bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration of the Second Messenger c-di-GMP into the Chemotactic Signaling Pathway
Authors: Russell Matthew H. , Bible Amber N. , Fang Xin , Gooding Jessica R. , Campagna Shawn R. , Gomelsky Mark , Alexandre Gladys
Published: March 2013

Elevated intracellular levels of the bacterial second messenger c-di-GMP are known to suppress motility and promote sessility. Bacterial chemotaxis guides motile cells in gradients of attractants and repellents over broad concentration ranges, thus allowing bacteria to quickly adapt to changes in their surroundings. Here, we describe a chemotaxis receptor that enhances, as opposed to suppresses, motility in response to temporary increases in intracellular c-di-GMP.
Azospirillum brasilense
’s preferred metabolism is adapted to microaerophily, and these motile cells quickly navigate to zones of low oxygen concentration by aerotaxis. We observed that changes in oxygen concentration result in rapid changes in intracellular c-di-GMP levels. The aerotaxis and chemotaxis receptor, Tlp1, binds c-di-GMP via its C-terminal PilZ domain and promotes persistent motility by increasing swimming velocity and decreasing swimming reversal frequency, which helps
A. brasilense
reach low-oxygen zones. If c-di-GMP levels remain high for extended periods,
A. brasilense
forms nonmotile clumps or biofilms on abiotic surfaces. These results suggest that association of increased c-di-GMP levels with sessility is correct on a long-term scale, while in the short-term c-di-GMP may actually promote, as opposed to suppress, motility. Our data suggest that sensing c-di-GMP by Tlp1 functions similar to methylation-based adaptation. Numerous chemotaxis receptors contain C-terminal PilZ domains or other sensory domains, suggesting that intracellular c-di-GMP as well as additional stimuli can be used to modulate adaptation of bacterial chemotaxis receptors.

IMPORTANCE
To adapt and compete under changing conditions, bacteria must not only detect and respond to various environmental cues but also be able to remain sensitive to further changes in the environmental conditions. In bacterial chemotaxis, chemosensory sensitivity is typically brought about by changes in the methylation status of chemotaxis receptors capable of modulating the ability of motile cells to navigate in gradients of various physicochemical cues. Here, we show that the ubiquitous second messenger c-di-GMP functions to modulate chemosensory sensitivity of a bacterial chemotaxis receptor in the alphaproteobacterium
Azospirillum brasilense
. Binding of c-di-GMP to the chemotaxis receptor promotes motility under conditions of elevated intracellular c-di-GMP levels. Our results revealed that the role of c-di-GMP as a sessile signal is overly simplistic. We also show that adaptation by sensing an intracellular metabolic cue, via PilZ or other domains, is likely widespread among bacterial chemotaxis receptors.
A Multifaceted Study of Pseudomonas aeruginosa Shutdown by Virulent Podovirus LUZ19
Authors: Lavigne Rob , Lecoutere Elke , Wagemans Jeroen , Cenens William , Aertsen Abram , Schoofs Liliane , Landuyt Bart , Paeshuyse Jan , Scheer Maurice , Schobert Max , Ceyssens Pieter-Jan
Published: March 2013

In contrast to the rapidly increasing knowledge on genome content and diversity of bacterial viruses, insights in intracellular phage development and its impact on bacterial physiology are very limited. We present a multifaceted study combining quantitative PCR (qPCR), microarray, RNA-seq, and two-dimensional gel electrophoresis (2D-GE), to obtain a global overview of alterations in DNA, RNA, and protein content in
Pseudomonas aeruginosa
PAO1 cells upon infection with the strictly lytic phage LUZ19. Viral genome replication occurs in the second half of the phage infection cycle and coincides with degradation of the bacterial genome. At the RNA level, there is a sharp increase in viral mRNAs from 23 to 60% of all transcripts after 5 and 15 min of infection, respectively. Although microarray analysis revealed a complex pattern of bacterial up- and downregulated genes, the accumulation of viral mRNA clearly coincides with a general breakdown of abundant bacterial transcripts. Two-dimensional gel electrophoretic analyses shows no bacterial protein degradation during phage infection, and seven stress-related bacterial proteins appear. Moreover, the two most abundantly expressed early and late-early phage proteins, LUZ19 gene product 13 (Gp13) and Gp21, completely inhibit
P. aeruginosa
growth when expressed from a single-copy plasmid. Since Gp13 encodes a predicted GNAT acetyltransferase, this observation points at a crucial but yet unexplored level of posttranslational viral control during infection.

