bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased apical Na+ permeability in cystic fibrosis is supported by a quantitative model of epithelial ion transport
Authors: O’Donoghue Donal L. , Dua Vivek , Moss Guy W. J. , Vergani Paola
Published: June 2013

Key points

Cystic fibrosis (CF) is a common genetic disease caused by loss‐of‐function mutations in the cystic fibrosis transmembrane conductance regulator gene, which encodes a channel protein, selective for anions.

In the lungs, the site of the most severe symptoms, CF causes abnormal electrolyte transport in epithelial cells which line the airways.

Airway epithelial ion transport can be assessed by measuring the trans‐epithelial potential difference (Vt) which shows characteristic changes in CF individuals. We developed a biophysical model of ion transport in human nasal epithelia, in order to investigate quantitatively which transport parameters underlie these observed bioelectric changes.

We found that loss of apical Cl− permeability alone is insufficient to explain the bioelectric properties of CF epithelia. An increase of apical Na+ permeability must also occur.

This insight has important implications for our understanding of the physiology of CF disease, and hence for potential therapies aimed at correcting the CF ion transport defect.

Abstract  Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes an anion channel. In the human lung CFTR loss causes abnormal ion transport across airway epithelial cells. As a result CF individuals produce thick mucus, suffer persistent bacterial infections and have a much reduced life expectancy. Trans‐epithelial potential difference (Vt) measurements are routinely carried out on nasal epithelia of CF patients in the clinic. CF epithelia exhibit a hyperpolarised basal Vt and a larger Vt change in response to amiloride (a blocker of the epithelial Na+ channel, ENaC). Are these altered bioelectric properties solely a result of electrical coupling between the ENaC and CFTR currents, or are they due to an increased ENaC permeability associated with CFTR loss? To examine these issues we have developed a quantitative mathematical model of human nasal epithelial ion transport. We find that while the loss of CFTR permeability hyperpolarises Vt and also increases amiloride‐sensitive Vt, these effects are too small to account for the magnitude of change observed in CF epithelia. Instead, a parallel increase in ENaC permeability is required to adequately fit observed experimental data. Our study provides quantitative predictions for the complex relationships between ionic permeabilities and nasal Vt, giving insights into the physiology of CF disease that have important implications for CF therapy.
Eccentric contractions increase the phosphorylation of tuberous sclerosis complex‐2 (TSC2) and alter the targeting of TSC2 and the mechanistic target of rapamycin to the lysosome
Authors: Jacobs Brittany L. , You Jae‐Sung , Frey John W. , Goodman Craig A. , Gundermann David M. , Hornberger Troy A.
Published: June 2013

Key points

Mechanical stimuli play a major role in the regulation of skeletal muscle mass.

Signalling through a protein kinase called the mechanistic target of rapamycin (mTOR) is essential for mechanically induced changes in muscle mass; however, the mechanism(s) via which mechanical stimuli regulate mTOR signalling have not been defined.

In this study, mouse skeletal muscles were stimulated with eccentric contractions (ECs) to determine if the mechanical activation of mTOR signalling is associated with changes in the phosphorylation of the tuberous sclerosis complex‐2 (TSC2) and the targeting of both mTOR and TSC2 to the lysosome.

Our results demonstrate that ECs induce hyper‐phosphorylation of TSC2, enhanced lysosomal targeting of mTOR and nearly abolish the lysosomal targeting of TSC2.

These novel observations suggest that alterations in the lysosomal targeting of mTOR/TSC2 could play a fundamental role in the mechanism via which mechanical stimuli regulate mTOR signalling and ultimately skeletal muscle mass.

Abstract  The goal of this study was to determine whether the mechanical activation of mechanistic target of rapamycin (mTOR) signalling is associated with changes in phosphorylation of tuberous sclerosis complex‐2 (TSC2) and targeting of mTOR and TSC2 to the lysosome. As a source of mechanical stimulation, mouse skeletal muscles were subjected to eccentric contractions (ECs). The results demonstrated that ECs induced hyper‐phosphorylation of TSC2 and at least part of this increase occurred on residue(s) that fall within RxRxxS/T consensus motif(s). Furthermore, in control muscles, we found that both mTOR and TSC2 are highly enriched at the lysosome. Intriguingly, ECs enhanced the lysosomal association of mTOR and almost completely abolished the lysosomal association of TSC2. Based on these results, we developed a new model that could potentially explain how mechanical stimuli activate mTOR signalling. Furthermore, this is the first study to reveal that the activation of mTOR is associated with the translocation of TSC2 away from the lysosome. Since a large number of signalling pathways rely on TSC2 to control mTOR signalling, our results have potentially revealed a fundamental mechanism via which not only mechanical, but also various other types of stimuli, control mTOR signalling.
TGF-β Induces Acetylation of Chromatin and of Ets-1 to Alleviate Repression of miR-192 in Diabetic Nephropathy
Authors: Kato Mitsuo , Dang Varun , Wang Mei , Park Jung Tak , Deshpande Supriya , Kadam Swati , Mardiros Armen , Zhan Yumei , Oettgen Peter , Putta Sumanth , Yuan Hang , Lanting Linda , Natarajan Rama
Published: June 2013

Acetylation of chromatin and Ets-1 contributes to induction of
miR-192
, a microRNA involved in kidney pathogenesis.
Multiple Inputs to Flowering
Authors: Hines Pamela J.
Published: June 2013

MicroRNAs regulate perennial flowering.
Phosphorylation-Mediated Knockdown
Authors: Gough Nancy R.
Published: June 2013

