), laser diodes (LDs) and modern solar cell since the concentrations [Formula: see text] and [Formula: see text] make the bandgap and lattice constant of [Formula: see text]-[Formula: see text] quaternary alloys tunable to desirable values.
The electron-longitudinal optical phonon scattering rate in GaInAsP/InP stepped quantum well
Authors: Li Zheng , Wang Hailong , Chen Li , Chen Sha , Gong Qian
Published: August 2016

Within the framework of effective mass approximation, the scattering rate via longitudinal optical (LO) phonon emission for an electron and the mean scattering rate via LO phonons emission for electrons initially in the first excited sub-band and finally in the ground sub-band in [Formula: see text] stepped quantum well (QW) is calculated adopting the shooting method and Fermi’s golden rule. The results show that the scattering rate and the mean scattering rate are highly dependent on alloy compositions, well width, initial electron energy, electron temperature and sub-band separation [Formula: see text] between the ground sub-band and the first excited sub-band. When [Formula: see text] is larger than the LO phonon energy, the scattering rate and the mean scattering rate increases with increasing Ga composition, decreasing As composition and increasing well width. However, when [Formula: see text] is smaller than the LO phonon energy, its change tendency is contrary. The scattering rate increases with decreasing initial electron energy if the separation between the initial electron energy and the ground state energy [Formula: see text] is not smaller than the LO phonon energy. The scattering rate and the mean scattering rate increases with rising electron temperature. The mean scattering rate reaches the maximum value when [Formula: see text] is equal to the LO phonon energy. The interruption in the scattering rate happens when the separation between the initial electron energy and [Formula: see text] is smaller than the LO phonon energy. The rapid decrease of the mean scattering rate happens when [Formula: see text] is smaller than the LO phonon energy if [Formula: see text] continues decreasing. In addition, both the scattering rate and the mean scattering rate show little change with different stepped layer widths.
Segregation simulation of binary granular matter under horizontal pendulum vibrations
Authors: Ma Xuedong , Zhang Yanbing , Ran Heli , Zhang Qingying
Published: August 2016

Segregation of binary granular matter with different densities under horizontal pendulum vibrations was investigated through numerical simulation using a 3D discrete element method (DEM). The particle segregation mechanism was theoretically analyzed using gap filling, momentum and kinetic energy. The effect of vibrator geometry on granular segregation was determined using the Lacey mixing index. This study shows that dynamic changes in particle gaps under periodic horizontal pendulum vibrations create a premise for particle segregation. The momentum of heavy particles is higher than that of light particles, which causes heavy particles to sink and light particles to float. With the same horizontal vibration parameters, segregation efficiency and stability, which are affected by the vibrator with a cylindrical convex geometry, are superior to that of the original vibrator and the vibrator with a cross-bar structure. Moreover, vibrator geometry influences the segregation speed of granular matter. Simulation results of granular segregation by using the DEM are consistent with the final experimental results, thereby confirming the accuracy of the simulation results and the reliability of the analysis.
Study of Split Capacitor DAC Mismatch and Calibration in SAR-ADC
Authors: Zhang Yun , Zhao Yiqiang , Dai Peng
Published: August 2016

Mismatch and parasitic effects of bridge capacitors in successive-approximation-register analog-to-digital converter’s (SAR-ADC) split capacitor digital-to-analog conversion (DAC) cause a significant performance deterioration. This paper presents a nonlinearity analysis based on an analytical model, and a modified calibration method utilizing a pre-bias bridge capacitor is accordingly proposed. The proposed method, which uses three-segment split capacitor DAC structure, can effectively eliminate over-calibration error caused by conventional structure. To verify the technique, a 14-bit SAR-ADC has been designed in 0.35-[Formula: see text]m 2P4M CMOS process with the PIP capacitor, and the simulation results show the method can further improve ADC performance.
Prospects for primordial gravitational waves in string inflation
Authors: Parameswaran Susha L. , Zavala Ivonne
Published: August 2016