IMPORTANCE
Massive genome sequencing has led to important insights into the enormous genetic diversity of bacterial viruses (bacteriophages). However, for nearly all known phages, information on the impact of the phage infection on host physiology and intracellular phage development is scarce. This aspect of phage research should be revitalized, as phages evolved genes which can shut down or redirect bacterial processes in a very efficient way, which can be exploited towards antibacterial design. In this context, we initiated a study of the human opportunistic pathogen
Pseudomonas aeruginosa
under attack by one its most common predators, the
Phikmvlikevirus
. By analyzing various stages of infection at different levels, this study uncovers new features of phage infection, representing a cornerstone for future studies on members of this phage genus.
Microanatomy at Cellular Resolution and Spatial Order of Physiological Differentiation in a Bacterial Biofilm
Authors: Serra Diego O. , Richter Anja M. , Klauck Gisela , Mika Franziska , Hengge Regine
Published: March 2013

Bacterial biofilms are highly structured multicellular communities whose formation involves flagella and an extracellular matrix of adhesins, amyloid fibers, and exopolysaccharides. Flagella are produced by still-dividing rod-shaped
Escherichia coli
cells during postexponential growth when nutrients become suboptimal. Upon entry into stationary phase, however, cells stop producing flagella, become ovoid, and generate amyloid curli fibers. These morphological changes, as well as accompanying global changes in gene expression and cellular physiology, depend on the induction of the stationary-phase sigma subunit of RNA polymerase, σ
S
(RpoS), the nucleotide second messengers cyclic AMP (cAMP), ppGpp, and cyclic-di-GMP, and a biofilm-controlling transcription factor, CsgD. Using flagella, curli fibers, a CsgD::GFP reporter, and cell morphology as “anatomical” hallmarks in fluorescence and scanning electron microscopy, different physiological zones in macrocolony biofilms of
E. coli
K-12 can be distinguished at cellular resolution. Small ovoid cells encased in a network of curli fibers form the outer biofilm layer. Inner regions are characterized by heterogeneous CsgD::GFP and curli expression. The bottom zone of the macrocolonies features elongated dividing cells and a tight mesh of entangled flagella, the formation of which requires flagellar motor function. Also, the cells in the outer-rim growth zone produce flagella, which wrap around and tether cells together. Adjacent to this growth zone, small chains and patches of shorter curli-surrounded cells appear side by side with flagellated curli-free cells before curli coverage finally becomes confluent, with essentially all cells in the surface layer being encased in “curli baskets.”

IMPORTANCE
Heterogeneity or cellular differentiation in biofilms is a commonly accepted concept, but direct evidence at the microscale has been difficult to obtain. Our study reveals the microanatomy and microphysiology of an
Escherichia coli
macrocolony biofilm at an unprecedented cellular resolution, with physiologically different zones and strata forming as a function of known global regulatory networks that respond to biofilm-intrinsic gradients of nutrient supply. In addition, this study identifies zones of heterogeneous and potentially bistable CsgD and curli expression, shows bacterial curli networks to strikingly resemble Alzheimer plaques, and suggests a new role of flagella as an architectural element in biofilms.
Living and Thriving on the Skin:
Malassezia
Genomes Tell the Story
Authors: Coelho Marco A. , Sampaio José Paulo , Gonçalves Paula
Published: March 2013

Our understanding of the interactions between normal skin microbiota and the human host has been greatly extended by recent investigations. In their recent study in
mBio
, A. Gioti et al. (mBio 4[1]:e00572-12, 2013) sequenced the genome of the atopic eczema-associated yeast,
Malassezia sympodialis
, and compared its gene content and organization with that of
Malassezia globosa
, a species implicated in dandruff. Their findings were also contrasted with those previously obtained for
Ustilago maydis
, which is a close relative but ecologically distinct plant parasite. Besides gaining additional insight into key host-specific adaptations and the particular function and molecular evolution of allergens related to atopic eczema, Gioti et al. also uncovered several lines of evidence that elegantly suggest the presence of an extant sexual cycle, with important implications in disease.
The Listeria monocytogenes ChiA Chitinase Enhances Virulence through Suppression of Host Innate Immunity
Authors: Chaudhuri Swarnava , Gantner Benjamin N. , Ye Richard D. , Cianciotto Nicholas P. , Freitag Nancy E.
Published: March 2013

