bluuebunny/crossref_metadata_2025 huggingface dataset:
Complementary functions of SK and Kv7/M potassium channels in excitability control and synaptic integration in rat hippocampal dentate granule cells
Authors: Mateos‐Aparicio Pedro , Murphy Ricardo , Storm Johan F.
Published: December 2013

Key points

Previous studies showed that different firing patterns of hippocampal dentate granule cells (DGCs) can trigger different network responses. However, the intrinsic DGC mechanisms controlling their excitability, spike patterns and synaptic integration in DGCs, remain poorly understood.

SK and Kv7/M channels play important roles controlling neuronal integration and excitability, but their specific roles vary between cell types. Both channel types are expressed in DGCs, but their roles are unclear.

We found that SK channels are the main generators of medium afterhyperpolarizations in DGCs, thus causing negative feedback regulation of spiking (spike frequency adaptation) and calcium influx.

In contrast, Kv7/M perform subthreshold and ‘feed‐forward’ control of input resistance, postsynaptic integration, action potential threshold and excitability, thus weakening EPSP–spike coupling.

Thus, in DGCs, the SK and Kv7/M channels seem to perform complementary functions in postsynaptic integration and excitability control. This may have important consequences for dentate network physiology.

The dentate granule cells (DGCs) form the most numerous neuron population of the hippocampal memory system, and its gateway for cortical input. Yet, we have only limited knowledge of the intrinsic membrane properties that shape their responses. Since SK and Kv7/M potassium channels are key mechanisms of neuronal spiking and excitability control, afterhyperpolarizations (AHPs) and synaptic integration, we studied their functions in DGCs. The specific SK channel blockers apamin or scyllatoxin increased spike frequency (excitability), reduced early spike frequency adaptation, fully blocked the medium‐duration AHP (mAHP) after a single spike or spike train, and increased postsynaptic EPSP summation after spiking, but had no effect on input resistance (Rinput) or spike threshold. In contrast, blockade of Kv7/M channels by XE991 increased Rinput, lowered the spike threshold, and increased excitability, postsynaptic EPSP summation, and EPSP–spike coupling, but only slightly reduced mAHP after spike trains (and not after single spikes). The SK and Kv7/M channel openers 1‐EBIO and retigabine, respectively, had effects opposite to the blockers. Computational modelling reproduced many of these effects. We conclude that SK and Kv7/M channels have complementary roles in DGCs. These mechanisms may be important for the dentate network function, as CA3 neurons can be activated or inhibition recruited depending on DGC firing rate.
The mitochondrial calcium uniporter complex: molecular components, structure and physiopathological implications
Authors: Marchi Saverio , Pinton Paolo
Published: December 2013

Although it has long been known that mitochondria take up Ca2+, the molecular identities of the channels and transporters involved in this process were revealed only recently. Here, we discuss the recent work that has led to the characterization of the mitochondrial calcium uniporter complex, which includes the channel‐forming subunit MCU (mitochondrial calcium uniporter) and its regulators MICU1, MICU2, MCUb, EMRE, MCUR1 and miR‐25. We review not only the biochemical identities and structures of the proteins required for mitochondrial Ca2+ uptake but also their implications in different physiopathological contexts.
Measuring Boltzmann's constant through holographic video microscopy of a single colloidal sphere
Authors: Krishnatreya Bhaskar Jyoti , Colen-Landy Arielle , Hasebe Paige , Bell Breanna A. , Jones Jasmine R. , Sunda-Meya Anderson , Grier David G.
Published: December 2013

The trajectory of a colloidal sphere diffusing in water records a history of the random forces exerted on the sphere by thermally driven fluctuations in the suspending fluid. The trajectory therefore can be used to characterize the spectrum of thermal fluctuations and thus to obtain an estimate for Boltzmann's constant. We demonstrate how to use holographic video microscopy to track a colloidal sphere's three-dimensional motions with nanometer precision while simultaneously measuring its radius to within a few nanometers. The combination of tracking and characterization data reliably yields Boltzmann's constant to within two percent and also provides the basis for many other useful and interesting measurements in statistical physics, physical chemistry, and materials science.
Bioluminescence and
19
F Magnetic Resonance Imaging Visualize the Efficacy of Lysostaphin Alone and in Combination with Oxacillin against Staphylococcus aureus in Murine Thigh and Catheter-Associated Infection Models
Authors: Hertlein Tobias , Sturm Volker , Lorenz Udo , Sumathy K. , Jakob Peter , Ohlsen Knut
Published: December 2013

Staphylococci are the leading cause of hospital-acquired infections worldwide. Increasingly, they resist antibiotic treatment owing to the development of multiple antibiotic resistance mechanisms in most strains. Therefore, the activity and efficacy of recombinant lysostaphin as a drug against this pathogen have been evaluated. Lysostaphin exerts high levels of activity against antibiotic-resistant strains of
Staphylococcus aureus
, including methicillin-resistant
S. aureus
(MRSA). The therapeutic value of lysostaphin has been analyzed in two different clinically relevant
in vivo
models, a catheter-associated infection model and a thigh infection model. We infected mice with luciferase-expressing
S. aureus
Xen 29, and the efficacies of lysostaphin, vancomycin, oxacillin, and combined lysostaphin-oxacillin were investigated by determining numbers of CFU, detecting bioluminescent signals, and measuring the accumulation of perfluorocarbon emulsion at the site of infection by
19
F magnetic resonance imaging. Lysostaphin treatment significantly reduced the bacterial burden in infected thigh muscles and, after systemic spreading from the catheter, in inner organs. The efficiency of lysostaphin treatment was even more pronounced in combinatorial therapy with oxacillin. These results suggest that recombinant lysostaphin may have potential as an anti-
S. aureus
drug worthy of further clinical development. In addition, both imaging technologies demonstrated efficacy patterns similar to that of CFU determination, although they proved to be less sensitive. Nonetheless, they served as powerful tools to provide additional information about the course and gravity of infection in a noninvasive manner, possibly allowing a reduction in the number of animals needed for research evaluation of new antibiotics in future studies.
Pharmacokinetics of Orally Administered Oseltamivir in Healthy Obese and Nonobese Thai Subjects
Authors: Jittamala Podjanee , Pukrittayakamee Sasithon , Tarning Joel , Lindegardh Niklas , Hanpithakpong Warunee , Taylor Walter Robert John , Lawpoolsri Saranath , Charunwattana Prakaykaew , Panapipat Salwaluk , White Nicholas J. , Day Nicholas P. J.
Published: December 2013