Assuming that the early universe had (i) a description using perturbative string theory and its field theory limit, (ii) an epoch of slow-roll inflation within a four-dimensional effective field theory and a hierarchy of scales [Formula: see text] that keeps the latter under control, we derive an upper bound on the amplitude of primordial gravitational waves. The bound is very sensitive to mild changes in numerical coefficients and the expansion parameters. For example, allowing couplings and mass-squared hierarchies [Formula: see text] implies [Formula: see text], but asking more safely for hierarchies [Formula: see text], the bound becomes [Formula: see text]. Moreover, large volumes — typically used in string models to keep backreaction and moduli stabilization under control — drive [Formula: see text] down. Consequently, any detection of inflationary gravitational waves would present an interesting but difficult challenge for string theory.
THE ROLE OF ADDITIONAL FOOD IN A PREDATOR–PREY MODEL WITH A PREY REFUGE
Authors: SAMANTA SUDIP , DHAR RIKHIYA , ELMOJTABA IBRAHIM M. , CHATTOPADHYAY JOYDEV
Published: August 2016

In this paper, we propose and analyze a predator–prey model with a prey refuge and additional food for predators. We study the impact of a prey refuge on the stability dynamics, when a constant proportion or a constant number of prey moves to the refuge area. The system dynamics are studied using both analytical and numerical techniques. We observe that the prey refuge can replace the predator–prey oscillations by a stable equilibrium if the refuge size crosses a threshold value. It is also observed that, if the refuge size is very high, then the extinction of the predator population is certain. Further, we observe that enhancement of additional food for predators prevents the extinction of the predator and also replaces the stable limit cycle with a stable equilibrium. Our results suggest that additional food for the predators enhances the stability and persistence of the system. Extensive numerical experiments are performed to illustrate our analytical findings.
Effect Of Interferon‐γ and TNF‐α on MUCl MUCIN Expression in Ovarian Carcinoma Cell Lines
Authors: Clark Sean , Mcguckin Michael A. , Hurst Terry , Ward Bruce G.
Published: August 2016

In view of the potential uses of cell surface tumour associated antigens in novel anticancer treatment. a study was designed to investigate whether the biological response modifiers interferon‐gamma (IFN‐γ) and tumour necrosis factor‐alpha (TNF‐α) could effect the expression of an epitope on the tumour associated MUC I epithelial mucin. Four ovarian carcinoma cell lines showing high (OAW42 and GG) and low (JAM and PEO1) basal expression of MUC1 were treated with 10‐1000 U/mL of IFN‐γor TNF‐α for one or five days. Changes in MUC1 expression in cells exposed to IFN‐γ or TNF‐α were monitored using an ELISA technique with the monoclonal antibody BC2 which reacts with a core protein epitope on the MUC1 mucin, and then corrected for the number of viable cells present. TNF‐α had little effect on MUC1 expression, but one or five days exposure to IFN‐γ significantly increased MUC1 expression (p < 0.01) in all cell lines including the two cell lines that initially showed little or no expression.
Manic Pseudo-Delirium–Two Case Reports
Authors: Hutchinson Gerard , David Anthony
Published: August 2016

We wish to report two cases which illustrate a subtype of bipolar affective disorder and suggest that it should be termed Manic Pseudo-Delirium (MP-D) as it incorporates features of both mania and delirium. This will facilitate consistent recognition and characterization since mania remains the primary diagnosis and delirium is not thought to co-exist with functional psychoses. Extensive investigations were done to exclude underlying medical causes for the delirium. Possible explanations for MP-D are put forward for their heuristic value in the hope that further research will improve understanding of the pathophysiology of both mania and delirium.
Reversible Aphasia in Adolescence: A Late-Onset form of Landau Kleffner Syndrome? Report of a Single Case
Authors: Denes Gianfranco , Mantovan Cristina , Ferruzza Emilia , Trevisan Carlo P. , Gallo Antonia
Published: August 2016

