bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxidative stress contributes to the augmented exercise pressor reflex in peripheral arterial disease patients
Authors: Muller Matthew D. , Drew Rachel C. , Blaha Cheryl A. , Mast Jessica L. , Cui Jian , Reed Amy B. , Sinoway Lawrence I.
Published: September 2012

Key points

Peripheral arterial disease (PAD) is a common and debilitating condition linked with heightened risk of cardiovascular mortality.

Dynamic exercise elicits augmented blood pressure responses in PAD that could put the patient at risk for adverse event but the underlying mechanisms are unknown.

The exercise pressor reflex is comprised of group III and group IV muscle afferents that increase their discharge in response to mechanical and/or chemical stimulation.

In this study, we demonstrate that mechanically sensitive muscle afferents cause augmented reflex elevations in blood pressure during dynamic plantar flexion exercise in PAD. These responses occur prior to claudication pain, are related to disease severity and can be partly reduced by acute antioxidant infusion.

Abstract  Exaggerated blood pressure (BP) responses to dynamic exercise predict cardiovascular mortality in patients with peripheral arterial disease (PAD). However, the underlying mechanisms are unclear and no attempt has been made to attenuate this response using antioxidants. Three physiological studies were conducted in patients with PAD and controls. In Protocol 1, subjects underwent 4 min of low‐intensity (0.5–2.0 kg), rhythmic plantar flexion in the supine posture. In Protocol 2, patients with PAD received high‐dose ascorbic acid intravenously before exercise. In Protocol 3, involuntary exercise was conducted via electrical stimulation of the tibial nerve. The primary outcome measure was Δ mean arterial pressure (MAP) during the first 20 s of exercise (i.e. the onset of sympathoexcitation by muscle afferents). Compared to controls, patients with PAD had significantly greater ΔMAP during plantar flexion, particularly at 0.5 kg with the most affected leg (11 ± 2 vs. 2 ± 1 mmHg) as well as the least affected leg (7 ± 1 vs. 1 ± 1 mmHg). This augmented response occurred before the onset of claudication pain and was attenuated by ∼50% with ascorbic acid. Electrically evoked exercise also elicited larger haemodynamic changes in patients with PAD compared to controls. Further, the ΔMAP during 0.5 kg plantar flexion inversely correlated with the ankle–brachial index, indicating that patients with more severe resting limb ischaemia have a larger BP response to exercise. The BP response to low‐intensity exercise was enhanced in PAD. Chronic limb ischaemia may sensitize muscle afferents and potentiate the BP response to muscle contraction in a dose‐dependent manner.
Dietary iodide controls its own absorption through post‐transcriptional regulation of the intestinal Na+/I− symporter
Authors: Nicola Juan Pablo , Reyna‐Neyra Andrea , Carrasco Nancy , Masini‐Repiso Ana Maria
Published: September 2012

Key points

Expression of the Na+/I− symporter (NIS) at the apical surface of the epithelium of the small intestine is key to I− absorption, the first step in I− metabolism.

Intracellular I− at high concentrations in enterocytes decreases its own NIS‐mediated uptake by a newly discovered mechanism, downregulating NIS expression at the plasma membrane, increasing NIS protein degradation and decreasing NIS mRNA levels by reducing NIS mRNA stability, involving the NIS 3′‐untranslated region.

In conclusion, we have uncovered that I− regulates intestinal NIS expression, and thus its own intestinal absorption, by a complex array of post‐transcriptional mechanisms.

Abstract  Dietary I− absorption in the gastrointestinal tract is the first step in I− metabolism. Given that I− is an essential constituent of the thyroid hormones, its concentrating mechanism is of significant physiological importance. We recently described the expression of the Na+/I− symporter (NIS) on the apical surface of the intestinal epithelium as a central component of the I− absorption system and reported reduced intestinal NIS expression in response to an I−‐rich diet in vivo. Here, we evaluated the mechanism involved in the regulation of NIS expression by I− itself in enterocytes. Excess I− reduced NIS‐mediated I− uptake in IEC‐6 cells in a dose‐ and time‐dependent fashion, which was correlated with a reduction of NIS expression at the plasma membrane. Perchlorate, a competitive inhibitor of NIS, prevented these effects, indicating that an increase in intracellular I− regulates NIS. Iodide induced rapid intracellular recruitment of plasma membrane NIS molecules and NIS protein degradation. Lower NIS mRNA levels were detected in response to I− treatment, although no transcriptional effect was observed. Interestingly, I− decreased NIS mRNA stability, affecting NIS translation. Heterologous green fluorescent protein‐based reporter constructs revealed a significant repressive effect of the I−‐targeting NIS mRNA 3′ untranslated region. In conclusion, excess I− downregulates NIS expression in enterocytes by virtue of a complex mechanism. Our data suggest that I− regulates intestinal NIS mRNA expression at the post‐transcriptional level as part of an autoregulatory effect of I− on its own metabolism.
Population-Based Study of the Increased Incidence of Skin and Soft Tissue Infections and Associated Antimicrobial Use
Authors: Marra Fawziah , Patrick David M. , Chong Mei , McKay Rachel , Hoang Linda , Bowie William R.
Published: September 2012