Phosphorylated chimeric proteins target signaling components for degradation.
Virulence of Vancomycin-Resistant Enterococcus faecium According to Linezolid Resistance and Clinical Outbreak Status
Authors: McLaughlin Milena , Malczynski Michael , Qi Chao , Barajas Grace , Radetski Jordan , Zembower Teresa , Scheetz Marc H.
Published: June 2013

Assessing clinical virulence differences between vancomycin-resistant
Enterococcus faecium
(VREF) strains resistant to linezolid (LRVRE) and linezolid-susceptible VRE (LSVRE) strains is difficult due to confounding patient variables.
Galleria mellonella
is a validated host interaction model allowing straightforward organism virulence assessment. The objective of this study was to assess the virulence of VREF in
G. mellonella
according to linezolid resistance and clinical outbreak status. A genetically related pair of VREF strains with and without genotypically confirmed linezolid resistance was selected for analysis. Additionally, six strains of LSVRE and two strains of LRVRE were selected according to epidemiologic outbreak status. Mortality of
G. mellonella
was assessed daily over a 5-day period and analyzed using Kaplan-Meier survival curves and log rank tests. Linezolid resistance did not have a significant effect on
G. mellonella
mortality in the genetically related pair (
P
= 0.93). There was no significant difference in mortality over time between strains (non-outbreak [i.e., no patient transmissions were recorded] [
n
= 2] versus outbreak [i.e., transmission occurred between 3 or more patients in a period of 30 days] [
n
= 6],
P
= 0.84; extensive transmission [i.e., the isolate was transmitted between at least 80 patients] [
n
= 2] versus limited transmission [i.e., the isolate was transmitted between fewer than 10 patients] [
n
= 4],
P
= 0.78). These results suggest that patients infected with LRVRE or outbreak strains of VREF are at no greater risk of poor outcomes mediated by organism virulence than those infected with LSVRE or non-outbreak strains.
Role of the LytSR Two-Component Regulatory System in Adaptation to Cationic Antimicrobial Peptides in Staphylococcus aureus
Authors: Yang Soo-Jin , Xiong Yan Q. , Yeaman Michael R. , Bayles Kenneth W. , Abdelhady Wessam , Bayer Arnold S.
Published: June 2013

Many host defense cationic antimicrobial peptides (HDPs) perturb the staphylococcal cell membrane (CM) and alter transmembrane potential (ΔΨ) as key parts of their lethal mechanism. Thus, a sense-response system for detecting and mediating adaptive responses to such stresses could impact organism survival; the
Staphylococcus aureus
LytSR two-component regulatory system (TCRS) may serve as such a ΔΨ sensor. One well-known target of this system is the
lrgAB
operon, which, along with the related
cidABC
operon, has been shown to be a regulator in the control of programmed cell death and lysis. We used an isogenic set of
S. aureus
strains: (i) UAMS-1, (ii) its isogenic Δ
lytS
and Δ
lrgAB
mutants, and (iii) plasmid-complemented Δ
lytSR
and Δ
lrgAB
mutants. The Δ
lytS
strain displayed significantly increased
in vitro
susceptibilities to all HDPs tested (neutrophil-derived human neutrophil peptide 1 [hNP-1], platelet-derived thrombin-induced platelet microbicidal proteins [tPMPs], and the tPMP-mimetic peptide RP-1), as well as to calcium-daptomycin (DAP), a cationic antimicrobial peptide (CAP). In contrast, the Δ
lrgAB
strain exhibited no significant changes in susceptibilities to these cationic peptides, indicating that although
lytSR
positively regulates transcription of
lrgAB
, increased HDP/CAP susceptibilities in the Δ
lytS
mutant were
lrgAB
independent. Further, parental UAMS-1 (but not the Δ
lytS
mutant) became more resistant to hNP-1 and DAP following pretreatment with carbonyl cyanide
m
-chlorophenylhydrazone (CCCP) (a CM-depolarizing agent). Of note,
lytSR
-dependent survival against CAP/HDP killing was not associated with changes in either surface positive charge, expression of
mprF
and
dlt
, or CM fluidity. The Δ
lytS
strain (but not the Δ
lrgAB
mutant) displayed a significant reduction in target tissue survival in an endocarditis model during DAP treatment. Collectively, these results suggest that the
lytSR
TCRS plays an important role in adaptive responses of
S. aureus
to CM-perturbing HDPs/CAPs, likely by functioning as a sense-response system for detecting subtle changes in ΔΨ.
Lethal Hydroxyl Radical Accumulation by a Lactococcal Bacteriocin, Lacticin Q
Authors: Li Mengqi , Yoneyama Fuminori , Toshimitsu Nayu , Zendo Takeshi , Nakayama Jiro , Sonomoto Kenji
Published: June 2013

The antimicrobial mechanism of a lactococcal bacteriocin, lacticin Q, can be described by the toroidal pore model without any receptor. However, lacticin Q showed different degrees of activity (selective antimicrobial activity) against Gram-positive bacteria even among related species. The ability of lacticin Q to induce pore formation in liposomes composed of lipids from different indicator strains indicated that its selective antimicrobial activity could not be attributed only to membrane lipid composition. We investigated the accumulation of deleterious hydroxyl radicals after exposure to lacticin Q as a contributing factor to cell death in the indicator strains. When lacticin Q of the same concentration as the MIC or minimum bactericidal concentration was added to the indicator cultures, high levels of hydroxyl radical accumulation were detected. Treatment with hydroxyl radical scavengers, thiourea and 2,2′-bipyridyl, decreased the levels of hydroxyl radical accumulation and recovered cell viability. These results suggest that, with or without pore formation, the final antimicrobial mechanism of lacticin Q is the accumulation of hydroxyl radicals, which varies by strain, resulting in the selective antimicrobial activity of lacticin Q.
Efficacy of Humanized Carbapenem Exposures against New Delhi Metallo-β-Lactamase (NDM-1)-Producing Enterobacteriaceae in a Murine Infection Model
Authors: Wiskirchen Dora E. , Nordmann Patrice , Crandon Jared L. , Nicolau David P.
Published: June 2013