An adolescent boy developed a long-lasting pattern of global aphasia, concomitant to focal (left temporal) EEG abnormalities; this was followed by complete recovery. Laboratory and neuroimaging studies were within normal limits. The possibility of a late-onset Landau Kleffner syndrome is discussed.
Grepafloxacin in Patients with Acute Bacterial Exacerbations of Chronic Bronchitis ‐ a Question of Speed in Bacterial Killing
Authors: Schentag Jerome J
Published: August 2016

OBJECTIVE: To characterize the population pharmacokinetics and pharmacodynamics of oral grepafloxacin in patients with acute bacterial exacerbations of chronic bronchitis (ABECB), with particular attention to the speed of bacterial killing. This was possible because the study design incorporated daily cultures of the patients’ sputum.

PATIENTS AND METHODS: The study group included 76 patients (43 male, 33 female) between 23 and 81 years of age who were part of a multicentre, randomized, double‐blind, dose‐response study. Patients were randomly assigned to receive oral regimens of grepafloxacin ‐ 200, 400 or 600 mg ‐ each administered once daily for 14 days. Daily cultures and quantitative Gram stains from serial 24 h collections of sputum were used to determine the days to eradication of each strain of bacteria. Grepafloxacin plasma concentration profiles were best fit by a pharmacokinetic model with first order absorption following a lag time between administration of the dose and onset of systemic absorption. Pharmacodynamic analysis was performed for three measures of antibacterial response: probability of bacteriological cure and probability of clinical cure, and time to eradication.

RESULTS: All three measures of response were strongly related to the 24 h area under the inhibitory curve (AUIC) (area under the curve/minimum inhibitory concentration). At an AUIC below of 75/serum inhibiting titre (SIT) x 24 h, the percentage probability of clinical cure was 71 %; at an AUIC between 75 and 175, it was 80% (P<0.05); and, at an AUTC above 175, it was 98% (P<0.01).

CONCLUSION: The speed of bacterial killing for grepafloxacin in ABECB patients was highly related to AUIC; values below 75 appear inadequate, and values greater than 175 were optimal.
Classification, Diagnosis and Treatment of Sinusitis: Evidence‐Based Clinical Practice Guidelines
Authors: Noyek Arnold , Brodovsky David , Coyle Stephen , Desrosiers Martin , Frenkiel Saul , Hawke Michael , Kellner James D , Kirkpatrick David A , Krajden Sigmund , Low Donald E , Mandell Lionel , Marlow Bernard , Martin Gerald F , Rival Richard , Shankar Lalitha , Vaughan David , Witterick Ian J
Published: August 2016

OBJECTIVE: To provide evidence‐based recommendations for classification, diagnosis and treatment of acute, chronic and recurrent acute sinusitis in adults and children.

DATA SOURCES: Review articles, textbooks, other published guidelines and recommendations of task force members.

STUDY SELECTION: One hundred and seventy‐one papers addressing one or all of the objectives.

DATA EXTRACTION: Relevant data were collated under each objective.

DATA SYNTHESIS: Validity of diagnostic and treatment evidence was assessed by using the methodological recommendations of Sackett et al and the canadian Task Force on Periodic Health Examination, respectively. Where there was a paucity of data, consensus of task force members was reached.