Environmental pathogens survive and replicate within the outside environment while maintaining the capacity to infect mammalian hosts. For some microorganisms, mammalian infection may be a relatively rare event. Understanding how environmental pathogens retain their ability to cause disease may provide insight into environmental reservoirs of disease and emerging infections.
Listeria monocytogenes
survives as a saprophyte in soil but is capable of causing serious invasive disease in susceptible individuals. The bacterium secretes virulence factors that promote cell invasion, bacterial replication, and cell-to-cell spread. Recently, an
L. monocytogenes
chitinase (ChiA) was shown to enhance bacterial infection in mice. Given that mammals do not synthesize chitin, the function of ChiA within infected animals was not clear. Here we have demonstrated that ChiA enhances
L. monocytogenes
survival
in vivo
through the suppression of host innate immunity.
L. monocytogenes
Δ
chiA
mutants were fully capable of establishing bacterial replication within target organs during the first 48 h of infection. By 72 to 96 h postinfection, however, numbers of Δ
chiA
bacteria diminished, indicative of an effective immune response to contain infection. The Δ
chiA
-associated virulence defect could be complemented in
trans
by wild-type
L. monocytogenes
, suggesting that secreted ChiA altered a target that resulted in a more permissive host environment for bacterial replication. ChiA secretion resulted in a dramatic decrease in inducible nitric oxide synthase (iNOS) expression, and Δ
chiA
mutant virulence was restored in
NOS2

−
/
−

mice lacking iNOS. This work is the first to demonstrate modulation of a specific host innate immune response by a bacterial chitinase.

IMPORTANCE
Bacterial chitinases have traditionally been viewed as enzymes that either hydrolyze chitin as a food source or serve as a defense mechanism against organisms containing structural chitin (such as fungi). Recent evidence indicates that bacterial chitinases and chitin-binding proteins contribute to pathogenesis, primarily via bacterial adherence to chitin-like molecules present on the surface of mammalian cells. In contrast, mammalian chitinases have been linked to immunity via inflammatory immune responses that occur outside the context of infection, and since mammals do not produce chitin, the targets of these mammalian chitinases have remained elusive. This work demonstrates that a
Listeria monocytogenes
-secreted chitinase has distinct functional roles that include chitin hydrolysis and suppression of host innate immunity. The established link between chitinase and the inhibition of host inducible nitric oxide synthase (iNOS) expression may help clarify the thus far elusive relationship observed between mammalian chitinase enzymes and host inflammatory responses occurring in the absence of infection.
Ultrasound guided V3 segment vertebral artery direct percutaneous puncture for basilar artery mechanical thrombectomy in acute stroke: a technical report
Authors: Desai Jamsheed A , Almekhlafi Mohammed A , Hill Michael D , Goyal Mayank , Eesa Muneer
Published: March 2013

A middle aged patient presented with acute ischemic stroke due to basilar artery occlusion. The patient clinically deteriorated despite intravenous thrombolysis and was referred for mechanical thrombectomy. The right vertebral artery was occluded and could not be accessed despite attempting various shaped catheters, even when a radial artery access was used. The left vertebral artery ended in the posterior inferior cerebellar artery. Eventually, ultrasound guided V3 segment vertebral artery direct puncture was successfully done and the procedure was completed. No access related complications were encountered. Direct cervical arterial puncture can be safely used by experienced operators as a last resort in acute stroke cases with difficult access.
Exercise training in children with asthma: a systematic review
Authors: Wanrooij Vera HM , Willeboordse Maartje , Dompeling Edward , van de Kant Kim DG
Published: March 2013

