bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Antimicrobial Susceptibility of Enterobacteriaceae Causing Urinary Tract Infections in Africa
Authors: Tansarli Giannoula S. , Athanasiou Stavros , Falagas Matthew E.
Published: May 2013

Our objective was to evaluate the antimicrobial susceptibility of
Enterobacteriaceae
causing urinary tract infections (UTIs) in adults in Africa. The PubMed database was systematically searched to identify relevant studies published after 2000. Google, World Health Organization, and African Field Epidemiology networks were also searched. Twenty-eight studies, accounting for 381,899 urine isolates from 14 African countries, met the inclusion criteria.
Escherichia coli
,
Klebsiella
spp., and
Proteus
spp. were the most commonly encountered uropathogens. Cefotaxime, imipenem, fosfomycin, and ciprofloxacin were the antibiotics with the highest activity against
E. coli
isolates from outpatients, with susceptibility being 92 to 99, 100, 100, and 68 to 91%, respectively. The susceptibility among
Klebsiella
spp. isolates from outpatients varied from 80 to 100% for amikacin and from 53 to 100% for ciprofloxacin, while susceptibility was 74 to 78, 97, and 77% for ciprofloxacin, amikacin, and fosfomycin, respectively, among
Klebsiella
species isolates from inpatients or patients with hospital-acquired UTIs. With regard to
Proteus
spp., the highest activity was observed among fluoroquinolones; 71 to 100% of the
P. mirabilis
isolates were susceptible to ciprofloxacin in four studies, and 74 to 100% of the
P. vulgaris
isolates were susceptible to ofloxacin in two studies. The currently available evidence suggests that the antimicrobial susceptibility patterns of
Enterobacteriaceae
uropathogens in African countries were similar to those in countries of southeast Europe. Further original studies are warranted from African countries for which there is limited published data.
Clinical Validation of the Analysis of Linezolid and Clarithromycin in Oral Fluid of Patients with Multidrug-Resistant Tuberculosis
Authors: Bolhuis M. S. , van Altena R. , van Hateren K. , de Lange W. C. M. , Greijdanus B. , Uges D. R. A. , Kosterink J. G. W. , van der Werf T. S. , Alffenaar J. W. C.
Published: May 2013

Linezolid plays an increasingly important role in the treatment of multidrug-resistant tuberculosis (MDR-TB). However, patients should be carefully monitored due to time- and dose-dependent toxicity. Clarithromycin plays a more modest role. Therapeutic drug monitoring may contribute to assessment of treatment regimens, helping to reduce toxicity while maintaining adequate drug exposure. Oral fluid sampling could provide a welcome alternative in cases where conventional plasma sampling is not possible or desirable. The aim of this study was to clinically validate the analysis of linezolid and clarithromycin and its metabolite hydroxyclarithromycin in oral fluid of patients with multidrug-resistant tuberculosis. Serum and oral fluid samples were simultaneously obtained and analyzed by using validated methods, after extensive cross-validation between the two matrices. Passing-Bablok regressions and Bland-Altman analysis showed that oral fluid analysis of linezolid and clarithromycin appeared to be suitable for therapeutic drug monitoring in MDR-TB patients. No correction factor is needed for the interpretation of linezolid oral fluid concentrations with a ratio of the linezolid concentration in serum to that in oral fluid of 0.97 (95% confidence interval [CI], 0.92 to 1.02). However, the clarithromycin concentration serum/clarithromycin concentration in oral fluid ratio is 3.07 (95% CI, 2.45 to 3.69). Analysis of hydroxyclarithromycin in oral fluid was not possible in this study due to a nonlinear relationship between the concentration in serum and that in oral fluid. In conclusion, the analysis of linezolid (no correction factor) and clarithromycin (correction factor of 3) in oral fluid is applicable for therapeutic drug monitoring in cases of multidrug-resistant tuberculosis as an alternative to conventional serum sampling. Easy sampling using a noninvasive technique may facilitate therapeutic drug monitoring for specific patient categories.
Identification of Cell-Penetrating Peptides That Are Bactericidal to Neisseria meningitidis and Prevent Inflammatory Responses upon Infection
Authors: Eriksson Olaspers Sara , Geörg Miriam , Sjölinder Hong , Sillard Rannar , Lindberg Staffan , Langel Ülo , Jonsson Ann-Beth
Published: May 2013

Meningococcal disease is characterized by a fast progression and a high mortality rate. Cell-penetrating peptides (CPPs), developed as vectors for cargo delivery into eukaryotic cells, share structural features with antimicrobial peptides. A screen identified two CPPs, transportan-10 (TP10) and model amphipathic peptide (MAP), with bactericidal action against
Neisseria meningitidis
. Both peptides were active in human whole blood at micromolar concentrations, while hemolysis remained negligible. Additionally, TP10 exhibited significant antibacterial activity
in vivo
. Uptake of SYTOX green into live meningococci was observed within minutes after TP10 treatment, suggesting that TP10 may act by membrane permeabilization. Apart from its bactericidal activity, TP10 suppressed inflammatory cytokine release from macrophages infected with
N. meningitidis
as well as from macrophages stimulated with enterobacterial and meningococcal lipopolysaccharide (LPS). Finally, incubation with TP10 reduced the binding of LPS to macrophages. This novel endotoxin-inhibiting property of TP10, together with its antimicrobial activity
in vivo
, indicates the possibility to design peptide-based therapies for infectious diseases.
A Mouse Model of Acinetobacter baumannii-Associated Pneumonia Using a Clinically Isolated Hypervirulent Strain
Authors: Harris Greg , Kuo Lee Rhonda , Lam Christopher K. , Kanzaki Gregory , Patel Girishchandra B. , Xu H. Howard , Chen Wangxue
Published: May 2013