CONCLUSIONS: Sinusitis is classified as acute, chronic or recurrent acute disease according to duration and frequency of symptoms and response to therapy (expert opinion). Potential risk factors, concomitant diseases and complications are identified (limited evidence). Diagnosis is based on symptoms, history and physical examination. For adults, independentpredictors of acute sinusitis include maxillary toothache, coloured nasal discharge, poor response to nasal decongestants/antihistamines and mucopurulent nasal secretions (good evidence); for children, cough, nasal discharge and fever are common (good evidence). For chronic disease that persists despite adequate therapy and recurrent acutedisease, referral to a specialist for investigative measures (nasal endoscopy, computed tomography) is often necessary to determine predisposing anatomical features. Level I evidence supports the use of antibiotics for the treatment of sinusitis; selection is based on the local pattern of bacterial resistance, relative efficacy, safety and cost. Amoxicillinclavulanate, cefuroxime axetil, cefixime, ciprofloxacin and clarithromycin are approved for the treatment of acute sinusitis in canada. Amoxicillin, amoxicillin‐clavulanate and cefuroxime axetil have been shown to be effective in children. Ciprofloxacin, amoxicillin‐clavulanate, clarithromycin and erythromycin have been shown to be effective in chronic disease, although no agents have been approved for this indication. Given changing patterns of bacterial resistance, more up‐to‐date comparative efficacy data are needed.
New Role of Quinolones in Respiratory Tract Infections
Authors: Grossman Ronald F
Published: August 2016

Because of limited activity of the standard quinolones such as ciprofloxacin and ofloxacin against some clinically important organisms including Streptococcus pneumoniae and methicillin‐resistant Staphylococcus aureus, new quinolones have been developed. In addition to their improved activity against S pneumoniae, some also demonstrate excellent anaerobic activity. None of the quinolones have a role to play in the treatment of paediatric infections. Quinolones (both older and newer agents) have demonstrated equivalent efficacy to standard antimicrobials in the treatment of acute sinusitis. Several groups have suggested that quinolones are excellent agents in the treatment of high risk patients with acute exacerbations of chronic bronchitis. These patients include the elderly, and those with frequent exacerbations, significant comorbid conditions. long duration of chronic bronchitis and major impairment of lung function. There is no evidence to suggest that the newer quinolones will differ from the currently available agents for th is disease. The major advantage of the newer quinolones appears to be in the treatment of patients with community‐acquired pneumonia where pneumococcal infection is a real concern. A new parenteral quinolone with pneumococcal activity may replace the standard macrolide/cephalosporin combination that is commonly prescribed. For patients with nosocomial pneumonia, the newer agents are alternative choices, especially among patients with early onset pneumonia (less than five days of hospitalization), but are unlikely to replace ciprofloxacin in the intensive care unit setting because of poor Pseudomonas aeruginosa coverage.
Novel Hypomorphic Mutation inFANCD2Gene Observed in a Fetus with Multiple Congenital Anomalies
Authors: Vazharova Radoslava , Vragaleva Svetlana , Dimitrova Violeta , Ivanov Samuil , Balabanski Lubomir , Malinov Maxim , Toncheva Draga
Published: August 2016

Congenital anomalies affect 1% to 2% of the newborns. The urinary tract and the kidneys are involved in 4-5% of the cases while upper-extremities abnormalities are present in 10%. Certain anomalies occur in isolation, whereas others are associated with systemic conditions. The prenatal detection of fetal anomalies compatible with life is a challenge for both the parents and the physician. The prognosis for the fetus/newborn and the reproductive decisions of the family largely depend on the causes underlying the disease. The reported case is of a G2P1 pregnant woman referred for routine ultrasound scan at 24 weeks of gestation (w.g.). The fetus had growth retardation, right kidney agenesis, bilateral absence of radial bones and thumbs, radial deviation of the wrists, and short humeri. Nuchal fold thickness was 5 mm and there was a single umbilical artery. After termination of pregnancy, SNP array genotyping and next-generation sequencing of targeted candidate-genes were performed trying to clarify the etiology of the fetal polymalformative syndrome. A new hypomorphic mutation inFANCD2gene was found to underlie this fetal anomaly. The case illustrates that patients/families affected by rare monogenic disorders may benefit from application of modern technologies like microarrays and NGS.
Investigation on Dynamic Propagation Characteristics of In-Plane Cracks in PVB Laminated Glass Plates
Authors: Xu Xiaoqing , Liu Bohan , Li Yibing
Published: August 2016