Exercise can provoke asthma symptoms, such as dyspnoea, in children with asthma. Exercise-induced bronchoconstriction (EIB) is prevalent in 40–90% of children with asthma. Conversely, exercise can improve physical fitness. The purpose of this paper is to provide a systematic review of the literature regarding the effects of exercise training in children with asthma, particularly in relation to: EIB, asthma control, pulmonary function, cardiorespiratory parameters and parameters of underlying pathophysiology. A systematic search in several databases was performed. Controlled trials that undertook a physical training programme in children with asthma (aged 6–18 years) were selected. Twenty-nine studies were included. Training had positive effects on several cardiorespiratory fitness parameters. A few studies demonstrated that training could improve EIB, especially in cases where there was sufficient room for improvement. Peak expiratory flow was the only lung function parameter that could be improved substantially by training. The effects of training on asthma control, airway inflammation and bronchial hyper-responsiveness were barely studied. Owing to the overall beneficial effects of training and the lack of negative effects, it can be concluded that physical exercise is safe and can be recommended in children with asthma. A training programme should have a minimum duration of 3 months, with at least two 60 min training sessions per week, and a training intensity set at the (personalised) ventilatory threshold. Further research is recommended regarding the effects of exercise on underlying pathophysiological mechanisms and asthma control in children with asthma.
The time course of in vivo recovery of transverse strain in high-stress tendons following exercise
Authors: Wearing Scott C , Smeathers James E , Hooper Sue L , Locke Simon , Purdam Craig , Cook Jill L
Published: March 2013

Objective

To evaluate the time course of the recovery of transverse strain in the Achilles and patellar tendon following a bout of resistance exercise.

Methods

Seventeen healthy adults underwent sonographic examination of the right patellar (n=9) and Achilles (n=8) tendons immediately prior to and following 90 repetitions of weight-bearing quadriceps and gastrocnemius-resistance exercise performed against an effective resistance of 175% and 250% body weight, respectively. Sagittal tendon thickness was determined 20 mm from the enthesis and transverse strain, as defined by the stretch ratio, was repeatedly monitored over a 24 h recovery period.

Results

Resistance exercise resulted in an immediate decrease in Achilles (t7=10.6, p<0.01) and patellar (t8=8.9, p<0.01) tendon thickness, resulting in an average transverse stretch ratio of 0.86±0.04 and 0.82±0.05, which was not significantly different between tendons. The magnitude of the immediate transverse strain response, however, was reduced with advancing age (r=0.63, p<0.01). Recovery in transverse strain was prolonged compared with the duration of loading and exponential in nature. The average primary recovery time was not significantly different between the Achilles (6.5±3.2 h) and patellar (7.1±3.2 h) tendons. Body weight accounted for 62% and 64% of the variation in recovery time, respectively.

Conclusions

Despite structural and biochemical differences between the Achilles and patellar tendon, the mechanisms underlying transverse creep recovery in vivo appear similar and are highly time dependent. These novel findings have important implications concerning the time required for the mechanical recovery of high-stress tendons following an acute bout of exercise.
Muscle strength in youth and cardiovascular risk in young adulthood (the European Youth Heart Study)
Authors: Grøntved Anders , Ried-Larsen Mathias , Møller Niels Christian , Kristensen Peter Lund , Froberg Karsten , Brage Søren , Andersen Lars Bo
Published: March 2013

Background

Whether muscle strength in youth is related to cardiovascular risk later in life independent of cardiorespiratory fitness is unclear.

Methods

We examined the independent association of isometric muscle strength in youth with cardiovascular risk factors in young adulthood using data from the Danish European Youth Heart Study; a population-based prospective cohort study among boys and girls (n=332) followed for up to 12 years. In youth maximal voluntary contractions during isometric back extension and abdominal flexion were determined using a strain-gauge dynamometer and cardiorespiratory fitness was obtained from a maximal cycle ergometer test. Cardiovascular risk factors were obtained in youth and in young adulthood. Associations were examined using multivariable-adjusted regression models including major confounding factors.

Results

Each 1 SD difference in isometric muscle strength in youth (0.17 N/kg) was inversely associated with body mass index (BMI; −0.60 kg/m2, 95% CI −0.97 to −0.22), triglyceride (−0.09 mmol/l, 95% CI −0.16 to −0.02), diastolic blood pressure (BP) (−1.22 mm Hg, 95% CI −2.15 to −0.29) and a composite cardiovascular risk factor score (−0.61 SD, 95% CI −1.03 to −0.20) in young adulthood in multivariable-adjusted analyses including fitness. Associations to triglyceride, diastolic BP and the cardiovascular risk factor score remained with additional adjustment for waist circumference or BMI. Each 1 SD difference in isometric muscle strength in youth was significantly associated with 0.59 (95% CI 0.40 to 0.87) lower odds of general overweight/obesity in young adulthood (p=0.007) and was marginally associated with incident raised BP, raised triglyceride and low high-density lipoprotein cholesterol.