Community-associated methicillin-resistant
Staphylococcus aureus
(CA-MRSA) has spread rapidly throughout the world in the last decade. We sought to demonstrate the impact of the emergence of CA-MRSA in Western Canada on physician visits, incision-and-drainage procedures, and antibiotic prescribing for skin and soft tissue infections (SSTI). We used the provincial physician billing system to determine the rate of physician visits (per 1,000 population per year) of SSTI and incision-and-drainage procedures. A database capturing all outpatient prescriptions in the province was anonymously linked to associated physician billing codes to quantify prescriptions associated with SSTI. Antibiotic prescriptions (overall and class specific) were expressed as their defined daily dose (DDD) per 1,000 inhabitants per day. Between 1996 and 2008, the rate of visits for all SSTI increased by 15%, and the majority of visits did not include an incision-and-drainage procedure. The rate of antibiotic prescribing for SSTI increased by 49%. The majority of this increase was attributable to the higher rates of use of clindamycin (627%), trimethoprim-sulfamethoxazole (380%), cephalosporins (160%), and amoxicillin-clavulanate (627%). Health care utilization and antibiotic prescribing rates for SSTI, but not incision-and-drainage procedures, have increased in association with the CA-MRSA epidemic. While much of the increase in antibiotic use reflects an appropriate change to trimethoprim-sulfamethoxazole, there is room for education regarding the limitations of cephalosporins and clindamycin, given current susceptibility profiles.
Identification of VanN-Type Vancomycin Resistance in an Enterococcus faecium Isolate from Chicken Meat in Japan
Authors: Nomura Takahiro , Tanimoto Koichi , Shibayama Keigo , Arakawa Yoshichika , Fujimoto Shuhei , Ike Yasuyoshi , Tomita Haruyoshi
Published: September 2012

Five VanN-type vancomycin-resistant
Enterococcus faecium
strains were isolated from a sample of domestic chicken meat in Japan. All isolates showed low-level resistance to vancomycin (MIC, 12 mg/liter) and had the same pulsed-field gel electrophoresis profile. The vancomycin resistance was encoded on a large plasmid (160 kbp) and was expressed constitutively. The VanN-type resistance operon was identical to the first resistance operon to be reported, with the exception of a 1-bp deletion in

vanT
N

and a 1-bp substitution in

vanS
N

.
Effect of PTX3 and Voriconazole Combination in a Rat Model of Invasive Pulmonary Aspergillosis
Authors: Lo Giudice Pietro , Campo Silvia , De Santis Rita , Salvatori Giovanni
Published: September 2012

This study evaluated the pharmacological activity of PTX3, administered in combination with voriconazole, in a rat model of pulmonary aspergillosis. The data indicated additive therapeutic activities of these compounds, as demonstrated by the amelioration of respiratory function changes, reduction of lung fungal burden, and increased survival. Overall, we provide clear evidence that the combination of PTX3 with a suboptimal dose of voriconazole might represent a therapeutic option under those clinical conditions where the use of voriconazole alone is not warranted for efficacy and tolerability reasons.
Effect of Transcriptional Activators SoxS, RobA, and RamA on Expression of Multidrug Efflux Pump AcrAB-TolC in Enterobacter cloacae
Authors: Pérez Astrid , Poza Margarita , Aranda Jesús , Latasa Cristina , Medrano Francisco Javier , Tomás María , Romero Antonio , Lasa Iñigo , Bou Germán
Published: September 2012

Control of membrane permeability is a key step in regulating the intracellular concentration of antibiotics. Efflux pumps confer innate resistance to a wide range of toxic compounds such as antibiotics, dyes, detergents, and disinfectants in members of the
Enterobacteriaceae
. The AcrAB-TolC efflux pump is involved in multidrug resistance in
Enterobacter cloacae
. However, the underlying mechanism that regulates the system in this microorganism remains unknown. In
Escherichia coli
, the transcription of
acrAB
is upregulated under global stress conditions by proteins such as MarA, SoxS, and Rob. In the present study, two clinical isolates of
E. cloacae
, EcDC64 (a multidrug-resistant strain overexpressing the AcrAB-TolC efflux pump) and Jc194 (a strain with a basal AcrAB-TolC expression level), were used to determine whether similar global stress responses operate in
E. cloacae
and also to establish the molecular mechanisms underlying this response. A decrease in susceptibility to erythromycin, tetracycline, telithromycin, ciprofloxacin, and chloramphenicol was observed in clinical isolate Jc194 and, to a lesser extent in EcDC64, in the presence of salicylate, decanoate, tetracycline, and paraquat. Increased expression of the
acrAB
promoter in the presence of the above-described conditions was observed by flow cytometry and reverse transcription-PCR, by using a reporter fusion protein (green fluorescent protein). The expression level of the AcrAB promoter decreased in
E. cloacae
EcDC64 derivates deficient in SoxS, RobA, and RamA. Accordingly, the expression level of the AcrAB promoter was higher in
E. cloacae
Jc194 strains overproducing SoxS, RobA, and RamA. Overall, the data showed that SoxS, RobA, and RamA regulators were associated with the upregulation of
acrAB
, thus conferring antimicrobial resistance as well as a stress response in
E. cloacae
. In summary, the regulatory proteins SoxS, RobA, and RamA were cloned and sequenced for the first time in this species. The involvement of these proteins in conferring antimicrobial resistance through upregulation of
acrAB
was demonstrated in
E. cloacae
.
Comparison of Genospecies and Antimicrobial Resistance Profiles of Isolates in the Acinetobacter calcoaceticus-Acinetobacter baumannii Complex from Various Clinical Specimens
Authors: Tien Ni , You Bang-Jau , Chang Hui-Lan , Lin Hsiu-Shen , Lee Chin-Yi , Chung Tung-Ching , Lu Jang-Jih , Chang Chao-Chin
Published: September 2012