Polyvinyl butyral (PVB) laminated glass has been widely used as an important component of mechanical and construction materials. Cracks on PVB laminated glass are rich in impact information, which contribute to its impact resistance design. In this paper, a three-dimensional (3D) numerical simulation model describing PVB laminated glass under impact loading is firstly established and validated qualitatively and quantitatively compared with the corresponding experimental results recorded by the high-speed photography system. In the meantime, the extended finite element method (XFEM) is introduced to analyze the crack propagation mechanism of laminated glass based on dynamic stress intensity factors (DSIFs) and propagations of stress waves. Parametric studies are then carried out to investigate the influence of five critical parameters, that is, plate dimension, crack length, impact energy, glass properties, and PVB properties, on crack propagation characteristics of laminated glass. Results show that the interaction between crack tip and stress waves as well as the propagations of stress waves corresponds to the fluctuations of DSIFs at crack tip. Both the structure and material variables are proven to play a very important role in glass cracking DSIFs and thus govern the crack propagation behavior. Results may provide fundamental explanation to the basic crack propagation mechanism on radial cracks in PVB laminated glass under impact loading conditions, thus to instruct its impact design improvement.
Fourier Transform Infrared Spectroscopy of “Bisphenol A”
Authors: Ullah Ramzan , Ahmad Ishaq , Zheng Yuxiang
Published: August 2016

FTIR (400–4000 cm−1) spectra of “Bisphenol A” are presented. Absorption peaks (400–4000 cm−1) are assigned on the basis of Density Functional Theory (DFT) with configuration as B3LYP 6-311G++ (3df 3pd). Calculated absorption peaks are in reasonable reconciliation with experimental absorption peaks after scaling with scale factor of 0.9679 except C-H and O-H stretching vibrations.
Myoinositol Attenuates the Cell Loss and Biochemical Changes Induced by Kainic Acid Status Epilepticus
Authors: Tsverava Lia , Lordkipanidze Tamar , Lepsveridze Eka , Nozadze Maia , Kikvidze Marina , Solomonia Revaz
Published: August 2016

Identification of compounds preventing or modifying the biochemical changes that underlie the epileptogenesis process and understanding the mechanism of their action are of great importance. We have previously shown that myoinositol (MI) daily treatment for 28 days prevents certain biochemical changes that are triggered by kainic acid (KA) induced status epilepticus (SE). However in these studies we have not detected any effects of MI on the first day after SE. In the present study we broadened our research and focused on other molecular and morphological changes at the early stages of SE induced by KA and effects of MI treatment on these changes. The increase in the amount of voltage-dependent anionic channel-1 (VDAC-1), cofilin, and caspase-3 activity was observed in the hippocampus of KA treated rats. Administration of MI 4 hours later after KA treatment abolishes these changes, whereas diazepam treatment by the same time schedule has no significant influence. The number of neuronal cells in CA1 and CA3 subfields of hippocampus is decreased after KA induced SE and MI posttreatment significantly attenuates this reduction. No significant changes are observed in the neocortex. Obtained results indicate that MI posttreatment after KA induced SE could successfully target the biochemical processes involved in apoptosis, reduces cell loss, and can be successfully used in the future for translational research.
Polyprenols ofGinkgo bilobaEnhance Antibacterial Activity of Five Classes of Antibiotics
Authors: Tao Ran , Wang Chengzhang , Ye Jianzhong , Zhou Hao , Chen Hongxia
Published: August 2016