Oseltamivir is the most widely used anti-influenza drug. In the 2009 H1N1 pandemic, in which the influenza viruses were oseltamivir sensitive, obesity was identified as a risk factor for severe disease and unfavorable outcomes. The aim of this study was to investigate the pharmacokinetic properties of oseltamivir and its active metabolite, oseltamivir carboxylate, in obese and nonobese healthy subjects. A single-dose, randomized, two-sequence crossover study was conducted in 12 obese and 12 nonobese healthy Thai volunteers. Each volunteer was given 75 mg and 150 mg oseltamivir orally with an intervening washout period of more than 3 days. The pharmacokinetic properties of oseltamivir and oseltamivir carboxylate were evaluated using a noncompartmental approach. The median (range) body mass indexes (BMIs) for obese subjects were 33.8 kg/m2(30.8 to 43.2) and 22.2 (18.8 to 24.2) for nonobese subjects. The pharmacokinetic parameters of oseltamivir carboxylate, the active metabolite of oseltamivir, were not significantly different between obese and nonobese subjects for both 75-mg and 150-mg doses. Both doses were well tolerated. Despite the lower dose per kilogram body weight in obese subjects, there was no significant difference in the exposure of oseltamivir carboxylate between the obese and nonobese groups. Standard dosing is appropriate for obese subjects. (The study was registered at ClinicalTrials.gov under registration no. NCT 01049763.)
Outcome of Intravenous Azithromycin Therapy in Patients with Complicated Scrub Typhus Compared with That of Doxycycline Therapy Using Propensity-Matched Analysis
Authors: Jang Mi-Ok , Jang Hee-Chang , Kim Uh Jin , Ahn Joon Hwan , Kang Seung-Ji , Jung Sook-In , Shin Hee-Young , Park Kyung-Hwa
Published: December 2013

There are no well-matched, controlled studies comparing azithromycin with doxycycline for the treatment of complicated scrub typhus. A retrospective propensity score-matched case-control study was performed for patients who presented with complicated scrub typhus and were treated with doxycycline or azithromycin between 2001 and 2011. Data on comorbidities, clinical manifestations, laboratory studies, treatments, and outcomes were extracted for analysis. The clinical characteristics and outcomes of the azithromycin-treated group (
n
= 73) were compared to those of the doxycycline-treated group (
n
= 108). Of 181 patients, 73 from each group were matched by propensity scores. There were no significant differences in baseline characteristics between the matched groups. The treatment success and survival rates were not significantly different (89% [65/73 patients] versus 96% [70/73 patients] and 96% [70/73 patients] versus 96% [70/73 patients], respectively [
P
> 0.05]). No difference was observed in the time to defervescence or length of hospital stay between the two groups (
P
> 0.05). In complicated scrub typhus patients (
n
= 181), multivariate analysis showed that only APACHE II score was an independent risk factor for mortality (95% confidence interval, 1.11 to 1.56;
P
< 0.001). Our data suggest that outcomes of azithromycin therapy are comparable to those of doxycycline therapy in patients with complicated scrub typhus.
Dihydroquinazolinone Inhibitors of Proliferation of Blood and Liver Stage Malaria Parasites
Authors: Derbyshire Emily R. , Min Jaeki , Guiguemde W. Armand , Clark Julie A. , Connelly Michele C. , Magalhães Andreia D. , Guy R. Kiplin , Clardy Jon
Published: December 2013

Drugs that target both the liver and blood stages of malaria will be needed to reduce the disease's substantial worldwide morbidity and mortality. Evaluation of a 259-member library of compounds that block proliferation of the blood stage of malaria revealed several scaffolds—dihydroquinazolinones, phenyldiazenylpyridines, piperazinyl methyl quinolones, and bis-benzimidazoles—with promising activity against the liver stage. Focused structure-activity studies on the dihydroquinazolinone scaffold revealed several molecules with excellent potency against both blood and liver stages. One promising early lead with dual activity is 2-(
p
-bromophenyl)-3-(2-(diethylamino)ethyl)-2,3-dihydroquinazolin-4(1
H
)-one with 50% effective concentrations (EC
50
s) of 0.46 μM and 0.34 μM against liver stage
Plasmodium berghei
ANKA and blood stage
Plasmodium falciparum
3D7 parasites, respectively. Structure-activity relationships revealed that liver stage activity for this compound class requires a 3-dialkyl amino ethyl group and is abolished by substitution at the
ortho
-position of the phenyl moiety. These compounds have minimal toxicity to mammalian cells and are thus attractive compounds for further development.
In Vitro
Efficacy of Corifungin against Acanthamoeba castellanii Trophozoites and Cysts
Authors: Debnath Anjan , Tunac Josefino B. , Silva-Olivares Angélica , Galindo-Gómez Silvia , Shibayama Mineko , McKerrow James H.
Published: December 2013