This study was conducted to compare the prevalences of antimicrobial resistance profiles of clinical isolates in the
Acinetobacter calcoaceticus-Acinetobacter baumannii
complex from sterile and nonsterile sites and to further study the relationship of antimicrobial resistance profiles and genospecies by amplified rRNA gene restriction analysis (ARDRA). A total of 1,381 isolates were tested with 12 different antibiotics to show their antimicrobial susceptibility profiles. A total of 205 clinical isolates were further analyzed by ARDRA of the intergenic spacer (ITS) region of the 16S-23S rRNA gene. It was found that the overall percentage of isolates from nonsterile sites (urine, sputum, pus, or catheter tip) that were resistant to the 12 antibiotics tested was significantly higher than that of isolates from sterile sites (cerebrospinal fluid [CSF], ascites fluid, and bloodstream) (46% versus 22%;
P
< 0.05). After ARDRA, it was found that 97% of the 62 isolates resistant to all antibiotics tested were the
A. baumannii
genospecies, which was identified in only 31% of the isolates susceptible to all antibiotics tested. More genospecies diversity was identified in the isolates susceptible to all antibiotics tested, including genospecies of 13TU (34%), genotype 3 (29%), and
A. calcoaceticus
(5%). Furthermore, as 91% (10/11) of the isolates from CSF were susceptible to all antibiotics tested, the
A. calcoaceticus-A. baumannii
complex isolates with multidrug resistance could be less invasive than the more susceptible isolates. This study also indicated current emergence of carbapenem-, fluoroquinolone-, aminoglycoside-, and cephalosporin-resistant
A. calcoaceticus-A. baumannii
complex isolates in Taiwan.
Screening of Antifungal Azole Drugs and Agrochemicals with an Adapted alamarBlue-Based Assay Demonstrates Antibacterial Activity of Croconazole against Mycobacterium ulcerans
Authors: Scherr Nicole , Röltgen Katharina , Witschel Matthias , Pluschke Gerd
Published: September 2012

An alamarBlue-based growth inhibition assay has been adapted for the thermosensitive and slow-growing pathogen
Mycobacterium ulcerans
. The standardized test procedure enables medium-throughput screening of preselected compound libraries. Testing of a set of 48 azoles with known antifungal activity led to the identification of an imidazole antifungal displaying an inhibitory dose (ID) of 9 μM for
M. ulcerans
.
Differences in the Frequency of 23S rRNA Gene Mutations in Mycoplasma pneumoniae between Children and Adults with Community-Acquired Pneumonia: Clinical Impact of Mutations Conferring Macrolide Resistance
Authors: Yoo Soo Jin , Kim Hyo-Bin , Choi Sang-Ho , Lee Sang-Oh , Kim Sung-Han , Hong Sang-Bum , Sung Heungsup , Kim Mi-Na
Published: September 2012

We investigated the frequency and clinical significance of macrolide resistance in adult and pediatric patients with community-acquired pneumonia from aMycoplasma pneumoniaeinfection. The frequency of the A2063G mutation in the 23S rRNA gene was significantly higher in children than in adults (61.3% [19/31] and 13.3% [8/60], respectively;P< 0.001). Patients with macrolide-resistantM. pneumoniaeinfections showed a longer duration of fever (P= 0.021) and required a longer duration of antibiotic treatment (P= 0.007).
A 90-Day Tenofovir Reservoir Intravaginal Ring for Mucosal HIV Prophylaxis
Authors: Johnson Todd J. , Clark Meredith R. , Albright Theodore H. , Nebeker Joel S. , Tuitupou Anthony L. , Clark Justin T. , Fabian Judit , McCabe R. Tyler , Chandra Neelima , Doncel Gustavo F. , Friend David R. , Kiser Patrick F.
Published: September 2012

A vaginal gel containing the antiretroviral tenofovir (TFV) recently demonstrated 39% protection against HIV infection in women. We designed and evaluated a novel reservoir TFV intravaginal ring (IVR) to potentially improve product effectiveness by providing a more controlled and sustained vaginal dose to maintain cervicovaginal concentrations. Polyurethane tubing of various hydrophilicities was filled with a high-density TFV/glycerol/water semisolid paste and then end-sealed to create IVRs.
In vitro
, TFV release increased with polyurethane hydrophilicity, with 35 weight percent water-swelling polyurethane IVRs achieving an approximately 10-mg/day release for 90 days with mechanical stiffness similar to that of the commercially available NuvaRing. This design was evaluated in two 90-day
in vivo
sheep studies for TFV pharmacokinetics and safety. Overall, TFV vaginal tissue, vaginal fluid, and plasma levels were relatively time independent over the 90-day duration at approximately 10
4
ng/g, 10
6
ng/g, and 10
1
ng/ml, respectively, near or exceeding the highest observed concentrations in a TFV 1% gel control group. TFV vaginal fluid concentrations were approximately 1,000-fold greater than levels shown to provide significant protection in women using the TFV 1% gel. There were no toxicological findings following placebo and TFV IVR treatment for 28 or 90 days, although slight to moderate increases in inflammatory infiltrates in the vaginal epithelia were observed in these animals compared to naïve animals. In summary, the controlled release of TFV from this reservoir IVR provided elevated sheep vaginal concentrations for 90 days to merit its further evaluation as an HIV prophylactic.
Targeting Essential Genes in Salmonella enterica Serovar Typhimurium with Antisense Peptide Nucleic Acid
Authors: Soofi Muhammad A. , Seleem Mohamed N.
Published: September 2012