Polyprenol (GBP) fromGinkgo bilobaLeaves (GBL) is an important lipid with many bioactive effects. The effect of GBP on antibacterial properties of five antibiotics belonging to different classes was through analysis of inhibition halos, MIC, and FIC index. And we studied the time-killing curves and Ca2+mobilization assay inStaphylococcus aureuscells treated with GBP microemulsion and gentamicin sulfate under MIC/2 conditions. These results showed that the GBP microemulsion (average diameter 90.2 nm) combining with gentamicin sulfate had the highest enhancing antibacterial effect againstStaphylococcus aureus, and the MIC value was 33.0 μg/mL. The increase of the antibacterial effect of tested antibiotics was positively correlated with the decrease of the average diameter of GBP microemulsion. Moreover, GBP microemulsion enhanced antibacterial effect and prolonged antibacterial time of GBP combining with gentamicin sulfate againstStaphylococcus aureus. GBP microemulsion could enhance the ability of gentamicin inducing an increase in intracellular calcium concentrations toStaphylococcus aureus. GBP microemulsion could help some classes of antibiotics to inhibit or kill bacteria. This study supports the fact that GBP microemulsion obviously can not only reduce the dosage of some classes of antibiotics, but also reduce the frequency of the antibiotic usein vitro.
Introducing Complexity Curtailing Techniques for the Tour Construction Heuristics for the Travelling Salesperson Problem
Authors: Ursani Ziauddin , Corne David W.
Published: August 2016

In this paper, complexity curtailing techniques are introduced to create faster version of insertion heuristics, that is, cheapest insertion heuristic (CIH) and largest insertion heuristic (LIH), effectively reducing their complexities fromO(n3)toO(n2)with no significant effect on quality of solution. This paper also examines relatively not very known heuristic concept of max difference and shows that it can be culminated into a full-fledged max difference insertion heuristic (MDIH) by defining its missing steps. Further to this the paper extends the complexity curtailing techniques to MDIH to create its faster version. The resultant heuristic, that is, fast max difference insertion heuristic (FMDIH), outperforms the “farthest insertion” heuristic (FIH) across a wide spectrum of popular datasets with statistical significance, even though both the heuristics have the same worst case complexity ofO(n2). It should be noted that FIH is considered best among lowest order complexity heuristics. The complexity curtailing techniques presented here open up the new area of research for their possible extension to other heuristics.
Motor Ingredients Derived from a Wearable Sensor-Based Virtual Reality System for Frozen Shoulder Rehabilitation
Authors: Lee Si-Huei , Yeh Shih-Ching , Chan Rai-Chi , Chen Shuya , Yang Geng , Zheng Li-Rong
Published: August 2016

Objective. This study aims to extract motor ingredients through data mining from wearable sensors in a virtual reality goal-directed shoulder rehabilitation (GDSR) system and to examine their effects toward clinical assessment.Design. A single-group before/after comparison.Setting. Outpatient research hospital.Subjects. 16 patients with frozen shoulder.Interventions. The rehabilitation treatment involved GDSR exercises, hot pack, and interferential therapy. All patients first received hot pack and interferential therapy on the shoulder joints before engaging in the exercises. The GDSR exercise sessions were 40 minutes twice a week for 4 weeks.Main Measures. Clinical assessments included Constant and Murley score, range of motion of the shoulder, and muscle strength of upper arm as main measures. Motor indices from sensor data and task performance were measured as secondary measures.Results. The pre- and posttest results for task performance, motor indices, and the clinical assessments indicated significant improvement for the majority of the assessed items. Correlation analysis between the task performance and clinical assessments revealed significant correlations among a number of items. Stepwise regression analysis showed that task performance effectively predicted the results of several clinical assessment items.Conclusions. The motor ingredients derived from the wearable sensor and task performance are applicable and adequate to examine and predict clinical improvement after GDSR training.
A Novel Two-Step Technique for Retrieving Fractured Peripherally Inserted Central Catheter Segments Migrating into the Heart or the Pulmonary Artery
Authors: Peng Juan , Zhang Xiao-Ming , Yang Lin , Xu Hao , Miao Nan-Dong , Ren Yong-Jun , Liu Kang , Min Xu-Li , Yang Ke , Yang Shi , Yang Cheng
Published: August 2016