Painful blinding keratitis and fatal granulomatous amebic encephalitis are caused by the free-living amebae
Acanthamoeba
spp. Several prescription eye medications are used to treat
Acanthamoeba
keratitis, but the infection can be difficult to control because of recurrence of infection. For the treatment of encephalitis, no single drug was found useful, and in spite of the use of a combination of multiple drugs, the mortality rate remains high. Therefore, efficient, novel drugs are urgently needed for the treatment of amebic keratitis and granulomatous amebic encephalitis. In this study, we identified corifungin, a water-soluble polyene macrolide, as amebicidal.
In vitro
, it was effective against both the trophozoites and the cysts. Transmission electron microscopy of
Acanthamoeba castellanii
incubated with corifungin showed the presence of swollen mitochondria, electron-dense granules, degeneration of cytoplasm architecture, and loss of nuclear chromatin structure. These changes were followed by lysis of amebae. Corifungin also induced the encystment process of
A. castellanii
. There were alterations in the cyst cell wall followed by lysis of the cysts. Corifungin is a promising therapeutic option for keratitis and granulomatous amebic encephalitis.
Ceftaroline Restores Daptomycin Activity against Daptomycin-Nonsusceptible Vancomycin-Resistant Enterococcus faecium
Authors: Sakoulas George , Rose Warren , Nonejuie Poochit , Olson Joshua , Pogliano Joseph , Humphries Romney , Nizet Victor
Published: December 2013

Daptomycin-nonsusceptible vancomycin-resistant
Enterococcus faecium
(VRE) strains are a formidable emerging threat to patients with comorbidities, leaving few therapeutic options in cases of severe invasive infections. Using a previously characterized isogenic pair of VRE strains from the same patient differing in their daptomycin susceptibilities (Etest MICs of 0.38 mg/liter and 10 mg/liter), we examined the effect of ceftaroline, ceftriaxone, and ampicillin on membrane fluidity and susceptibility of VRE to surface binding and killing by daptomycin and human cathelicidin antimicrobial peptide LL37. Synergy was noted
in vitro
between daptomycin, ampicillin, and ceftaroline for the daptomycin-susceptible VRE strain, but only ceftaroline showed synergy against the daptomycin-nonsusceptible VRE strain (∼2 log
10
CFU reduction at 24 h). Ceftaroline cotreatment increased daptomycin surface binding with an associated increase in membrane fluidity and an increase in the net negative surface charge of the bacteria as evidenced by increased poly-
l
-lysine binding. Consistent with the observed biophysical changes, ceftaroline resulted in increased binding and killing of daptomycin-nonsusceptible VRE by human cathelicidin LL37. Using a pair of daptomycin-susceptible/nonsusceptible VRE strains, we noted that VRE is ceftaroline resistant, yet ceftaroline confers significant effects on growth rate as well as biophysical changes on the cell surface of VRE that can potentiate the activity of daptomycin and innate cationic host defense peptides, such as cathelicidin. Although limited to just 2 strains, these finding suggest that additional
in vivo
and
in vitro
studies need to be done to explore the possibility of using ceftaroline as adjunctive anti-VRE therapy.
In Vitro
Characterization of a Sustained-Release Formulation for Enfuvirtide
Authors: Rothstein Sam N. , Huber Kelly D. , Sluis-Cremer Nicolas , Little Steven R.
Published: December 2013

Although approved by the U.S. Food and Drug Administration, enfuvirtide is rarely used in combination antiretroviral therapies (cART) to treat HIV-1 infection, primarily because of its intense dosing schedule that requires twice-daily subcutaneous injection. Here, we describe the development of enfuvirtide-loaded, degradable poly(lactic-co-glycolic) acid microparticles that provide linear
in vitro
release of the drug over an 18-day period. This sustained-release formulation could make enfuvirtide more attractive for use in cART.
Fluxes of Ca
2+
and K
+
Are Required for the Listeriolysin O-Dependent Internalization Pathway of Listeria monocytogenes
Authors: Vadia Stephen , Seveau Stephanie
Published: December 2013

Listeria monocytogenes
is responsible for the life-threatening food-borne disease listeriosis. This disease mainly affects elderly and immunocompromised individuals, causing bacteremia and meningoencephalitis. In pregnant women,
L. monocytogenes
infection leads to abortion and severe infection of the fetus or newborn. The
L. monocytogenes
intracellular life cycle is critical for pathogenesis. Previous studies have established that the major virulence factor of
L. monocytogenes
, the pore-forming toxin listeriolysin O (LLO), is sufficient to induce
L. monocytogenes
internalization into human epithelial cell lines. This internalization pathway strictly requires the formation of LLO pores in the plasma membrane and can be stimulated by the heterologous pore-forming toxin pneumolysin, suggesting that LLO acts nonspecifically by forming transmembrane pores. The present work tested the hypothesis that Ca
2+
and K
+
fluxes subsequent to perforation by LLO control
L. monocytogenes
internalization. We report that
L. monocytogenes
perforates the host cell plasma membrane in an LLO-dependent fashion at the early stage of invasion. In response to perforation, host cells undergo Ca
2+
-dependent but K
+
-independent resealing of their plasma membrane. In contrast to the plasma membrane resealing process, LLO-induced
L. monocytogenes
internalization requires both Ca
2+
and K
+
fluxes. Further linking ion fluxes to bacterial internalization, treating cells with a combination of Ca
2+
and K
+
ionophores but not with individual ionophores is sufficient to induce efficient internalization of large cargoes, such as 1-μm polystyrene beads and bacteria. We propose that LLO-induced
L. monocytogenes
internalization requires a Ca
2+
- and K
+
-dependent internalization pathway that is mechanistically distinct from the process of plasma membrane resealing.
Uropathogenic Escherichia coli Modulates Innate Immunity To Suppress Th1-Mediated Inflammatory Responses during Infectious Epididymitis
Authors: Lang Tali , Hudemann Christoph , Tchatalbachev Svetlin , Stammler Angelika , Michel Vera , Aslani Ferial , Bhushan Sudhanshu , Chakraborty Trinad , Renz Harald , Meinhardt Andreas
Published: December 2013