We investigated the capability of antisense peptide nucleic acids (PNAs) conjugated to the (KFF)
3
K cell-penetrating peptide to target possible essential genes (
ligA
,
rpoA
,
rpoD
,
engA
,
tsf
, and
kdtA
) in
Salmonella enterica
serovar Typhimurium and inhibit bacterial growth
in vitr
o and in cell culture. All targeted PNA-based gene inhibition has shown great potency in gene expression inhibition in a sequence-specific and dose-dependent manner at micromolar concentrations. Among tested PNAs, the anti-
rpoA
and -
rpoD
PNAs showed the greatest potency.
Noninvasive Determination of 2-[
18
F]-Fluoroisonicotinic Acid Hydrazide Pharmacokinetics by Positron Emission Tomography in Mycobacterium tuberculosis-Infected Mice
Authors: Weinstein E. A. , Liu L. , Ordonez A. A. , Wang H. , Hooker J. M. , Tonge P. J. , Jain S. K.
Published: September 2012

Tuberculosis (TB) is a global pandemic requiring sustained therapy to facilitate curing and to prevent the emergence of drug resistance. There are few adequate tools to evaluate drug dynamics within infected tissues
in vivo
. In this report, we evaluated a fluorinated analog of isoniazid (INH), 2-[
18
F]fluoroisonicotinic acid hydrazide (2-[
18
F]-INH), as a probe for imaging
Mycobacterium tuberculosis
-infected mice by dynamic positron emission tomography (PET). We developed a tail vein catheter system to safely deliver drugs to
M. tuberculosis
aerosol-infected mice inside sealed biocontainment devices. Imaging was rapid and noninvasive, and it could simultaneously visualize multiple tissues. Dynamic PET imaging demonstrated that 2-[
18
F]-INH was extensively distributed and rapidly accumulated at the sites of infection, including necrotic pulmonary TB lesions. Compared to uninfected animals,
M. tuberculosis
-infected mice had a significantly higher PET signal within the lungs (
P
< 0.05) despite similar PET activity in the liver (
P
> 0.85), suggesting that 2-[
18
F]-INH accumulated at the site of the pulmonary infection. Furthermore, our data indicated that similar to INH, 2-[
18
F]-INH required specific activation and accumulated within the bacterium. Pathogen-specific metabolism makes positron-emitting INH analogs attractive candidates for development into imaging probes with the potential to both detect bacteria and yield pharmacokinetic data
in situ
. Since PET imaging is currently used clinically, this approach could be translated from preclinical studies to use in humans.
Role for Telomerase in Listeria monocytogenes Infection
Authors: Samba-Louaka Ascel , Stavru Fabrizia , Cossart Pascale
Published: September 2012

Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the human telomerase complex. Growing evidence suggests that hTERT also contributes to the cell physiology independently of telomere elongation. However, its role in bacterial infection is unknown. Here we show that hTERT is critical forListeria monocytogenesinfection, as the depletion of hTERT impaired bacterial intracellular replication. In addition, we observed thatL. monocytogenescaused a decrease in hTERT levels at early time points of the infectious process. This effect was mediated by the pore-forming toxin listeriolysin O (LLO) and did not require bacterial entry into host cells. Calcium influx through the LLO pores contributed to a proteasome-independent decrease in hTERT protein levels. Together, our data provide evidence that these bacteria trigger hTERT degradation, an event that is detrimental to bacterial replication.
Progressive Cross-Reactivity in IgE Responses: an Explanation for the Slow Development of Human Immunity to Schistosomiasis?
Authors: Fitzsimmons Colin M. , Jones Frances M. , Pinot de Moira Angela , Protasio Anna V. , Khalife Jamal , Dickinson Harriet A. , Tukahebwa Edridah M. , Dunne David W.
Published: September 2012

People in regions of
Schistosoma mansoni
endemicity slowly acquire immunity, but why this takes years to develop is still not clear. It has been associated with increases in parasite-specific IgE, induced, some investigators propose, to antigens exposed during the death of adult worms. These antigens include members of the tegumental-allergen-like protein family (TAL1 to TAL13). Previously, in a group of
S. mansoni
-infected Ugandan males, we showed that IgE responses to three TALs expressed in worms (TAL1, -3, and -5) became more prevalent with age. Now, in a subcohort we examined associations of these responses with resistance to reinfection and use the data to propose a mechanism for the slow development of immunity. IgE was measured 9 weeks posttreatment and at reinfection at 2 years (
n
= 144). An anti-TAL5 IgE (herein referred to as TAL5 IgE) response was associated with reduced reinfection even after adjusting for age using regression analysis (geometric mean odds ratio, 0.24;
P
= 0.016). TAL5 IgE responders were a subset of TAL3 IgE responders, themselves a subset of TAL1 responders. TAL3 IgE and TAL5 IgE were highly cross-reactive, with TAL3 the immunizing antigen and TAL5 the cross-reactive antigen. Transcriptional and translational studies show that TAL3 is most abundant in adult worms and that TAL5 is most abundant in infectious larvae. We propose that in chronic schistosomiasis, older individuals have repeatedly experienced IgE antigens exposed when adult worms die (e.g., TAL3) and that this leads to increasing cross-reactivity with antigens of invading larvae (e.g., TAL5). Progressive accumulation of worm/larvae cross-reactivity could explain the age-dependent immunity observed in areas of endemicity.
Crucial Role of Gamma Interferon-Producing CD4+Th1 Cells but Dispensable Function of CD8+T Cell, B Cell, Th2, and Th17 Responses in the Control of Brucella melitensis Infection in Mice
Authors: Vitry Marie-Alice , De Trez Carl , Goriely Stanislas , Dumoutier Laure , Akira Shizuo , Ryffel Bernhard , Carlier Yves , Letesson Jean-Jacques , Muraille Eric
Published: September 2012