Objective. To report the experience of a percutaneous technique for retrieving fractured peripherally inserted central catheter (PICC) segments migrating into the heart or the pulmonary artery.Method. From April 2013 to July 2015, we performed percutaneous retrieval of fractured PICC segments migrating into the heart or the pulmonary artery in five cancer patients who had undergone chemotherapy via PICC. The fractures were diagnosed with chest plain radiography. The patients included three cases of breast cancer, one case of rectal cancer, and one case of lower limb Ewing’s tumor. The fractures were retained in the vessels of the patients for 1 to 3 days. All the fractures were retrieved by using a novel two-step technique in the digital subtraction angiography (DSA) suite. This two-step technique involves inserting a pigtail catheter to the heart or the pulmonary artery to grasp the fractured catheter fragment and bring it to the lower segment of the inferior vena cava, followed by grasping and removing the catheter fragment with a retrieval loop system of the vena cava filter retrieval set.Result. The fractured PICC segments were removed successfully in all five patients via unilateral (four patients) or bilateral (one patient) femoral vein access. No complications occurred during the interventional procedure.Conclusion. Percutaneous retrieval can be a safe, convenient, and minimally invasive method for the removal of fractured PICC segments. The technique reported in this paper will be applicable for the retrieval of fractured PICC segments and other catheter fragments migrating into the heart or the pulmonary artery.
Repository Corticotropin Injection for Treatment of Idiopathic Inflammatory Myopathies
Authors: Patel Aarat , Seely Georgia , Aggarwal Rohit
Published: August 2016

Idiopathic inflammatory myopathies are a group of systemic autoimmune diseases that involve inflammation of skeletal muscle. The two most common forms are dermatomyositis and polymyositis, the former of which entails a skin component. There are few approved therapeutics available for treatment of this group of diseases and the first-line therapy is usually corticosteroid treatment. Considering that a large proportion of patients do not respond to or cannot tolerate corticosteroids, additional treatments are required. There are second-line therapies available, but many patients are also refractory to those options. H.P. Acthar® Gel (repository corticotropin injection [RCI]) is a melanocortin peptide that can induce steroid-dependent effects and steroid-independent effects. Herein, we present a series of cases that involved the use of RCI in the management of dermatomyositis and polymyositis. RCI treatments resulted in improvement in three of four patients, despite failure with previous therapies. The use of RCI did not exacerbate any comorbidity and no significant changes in blood pressure, weight, or glycemic control were observed. Overall, these results are encouraging and suggest that randomized, controlled clinical trials applying RCI to dermatomyositis and polymyositis are warranted.
Antifungal Susceptibility Patterns ofCandidaSpecies Recovered from Endotracheal Tube in an Intensive Care Unit
Authors: Baghdadi Elham , Khodavaisy Sadegh , Rezaie Sassan , Abolghasem Sara , Kiasat Neda , Salehi Zahra , Sharifynia Somayeh , Aala Farzad
Published: August 2016

Aims. Biofilms formed byCandidaspecies which associated with drastically enhanced resistance against most antimicrobial agents. The aim of this study was to identify and determine the antifungal susceptibility pattern ofCandidaspecies isolated from endotracheal tubes from ICU patients.Methods. One hundred forty ICU patients with tracheal tubes who were intubated and mechanically ventilated were surveyed for endotracheal tube biofilms. Samples were processed for quantitative microbial culture. Yeast isolates were identified to the species level based on morphological characteristics and their identity was confirmed by PCR-RFLP. Antifungal susceptibility testing was determined according to CLSI document (M27-A3).Results.Ninety-five strains ofCandidawere obtained from endotracheal tubes of whichC. albicans(n=34; 35.7%) was the most frequently isolated species followed by other species which includedC. glabrata(n=24; 25.2%),C. parapsilosis(n=16; 16.8%),C. tropicalis(n=12; 12.6%), andC. krusei(n=9; 9.4%). The resulting MIC90for allCandidaspecies were in increasing order as follows: caspofungin (0.5 μg/mL); amphotericin B (2 μg/mL); voriconazole (8.8 μg/mL); itraconazole (16 μg/mL); and fluconazole (64 μg/mL).Conclusion.Candidaspecies recovered from endotracheal tube are the most susceptible to caspofungin.