Infectious epididymitis in men, a frequent entity in urological outpatient settings, is commonly caused by bacteria originating from the anal region ascending the genitourinary tract. One of the most prevalent pathogens associated with epididymitis isEscherichia coli. In our previous study, we showed that semen quality is compromised in men following epididymitis associated with specificE. colipathovars. Thus, our aim was to investigate possible differences in immune responses elicited during epididymitis following infection with the uropathogenicE. coli(UPEC) strain CFT073 and the nonpathogenic entericE. coli(NPEC) strain 470. Employing anin vivoexperimental epididymitis model, C57BL/6 mice were infected with UPEC CFT073, NPEC 470, or phosphate-buffered saline (PBS) as a sham control for up to 7 days. After infection with NPEC 470, the expression of proinflammatory cytokines interleukin-1 (IL-1), IL-6, and tumor necrosis factor alpha in the epididymis was significantly increased. Conversely, UPEC CFT073-challenged mice displayed inflammatory gene expression at levels comparable to sham PBS-treated animals. Moreover, by day 7 only NPEC-infected animals showed activation of adaptive immunity evident by a substantial influx of CD3+and F4/80+cells in the epididymal interstitium. This correlated with enhanced production of Th1-associated cytokines IL-2 and gamma interferon (IFN-γ). Furthermore, splenocytes isolated from UPEC-infected mice exhibited diminished T-cell responses with significantly reduced secretion of IL-2 and IFN-γ in contrast to NPEC-infected animals. Overall, these findings provide new insights into understanding pathogen-specific modulation of host immunity during acute phases of epididymitis, which may influence severity of disease and clinical outcomes.
The Nod1, Nod2, and Rip2 Axis Contributes to Host Immune Defense against Intracellular Acinetobacter baumannii Infection
Authors: Bist Pradeep , Dikshit Neha , Koh Tse Hsien , Mortellaro Alessandra , Tan Thuan Tong , Sukumaran Bindu
Published: December 2013

Acinetobacter baumannii
is a major extensively drug-resistant lethal human nosocomial bacterium. However, the host innate immune mechanisms controlling
A. baumannii
are not well understood. Although viewed as an extracellular pathogen,
A. baumannii
can also invade and survive intracellularly. However, whether host innate immune pathways sensing intracellular bacteria contribute to immunity against
A. baumannii
is not known. Here, we provide evidence for the first time that intracellular antibacterial innate immune receptors Nod1 and Nod2, and their adaptor Rip2, play critical roles in the sensing and clearance of
A. baumannii
by human airway epithelial cells
in vitro
.
A. baumannii
infection upregulated Rip2 expression. Silencing of Nod1, Nod2, and Rip2 expression profoundly increased intracellular invasion and prolonged the multiplication and survival of
A. baumannii
in lung epithelial cells. Notably, the Nod1/2-Rip2 axis did not contribute to the control of
A. baumannii
infection of human macrophages, indicating that they play cell type-specific roles. The Nod1/2-Rip2 axis was needed for
A. baumannii
infection-induced activation of NF-κB but not mitogen-activated protein kinases. Moreover, the Nod1/2-Rip2 axis was critical to induce optimal cytokine and chemokine responses to
A. baumannii
infection. Mechanistic studies showed that the Nod1/2 pathway contributed to the innate control of
A. baumannii
infection through the production of β-defensin 2 by airway epithelial cells. This study revealed new insights into the immune control of
A. baumannii
and may contribute to the development of effective immune therapeutics and vaccines against
A. baumannii
.
High-Temperature Protein G Is an Essential Virulence Factor of Leptospira interrogans
Authors: King Amy M. , Pretre Gabriela , Bartpho Thanatchaporn , Sermswan Rasana W. , Toma Claudia , Suzuki Toshihiko , Eshghi Azad , Picardeau Mathieu , Adler Ben , Murray Gerald L.
Published: December 2013

Leptospira interrogans
is a global zoonotic pathogen and is the causative agent of leptospirosis, an endemic disease of humans and animals worldwide. There is limited understanding of leptospiral pathogenesis; therefore, further elucidation of the mechanisms involved would aid in vaccine development and the prevention of infection. HtpG (
h
igh-
t
emperature
p
rotein
G
) is the bacterial homolog to the highly conserved molecular chaperone Hsp90 and is important in the stress responses of many bacteria. The specific role of HtpG, especially in bacterial pathogenesis, remains largely unknown. Through the use of an
L. interrogans
htpG
transposon insertion mutant, this study demonstrates that
L. interrogans
HtpG is essential for virulence in the hamster model of acute leptospirosis. Complementation of the
htpG
mutant completely restored virulence. Surprisingly, the
htpG
mutant did not appear to show sensitivity to heat or oxidative stress, phenotypes common in
htpG
mutants in other bacterial species. Furthermore, the mutant did not show increased sensitivity to serum complement, reduced survival within macrophages, or altered protein or lipopolysaccharide expression. The underlying cause for attenuation thus remains unknown, but HtpG is a novel leptospiral virulence factor and one of only a very small number identified to date.
Novel Role for the
yceGH
Tellurite Resistance Genes in the Pathogenesis of Bacillus anthracis
Authors: Franks Sarah E. , Ebrahimi Celia , Hollands Andrew , Okumura Cheryl Y. , Aroian Raffi V. , Nizet Victor , McGillivray Shauna M.
Published: December 2013