Enterobacteriaceae
producing the novel carbapenemase New Delhi metallo-β-lactamase (NDM-1) are emerging worldwide. While these organisms often display high levels of
in vitro
resistance to multiple antibiotics,
in vivo
efficacy data are lacking. Here, the activities of humanized ertapenem and doripenem exposures were characterized against a wild-type
K. pneumoniae
and its derived isogenic strains harboring either an NDM-1 or KPC-2 plasmid in immunocompetent mice. In addition, four clinical isolates expressing NDM-1 were evaluated. Human-simulated regimens of ertapenem at 1 g every 24 h and high-dose, prolonged infusion of doripenem at 2 g every 8 h as a 4-h infusion were evaluated over 24 h, and efficacy was determined by the change in bacterial density compared to that in 24-h growth controls. CFU reductions in bacterial density of greater than 1 log unit were observed against the wild-type strain as well as the derived isogenic NDM-1 strain, while no reduction was observed against the derived KPC-2 strain. Postexposure MICs confirmed the
in vitro
maintenance of the ertapenem resistance marker in both the NDM-1 and KPC-2 strains. Similar to the case for the isogenically derived NDM-1 strain, bacterial density was reduced at 24 h against all four clinical NDM-1 isolates showing variable levels of MICs for carbapenems, with near-maximal activity of both agents occurring when the doripenem MIC was ≤8 μg/ml. While carbapenem monotherapy does not appear to be an option against KPC-based infections, these data suggest that carbapenem monotherapy may be a viable option for treating NDM-1-producing
Enterobacteriaceae
under certain conditions, and this warrants further
in vivo
exploration.
Efficacy and Safety of Metronidazole for Pulmonary Multidrug-Resistant Tuberculosis
Authors: Carroll Matthew W. , Jeon Doosoo , Mountz James M. , Lee Jong Doo , Jeong Yeon Joo , Zia Nadeem , Lee Myungsun , Lee Jongseok , Via Laura E. , Lee Soyoung , Eum Seok-Yong , Lee Sung-Joong , Goldfeder Lisa C. , Cai Ying , Jin Boyoung , Kim Youngran , Oh Taegwon , Chen Ray Y. , Dodd Lori E. , Gu Wenjuan , Dartois Veronique , Park Seung-Kyu , Kim Cheon Tae , Barry Clifton E. , Cho Sang-Nae
Published: June 2013

Pulmonary lesions from active tuberculosis patients are thought to contain persistent, nonreplicating bacilli that arise from hypoxic stress. Metronidazole, approved for anaerobic infections, has antituberculosis activity against anoxic bacilli
in vitro
and in some animal models and may target persistent, nonreplicating bacilli. In this double-blind, placebo-controlled trial, pulmonary multidrug-resistant tuberculosis subjects were randomly assigned to receive metronidazole (500 mg thrice daily) or placebo for 8 weeks in addition to an individualized background regimen. Outcomes were measured radiologically (change on high-resolution computed tomography [HRCT]), microbiologically (time to sputum smear and culture conversion), and clinically (status 6 months after stopping therapy). Enrollment was stopped early due to excessive peripheral neuropathies in the metronidazole arm. Among 35 randomized subjects, 31 (15 metronidazole, 16 placebo) were included in the modified intent-to-treat analysis. There were no significant differences by arm in improvement of HRCT lesions from baseline to 2 or 6 months. More subjects in the metronidazole arm converted their sputum smear (
P
= 0.04) and liquid culture (
P
= 0.04) to negative at 1 month, but these differences were lost by 2 months. Overall, 81% showed clinical success 6 months after stopping therapy, with no differences by arm. However, 8/16 (50%) of subjects in the metronidazole group and 2/17 (12%) of those in the placebo group developed peripheral neuropathy. Subjects who received metronidazole were 4.3-fold (95% confidence interval [CI], 1.1 to 17.1) more likely to develop peripheral neuropathies than subjects who received placebo. Metronidazole may have increased early sputum smear and culture conversion but was too neurotoxic to use over the longer term. Newer nitroimidazoles with both aerobic and anaerobic activity, now in clinical trials, may increase the sterilizing potency of future treatment regimens.
Candida albicans Mucin Msb2 Is a Broad-Range Protectant against Antimicrobial Peptides
Authors: Swidergall Marc , Ernst Andreas M. , Ernst Joachim F.
Published: June 2013

The human fungal pathogen
Candida albicans
releases a large glycofragment of the Msb2 surface protein (Msb2*) into the growth environment, which protects against the action of human antimicrobial peptides (AMPs) LL-37 and histatin-5. Quantitation of Msb2*/LL-37 interactions by microscale thermophoresis revealed high-affinity binding (dissociation constant [

K
D

] = 73 nM), which was lost or greatly diminished by lack of
O
-glycosylation or by Msb2* denaturation. Msb2* also interacted with human α- and β-defensins and protected
C. albicans
against these AMPs. In addition, the lipopeptide antibiotic daptomycin was bound and inactivated by Msb2*, which prevented the killing of bacterial pathogens
Staphylococcus aureus
,
Enterococcus faecalis
, and
Corynebacterium pseudodiphtheriticum
. In coculturings or mixed biofilms of
S. aureus
with
C. albicans
wild-type but not
msb2
mutant strains, the protective effects of Msb2* on the bactericidal action of daptomycin were demonstrated. These results suggest that tight binding of shed Msb2* to AMPs that occurs during bacterial coinfections with
C. albicans
compromises antibacterial therapy by inactivating a relevant reserve antibiotic.
Molecular Characterization of an
rsmD
-Like rRNA Methyltransferase from the Wolbachia Endosymbiont of Brugia malayi and Antifilarial Activity of Specific Inhibitors of the Enzyme
Authors: Rana Ajay Kumar , Chandra Sharat , Siddiqi Mohammad Imran , Misra-Bhattacharya Shailja
Published: June 2013