Brucellaspp. are facultative intracellular bacterial pathogens responsible for brucellosis, a worldwide zoonosis that causes abortion in domestic animals and chronic febrile disease associated with serious complications in humans. There is currently no approved vaccine against human brucellosis, and antibiotic therapy is long and costly. Development of a safe protective vaccine requires a better understanding of the roles played by components of adaptive immunity in the control ofBrucellainfection. The importance of lymphocyte subsets in the control ofBrucellagrowth has been investigated separately by various research groups and remains unclear or controversial. Here, we used a large panel of genetically deficient mice to compare the importance of B cells, transporter associated with antigen processing (TAP-1), and major histocompatibility complex class II-dependent pathways of antigen presentation as well as T helper 1 (Th1), Th2, and Th17-mediated responses on the immune control ofBrucella melitensis16 M infection. We clearly confirmed the key function played by gamma interferon (IFN-γ)-producing Th1 CD4+T cells in the control ofB. melitensisinfection, whereas IFN-γ-producing CD8+T cells or B cell-mediated humoral immunity plays only a modest role in the clearance of bacteria during primary infection. In the presence of a Th1 response, Th2 or Th17 responses do not really develop or play a positive or negative role during the course ofB. melitensisinfection. On the whole, these results could improve our ability to develop protective vaccines or therapeutic treatments against brucellosis.
Transient Deficiency of Dendritic Cells Results in Lack of a Merozoite Surface Protein 1-Specific CD4 T Cell Response during Peak Plasmodium chabaudi Blood-Stage Infection
Authors: Sponaas Anne-Marit , Belyaev Nikolai , Falck-Hansen Mika , Potocnik Alexandre , Langhorne Jean
Published: September 2012

Splenic dendritic cells are crucial for controlling the immune response to malaria by initiating a CD4 gamma interferon (IFN-γ) response early in a blood-stage infection, which contributes to parasite clearance as well as to acute-stage immunopathology. CD8−CD11chighdendritic cells have been described previously to be important antigen-presenting cells for induction of these CD4 T cell responses in the spleens ofPlasmodium chabaudi-infected mice. However, when isolated during the period of maximum parasitemia and shortly thereafter, the dendritic cells transiently lose their ability to stimulate T cells, recovering only as the parasitemia is controlled. This loss of a CD4 T cell response is also observedin vivoduring this part of the infection. CD4 T cells from a T cell receptor-transgenic mouse recognizing a peptide of merozoite surface protein 1 (MSP1) injected into BALB/c mice during peak parasitemia proliferate poorly, and very few cells produce IFN-γ and interleukin-2 (IL-2), compared with transgenic T cells injected earlier in the blood-stage infection. CD8−dendritic cells at day 10 can process and present peptides on major histocompatibility complex (MHC) class II with an efficiency similar to that of dendritic cells from earlier in infection. The failure of the day 10 dendritic cells to activate MSP1-specific CD4 T cells fullyin vitrois associated with reduced expression of CD86 and lower production of IL-12 rather than with induction of inhibitory DC receptors or production of IL-10.
FMS-Like Tyrosine Kinase 3 Ligand Treatment of Mice Aggravates Acute Lung Injury in Response to Streptococcus pneumoniae: Role of Pneumolysin
Authors: Brumshagen Christina , Maus Regina , Bischof Andrea , Ueberberg Bianca , Bohling Jennifer , Osterholzer John J. , Ogunniyi Abiodun D. , Paton James C. , Welte Tobias , Maus Ulrich A.
Published: September 2012

FMS-like tyrosine kinase-3 ligand (Flt3L) is a dendritic cell (DC) growth and differentiation factor with potential in antitumor therapies and antibacterial immunization strategies. However, the effect of systemic Flt3L treatment on lung-protective immunity against bacterial infection is incompletely defined. Here, we examined the impact of deficient (in Flt3L knockout [KO] mice), normal (in wild-type [WT] mice), or increased Flt3L availability (in WT mice pretreated with Flt3L for 3, 5, or 7 days) on lung DC subset profiles and lung-protective immunity against the major lung-tropic pathogen,
Streptococcus pneumoniae
. Although in Flt3L-deficient mice the numbers of DCs positive for CD11b (CD11b
pos
DCs) and for CD103 (CD103
pos
DCs) were diminished, lung permeability, a marker of injury, was unaltered in response to
S. pneumoniae
. In contrast, WT mice pretreated with Flt3L particularly responded with increased numbers of CD11b
pos
DCs and with less pronounced numbers of CD103
pos
DCs and impaired bacterial clearance and with increased lung permeability following
S. pneumonia
e challenge. Notably, infection of Flt3L-pretreated mice with
S. pneumoniae
lacking the pore-forming toxin, pneumolysin (PLY), resulted in substantially less lung CD11b
pos
DCs activation and reduced lung permeability. Collectively, this study establishes that Flt3L treatment enhances the accumulation of proinflammatory activated lung CD11b
pos
DCs which contribute to acute lung injury in response to PLY released by
S. pneumoniae
.
Prenatal ultrasound diagnosis of holoprosencephaly and associated anomalies
Authors: Chaudhari Hemang D , Thakkar Gurudatt , Darji Parth , Khokhani Pratik
Published: September 2012

Holoprosencephaly is a rare spectrum of cerebral and facial malformations resulting from incomplete division of the embryonic forebrain (prosencephalon) into distinct lateral cerebral hemisphere. Holoprosencephaly spectrum in the fetus is often associated with other anomalies, particularly of the face and extremities. Here we present three different cases of patients with holoprosencephaly who failed to attain routine sonography during 11–20 weeks owing to some unavoidable circumstances. Two of them were diagnosed during the third trimester and one in the late second trimester. Ultrasound findings of associated anomalies were confirmed after a clinical examination of the delivered fetuses.
Penoscrotal entrapment: a safe, innovative technique for removing metal constricting devices
Authors: Wu Xilin , Batra Ramesh , Al-Akraa Mahmoud , Seneviratne Lasantha Niroshan
Published: September 2012