Acinetobacter baumannii
is an important emerging pathogen in health care-acquired infections and is responsible for severe nosocomial and community-acquired pneumonia. Currently available mouse models of
A. baumannii
pneumonia show poor colonization with little to no extrapulmonary dissemination. Here, we describe a mouse model of
A. baumannii
pneumonia using a clinical isolate (LAC-4 strain) that reliably reproduces the most relevant features of human pulmonary
A. baumannii
infection and pathology. Using this model, we have shown that LAC-4 infection induced rapid bacterial replication in the lungs, significant extrapulmonary dissemination, and severe bacteremia by 24 h postintranasal inoculation. Infected mice showed severe bronchopneumonia and dilatation and inflammatory cell infiltration in the perivascular space. More significantly, 100% of C57BL/6 and BALB/c mice succumbed to 10
8
CFU of LAC-4 inoculation within 48 h. When this model was used to assess the efficacy of antimicrobials, all mice treated with imipenem and tigecycline survived a lethal intranasal challenge, with minimal clinical signs and body weight loss. Moreover, intranasal immunization of mice with formalin-fixed LAC-4 protected 40% of mice from a lethal (100× 100% lethal dose) intraperitoneal challenge. Thus, this model offers a reproducible acute course of
A. baumannii
pneumonia without requiring additional manipulation of host immune status, which will facilitate the development of therapeutic agents and vaccines against
A. baumannii
pneumonia in humans.
Intraocular Penetration of Intravenous Micafungin in Inflamed Human Eyes
Authors: Mochizuki Kiyofumi , Sawada Akira , Suemori Shinsuke , Kawakami Hideaki , Niwa Yoshiaki , Kondo Yuji , Ohkusu Kiyofumi , Yamada Noriaki , Ogura Shinji , Yaguchi Takashi , Nishimura Kazuko , Kishino Satoshi
Published: May 2013

Eight eyes of 7 patients with fungal disease received intravenous injections of 150 to 300 mg micafungin, and samples of blood, cornea, retina-choroid, aqueous humor, and vitreous humor were collected. The micafungin levels in all collected samples exceeded the MICs; however, the levels in the vitreous and aqueous humors were lower. Our findings suggest that intravenous micafungin should be given in combination with intravitreal antifungal agents after vitrectomy in severe cases of intraocular fungal diseases.
Isoniazid, Rifampin, and Pyrazinamide Plasma Concentrations in Relation to Treatment Response in Indonesian Pulmonary Tuberculosis Patients
Authors: Burhan Erlina , Ruesen Carolien , Ruslami Rovina , Ginanjar Arum , Mangunnegoro Hadiarto , Ascobat Purwantyastuti , Donders Rogier , van Crevel Reinout , Aarnoutse Rob
Published: May 2013

Numerous studies have reported low concentrations of antituberculosis drugs in tuberculosis (TB) patients, but few studies have examined whether low drug concentrations affect TB treatment response. We examined steady-state plasma concentrations of isoniazid, rifampin, and pyrazinamide at 2 h after the administration of drugs (
C
2 h
) among 181 patients with pulmonary tuberculosis in Indonesia and related these to bacteriological response during treatment.
C
2 h
values below reference values for either isoniazid, rifampin, or pyrazinamide were found in 91% of patients; 60% had at least two low
C
2 h
concentrations. The isoniazid
C
2 h
was noticeably lower in fast versus slow acetylators (0.9 mg/liter versus 2.2 mg/liter,
P
< 0.001). At the end of treatment, 82% of the patients were cured, whereas 30 patients (17%) had dropped out during the study, and 2 patients (1%) failed treatment. No association was found between
C
2 h
concentrations and sputum culture results at 8 weeks of treatment.
Post hoc
analysis showed that patients with low pyrazinamide
C
2 h
(
P
= 0.01) and patients with large extensive lung lesions (
P
= 0.01) were at risk of at least one positive culture at week 4, 8, or 24/32. Antituberculosis drug concentrations were often low, but treatment response was nevertheless good. No association was found between drug concentrations and 8 weeks culture conversion, but low pyrazinamide drug concentrations may be associated with a less favorable bacteriological response. The use of higher doses of pyrazinamide may warrant further investigation.
Treatment of High-Level Gentamicin-Resistant Enterococcus faecalis Endocarditis with Daptomycin plus Ceftaroline
Authors: Sakoulas George , Nonejuie Poochit , Nizet Victor , Pogliano Joseph , Crum-Cianflone Nancy , Haddad Fadi
Published: May 2013

A recurrent case of left-sided endocarditis caused by high-level aminoglycoside-resistant
Enterococcus faecalis
was successfully treated with ceftaroline and daptomycin. This combination demonstrated excellent synergy
in vitro
. Mechanistically, ceftaroline enhanced binding of daptomycin to the cell membrane and sensitized
E. faecalis
to killing by human cathelicidin LL-37, a cationic innate host defense peptide. Daptomycin plus ceftaroline may be considered in salvage therapy in
E. faecalis
endovascular infections and requires further study.
Evaluation of Pharmacokinetic Interaction between PA-824 and Midazolam in Healthy Adult Subjects
Authors: Winter Helen , Egizi Erica , Erondu Ngozi , Ginsberg Ann , Rouse Doris J. , Severynse-Stevens Diana , Pauli Elliott , Everitt Daniel
Published: May 2013