The endosymbiotic organism
Wolbachia
is an attractive antifilarial drug target. Here we report on the cloning and expression of an
rsmD
-like rRNA methyltransferase from the
Wolbachia
endosymbiont of
Brugia malayi
, its molecular properties, and assays for specific inhibitors. The gene was found to be expressed in all the major life stages of
B. malayi
. The purified enzyme expressed in
Escherichia coli
was found to be in monomer form in its native state. The activities of the specific inhibitors (heteroaryl compounds) against the enzyme were tested with
B. malayi
adult and microfilariae for 7 days
in vitro
at various concentrations, and NSC-659390 proved to be the most potent compound (50% inhibitory concentration [IC
50
], 0.32 μM), followed by NSC-658343 (IC
50
, 4.13 μM) and NSC-657589 (IC
50
, 7.5 μM). On intraperitoneal administration at 5 mg/kg of body weight for 7 days to adult jirds into which
B. malayi
had been transplanted intraperitoneally, all the compounds killed a significant proportion of the implanted worms. A very similar result was observed in infected mastomys when inhibitors were administered. Docking studies of enzyme and inhibitors and an
in vitro
tryptophan quenching experiment were also performed to understand the binding mode and affinity. The specific inhibitors of the enzyme showed a higher affinity for the catalytic site of the enzyme than the nonspecific inhibitors and were found to be potent enough to kill the worm (both adults and microfilariae)
in vitro
as well as
in vivo
in a matter of days at micromolar concentrations. The findings suggest that these compounds be evaluated against other pathogens possessing a methyltransferase with a DPPY motif and warrant the design and synthesis of more such inhibitors.
Antibiotic Trapping by Plasmid-Encoded CMY-2 β-Lactamase Combined with Reduced Outer Membrane Permeability as a Mechanism of Carbapenem Resistance in Escherichia coli
Authors: Goessens Wil H. F. , van der Bij Akke K. , van Boxtel Ria , Pitout Johann D. D. , van Ulsen Peter , Melles Damian C. , Tommassen Jan
Published: June 2013

A liver transplant patient was admitted with cholangitis, for which meropenem therapy was started. Initial cultures showed a carbapenem-susceptible (CS)
Escherichia coli
strain, but during admission, a carbapenem-resistant (CR)
E. coli
strain was isolated. Analysis of the outer membrane protein profiles showed that both CS and CR
E. coli
lacked the porins OmpF and OmpC. Furthermore, PCR and sequence analysis revealed that both CS and CR
E. coli
possessed
bla
CTX-M-15
and
bla
OXA-1
. The CR
E. coli
strain additionally harbored
bla
CMY-2
and demonstrated a >15-fold increase in β-lactamase activity against nitrocefin, but no hydrolysis of meropenem was detected. However, nitrocefin hydrolysis appeared strongly inhibited by meropenem. Furthermore, the CMY-2 enzyme demonstrated lower electrophoretic mobility after its incubation either
in vitro
or
in vivo
with meropenem, indicative of its covalent modification with meropenem. The presence of the acyl-enzyme complex was confirmed by mass spectrometry. By transformation of the CMY-2-encoding plasmid into various
E. coli
strains, it was established that both porin deficiency and high-level expression of the enzyme were needed to confer meropenem resistance. In conclusion, carbapenem resistance emerged by a combination of elevated β-lactamase production and lack of porin expression. Due to the reduced outer membrane permeability, only small amounts of meropenem can enter the periplasm, where they are trapped but not degraded by the large amount of the β-lactamase. This study, therefore, provides evidence that the mechanism of “trapping” by CMY-2 β-lactamase plays a role in carbapenem resistance.
Bacterial and Clinical Characteristics of Health Care- and Community-Acquired Bloodstream Infections Due to Pseudomonas aeruginosa
Authors: Hattemer Angela , Hauser Alan , Diaz Maureen , Scheetz Marc , Shah Nirav , Allen Jonathan P. , Porhomayon Jahan , El-Solh Ali A.
Published: June 2013

Health care-associated infections, including
Pseudomonas aeruginosa
bloodstream infection, have been linked to delays in appropriate antibiotic therapy and an increased mortality rate. The objective of this study was to evaluate intrinsic virulence, bacterial resistance, and clinical outcomes of health care-associated bloodstream infections (HCABSIs) in comparison with those of community-acquired bloodstream infections (CABSIs) caused by
P. aeruginosa
. We conducted a retrospective multicenter study of consecutive
P. aeruginosa
bacteremia patients at two university-affiliated hospitals. Demographic, clinical, and treatment data were collected. Microbiologic analyses included
in vitro
susceptibility profiles and type III secretory (TTS) phenotypes. Sixty CABSI and 90 HCABSI episodes were analyzed. Patients with HCABSIs had more organ dysfunction at the time of bacteremia (
P
= 0.05) and were more likely to have been exposed to antimicrobial therapy (
P
< 0.001) than those with CABSIs. Ninety-two percent of the carbapenem-resistant
P. aeruginosa
infections were characterized as HCABSIs. The 30-day mortality rate for CABSIs was 26% versus 36% for HCABSIs (
P
= 0.38). The sequential organ failure assessment score at the time of bacteremia (hazard ratio [HR], 1.2; 95% confidence interval [CI], 1.1 to 1.3) and the TTS phenotype (HR 2.1; 95% CI, 1.1 to 3.9) were found to be independent predictors of the 30-day mortality rate. No mortality rate difference was observed between CABSIs and HCABSIs caused by
P. aeruginosa
. Severity of illness and expression of TTS proteins were the strongest predictors of the 30-day mortality rate due to
P. aeruginosa
bacteremia. Future
P. aeruginosa
bacteremia trials designed to neutralize TTS proteins are warranted.
Agitation after minor trauma: combativeness as a cardinal catatonic feature
Authors: Luykx Jurjen Justin , Post Elmar Hendrik , Erf Maaike van der , Van Hecke Jan
Published: June 2013