Penoscrotal entrapment is a rare urological emergency that requires urgent treatment to avoid penile ischaemia and subsequent erectile dysfunction. Non-metallic and thin metallic objects are easily removed via cutting, while thick metallic constricting devices require specialist saws or motorised cutters, all of which may be difficult to locate in the emergency setting. We report a case of a 45-year-old patient who presented with a 48-h history of gross penoscrotal oedema secondary to entrapment by a thick metal ring (internal diameter 55 mm, external diameter 74 mm and thickness 19 mm). The positioning, thickness of the ring, delayed presentation and extensive oedema meant its removal was especially challenging. We improvised a simple, three-step technique (aspiration, strapping and sling) which enabled the metal ring to be removed without the need for specialist equipment. We would encourage others to employ this safe technique in an emergency setting.
Recurrent hyperphosphatemic tumoural calcinosis
Authors: Amit Sonal , Agarwal Asha , Nigam Anand , Rao Yashwant Kumar
Published: September 2012

Tumoural calcinosis (TC) is a benign gradually developing disorder that can occur in a variety of clinical settings, characterised by subcutaneous deposition of calcium phosphate with or without giant cell reaction. We describe a case of 11-year-old girl presenting with recurrent hard swellings in the vicinity of shoulder and hip joints associated with elevated serum phosphate and normal serum calcium levels. TC has been mainly reported from Africa, with very few cases reported from India. After the diagnosis of hyperphosphatemic TC was established, the patient was treated with oral sevelamer and is under constant follow-up to detect recurrence, if any. The present case highlights the fact that although an uncommon lesion, TC must be considered in the differential diagnosis of subcutaneous hard lump in the vicinity of a joint.
Recurrence of a paediatric arteriovenous malformation 9 years postcomplete excision: case report and review of literature
Authors: McCarthy Claire , Kaliaperumal Chandrasekaran , O'Sullivan Michael
Published: September 2012

Cerebral arteriovenous malformations (AVMs) are a common congenital vascular anomaly, which often present in both children and adults. Surgery is considered curative once postoperative angiography confirms the absence of vessels. We describe a 6-year-old girl, who had a Spetzler-Martin Grade II AVM resected successfully, in which a recurrent AVM was detected on routine follow-up over 9 years post excision. The aetiopathogenesis of this rare occurrence with a review of literature is discussed. Long-term postoperative follow-up in the form of MRI/MR angiogram is recommended for all fully resected AVMs in the paediatric age group, anticipating the possibility of future recurrence.
Extensive extracranial and intracranial Varicella zoster vasculopathy
Authors: Verma Rajesh , Lalla Rakesh , Patil Tushar B
Published: September 2012

Varicella zoster virus (VZV)-induced vasculopathy is an uncommon cause of stroke in a young immunocompetent host. Owing to scarcity of data of VZV-induced vasculopathy and lack of awareness about this condition and its diagnostic test, these cases may be easily missed. In this case, we report an immunocompetent host presenting right-side hemiplegia with motor aphasia and complete loss of vision in the left eye due to complete occlusion of the left common carotid artery without any history of skin rash preceding stroke. Cerebrospinal fluid analysis for varicella antibody revealed very high titres and CT aortogram demonstrated aortoarteritis with occlusion of left common carotid artery. To our knowledge, varicella zoster vasculopathy-associated aortoarteritis has not been described in the literature.
Giant cavernous carotid artery aneurysm mimicking a fungal granuloma and presenting with massive epistaxis
Authors: Roopesh Kumar V R , Madhugiri Venkatesh S , Sasidharan Gopalakrishnan M , Gundamaneni Sudheer K
Published: September 2012

A 42-year-old man presented with frequent minor nasal bleeds since 1 month. He was undergoing chemotherapy for pulmonary tuberculosis. MRI brain revealed a space occupying lesion in the right cavernous sinus extending to sphenoid sinus, with T2 inversion. An initial diagnosis of fungal granuloma was made and endoscopic trans-nasal biopsy was attempted. During surgery, a pink pulsating mass was seen in the sphenoid sinus and the procedure was abandoned. A cerebral CT-angiography done subsequently revealed a giant right cavernous segment internal carotid artery (ICA) aneurysm. He was then referred to our centre and upon admission he collapsed secondary to a major bout of epistaxis. An emergency cervical carotid artery ligation resulted in transient control of epistaxis. Owing to recurrence of bleed, trapping of the aneurysm was done resulting in cure. The present case shows that a giant cavernous ICA aneurysm can occasionally be erroneously diagnosed as fungal granuloma.
Appendiceal torsion associated with undescended caecum: a case report and review of the literature
Authors: Dimitriadis Panagiotis A , Makar Ragai R , Randall Jon K , Ramus James
Published: September 2012

Torsion of the vermiform appendix is a rare disorder that causes symptoms similar to those of acute appendicitis. Primary and secondary causes of appendiceal torsion have been reported in the literature. Laparoscopy appears to be the most appropriate modality for diagnosis and treatment where the condition is suspected. To our knowledge this is the first case of appendiceal torsion in an adult causing right upper quadrant pain related to caecal malposition.
KMS STATES ON NICA–TOEPLITZ ALGEBRAS OF PRODUCT SYSTEMS
Authors: HONG JEONG HEE , LARSEN NADIA S. , SZYMAŃSKI WOJCIECH
Published: September 2012