This study assessed the safety, tolerability, and pharmacokinetic interaction between PA-824, a novel antitubercular nitroimidazo-oxazine, and midazolam, a CYP3A4 substrate, in 14 healthy adult male and female subjects. The study followed up on observations
in vitro
that PA-824 caused weak and time-dependent inhibition of CYP3A4. Subjects received a single oral dose of midazolam (2 mg), followed by a 2-day washout. After the washout, all subjects received PA-824 (400 mg) once daily for 14 consecutive days. On day 14, all subjects received the final PA-824 dose coadministered with a 2-mg oral dose of midazolam. The pharmacokinetic endpoints AUC

0–
t

, AUC
0–∞
, and
C
max
for midazolam and 1-hydroxy midazolam were compared between midazolam administered alone versus midazolam coadministered with PA-824. Statistical analysis demonstrated that the mean midazolam values of
C
max
, AUC

0–
t

, and AUC
0–∞
parameters were reduced by ca. 16, 15, and 15%, respectively, when PA-824 was coadministered with midazolam. The total exposure (AUC) of 1-hydroxy midazolam was 13 to 14% greater when coadministered with PA-824 compared to midazolam administered alone. The
C
max
of 1-hydroxy midazolam was similar between treatments. Based on these results, PA-824 does not inhibit or induce CYP3A4 to a clinically meaningful extent and is not likely to markedly affect the pharmacokinetics of CYP3A4 metabolized drugs.
Malaria Modifies Neonatal and Early-Life Toll-Like Receptor Cytokine Responses
Authors: Gbédandé Komi , Varani Stefania , Ibitokou Samad , Houngbegnon Parfait , Borgella Sophie , Nouatin Odilon , Ezinmegnon Sem , Adeothy Adicatou-laï , Cottrell Gilles , Massougbodji Achille , Moutairou Kabirou , Troye-Blomberg Marita , Deloron Philippe , Fievet Nadine , Luty Adrian J. F.
Published: May 2013

Protection from infections in early life relies extensively on innate immunity, but it is unknown whether and how maternal infections modulate infants' innate immune responses, thereby altering susceptibility to infections.
Plasmodium falciparum
causes pregnancy-associated malaria (PAM), and epidemiological studies have shown that PAM enhances infants' susceptibility to infection with
P. falciparum
. We investigated how PAM-mediated exposures
in utero
affect innate immune responses and their relationship with infection in infancy. In a prospective study of mothers and their babies in Benin, we investigated changes in Toll-like receptor (TLR)-mediated cytokine responses related to
P. falciparum
infections. Whole-blood samples from 134 infants at birth and at 3, 6, and 12 months of age were stimulated with agonists specific for TLR3, TLR4, TLR7/8, and TLR9. TLR-mediated interleukin 6 (IL-6) and IL-10 production was robust at birth and then stabilized, whereas tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) responses were weak at birth and then increased. In multivariate analyses, maternal
P. falciparum
infections at delivery were associated with significantly higher TLR3-mediated IL-6 and IL-10 responses in the first 3 months of life (
P
< 0.05) and with significantly higher TLR3-, TLR7/8-, and TLR9-mediated TNF-α responses between 6 and 12 months of age (
P
< 0.05). Prospective analyses showed that higher TLR3- and TLR7/8-mediated IL-10 responses at birth were associated with a significantly higher risk of
P. falciparum
infection in infancy (
P
< 0.05). Neonatal and infant intracellular TLR-mediated cytokine responses are conditioned by
in utero
exposure through PAM late in pregnancy. Enhanced TLR-mediated IL-10 responses at birth are associated with an increased risk of
P. falciparum
infection, suggesting a compromised ability to combat infection in early life.
Binding of Pk-Trisaccharide Analogs of Globotriaosylceramide to Shiga Toxin Variants
Authors: Yosief Hailemichael O. , Iyer Suri S. , Weiss Alison A.
Published: May 2013

The two major forms of Shiga toxin, Stx1 and Stx2, use the glycolipid globotriaosylceramide (Gb3) as their cellular receptor. Stx1 primarily recognizes the Pk-trisaccharide portion and has three Pk binding sites per B monomer. The Stx2a subtype requires glycolipid residues in addition to Pk. We synthesized analogs of Pk to examine the binding preferences of Stx1 and Stx2 subtypes a to d. Furthermore, to determine how many binding sites must be engaged, the Pk analogues were conjugated to biotinylated mono- and biantennary platforms, allowing for the display of two to four Pk analogues per streptavidin molecule. Stx binding to Pk analogues immobilized on streptavidin-coated plates was assessed by enzyme-linked immunosorbent assay (ELISA). Stx1, but not the Stx2 subtypes, bound to native Pk. Stx2a and Stx2c bound to the Pk analog with a terminal GalNAc (NAc-Pk), while Stx1, Stx2b, and Stx2d did not bind to this analog. Interestingly, the purified Stx2d B subunit bound to NAc-Pk, suggesting that the A subunit of Stx2d interferes with binding. Disaccharide analogs (Galα1-4Gal, GalNAcα1-4Gal, and Galα1-4GalNAc) did not support the binding of any of the Stx forms, indicating that the trisaccharide is necessary for binding. Studies with monoantennary and biantennary analogs and mixtures suggest that Stx1, Stx2a, and Stx2c need to engage at least three Pk analogues for effective binding. To our knowledge, this is the first study examining the minimum number of Pk analogs required for effective binding and the first report documenting the role of the A subunit in influencing Stx2 binding.
Clearance of Pseudomonas aeruginosa Foreign-Body Biofilm Infections through Reduction of the Cyclic Di-GMP Level in the Bacteria
Authors: Christensen Louise D. , van Gennip Maria , Rybtke Morten T. , Wu Hong , Chiang Wen-Chi , Alhede Morten , Høiby Niels , Nielsen Thomas E. , Givskov Michael , Tolker-Nielsen Tim
Published: May 2013