Catatonia is a syndrome of motor dysregulation, usually associated with psychiatric, neurological, systemic and drug-related diseases. Retarded and excited types exist, both of which often go unrecognised in clinical practice. We describe a 64-year-old woman who gradually developed insomnia, started communicating less, complained of feeling restless and ended up injuring relatives. Initiation of symptoms followed a fibula fracture. The patient was diagnosed with excited-type catatonia with prominent combativeness because of minor trauma and rapidly recovered after lorazepam treatment instatement. Our case demonstrates that catatonia can follow minor traumatic injury and how excited-type catatonic features may go unrecognised in general practitioner and specialist settings. Moreover, we show that catatonia may be recurrent, necessitating long-term treatment and very gradual lorazepam tapering.
Tubercular retinal vasculitis
Authors: Patricio Maria Sara , Portelinha Joana , Passarinho Maria Picoto , Guedes Marta Esteves
Published: June 2013

Intraocular tuberculosis (TB) infection can have different clinical manifestations including retinal vasculitis. It more frequently involves the veins and is associated with retina haemorrhages and neovascularisation. The diagnosis may be difficult and presumptive being based on clinical findings and evidence of systemic TB infection. The authors present a case of a 61-year-old woman with blurred vision and floaters in her left eye for 6 years, associated with recurrent vitreous haemorrahages. A temporal branch retinal vein occlusion was presumed. Four years later her right eye was also involved. Her best-corrected visual acuity (BCVA) was 20/50 in both eyes. Fundoscopic examination showed bilateral venous occlusion with vascular staining on fluorescein angiography suggestive of vasculitis secondary to Eales Disease (ED). The interferon gamma release assay (IGRA-QuantiFERON-TB Gold) was positive and antituberculosis treatment (ATT) was started. Her final BCVA was 20/20 bilaterally, without recurrences over a follow-up of 15 months. The use of ATT is likely to reduce recurrent vitreous haemorrhages and eliminate future recurrences.
Prenatal diagnosis of caudal dysplasia sequence associated with undiagnosed type I diabetes
Authors: Palacios-Marqués Ana , Oliver Cecilia , Martín-Bayón Tina , Martinez-Escoriza Juan Carlos
Published: June 2013

Caudal regression or caudal dysplasia sequence (CDS) is a rare congenital malformation, which includes a wide spectrum of musculoskeletal abnormalities involving the lumbosacral spine, pelvis and lower limbs. It can be associated to visceral defects in various degrees. Maternal diabetes, genetic predisposition and vascular hypoperfusion have been suggested as possible causative factors. Women with diabetes who are dependent on insulin are 200–400 times more likely to have a child with caudal regression, making CDS the most characteristic fetal abnormality of diabetic embryopathy. Prenatal diagnosis is possible by ultrasonographic examination. The sonographic findings include abrupt interruption of the lumbar spine and ‘Buddha or frog position’ of the lower limbs. MRI has demonstrated the level of the vertebral anomalies as well as the associated abnormalities and this is crucial because the prognosis of this condition depends on the severity of the lesion and the presence of associated disorders.
Splenic injury after colonoscopy requiring splenectomy
Authors: McBride Rachael , Dasari Bobby , Magowan Hannah , Mullan Michael , Yousaf Mahammad , Mackle Eamon
Published: June 2013

We present a case of a middle-aged woman, who presented with abdominal pain less than 24 h following an uneventful colonoscopy for rectal bleeding. Initial diagnosis was thought to be colonic perforation. An urgent CT scan performed owing to dropping haemoglobin and blood pressure revealed a large perisplenic haematoma. An urgent laparotomy was performed in which the patient had a total blood loss of 2500 ml and required splenectomy. The patient recovered well postoperatively.Colonoscopy is a commonly performed procedure in which complications of perforation and bleeding are well recognised. This case represents one of the rare but serious complications that endoscopists and patients should be aware of to aid prevention and early diagnosis.
An unusual aetiology for internuclear ophthalmoplegia
Authors: Vishwas Mellekate Shadaksharappa , Whitlow Christopher T , Haq Ihtsham ul
Published: June 2013

Typical causes of internuclear ophthalmoplegia (INO) include arterial infarcts, demyelinating conditions, inflammation and trauma. We here report the unique case of a 33-year-old man with INO of the right eye caused by infarction of the right midbrain, confirmed by diffusion-weighted MRI. At presentation he displayed impaired adduction of the right eye with normal movement of the left. CT angiogram revealed an underlying developmental venous anomaly (DVA), raising the concern of venous infarction. His symptoms improved with aggressive management of blood pressure and risk factors. The patient had vascular risk factors—smoking, hypertension and dyslipidaemia—and we theorise that the hyalinised and inelastic walls of our patient's DVA were more vulnerable to the thrombogenic effects of his risk factors, predisposing him to this event. Venous infarcts owing to DVA are rare. To our knowledge INO secondary to venous infarct has not been reported, and should be considered in the differential of such cases.
Craniopharyngioma and epidermoid tumour in same child: a rare association
Authors: Singh Deepak Kumar , Singh Neha , Parihar Anit , Singh Ragini
Published: June 2013