We investigate KMS states of Fowler's Nica–Toeplitz algebra [Formula: see text] associated to a compactly aligned product system X over a semigroup P of Hilbert bimodules. This analysis relies on restrictions of these states to the core algebra which satisfy appropriate scaling conditions. The concept of product system of finite type is introduced. If (G, P) is a lattice ordered group and X is a product system of finite type over P satisfying certain coherence properties, we construct KMSβstates of [Formula: see text] associated to a scalar dynamics from traces on the coefficient algebra of the product system. Our results were motivated by, and generalize some of the results of Laca and Raeburn obtained for the Toeplitz algebra of the affine semigroup over the natural numbers.
GRAVITATION AND VACUUM ENTANGLEMENT ENTROPY
Authors: JACOBSON TED
Published: September 2012

The vacuum of quantum fields contains correlated fluctuations. When restricted to one side of a surface these have a huge entropy of entanglement that scales with the surface area. If UV physics renders this entropy finite, then a thermodynamic argument implies the existence of gravity. That is, the causal structure of spacetime must be dynamical and governed by the Einstein equation with Newton's constant inversely proportional to the entropy density. Conversely, the existence of gravity makes the entanglement entropy finite. This thermodynamic reasoning is powerful despite the lack of a detailed description of the dynamics at the cutoff scale, but it has its limitations. In particular, we should not expect to understand corrections to Einstein gravity in this way.
REALISTIC CYCLIC MAGNETIC UNIVERSE
Authors: MEDEIROS L. G.
Published: September 2012

This work presents a complete cyclic cosmological scenario based on nonlinear magnetic field. It is constructed from a model composed of five fluids, namely baryonic matter, dark matter, radiation, neutrinos and a cosmological magnetic field. The first four fluids are treated in the standard way and the fifth fluid, the magnetic field, is described by a nonlinear electrodynamics. The free parameters are fitted by observational data (SNIa, CMB, extragalactic magnetic fields, etc.) and by simple theoretical considerations. As a result arises a cyclic cosmological model that preserves the main successes of the standard Big Bang model and solves some other problems such as the initial singularity, the present acceleration and the Big Rip.
GÖDEL-TYPE UNIVERSES IN f(T) GRAVITY
Authors: LIU DI , WU PUXUN , YU HONGWEI
Published: September 2012

The issue of causality in f(T) gravity is investigated by examining the possibility of existence of the closed timelike curves in the Gödel-type metric. By assuming a perfect fluid as the matter source, we find that the fluid must have an equation of state parameter greater than minus one in order to allow the Gödel solutions to exist, and furthermore the critical radius rc, beyond which the causality is broken down, is finite and it depends on both matter and gravity. Remarkably, for certain f(T) models, the perfect fluid that allows the Gödel-type solutions can even be normal matter, such as pressureless matter or radiation. However, if the matter source is a special scalar field rather than a perfect fluid, then rc→ ∞ and the causality violation is thus avoided.
ON THE SEMICLASSICAL LIMIT OF LOOP QUANTUM COSMOLOGY
Authors: CORICHI ALEJANDRO , MONTOYA EDISON
Published: September 2012

We consider a k = 0 Friedman–Robertson–Walker (FRW) model within loop quantum cosmology (LQC) and explore the issue of its semiclassical limit. The model is exactly solvable and allows us to construct analytical (Gaussian) coherent-state solutions for each point on the space of classical states. We propose physical criteria that select from these coherent states, those that display semiclassical behavior, and study their properties in the deep Planck regime. Furthermore, we consider generalized squeezed states and compare them to the Gaussian states. The issue of semiclassicality preservation across the bounce is studied and shown to be generic for all the states considered. Finally, we comment on some implications these results have, depending on the topology of the spatial slice. In particular, we consider the issue of the recovery, within our class of states, of a scaling symmetry present in the classical description of the system when the spatial topology is noncompact.
RADIATION BOUNDARY CONDITIONS FOR THE HELMHOLTZ EQUATION FOR ELLIPSOIDAL, PROLATE SPHEROIDAL, OBLATE SPHEROIDAL AND SPHERICAL DOMAIN BOUNDARIES
Authors: BURNETT DAVID S.
Published: September 2012

One of the most popular radiation boundary conditions for the Helmholtz equation in exterior 3-D regions has been the sequence of operators developed by Bayliss et al.1 for computational domains with spherical exterior boundaries. The present paper extends those spherical operators to triaxial ellipsoidal boundaries by utilizing two mathematical constructs originally developed for ellipsoidal acoustic infinite elements.2 The two constructs are: (i) a radial/angular coordinate system for ellipsoidal geometry, and (ii) a convergent ellipsoidal radial expansion for exterior fields, analogous to the classical spherical multipole expansion. The ellipsoidal radial and angular coordinates are smooth generalizations of the traditional radial and angular coordinates used in spherical, prolate spheroidal and oblate spheroidal systems. As a result, all four coordinate systems and their corresponding radiation boundary conditions are included within this single ellipsoidal system, varying smoothly from one to the other. The geometric flexibility of this system enables the exterior boundary of the computational domain to closely circumscribe objects with a wide range of aspect ratios, thereby reducing the size and cost of 3-D computational models.
MR IMAGING OF SUPRASCAPULAR NEUROPATHIES
Authors: Sureka Jyoti , Panwar Sanuj
Published: September 2012