Opportunistic pathogenic bacteria can engage in biofilm-based infections that evade immune responses and develop into chronic conditions. Because conventional antimicrobials cannot efficiently eradicate biofilms, there is an urgent need to develop alternative measures to combat biofilm infections. It has recently been established that the secondary messenger cyclic diguanosine monophosphate (c-di-GMP) functions as a positive regulator of biofilm formation in several different bacteria. In the present study we investigated whether manipulation of the c-di-GMP level in bacteria potentially can be used for biofilm control
in vivo
. We constructed a
Pseudomonas aeruginosa
strain in which a reduction in the c-di-GMP level can be achieved via induction of the
Escherichia coli
YhjH c-di-GMP phosphodiesterase. Initial experiments showed that induction of
yhjH
expression led to dispersal of the majority of the bacteria in
in vitro
-grown
P. aeruginosa
biofilms. Subsequently, we demonstrated that
P. aeruginosa
biofilms growing on silicone implants, located in the peritoneal cavity of mice, dispersed after induction of the YhjH protein. Bacteria accumulated temporarily in the spleen after induction of biofilm dispersal, but the mice tolerated the dispersed bacteria well. The present work provides proof of the concept that modulation of the c-di-GMP level in bacteria is a viable strategy for biofilm control.
Leptospiral Outer Membrane Protein LipL41 Is Not Essential for Acute Leptospirosis but Requires a Small Chaperone Protein, Lep, for Stable Expression
Authors: King Amy M. , Bartpho Thanatchaporn , Sermswan Rasana W. , Bulach Dieter M. , Eshghi Azad , Picardeau Mathieu , Adler Ben , Murray Gerald L.
Published: May 2013

Leptospirosis is a worldwide zoonosis caused by pathogenic
Leptospira
spp., but knowledge of leptospiral pathogenesis remains limited. However, the development of mutagenesis systems has allowed the investigation of putative virulence factors and their involvement in leptospirosis. LipL41 is the third most abundant lipoprotein found in the outer membranes of pathogenic leptospires and has been considered a putative virulence factor. LipL41 is encoded on the large chromosome 28 bp upstream of a small open reading frame encoding a hypothetical protein of unknown function. This gene was named
lep
, for
L
ipL41
e
xpression
p
artner. In this study,
lipL41
was found to be cotranscribed with
lep
. Two transposon mutants were characterized: a
lipL41
mutant and a
lep
mutant. In the
lep
mutant, LipL41 protein levels were reduced by approximately 90%. Lep was shown through cross-linking and coexpression experiments to bind to LipL41. Lep is proposed to be a molecular chaperone essential for the stable expression of LipL41. The roles of LipL41 and Lep in the pathogenesis of
Leptospira interrogans
were investigated; surprisingly, neither of these two unique proteins was essential for acute leptospirosis.
Human Endothelial Cells Internalize Candida parapsilosis via N-WASP-Mediated Endocytosis
Authors: Shintaku Tatsushi , Glass Kyle A. , Hirakawa Matthew P. , Longley Sarah J. , Bennett Richard J. , Bliss Joseph M. , Shaw Sunil K.
Published: May 2013

Candida parapsilosis
is a frequent cause of disseminated candidiasis and is associated with significant morbidity and mortality. Although important in pathogenesis, interactions of this organism with endothelial cells have received less attention than those of
Candida albicans
. Internalization of
C. parapsilosis
by monolayers of human endothelial cells was examined in an
in vitro
assay and compared to that of
C. albicans
. Both live and heat-killed yeast were efficiently internalized, with heat-killed yeast subsequently being detected in an acidic subcompartment. Internalization was marked by a process of engulfment by thin membrane extensions from the endothelium. Efficiency of internalization differed among different clinical isolates and species of yeast. Opsonization of
C. parapsilosis
by serum factors was not sufficient to cause endocytosis; instead, serum appeared to directly stimulate endothelial uptake. Colocalization of endothelial actin and N-WASP at sites of
C. parapsilosis
internalization was observed. A Förster-resonance energy transfer (FRET) probe for N-WASP activity showed active N-WASP at sites of internalization for both live and heat-killed
C. parapsilosis
and
C. albicans
. An actin nucleation inhibitor (cytochalasin D) and an N-WASP inhibitor (wiskostatin) both inhibited uptake of heat-killed
C. parapsilosis
, as did short interfering RNA-mediated ablation of N-WASP. Thus, endocytosis by endothelial cells may represent a means of traversal of the blood vessel wall by yeast during disseminated candidiasis, and N-WASP may play a key role in the process.
Cdc42 Promotes Host Defenses against Fatal Infection
Authors: Lee Keunwook , Boyd Kelli L. , Parekh Diptiben V. , Kehl-Fie Thomas E. , Baldwin H. Scott , Brakebusch Cord , Skaar Eric P. , Boothby Mark , Zent Roy
Published: May 2013

The small Rho GTPase Cdc42 regulates key signaling pathways required for multiple cell functions, including maintenance of shape, polarity, proliferation, invasion, migration, differentiation, and morphogenesis. As the role of Cdc42-dependent signaling in fibroblastsin vivois unknown, we attempted to specifically delete it in these cells by crossing the Cdc42fl/flmouse with an fibroblast-specific protein 1 (FSP1)-Cre mouse, which is thought to mediate recombination exclusively in fibroblasts. Surprisingly, the FSP1-Cre;Cdc42fl/flmice died at 3 weeks of age due to overwhelming suppurative upper airway infections that were associated with neutrophilia and lymphopenia. Even though major aberrations in lymphoid tissue development were present in the mice, the principal cause of death was severe migration and killing abnormalities of the neutrophil population resulting in an inability to control infection. We also show that in addition to fibroblasts, FSP1-Cre deleted Cdc42 very efficiently in all leukocytes. Thus, by using this nonspecific Cre mouse, we inadvertently demonstrated the importance of Cdc42 in host protection from lethal infections and suggest a critical role for this small GTPase in innate immunity.
Upregulation of the Host SLC11A1 Gene by Clostridium difficile Toxin B Facilitates Glucosylation of Rho GTPases and Enhances Toxin Lethality
Authors: Feng Yanan , Cohen Stanley N.
Published: May 2013