Bacillus anthracis
, the causative agent of anthrax, relies on multiple virulence factors to subvert the host immune defense. Using
Caenorhabditis elegans
as an infection model, we screened approximately 5,000 transposon mutants of
B. anthracis
Sterne for decreased virulence. One of the attenuated mutants resulted in loss of expression of
yceG
and
yceH
, the last two genes in a six-gene cluster of tellurite resistance genes. We generated an analogous insertional mutant to confirm the phenotype and characterize the role of
yceGH
in resistance to host defenses. Loss of
yceGH
rendered the mutants more sensitive to tellurite toxicity as well as to host defenses such as reactive oxygen species and the cathelicidin family of antimicrobial peptides. Additionally, we see decreased survival in mammalian models of infection, including human whole blood and in mice. We identify a novel role for the
yceGH
genes in
B. anthracis
Sterne virulence and suggest that
C. elegan
s is a useful infection model to study anthrax pathogenesis.
Utilisation of preventative health check-ups in the UK: findings from individual-level repeated cross-sectional data from 1992 to 2008
Authors: Labeit Alexander , Peinemann Frank , Baker Richard
Published: December 2013

Objectives

To analyse and compare the determinants of screening uptake for different National Health Service (NHS) health check-ups in the UK.

Design

Individual-level analysis of repeated cross-sectional surveys with balanced panel data.

Setting

The UK.

Participants

Individuals taking part in the British Household Panel Survey (BHPS), 1992–2008.

Outcome measure

Uptake of NHS health check-ups for cervical cancer screening, breast cancer screening, blood pressure checks, cholesterol tests, dental screening and eyesight tests.

Methods

Dynamic panel data models (random effects panel probit with initial conditions).

Results

Having had a health check-up 1 year before, and previously in accordance with the recommended schedule, was associated with higher uptake of health check-ups. Individuals who visited a general practitioner (GP) had a significantly higher uptake in 5 of the 6 health check-ups. Uptake was highest in the recommended age group for breast and cervical cancer screening. For all health check-ups, age had a non-linear relationship. Lower self-rated health status was associated with increased uptake of blood pressure checks and cholesterol tests; smoking was associated with decreased uptake of 4 health check-ups. The effects of socioeconomic variables differed for the different health check-ups. Ethnicity did not have a significant influence on any health check-up. Permanent household income had an influence only on eyesight tests and dental screening.

Conclusions

Common determinants for having health check-ups are age, screening history and a GP visit. Policy interventions to increase uptake should consider the central role of the GP in promoting screening examinations and in preserving a high level of uptake. Possible economic barriers to access for prevention exist for dental screening and eyesight tests, and could be a target for policy intervention.

Trial registration

This observational study was not registered.
Improving the identification of people with dementia in primary care: evaluation of the impact of primary care dementia coding guidance on identified prevalence
Authors: Russell Paul , Banerjee Sube , Watt Jen , Adleman Rosalyn , Agoe Belinda , Burnie Nerida , Carefull Alex , Chandan Kiran , Constable Dominie , Daniels Mark , Davies David , Deshmukh Sid , Huddart Martin , Jabin Ashrafi , Jarrett Penelope , King Jenifer , Koch Tamar , Kumar Sanjoy , Lees Stavroula , Mir Sinan , Naidoo Dominic , Nyame Sylvia , Sasae Ryuichiro , Sharma Tushar , Thormod Clare , Vedavanam Krish , Wilton Anja , Flaherty Breda
Published: December 2013

Objective

Improving dementia care is a policy priority nationally and internationally; there is a ‘diagnosis gap’ with less than half of the cases of dementia ever diagnosed. The English Health Department's Quality and Outcomes Framework (QOF) encourages primary care recognition and recording of dementia. The codes for dementia are complex with the possibility of underidentification through miscoding. We developed guidance on coding of dementia; we report the impact of applying this to ‘clean up’ dementia coding and records at a practice level.

Design

The guidance had five elements: (1) identify Read Codes for dementia; (2) access QOF dementia register; (3) generate lists of patients who may have dementia; (4) compare search with QOF data and (5) review cases. In each practice, one general practitioner conducted the exercise. The number of dementia QOF registers before and after the exercise was recorded with the hours taken to complete the exercise.

Setting

London primary care.

Participants

23 (85%) of 27 practices participated, covering 79 312 (19 562 over 65 s) participants.

Outcomes

The number on dementia QOF registers; time taken.

Results

The number of people with dementia on QOF registers increased from 1007 to 1139 (χ2=8.17, p=0.004), raising identification rates by 8.8%. It took 4.7 h per practice, on an average.

Conclusions

These data demonstrate the potential of a simple primary care coding exercise, requiring no specific training, to increase the dementia identification rate. An improvement of 8.8% between 2011 and 2012 is equivalent to that of the fourth most improved primary care trust in the UK. In absolute terms, if this effects were mirrored across the UK primary care, the number of cases with dementia identified would rise by over 70 000 from 364 329 to 434 488 raising the recognition rate from 46% to 54.8%. Implementing this exercise appears to be a simple and effective way to improve recognition rates in primary care.
An observational study of retail availability and in-store marketing of e-cigarettes in London: potential to undermine recent tobacco control gains?
Authors: Hsu Robert , Myers Allison E , Ribisl Kurt M , Marteau Theresa M
Published: December 2013

Objectives

E-cigarette companies and vendors claim the potential of e-cigarettes to help smokers reduce or quit tobacco use. E-cigarettes also have the potential to renormalise smoking. The purpose of this study was to describe the availability and in-store marketing of e-cigarettes in London, UK stores selling tobacco and alcohol.