Suprascapular neuropathy has become increasingly recognized entity which is often overlooked and mistaken for other causes of shoulder pain and dysfunction like rotator cuff injury, shoulder impingement syndrome, cervical spondylosis and brachial plexopathy. It can be caused by a variety of anatomic and pathologic entities as the nerve courses from the brachial plexus through the suprascapular and spinoglenoid notches to innervate the supraspinatus and infraspinatus muscles. Because of the widespread availability of high-field MRI scanners now it is possible to detect the subtle perineural pathology, thereby excluding the other common causes of shoulder pain. There are scattered case reports and reviews describing suprascapular nerve (SSN) abnormalities using MRI. This article comprehensively reviews different pathologic abnormalities involving the SSN and illustrates their MR features, clinical presentation, correlation with electrophysiologic studies and surgical findings based on a review of 24 cases. We found the different clinical entities which includes trauma and a spectrum of nontraumatic etiology such as idiopathic, mass lesions compressing the nerve, intrinsic lesion like intraneural ganglion cysts of SSN, repetitive overuse, viral neuritis and chemotherapy induced neuropathy.
UTILITY MAXIMIZATION WITH INTERMEDIATE CONSUMPTION UNDER RESTRICTED INFORMATION FOR JUMP MARKET MODELS
Authors: CECI CLAUDIA
Published: September 2012

The contribution of this paper is twofold: we study power utility maximization problems (with and without intermediate consumption) in a partially observed financial market with jumps and we solve by the innovation method the arising filtering problem. We consider a Markovian model where the risky asset dynamics St follows a pure jump process whose local characteristics are not observable by investors. More precisely, the stock price process dynamics depends on an unobservable stochastic factor Xt described by a jump-diffusion process. We assume that agents' decisions are based on the knowledge of an information flow, [Formula: see text], containing the asset price history, [Formula: see text]. Using projection on the filtration [Formula: see text], the partially observable investment-consumption problem is reduced to a full observable stochastic control problem. The homogeneity of the power utility functions leads to a factorization of the associated value process into a part depending on the current wealth and the so called opportunity process Jt. In the case where [Formula: see text], Jt and the optimal investment-consumption strategy are represented in terms of solutions to a backward stochastic differential equation (BSDE) driven by the [Formula: see text]-compensated martingale random measure associated to St, which can be obtained by filtering techniques (Ceci, 2006; Ceci and Gerardi, 2006). Next, we extend the study to the case [Formula: see text], where ηt gives observations of Xt in additional Gaussian noise. This setup can be viewed as an abstract form of "insider information". The opportunity process Jt is now characterized as a solution to a BSDE driven by the [Formula: see text]-compensated martingale random measure and the so called innovation process. Computation of these quantities leads to a filtering problem with mixed type observation and whose solution is discussed via the innovation approach.
DUPIRE'S EQUATION FOR BUBBLES
Authors: EKSTRÖM ERIK , TYSK JOHAN
Published: September 2012

We study Dupire's equation for local volatility models with bubbles, i.e. for models in which the discounted underlying asset follows a strict local martingale. If option prices are given by risk-neutral valuation, then the discounted option price process is a true martingale, and we show that the Dupire equation for call options contains extra terms compared to the usual equation. However, the Dupire equation for put options takes the usual form. Moreover, uniqueness of solutions to the Dupire equation is lost in general, and we show how to single out the option price among all possible solutions. The Dupire equation for models in which the discounted derivative price process is merely a local martingale is also studied.
MODELLING THE BID AND ASK PRICES OF ILLIQUID CDSs
Authors: WALKER MICHAEL B.
Published: September 2012

CDS (credit default swap) contracts that were initiated some time ago frequently have spreads and/or maturities that are not available on the current market of CDSs, and are thus illiquid. This article introduces an incomplete-market approach to valuing illiquid CDSs that, in contrast to the risk-neutral approach of current market practice, allows a dealer who buys an illiquid CDS from an investor to determine ask and bid prices (which differ) in such a way as to guarantee a minimum positive expected rate of return on the deal. An alternative procedure, which replaces the expected rate of return by an analogue of the Sharpe ratio, is also discussed. The approach to pricing just described belongs to the good-deal category of approaches, since the dealer decides what it would take to make an appropriate expected rate of return, and sets the bid and ask prices accordingly. A number of different hedges are discussed and compared within the general framework developed in the article. The approach is implemented numerically, and example plots of important quantities are given. The paper also develops a useful result in linear programming theory in the case that the cost vector is random.
THEORETICAL STUDY OF THE SUBSTITUENT EFFECTS ON THE REACTION ENTHALPIES OF THE ANTIOXIDANT MECHANISMS OF STOBADINE DERIVATIVES IN THE GAS-PHASE AND WATER
Authors: NAJAFI MEYSAM , NAJAFI MOHAMMAD , NAJAFI HOUSHANG
Published: September 2012

In this paper the reaction enthalpies of three antioxidant action mechanisms, HAT, SET–PT, and SPLET, for mono-substituted Stobadines were calculated in gas-phase and water. Results show that electron-withdrawing substituents increase the bond dissociation enthalpy (BDE), ionization potential (IP), and electron transfer enthalpy (ETE), while electron-donating ones cause a rise in the proton dissociation enthalpy (PDE) and proton affinity (PA). In comparison to gas-phase, water attenuates the substituent effect on all reaction enthalpies. Results show that IP and BDE values can be successfully correlated with the indolic N–H bond length after electron abstraction, R(N–H+•), and the partial charge on the indolyl radical nitrogen atom, q( N ). Furthermore, calculated IP and PA values for mono-substituted Stobadines show linear dependence on the energy of the highest occupied molecular orbital (E HOMO ) of studied molecules in the two environments. SPLET represents the thermodynamically preferred mechanism in water.
CONVERGENCE OF THE DISCRETE WAVELET TRANSFORM
Authors: NAVARRO JAIME , HERRERA OSCAR
Published: September 2012

The discrete wavelet transform; depending of the pair of integers (m, n), applied to functions f in L2(R) with respect to an admissible function h in L2(R) of class C∞ with compact support, is used to prove that f is continuous at x = 0, and furthermore at any x = b in R if and only if there exists the convergence of the discrete wavelet transform, as (m, n) → (-∞, n1) for any integer n1.