Pseudomembranous enterocolitis associated withClostridium difficileinfection is an important cause of morbidity and mortality in patients being treated with antibiotics. Two closely related large protein toxins produced byC. difficile, TcdA and TcdB, which act identically but at different efficiencies to glucosylate low-molecular-weight Rho GTPases, underlie the microbe's pathogenicity. Using antisense RNA encoded by a library of human expressed sequence tags (ESTs), we randomly inactivated host chromosomal genes in HeLa cells and isolated clones that survived exposure to ordinarily lethal doses of TcdB. This phenotypic screening and subsequent analysis identified solute carrier family 11 member 1 (SLC11A1; formerly NRAMP1), a divalent cation transporter crucial to host defense against certain microbes, as an enhancer of TcdB lethality. Whereas SLC11A1 normally is poorly expressed in human cells of nonmyeloid lineage, TcdB increased SLC11A1 mRNA abundance in such cells through the actions of the RNA-binding protein HuR. We show that short hairpin RNA (shRNA) directed against SLC11A1 reduced TcdB glucosylation of small Rho GTPases and, consequently, toxin lethality. Consistent with the previously known role of SLC11A1 in cation transport, these effects were enhanced by elevation of Mn2+in media; conversely, they were decreased by treatment with a chelator of divalent cations. Our findings reveal an unsuspected role for SLC11A1 in determiningC. difficilepathogenicity, demonstrate the novel ability of a bacterial toxin to increase its cytotoxicity, establish a mechanistic basis for these effects, and suggest a therapeutic approach to mitigate cell killing byC. difficiletoxins A and B.
Antiglycine receptor-related stiff limb syndrome in a patient with chronic lymphocytic leukaemia
Authors: Derksen Angelika , Stettner Mark , Stöcker Winfried , Seitz Rüdiger J
Published: May 2013

We report a 61-year-old man presenting with rapidly progressive stiffness and painful muscle spasms in the lower extremity muscles. The patient was diagnosed with chronic lymphocytic leukaemia (CLL) approximately a year before symptom onset. Electromyography displayed continuous motor unit activity and immunocytochemistry showed a positive staining for antiglycine receptor (anti-GlyR) antibodies. The clinical course was complicated by autonomic instability and cardiac arrest, but stabilised under continuous therapy with plasma exchange and symptomatic treatment with baclofen and clonazepam. Anti-GlyR antibodies induce rare, but severe, variants of stiff person syndrome that can be of paraneoplastic origin and life threatening due to autonomic dysfunction.
Adrenal myelolipoma's connection with adenoma in the same adrenal gland
Authors: Gurbuz Esma , Sayar Hamide , Bakaris Sevgi , Inci Mehmet Fatih
Published: May 2013

Adrenal myelolipoma is a rare benign tumour. This tumour is generally considered as a type of hormonally inactive neoplasm, which is composed of mature adipose tissue and normal haematopoietic cells. Rarely adrenal myelolipoma and adrenal cortical adenoma could be found together in the same gland. Due to myelolipoma's asymptomatic character, it is generally diagnosed incidentally. In fact, myelolipoma can now be easily detected because of improved techniques such as ultrasound, CT and MRI and widespread use of imaging. Because of this a 66-year-old male patient with abdominal pain, proved that adrenal myelolipoma and non-functional adrenal cortical adenoma are rare in the same gland. The case presented here deals with different outcome which is rare in the literature.
Two cases of femoral hydatidosis secondary to canine tapeworm treated by albendazole and prosthetic reconstruction
Authors: Leslé Florence , Magrino Baptiste , Dupouy-Camet Jean , Sailhan Fréderic
Published: May 2013

Osseous hydatidosis is a very severe and recurrent complication of hydatidosis. The two cases reported here illustrate the severity of this invasive and destructive osseous parasitosis located at the femur and the hip joint, which required extensive resection and prosthetic reconstruction. The first case had a long history of liver and lung hydatidosis with a wide ‘en-bloc’ extra-articular resection of the right hip joint including the proximal femur; the second case had an ‘en-bloc’ total femur resection and total femur prosthesis. Preoperative and postoperative chemotherapy with albendazole was combined with surgery and was applied for many months. These two cases occurred several years after the incomplete treatments of recurrent lung or liver hydatidosis and might have been prevented if chemotherapy had been initially applied.
Distribution of Al and adsorption of NH3 and pyridine in ZSM-12: a computational study
Authors: Feng Gang , Lian Ying-Ying , Yang Deqin , Liu Jianwen , Kong Dejin
Published: May 2013

The distribution of Al and the adsorption of NH3 and pyridine in both Na-form and H-form ZSM-12 were investigated using dispersion-corrected density functional theory. It was found that the energy differences for Al atoms in the different T sites of ZSM-12 (both H form and Na form) were less than 0.3 eV, which indicates that the Al atoms could distribute in all kinds of T sites in ZSM-12. In addition, the small energy difference indicates that both H and Na atoms could stay in either the small cage or the main channel of ZSM-12. The adsorption of NH3 and pyridine on NaZSM-12 is weak, while the adsorption of NH3 and pyridine on HZSM-12 is strong, as they could form NH4+ and NC5H6+ species in the presence of protons. Both NH3 and pyridine could adsorb on the Lewis Al3+ sites in HZSM-12, while the adsorption of NH3 and pyridine on the Lewis acid sites are less stable than on the Brønsted acid sites of ZSM-12.
A mild and efficient protocol to synthesize chromones, isoflavones, and homoisoflavones using the complex 2,4,6-trichloro-1,3,5-triazine/dimethylformamide
Authors: Basha G. Mahaboob , Yadav S. Kumar , Srinuvasarao R. , Prasanthi S. , Ramu T. , Mangarao N. , Siddaiah V.
Published: May 2013