Design

Observational study.

Setting

Small and large stores selling alcohol and tobacco in London, UK.

Primary and secondary outcome measures

The number of stores selling e-cigarettes, the number of stores with an interior or exterior e-cigarette advertisement, the number of stores with an e-cigarette point-of-sale movable display, store size, deprivation index score for store's corresponding lower super output area.

Results

Audits were completed in 108 of 128 selected stores. 62 of the audited stores (57%) sold e-cigarettes. E-cigarette availability was unrelated to store size. There was a statistically non-significant trend towards increased availability in more deprived areas (p=0.069). 31 of the 62 stores (50%) selling e-cigarettes had a point-of-sale movable display, with all but one found in small stores. Two small stores had interior advertisements and eight had exterior advertisements. No advertisements were observed in large stores.

Conclusions

This audit revealed widespread availability of e-cigarettes and in-store marketing in London, UK. Even if e-cigarettes prove to be an effective cessation aid, their sale and use are resulting in an increasing public presence of cigarette-like images and smoking behaviour. After decades of work to denormalise smoking, these findings raise the question of whether e-cigarettes are renormalising smoking.
NUMERICAL SCHEMES FOR OPTION PRICING IN REGIME-SWITCHING JUMP DIFFUSION MODELS
Authors: FLORESCU IONUT , LIU RUIHUA , MARIANI MARIA CRISTINA , SEWELL GRANVILLE
Published: December 2013

In this paper, we present algorithms to solve a complex system of partial integro-differential equations (PIDE's) of parabolic type. The system is motivated by applications in finance where the solution of the system gives the price of European options in a regime-switching jump diffusion model. The new algorithms are based on theoretical analysis in Florescu et al. (2012) where the proof of convergence of the algorithms is carried out. The problems are also solved using a more traditional approach, where the integral terms (but not the derivative terms) are treated explicitly. Another contribution of this work details a novel type of jump distribution. Empirical evidence suggests that this type of distribution may be more appropriate to model jumps as it makes them more clearly distinguishable from the signal variability.
A Quantum Critical Point Lying Beneath the Superconducting Dome in Iron Pnictides
Authors: Shibauchi T. , Carrington A. , Matsuda Y.
Published: December 2013

Whether a quantum critical point (QCP) lies beneath the superconducting dome has been a long-standing issue that remains unresolved in many classes of unconventional superconductors, notably cuprates, heavy fermions, and, most recently, iron pnictides. The existence of a QCP may offer a route to understanding the origin of unconventional superconductors’ anomalous non-Fermi liquid properties, the microscopic coexistence between unconventional superconductivity and magnetic or some other exotic order, and, ultimately, the mechanism of superconductivity itself. The isovalent substituted iron pnictide BaFe2(As1−xPx)2 offers a new platform for the study of quantum criticality, providing a unique opportunity to study the evolution of the electronic properties in a wide range of the phase diagram. Recent experiments in BaFe2(As1−xPx)2 have provided the first clear and unambiguous evidence of a second-order quantum phase transition lying beneath the superconducting dome.
Probabilistic Expectations in Developing Countries
Authors: Delavande Adeline
Published: December 2013

Many decisions are made under uncertainty, and individuals are likely to form subjective expectations about the probabilities of events that are relevant to their decisions. I review here a recent and growing literature that uses probabilistic expectations elicited from survey respondents in developing countries. I first present an illustrative model of one particular decision under uncertainty—the choice of a college—to exemplify the importance of subjective expectations data for identification purposes. I then review existing evidence emphasizing that it is feasible to elicit probabilities from survey respondents in low-literacy settings and describe common patterns of answers. Finally, I describe existing applications, many of which seek to assess how expectations influence behavior, in various domains, including health, education, agricultural production, and migration.
Microbial Origins of Chronic Diseases
Authors: Gargano Lisa M. , Hughes James M.
Published: December 2013

Chronic diseases such as cardiovascular disease and cancer are among the leading causes of death worldwide and have been on the rise over the past decade. Associations between microbial agents and development of chronic diseases have been made in the past, and new connections are currently being assessed. Investigators are examining the relationship between infectious agents and chronic disease using new technologies with more rigor and specificity. This review examines microbial agents' links to and associations with cardiovascular diseases, cancer, neurodegenerative diseases, renal diseases, psychiatric disorders, and obesity and addresses the important role of the human microbiome in maintenance of health and its potential role in chronic diseases. These associations and relationships will impact future research priorities, surveillance approaches, treatment strategies, and prevention programs for chronic diseases.
Synthesis, Spectral, Thermal, Electrochemical, and Biocidal Activity of Tolyl/Benzyl Dithiocarbonates of Zinc(II)
Authors: Kalgotra Nidhi , Gupta Bhawana , Andotra Savit , Kumar Sandeep , Pandey Sushil Kumar
Published: December 2013