Simultaneous occurrence of histologically different primary brain tumours is rare, and its preoperative diagnosis is still challenging. The explanations for the simultaneous occurrence of different primary intracranial tumours in the absence of phacomatoses or prior radiation exposure are at present hypothetical, and these tumours could be simply coincidental. Herein, we report a case of a boy presenting with features of raised intracranial pressure and right-sided sensorineural hearing loss. Brain MRI revealed two different neoplastic pathologies at different sites: an intrasellar and suprasellar craniopharyngioma and a right cerebello-pontine angle epidermoid. To the best of our knowledge, this is the first report in literature of a craniopharyngioma coexisting with an epidermoid, in the same individual.
Fixed functional space maintainer: novel aesthetic approach for missing maxillary primary anterior teeth
Authors: Khare Vikram , Nayak Prathibha Anand , Khandelwal Vishal , Nayak Ullal Anand
Published: June 2013

The first-line treatment of non-restorable traumatically injured or carious deciduous teeth is extraction which may be a curse for the future dentition as well as social activity of a child. Various therapeutic modalities from removable partial dentures to fixed space maintainer can be used for replacement of such lost teeth. Two types of fixed aesthetic space maintainers for replacing premature loss of maxillary deciduous incisors in 4-year-old children are discussed.
Taurodontism in deciduous molars
Authors: Bafna Yash , Kambalimath H V , Khandelwal Vishal , Nayak Prathibha
Published: June 2013

Taurodont teeth are characterised by large pulp chambers at the expense of roots. An enlarged pulp chamber, apical displacement of the pulpal floor and no constriction at the level of the cement-enamel junction are the characteristic features of taurodont tooth. It appears more frequently as an isolated anomaly but its association with syndromes and other abnormalities have also been reported. Permanent dentition is more commonly affected than deciduous dentition. This paper presents a case report of taurodontism in relation to mandibular deciduous second molars.
Assessing the uptake of the Liverpool Care Pathway for dying patients: a systematic review
Authors: Stocker Rachel , Close Helen
Published: June 2013

Improving the care of the dying is regarded as a national priority and current guidelines stipulate the need to provide holistic palliative care. Despite this, many dying patients and carers report low levels of comfort and satisfaction with care. Reasons include poor coordination of care, variability in communication and crisis-driven interventions. Integrated care pathways aim to support care coordination and open communication with patients and carers. One example is the Liverpool Care Pathway (LCP). Using the LCP entails assessment of eligibility criteria which requires skills, knowledge and clinical judgement about its timing. This can be problematic, and little is known about actual uptake, characteristics of assessed patients and reasons for inclusion/exclusion. A comprehensive systematic review was conducted for papers published between January 1990 and July 2012 providing information on LCP uptake. 17 papers met inclusion criteria. A total of 18 052 patients were placed on the LCP, in a variety of inpatient and primary care settings, and cancer and non-cancer diagnoses. 47.4% of dying patients identified were placed on the LCP. Although the LCP is widely recommended, it is only used for around half of dying patients. Reasons may include lack of knowledge, high staff turnover and concerns about applicability particularly for unpredictable dying trajectories. The proportion of patients who meet the eligibility criteria and the reasons surrounding low uptake remain unclear. Research is urgently required to further quantify the variable use of the LCP, and to investigate whether alternative approaches should be developed for non-cancer groups.
Investigation of the long-term tunnel settlement mechanisms of the first metro line in Shanghai
Authors: Ng C.W.W. , Liu G.B. , Li Q.
Published: June 2013

The long-term performance of a metro tunnel is obviously a major concern for the authority and designers responsible for its construction, as excessive tunnel settlement would affect the serviceability and safety of the entire metro system. In this study, measured long-term settlement of the 16.4 km long tunnel of Shanghai Metro Line 1 from 1994 to 2007 (a period of 12.5 years) is reported and discussed. The tunnel settlement was continuous with time, and reached a maximum of 288 mm. To assist in the investigation of the mechanisms of long-term tunnel settlement, records of groundwater pumping and subsurface soil compression between 1985 and 2007 are analyzed. Four possible causes — namely, effects of tunnel construction, cyclic loading due to running trains, secondary compression of soft clay, and groundwater pumping in sandy aquifers — are investigated. From the measurements of subsurface soil compression, it is revealed that the observed large tunnel settlement was mainly caused by the compression of sandy Aquifer IV due to groundwater pumping. The measured compression of sandy Aquifer IV accounted for about 65% of the maximum tunnel settlement of Line 1. Soil yielding due to an increase in effective stress was induced by a significant decline in groundwater level. The observed continuing settlement of the tunnel over the 12.5 years was the result of secondary compression (creep), which is a common feature of Aquifer IV at various locations in Shanghai.
UNIFORM COULOMB FIELD AS ORIGIN OF "FERMI ARCS" IN AN ANISOTROPIC BOSON-FERMION GAS MIXTURE
Authors: MAMEDOV T. A. , DE LLANO M.
Published: June 2013