A mild and efficient one-flask method has been developed for the synthesis of chromones, isoflavones, and homoisoflavones from 2-hydroxyacetophenones, deoxybenzoins, and dihydrochalcones, respectively, via one-carbon extension using the complex 2,4,6-trichloro-1,3,5-triazine/dimethylformamide. Deoxybenzoins and dihydrochalcones were prepared in situ by the reaction of readily available substituted phenols with phenylacetic acids and 3-phenylpropanoic acids, respectively. This method allows the synthesis of a wide range of compounds with multiple phenolic hydroxyls and other substituents. The methodology has been applied to the synthesis of three naturally occurring isoflavones such as formononetin (9c), daidzein (9d), and retusin (9h).
Mixed-severity fire regimes: How well are they represented by existing fire-regime classification systems?
Authors: Marcoux Hélène M. , Gergel Sarah E. , Daniels Lori D.
Published: May 2013

Maps depicting historic fire regimes provide critical baselines for sustainable forest management and wildfire risk assessments. However, given our poor understanding of mixed-severity fire regimes, we asked if there may be considerable errors in fire-regime classification systems used to create landscape-level maps. We used dendrochronological field data (fire scars and tree establishment dates) from 20 randomly selected sites in southern British Columbia to evaluate two classification systems (Natural Disturbance Type (NDT) and Historical Natural Fire Regime (HNFR)) used by managers to map fire regimes. We found evidence of mixed-severity fires at 55% of sites. Each classification system made considerable and contrasting errors predicting mixed-severity regimes (relative to field data), and the discrepancies varied with elevation. The NDT system underrepresented low-to-moderate-severity fires at lower elevations, whereas the HNFR system overpredicted their occurrence at higher elevations. Errors are attributed to underlying assumptions about disturbances in the two classification systems, as well as limitations of the research methods used to estimate fire frequency in mixed-severity regimes (i.e., methods more relevant to high- versus low-severity regimes). Ecological heterogeneity created by mixed-severity regimes potentially influences decisions related to conservation, silviculture, wildfire, and fuel mitigation. Thus, understanding underlying assumptions and errors in mapping fire regimes is critical.
Age and size effects on seed productivity of northern black spruce
Authors: Viglas Jayme N. , Brown Carissa D. , Johnstone Jill F.
Published: May 2013

Slow-growing conifers of the northern boreal forest may require several decades to reach reproductive maturity, making them vulnerable to increases in disturbance frequency. Here, we examine the relationship between stand age and seed productivity of black spruce (Picea mariana (Mill.) Britton, Sterns & Poggenb.) in Yukon Territory and Alaska. Black spruce trees were aged and surveyed for cone production and seed viability across 30 even-aged stands ranging from 12 to 197 years old. Logistic regression indicated that individual trees had a ∼50% probability of producing cones by age 30 years, which increased to 90% by age 100 years. Cone and seed production increased steadily with age or basal area at both the tree and stand level, with no evidence of declining seed production in trees older than 150 years. Using published seed:seedling ratios, we estimated that postfire recruitment will be limited by seed availability in stands for up to 50 years (on high-quality seedbeds) to 150 years (low-quality seedbeds) after fire. By quantifying these age and seed productivity relationships, we can improve our ability to predict the sensitivity of conifer seed production to a range of disturbance frequencies and thus anticipate changes in boreal forest resilience to altered fire regime.
Phenotype microarray screening of carbon sources used byVibrio choleraeidentifies genes regulated by the cAMP receptor protein
Authors: Chen Baoli , Liang Weili , Wu Rui , Liang Pu , Kan Biao
Published: May 2013

The cyclic AMP receptor protein (CRP) regulates genes involved in carbon source metabolism, iron uptake, and virulence in bacteria. Identifying the carbon sources utilized by bacteria that are regulated by CRP will help elucidate the CRP regulation cascade and associated responses to environmental stimuli. CRP-dependent regulation of carbon source metabolism in Vibrio cholerae is not thoroughly understood. To identify the candidate carbon sources utilized by V. cholerae that are affected by CRP, we used high-throughput screening to compare the metabolic differences between wild-type and CRP mutant strains of V. cholerae O1 El Tor. Phenotype microarray was used for primary screening of the wild-type and mutant strains, followed by minimal media growth assays and quantitative RT-PCR to validate the candidate carbon sources. In total, 24 carbon sources were subject to CRP regulation, 11 of which have not been previously reported in bacteria. The genes known to be involved in the metabolism of 4 of the carbon sources identified were verified by quantitative RT-PCR. In addition, gel shift experiments showed that CRP bound directly to VCA0053 and VC0391 promoters. Overall, this comprehensive analysis of CRP-mediated catabolite control in V. cholerae has identified new candidate carbon sources for in-depth experimental studies.
FUZZY AHP APPROACH TO THE COMPETENCE OF ENGINEERING MANPOWER OUTSOURCING
Authors: LAI WEN-HSIANG
Published: May 2013