Tolyl/benzyl dithiocarbonates of zinc(II) [(o-,m-,p-CH3C6H4 and C6H5CH2OCS2)2Zn] have been synthesized in 1 : 2 molar ratio by the reaction of zinc chloride, ZnCl2, with sodium salts of tolyl/benzyl dithiocarbonates (o-,m-,p-CH3C6H4O/C6H5CH2O)CS2Na, in aqueous medium. These complexes were further reacted with nitrogen and phosphorous donor ligands to obtain donor stabilized complex of the type [[(o-,m-,p-CH3C6H4 and C6H5CH2)OCS2]2Zn.nL], (L = Bipy, Phen for n=1 and PPh3, Py for n=2). These complexes were characterised by elemental analysis, mass, IR, and NMR (1H, 13C, and 31P) spectroscopies. The thermal analysis (TGA/DTA), cyclic voltammetry, and SEM have also been done. Distorted tetrahedral and octahedral geometries around the Zn(II) metal are proposed. These complexes have depicted potential antibacterial and antifungal activity.
Health-Related Quality of Life Measures for Physically Active Elderly in Community Exercise Programs in Catalonia: Comparative Analysis with Sedentary People
Authors: Fortuño-Godes Jesús , Guerra-Balic Myriam , Cabedo-Sanromà Josep
Published: December 2013

Objective. To evaluate Health-Related Quality of Life (HRQoL), medication used, and Stock of Health Capital (SHC) in physically active elderly participants in Community Exercise Programs (CEPs) compared to a sedentary group.Methods. EuroQol standardized instrument was completed by physically active elderly (n= 2,185) who participated in CEPs. Common items were compared to HRQoL data of 1,874 sedentary elderly people, taken from the Catalan Health Survey 2006 (CHS’06). Visual Analogue Scale (VAS) outcomes and medication used were assessed through parametric statistics. Dimensions of health conditions were compared, between sedentary people and physically active elderly participants in CEPs. SHC results were obtained combining the EuroQol scores and Life Expectancy (LE) values. An economic value of €34,858.70 was assigned to these years of LE.Results. Physically active subjects had better HRQoL values (75.36 in males and 70.71 in females) than CHS’06 sedentary subjects (58.35 in males and 50.59 in females). Medication used was different between physically active subjects (1.89 in males and 2.87 in females) and CHS’06 sedentary subjects (4.34 in males and 4.21 in females). SHC data for physically active elderly (€465,988.31/QALY in males and €522,550.31/QALY in females) were higher than for CHS’06 sedentary subjects (€363,689.33/QALY in males and €346,615.91/QALY in females).
A Systematic Approach to OptimizinghValue for Fuzzy Linear Regression with Symmetric Triangular Fuzzy Numbers
Authors: Liu Xilong , Chen Yizeng
Published: December 2013

A systematic approach is proposed to optimizehvalue for fuzzy linear regression (FLR) analysis using minimum fuzziness criteria with symmetric triangular fuzzy numbers (TFNs). Firstly, a new concept of credibility is defined to evaluate the performance of FLR models with differenthvalues when a set of sample data pairs is given. Secondly, based on the defined concept of credibility, a programming model is formulated to optimize the value ofh. Finally, both the numerical study and the real application show that the approach proposed in this paper is effective and efficient; that is, optimal value forhcan be determined definitely with respect to a set of given sample data pairs.
Analysis and Optimization of Dynamic Measurement Precision of Fiber Optic Gyroscope
Authors: Li Hui , Cui Liyang , Lin Zhili , Zhang Chunxi
Published: December 2013

In order to improve the dynamic performance of high precision interferometer fiber optic gyroscope (IFOG), the influencing factors of the fast response characteristics are analyzed based on a proposed assistant design setup, and a high dynamic detection method is proposed to suppress the adverse effects of the key influencing factors. The assistant design platform is built by using the virtual instrument technology for IFOG, which can monitor the closed-loop state variables in real time for analyzing the influence of both the optical components and detection circuit on the dynamic performance of IFOG. The analysis results indicate that nonlinearity of optical Sagnac effect, optical parameter uncertainty, dynamic characteristics of internal modules and time delay of signal detection circuit are the major causes of dynamic performance deterioration, which can induce potential system instability in practical control systems. By taking all these factors into consideration, we design a robust control algorithm to realize the high dynamic closed-loop detection of IFOG. Finally, experiments show that the improved 0.01 deg/h high precision IFOG with the proposed control algorithm can achieve fast tracking and good dynamic measurement precision.
Bariatric Surgery in Moderately Obese Patients: A Prospective Study
Authors: Cerci M. , Bellini M. I. , Russo F. , Benavoli D. , Capperucci M. , Gaspari A. L. , Gentileschi P.
Published: December 2013

Introduction. Moderate obesity (BMI 30–35 kg/m2) affects 25% of the western population. The role of bariatric surgery in this context is currently debated, reserved for patients with comorbidity, as an alternative to conservative medical treatment. We describe our experience in moderately obese patients treated with bariatric surgery.Materials and Methods. Between September 2011 and September 2012, 25 patients with grade I obesity and comorbidities underwent bariatric surgery: preoperative mean BMI 33.2 kg/m2, 10 males, mean age 42 years. In presence of type 2 diabetes mellitus (T2DM) (56%), gastric bypass was performed; in cases with hypertension (64%) and obstructive sleep apnea (OSA) (12%), sleeve gastrectomy was performed. All operations were performed laparoscopically.Results. Mean follow-up was 12.4 months. A postoperative complication occurred: bleeding from the trocar site was resolved with surgery in local anesthesia. Reduction in average BMI was 6 points, with a value of 27.2 kg/m2. Of the 14 patients with T2DM, 12 (86%) discontinued medical therapy because of a normalization of glycemia. Of the 16 patients with arterial hypertension, 14 (87%) showed remission and 2 (13%) improvement. Complete remission was observed in patients with OSAS.Conclusions. The results of our study support the validity of bariatric surgery in patients with BMI 30–35 kg/m2. Our opinion is that, in the future, bariatric surgery could be successful in selected cases of moderately obese patients.
Antibacterial Activity of Nanocomposites of Copper and Cellulose
Authors: Pinto Ricardo J. B. , Daina Sara , Sadocco Patrizia , Neto Carlos Pascoal , Trindade Tito
Published: December 2013