A recent boson-fermion (BF) binary gas mixture model is extended to include: (i) anisotropy of the BF interaction and (ii) momentum-independent Coulomb repulsions. It is applied to account for the peculiarities of the pseudogap observed as function of absolute temperature T and concentration x of holes doped onto the CuO 2 planes and to study the further transformation of the pseudogap into the real superconducting gap, as T is lowered. Using two-time Green functions it is shown that pair breakings depend on the separation between the boson and fermion spectra of the BF mixture. As this separation shrinks, the pair-breaking ability of the Coulomb interaction weakens and disappears at the BEC Tc, i.e., at the T below which a complete softening of bosons occurs. Simultaneous inclusion of both effects (i) and (ii) produces, as T is lowered, "islands" in momentum space of incoherent Cooper pairs above the Fermi sea. These islands grow upon further cooling and merge together just before Tc is reached. The new extended BF model predicts a pseudogap phase in 2D high-Tc superconductors with lines of points, or loci, on the Fermi surface along which the pseudogap vanishes. This explains the origin of T-dependent "Fermi arcs" observed in ARPES experiments.
ELASTIC AND THERMAL PROPERTIES OF Sr1-xCaxRuO3
Authors: THAKUR RASNA , THAKUR RAJESH K. , GAUR N. K.
Published: June 2013

We have investigated the elastic and thermal properties of Sr 1-x Ca x RuO 3(0≤x ≤1) perovskite using a modified rigid ion model (MRIM). The trend of variation of our computed specific heat in the temperature range 1 K ≤ T ≤ 1000 K are in good agreement with corresponding experimental data for almost all the compositions (x). The specific heat found to increase with temperature from 1 K to 300 K, while they decrease with concentration (x) for these perovskite ruthenates. Besides, we have reported the thermal properties, like thermal expansion (α), molecular force constant (f), Reststrahlen frequency (υ), cohesive energy (ϕ), Debye temperature (θD) and Gruneisen parameter (γ).
LOCALIZATION OF THE ENERGY STATES OF LEAD INDUCING THE EFFECT OF RECTIFICATION AND NEGATIVE DIFFERENTIAL RESISTANCE PREDICTED BY FIRST-PRINCIPLES STUDY
Authors: MIN Y. , FANG J. H. , ZHONG C. G. , DONG Z. C. , CHEN C. P. , YAO K. L.
Published: June 2013

The first-principles calculations of the transport characteristics of 4-(5-(2-(5-(4-mercaptophenyl)thiophene-2-yl)ethyl)pyridin-2-yl)benzenethiol sandwiched between two gold leads are performed. The effect of rectification and negative differential resistance (NDR) are obtained, which promise the potential applications in the field of molecular electronics. The rectification effect is 4.49. The peak/valley ratio of the NDR effect is as large as 4.51 for the forward bias and 12.09 for the reverse bias. The strong coupling between gold lead and molecule through thiolate results in the localization of the energy states of gold lead, which may induce the effect of rectification and NDR.
PARAMETRIC VIBRATION OF STAY CABLES UNDER AXIAL NARROW-BAND STOCHASTIC EXCITATION
Authors: GU MING , REN SHU-YAN
Published: June 2013

The differential equation for inclined cables under axial narrow-band stochastic excitations is established with consideration of the cable sag and variations of cable tension along the cable. Gaussian and first-order non-Gaussian closed-form solutions are derived by employing the statistical moment truncation method to solve the moment equation. A long cable (Cable A20 of No. 2 Nanjing Bridge over the Yangtze River) is taken as an example to demonstrate the application of the theoretical model presented. The Monte Carlo method is also adopted to simulate the responses of the cable numerically under investigation. The general response characteristics of the cable are analyzed, particularly, the variation characteristics of the response of the cable depending on the excitation bandwidth when the ratio of the central frequency of excitation to the first frequency of cable is equal to one or two. Parametric vibrations of the real Cable A20 excited by the buffeting vibration of the bridge deck of No. 2 Nanjing Bridge over the Yangtze River are also calculated.
HOMOTOPY SIMULATION OF TWO-PHASE THERMO-HEMODYNAMIC FILTRATION IN A HIGH PERMEABILITY BLOOD PURIFICATION DEVICE
Authors: BÉG O. ANWAR , RASHIDI M. M. , RAHIMZADEH N. , BÉG TASVEER A. , HUNG TIN-KAN
Published: June 2013

A two-phase thermo-hydrodynamic model is presented for transport in the vertical chamber of a porous media blood filtration device. A non-Darcy drag force formulation was employed. The Marble–Drew fluid–particle suspension model was used to simulate the plasma phase and the suspension (erythrocyte) particle phase. The non-dimensional transport equations were solved using a semi-computational procedure known as the homotopy analysis method (HAM). With the judicious use of the auxiliary parameter ℏ, HAM affords a powerful mechanism to adjust and control the convergence region of solution series. This method provides an efficient approximate analytical solution with high accuracy, minimal calculation and avoidance of physically unrealistic assumptions. Detailed computations are presented for the effects of Grashof number (Gr), momentum inverse Stokes number (Skm), Darcy number (Da), Forchheimer number (Fs), particle loading parameter (PL), buoyancy parameter (B) and temperature inverse Stokes number (SkT) on the dimensionless fluid phase velocity (U), dimensionless particle phase velocity (Up), dimensionless fluid phase temperature (Φ) and the dimensionless temperature of particle phase (Φp). A Prandtl number of 25 was used to simulate blood at room temperature. Excellent correlation was obtained between the HAM and numerical shooting quadrature solutions. The results indicated that there is a strong decrease in fluid phase velocities with increasing Darcian (first order) drag and second-order Forchheimer drag, and a weaker reduction in particle phase velocity field. Applications of the study include porous media bio-filtration devices and dialysis simulations.
Optical and physico-chemical properties of tetrapyrrole molecules in nanoporous silicate gel matrices
Authors: Arabei Serguei M. , Pavich Tatiana A. , Solovyov Konstantin N.
Published: June 2013