Outsourcing strategies reveal trends in strategic business administration. Over the past 80 years, outsourcing has become one of the most important concepts in business management and operation. In Taiwan, optoelectronics, semiconductors, and information technology (IT) are the major industries engaging in engineering manpower outsourcing (EMO) due to their capital intensity and their requirements for a large quantity of high-quality engineers. This study analyzes the EMO competence of Taiwan's enterprises using expert interviews, analytic hierarchy process (AHP) analysis, and a fuzzy logic inference system (FLIS). This study shows that EMO competence can be divided into three influential variables: cost, resources, and strategy. The results of this research indicate that the cost variable has the greatest influence on EMO. The results of fuzzy analysis demonstrate that if enterprises intend to improve their EMO, they must consider the combination of the direct cost and talents sub-variables within the resource variable to be more important than the various sub-variable combinations of cost and strategy. Moreover, empirical results also show that the internal operation (IO) sub-variable has a significant impact on the strategy variable and that the internal training (IT) and external alliance (EA) sub-variables have little influence on the strategy variable with respect to EMO.
ON THE RIEMANN CURVATURE OPERATORS IN RANDERS SPACES
Authors: RAFIE-RAD M.
Published: May 2013

The Riemann curvature in Riemann–Finsler geometry can be regarded as a collection of linear operators on the tangent spaces. The algebraic properties of these operators may be linked to the geometry and the topology of the underlying space. The principal curvatures of a Finsler space (M, F) at a point x are the eigenvalues of the Riemann curvature operator at x. They are real functions κ on the slit tangent manifold TM0. A principal curvature κ(x, y) is said to be isotropic (respectively, quadratic) if κ(x, y)/F(x, y) is a function of x only (respectively, κ(x, y) is quadratic with respect to y). On the other hand, the Randers metrics are the most popular and prominent metrics in pure and applied disciplines. Here, it is proved that if a Randers metric admits an isotropic principal curvature, then F is of isotropic S-curvature. The same result is also established for F to admit a quadratic principal curvature. These results extend Shen's verbal results about Randers metrics of scalar flag curvature K = K(x) as well as those Randers metrics with quadratic Riemann curvature operator. The Riemann curvature [Formula: see text] may be broken into two operators [Formula: see text] and [Formula: see text]. The isotropic and quadratic principal curvature are characterized in terms of the eigenvalues of [Formula: see text] and [Formula: see text].
LIE–HAMILTON SYSTEMS: THEORY AND APPLICATIONS
Authors: CARIÑENA J. F. , DE LUCAS J. , SARDÓN C.
Published: May 2013

This work concerns the definition and analysis of a new class of Lie systems on Poisson manifolds enjoying rich geometric features: the Lie–Hamilton systems. We devise methods to study their superposition rules, time independent constants of motion and Lie symmetries, linearizability conditions, etc. Our results are illustrated by examples of physical and mathematical interest.
2D RICCI FLAT GRADIENT SOLITONS ARISING FROM REMARKABLE MODELS IN PHYSICS
Authors: BERCU GABRIEL
Published: May 2013

On a pseudo-Riemannian manifold (M, g) we consider ∇ the Levi-Cività connection associated to metric g and a function f : M → ℝ whose pseudo-Riemannian Hessian [Formula: see text] is non-degenerate and with constant signature. We study properties of the pseudo-Riemannian manifold (M, h), [Formula: see text] in terms of local computation. Investigating the conditions for existence of the equal connections [Formula: see text], produced by g and h, we determine classes of explicit Ricci flat gradient solitons for some particular forms of g, arising from remarkable physics models.
GEOMETRIC FORMULATION OF NON-AUTONOMOUS MECHANICS
Authors: SARDANASHVILY G.
Published: May 2013

We address classical and quantum mechanics in a general setting of arbitrary time-dependent transformations. Classical non-relativistic mechanics is formulated as a particular field theory on smooth fiber bundles over a time axis ℝ. Connections on these bundles describe reference frames. Quantum non-autonomous mechanics is phrased in geometric terms of Banach and Hilbert bundles and connections on these bundles. A quantization scheme speaking this language is geometric quantization.
TOWARDS SUSTAINABLE COMPETITIVENESS: COMPARISON OF THE SUCCESSFUL AND UNSUCCESSFUL ECO-INNOVATORS
Authors: FORSMAN HELENA , TEMEL SERDAL , UOTILA MARJO
Published: May 2013

This paper examines the links between eco-innovations and competitiveness. It explores how superior competitiveness is created and how existing competitiveness is lost. The study utilises multiple case studies following the replication approach. The empirical evidence is based on five case firms that have created superior competitiveness and five case firms that have lost their competitiveness. Competitiveness is monitored having emphasis on market-related, efficiency-related, risk-related and image-related issues. The longitudinal data covers ten years from 2002 to 2011. This study provides two contributions to academic literature. First, it deepens the existing knowledge of how firms have created competitiveness through the development of eco-innovations or how the firms have lost their competitiveness. Second, it illustrates a journey of ten years during which the successful eco-innovators created their superior competitiveness. Also, the journey of the unsuccessful eco-innovators is described.
Detecting giant electrocaloric properties of ferroelectric SbSI at room temperature
Authors: Hamad Mahmoud A.
Published: May 2013

In this work, ferroelectric SbSI shows a giant electrocaloric effect at room temperature under very low electric field shift of 0.37 kV cm-1. It is shown that the cooling ΔT per unit field MVm-1 is 2.97. This value is significantly larger, and is comparable with the value of 0.254 for PbZr 0.95 Ti 0.05 O 3 thin film under electric field shift of 30 kV cm-1. Moreover, the reduction in operating temperature opens up many more possibilities and widens the potential for applications in cooling systems.
The
c.
1000–900 Ma and
c.
550–500 Ma tectonothermal events in the Prince Charles Mountains–Prydz Bay region, East Antarctica, and their relations to supercontinent evolution
Authors: Liu Xiaochun , Zhao Yue , Hu Jianmin
Published: May 2013