The design of cheap and safe antibacterial materials for widespread use has been a challenge in materials science. The use of copper nanostructures combined with abundant biopolymers such as cellulose offers a potential approach to achieve such materials though this has been less investigated as compared to other composites. Here, nanocomposites comprising copper nanofillers in cellulose matrices have been prepared byin situandex situmethods. Two cellulose matrices (vegetable and bacterial) were investigated together with morphological distinct copper particulates (nanoparticles and nanowires). A study on the antibacterial activity of these nanocomposites was carried out forStaphylococcus aureusandKlebsiella pneumoniae, as pathogen microorganisms. The results showed that the chemical nature and morphology of the nanofillers have great effect on the antibacterial activity, with an increase in the antibacterial activity with increasing copper content in the composites. The cellulosic matrices also show an effect on the antibacterial efficiency of the nanocomposites, with vegetal cellulose fibers acting as the most effective substrate. Regarding the results obtained, we anticipate the development of new approaches to prepare cellulose/copper based nanocomposites thereby producing a wide range of interesting antibacterial materials with potential use in diverse applications such as packaging or paper coatings.
Novel Ag/Kaolin Nanocomposite as Adsorbent for Removal of Acid Cyanine 5R from Aqueous Solution
Authors: Hashemian Saeedeh , Reza Shahedi Mohammad
Published: December 2013

Ag/kaolin nanocomposite was prepared by reduction of Ag+ ion with ethanol at alkaline condition on kaolin surface. Nanocomposite was characterized by FTIR, XRD, TEM, and BET methods. Results showed the Ag/kaolin composite has particle size 50 nm. The surface area was increased from kaolin to Ag/kaolin from 1.0215 to 7.409 m2 g−1, respectively. Ag/kaolin nanocomposite was used for adsorption of acid cyanine 5R (AC5R) from aqueous solution. The effect of parameters such as contact time, pH, and mass of nano composite has been investigated. The maximum percentage of adsorption of AC5R was found at pH 3 and contact time of 60 min. The higher percentage removal of AC5R by Ag/kaolin than kaolin can be attributed to catalytic activity of Ag on the surface of kaolin. The experimental data was fitted by pseudo‐second‐order kinetic model. The adsorption isotherm data could be well interpreted by Langmuir isotherm model. From the results of thermodynamic study, the adsorption process of AC5R onto Ag/kaolin nanocomposite was spontaneous and endothermic process. The process is clean and safe for purifying of water pollution.
Theoretical Investigation of the D83V Mutation within the Myocyte-Specific Enhancer Factor-2 Beta and Its Role in Cancer
Authors: Yakovenko Oleksandr , Morin Ryan , Vashchenko Ganna , Jones Steven J. M.
Published: December 2013

The D83V mutation in the myocyte-specific enhancer factor-2 beta (MEF2B) gene is frequently observed in lymphomas. Surprisingly, this apparent gain-of-function mutation is within a protein that is involved in the promotion of apoptosis in B cells. To investigate the oncogenic effects of this alteration and explain its predominance over other known loss-of-function mutations of MEF2B, we propose a hypothesis that this mutation influences the dynamic folding of the C-terminal loop of the N-terminal domain of MEF2B. According to our hypothesis, the mutation allows MEF2B to bind promiscuously to a wider variety of gene promoters. A large set of molecular dynamic simulations (MD) was conducted to investigate the effects of D83V mutation in silico and support the hypothesis.
Construction and Immunogenicity of DNA Vaccines Encoding Fusion Protein of Porcine IFN-λ1 and GP5 Gene of Porcine Reproductive and Respiratory Syndrome Virus
Authors: Du Luping , Li Bin , He Kongwang , Zhang Haibin , Huang Kehe , Xiao Shaobo
Published: December 2013

Porcine reproductive and respiratory syndrome virus (PRRSV) has been mainly responsible for the catastrophic economic losses in pig industry worldwide. The commercial vaccines only provide a limited protection against PRRSV infection. Thus, the focus and direction is to develop safer and more effective vaccines in the research field of PRRS. The immune modulators are being considered to enhance the effectiveness of PRRSV vaccines. IFN-λ1 belongs to type III interferon, a new interferon family. IFN-λ1 is an important cytokine with multiple functions in innate and acquired immunity. In this study, porcine IFN-λ1 (PoIFN-λ1) was evaluated for its adjuvant effects on the immunity of a DNA vaccine carrying the GP5 gene of PRRSV. Groups of mice were immunized twice at 2-week interval with 100 μg of the plasmid DNA vaccine pcDNA3.1-SynORF5, pcDNA3.1-PoIFN-λ1-SynORF5, and the blank vector pcDNA3.1, respectively. The results showed that pcDNA3.1-PoIFN-λ1-SynORF5 can significantly enhance GP5-specific ELISA antibody, PRRSV-specific neutralizing antibody, IFN-γlevel, and lymphocyte proliferation ratherthan the responses induced by pcDNA3.1-SynORF5. Therefore, type III interferon PoIFN-λ1 could enhance the immune responses of DNA vaccine of PRRSV, highlighting the potential value of PoIFN-λ1 as a molecular adjuvant in the prevention of PRRSV infection.