In this mini-review, we present the main results of our works on the spectroscopy of the molecules of tetrapyrrole pigments incorporated into nanoporous gel matrices. Xerogels activated by organic dyes are promising materials for applications in various fields of technology. The influence of the technique of embedment of the activator molecules on their physico-chemical properties has been analyzed. The specificity of the action of a silicate matrix as external medium, as compared to liquid and solid solutions, is shown.
Ammonia sorption studies into thin layers of hexadecafluorinated cobalt phthalocyanine using optical techniques
Authors: Basova Tamara V. , Hassan Aseel
Published: June 2013

In the present work, the optical response of CoPcF16 films upon exposure to ammonia vapor in the concentration range 50 to 1000 ppm was measured by total internal reflection ellipsometry. It was demonstrated that the sorption of NH3 molecules causes substantial shift of the Δ(λ) spectrum which is determined by the increase in film thickness and change of its optical parameters. It was found that the CoPcF16 films deposited at substrate temperature of 220 °C are characterized by larger grains and more developed surface demonstrating higher optical response than films deposited at substrate temperature of 60 °C. In order to gain an insight into the sorption mechanism at molecular level, we have studied the interaction of ammonia vapor with hexadecafluorinated cobalt phthalocyanine using infrared spectroscopy. It was shown that the detection of ammonia was found to be governed primarily by coordination to the metal center.
STRATEGIC ENVIRONMENTAL ASSESSMENTS FOR RENEWABLE ENERGY DEVELOPMENT — COMPARING THE UNITED STATES AND GERMANY
Authors: GEIßLER GESA
Published: June 2013

Germany and the United States are amongst the leading countries regarding installed renewable energy capacity and are steadily adding new facilities. As balancing the strive for a low carbon energy supply with other environmental interests, such as biodiversity conservation, becomes more prevalent with increasing numbers of wind, solar, biomass, geothermal, and hydro-power facilities, the call for a strategic-level consideration of environmental impacts (SEA) becomes louder. The paper compares the practice of SEAs for renewable energy plans, programmes, and policies in terms of discussion of alternatives, consideration of cumulative effects, and public involvement. A case study analysis compares SEAs from Germany and the United States and evaluates their performance.

Results indicate large differences between both countries, with Germany performing less well on average. Therefore, a strong need for improvement becomes obvious. A general conclusion is that both countries need to become more open to strategic assessment of environmental impacts from renewable energy policies, strategies, and legislation (policy SEA), in order to allow for meaningful assessment of alternatives and achieve an environmentally sound low carbon future.
STRATEGIC ENVIRONMENTAL ASSESSMENT AND ADVANCED RENEWABLE ENERGY IN ONTARIO: MOVING FORWARD OR BLOWING IN THE WIND?
Authors: MULVIHILL PETER , WINFIELD MARK , ETCHEVERRY JOSE
Published: June 2013

This article explores the Canadian province of Ontario's approach to environmental assessment and SEA to electricity issues, its efforts to adapt these processes to facilitate the rapid development of renewable energy sources, and the potential contributions that an SEA approach might have made to these efforts. The province's experience may carry useful lessons for other jurisdictions considering the interplay between environmental assessment processes and strategies designed to move energy systems in the direction of greater sustainability.
EIA FOR WIND FARMS IN THE UNITED KINGDOM AND GERMANY
Authors: PHYLIP-JONES JOHN , FISCHER THOMAS B.
Published: June 2013

In this paper we establish how effectively EIA is currently utilised in the deployment of onshore and offshore wind energy in the United Kingdom (UK) and Germany. In this context, the quality of EIA documentation and the coverage of a range of key EIA aspects of 20 developments are evaluated. Furthermore, the impact of EIA on decision making is established, based on opinions of decision makers and other stakeholders. We find that whilst there are certain weaknesses, overall EIA information is central to decision making, and EIA is resulting in major project modifications. Our results differ from the findings of most previous studies which usually observed a moderate impact on decision making only.
Electrical Conductivity of Mantle Minerals: Role of Water in Conductivity Anomalies
Authors: Yoshino Takashi , Katsura Tomoo
Published: June 2013

The electrical conductivity of Earth's mantle has recently become an interesting topic across diverse Earth science communities. Many electrical conductivity data of mantle phases have been accumulated through the development of high-pressure experiments. These data will provide information on valence states, water concentration, Fe concentration, oxygen fugacity, and the connectivity of the conductive phase in geological materials such as minerals, melts, and rocks. Although several groups have measured the electrical conductivity of mantle materials at high pressure, they have provided inconsistent results, especially with regard to the effect of water. Thus, it is timely to review the problems underlying experimental techniques. We discuss the current understanding of the effect of water on the electrical conductivity of nominally anhydrous mantle minerals, with some speculation on the form of volatile components in Earth's interior. Finally, we consider the role of water in major conductivity anomalies observed in the upper mantle and transition zone.
Enceladus: An Active Ice World in the Saturn System
Authors: Spencer John R. , Nimmo Francis
Published: June 2013

Enceladus, one of the mid-sized icy moons of Saturn, has an importance to planetary science far greater than its modest 504-km diameter would suggest. Intensive exploration of Enceladus by the Cassini Saturn orbiter has revealed that it is the only known icy world in the solar system with ongoing deep-seated geological activity. Active tectonic fractures at Enceladus's south pole, dubbed “tiger stripes,” warmed by internal tidally generated heat, spew supersonic jets of water vapor, other gases, and ice particles into circum-Saturnian space. A subsurface saltwater sea probably exists under the south pole, between the ice shell and the silicate core. Because of evidence that liquid water is probably present at the jet sources, Enceladus is also of great astrobiological interest as a potential habitat for life.