The Prince Charles Mountains (PCM)–Prydz Bay region in East Antarctica experienced the late Mesoproterozoic/early Neoproterozoic (
c.
1000–900 Ma) and late Neoproterozoic/Cambrian (
c.
550–500 Ma) tectonothermal events. The late Mesoproterozoic/early Neoproterozoic tectonothermal event dominates the Rayner Complex and spreads over the main part of the Prydz Belt. This event includes two episodes (or stages) of metamorphism accompanying the intrusion of syn- to post-orogenic granitoids at
c.
1000–960 Ma and
c.
940–900 Ma. The
c.
1000–960 Ma metamorphism in the northern PCM and Mawson Coast records medium- to low-pressure granulite facies conditions accompanied by a near-isobaric cooling path, whereas the
c.
940–900 Ma metamorphism in Kemp Land reaches relatively higher
P
–
T
conditions followed by a near-isothermal decompression or decompressive cooling path. The late Mesoproterozoic/early Neoproterozoic orogeny (i.e. the Rayner orogeny) involved a long-lived (
c.
1380–1020 Ma) magmatic accretion along continental/oceanic arcs and a protracted or two-stage collision of the Indian craton with a portion of East Antarctica, forming the Indian–Antarctic continental block independent of the Rodinia supercontinent. The late Neoproterozoic/Cambrian tectonothermal event pervasively overprinted on both Archaean–Proterozoic basements and cover sequences in the Prydz Belt. Except for high-pressure granulite boulders from the Grove Mountains, the metamorphism of most rocks records medium-pressure granulite facies conditions with a clockwise
P–T
path. In contrast, this event is lower grade (greenschist–amphibolite facies) and localized in the PCM. Regionally, the late Neoproterozoic/Cambrian tectonothermal event seems to have developed on the southeastern margin of the Indo-Antarctic continental block, suggesting that the major suture should be located southeastwards of the presently exposed Prydz Belt. The precise dating for different rock types reveals that the late Neoproterozoic/Cambrian orogeny (i.e. the Prydz orogeny) commenced at
c.
570 Ma and lasted until
c.
490 Ma, which is roughly contemporaneous with the late collisional stage of the Brasiliano/Pan-African orogenic systems in Gondwanaland. Therefore, the final assembly of the Gondwana supercontinent may have been completed by the collision of a number of cratonic blocks during the same time period.
Composition of the Extracellular Matrix of Lymphatic Novel Threadlike Structures: Is It Keratin?
Authors: Huh Hyub , Lee Byung-Cheon , Park Sang-Hyun , Yoon Ji Woong , Lee Soo Jae , Cho Eun Jung , Yoon Seung Zhoo
Published: May 2013

Background. The lumen of novel threadlike structures (NTSs) is enclosed by a single layer of endothelial cells surrounded by extracellular matrix (ECM). We hypothesized that collagen may be a component of the ECM associated with lymphatic NTSs.Methods. Six female New Zealand white rabbits were anesthetized, and the NTS structures within lymphatic vessels were identified by contrast-enhanced stereomicroscopy or alcian blue staining. Isolated NTS specimens were stained with acridine orange, YOYO-1, and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI). The structural and molecular composition of the ECM was investigated using transmission electron microscopy (TEM), electrospray ionization-mass spectrometry, and proteomic analysis.Results. The lymph vessel wall was stained red by DiI, and rod-shaped nuclei were stained green by YOYO-1. The area surrounding the NTS was also stained red and contained green rod-shaped nuclei. TEM images showed that the NTS consisted of many ECM fibers and the ECM fibers appeared to be ~100 nm in diameter and had narrowly spaced striated bands. Proteomic analysis of the lymphatic NTS-associated ECM identified 4 proteins: keratin 10, cytokeratin 3, cytokeratin 12, and soluble adenylyl cyclase.Conclusion. The TEM study suggested that the lymphatic NTS-associated ECM did not contain collagen. This was confirmed by proteomic analysis, which showed that keratin was the major component of the ECM.
Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling
Authors: Mattes W. B. , Kamp H. G. , Fabian E. , Herold M. , Krennrich G. , Looser R. , Mellert W. , Prokoudine A. , Strauss V. , van Ravenzwaay B. , Walk T. , Naraoka H. , Omura K. , Schuppe-Koistinen I. , Nadanaciva S. , Bush E. D. , Moeller N. , Ruiz-Noppinger P. , Piccoli S. P.
Published: May 2013

Addressing safety concerns such as drug-induced kidney injury (DIKI) early in the drug pharmaceutical development process ensures both patient safety and efficient clinical development. We describe a unique adjunct to standard safety assessment wherein the metabolite profile of treated animals is compared with the MetaMap Tox metabolomics database in order to predict the potential for a wide variety of adverse events, including DIKI. To examine this approach, a study of five compounds (phenytoin, cyclosporin A, doxorubicin, captopril, and lisinopril) was initiated by the Technology Evaluation Consortium under the auspices of the Drug Safety Executive Council (DSEC). The metabolite profiles for rats treated with these compounds matched established reference patterns in the MetaMap Tox metabolomics database indicative of each compound’s well-described clinical toxicities. For example, the DIKI associated with cyclosporine A and doxorubicin was correctly predicted by metabolite profiling, while no evidence for DIKI was found for phenytoin, consistent with its clinical picture. In some cases the clinical toxicity (hepatotoxicity), not generally seen in animal studies, was detected with MetaMap Tox. Thus metabolite profiling coupled with the MetaMap Tox metabolomics database offers a unique and powerful approach for augmenting safety assessment and avoiding clinical adverse events such as DIKI.