Conclusions

This study suggests that greater isometric muscle strength in youth is associated with lower levels of cardiovascular risk factors in young adulthood independent of fitness, adiposity and other confounding factors.
Effect of dynamic humeral centring (DHC) treatment on painful active elevation of the arm in subacromial impingement syndrome. Secondary analysis of data from an RCT
Authors: Beaudreuil Johann , Lasbleiz Sandra , Aout Mounir , Vicaut Eric , Yelnik Alain , Bardin Thomas , Orcel Philippe
Published: March 2013

Background

The physiotherapy dynamic humeral centring (DHC) aims to prevent subacromial impingement of rotator cuff tendons during elevation of the arm. The objective of the study was to determine whether DHC acts via an effect on subacromial impingement mechanism by assessing its effect on painful elevation of the arm in subacromial impingement syndrome.

Methods

This is a secondary analysis of results of a randomised controlled trial of the effectiveness of DHC. Sixty-nine patients with subacromial impingement syndrome were prospectively included. Patients and the assessor were blinded to the study hypothesis and treatment, respectively. Patients underwent DHC or non-specific mobilisation as a control for 6 weeks in 15 supervised individual outpatient sessions with home exercises. Outcomes were pain-free range of motion and presence of painful arc of the shoulder, both in active flexion and abduction of the arm at 3 months.

Results

At 3 months, pain-free range of motion, both flexion and abduction, was greater in the DHC group than in the mobilisation group. The number of patients with painful arc during flexion was decreased in the DHC group.

Conclusions

DHC improves painful active elevation of the arm. We suggest that DHC may act via a specific effect on subacromial impingement mechanism.
Intravenous nicardipine and labetalol use in hypertensive patients with signs or symptoms suggestive of end-organ damage in the emergency department: a subgroup analysis of the CLUE trial
Authors: Cannon Chad M , Levy Phillip , Baumann Brigitte M , Borczuk Pierre , Chandra Abhinav , Cline David M , Diercks Deborah B , Hiestand Brian , Hsu Amy , Jois Preeti , Kaminski Brian , Nowak Richard M , Schrock Jon W , Varon Joseph , Peacock W Frank
Published: March 2013

Objective

To compare the efficacy of Food and Drug Administration recommended dosing of nicardipine versus labetalol for the management of hypertensive patients with signs and/or symptoms (S/S) suggestive of end-organ damage (EOD).

Design

Secondary analysis of the multicentre prospective, randomised CLUE trial.

Setting

13 academic emergency departments in the USA.

Participants

Eligible patients had two systolic blood pressure (SBP) measures ≥180 mm Hg at least 10 min apart, no contraindications to nicardipine or labetalol and predefined S/S suggestive of EOD on arrival.

Interventions

Medications were administered by continuous infusion (nicardipine) or repeat intravenous bolus (labetalol) for a study period of 30 min or until a specified target SBP ±20 mm Hg was achieved.

Primary outcome measure

Percentage of participants achieving a predefined target SBP range (TR) defined as an SBP within ±20 mm Hg as established by the treating physician.

Results

Of the 141 eligible patients, 49.6% received nicardipine, 51.7% were women and 81.6% were black. Mean age was 52.2±13.9 years. Median initial SBP did not differ in the nicardipine (210.5 (IQR 197–226) mm Hg) and labetalol (210 (200–226) mm Hg) groups (p=0.862). Nicardipine patients were more likely to have a history of diabetes (41.4% vs 25.7%, p=0.05) but there were no other historical, demographic or laboratory differences between groups. Within 30 min, nicardipine patients more often reached the target SBP range than those receiving labetalol (91.4% vs 76.1%, difference=15.3% (95% CI 3.5% to 27.3%); p=0.01). On multivariable modelling with adjustment for gender and clinical site, nicardipine patients were more likely to be in TR by 30 min than patients receiving labetalol (OR 3.65, 95% CI 1.31 to 10.18, C statistic=0.72).

Conclusions

In the setting of hypertension with suspected EOD, patients treated with nicardipine are more likely to reach prespecified SBP targets within 30 min than patients receiving labetalol.

Clinical Trial Registration

NCT00765648, clinicaltrials.gov
Fetal intracranial haemorrhages caused by fetal and neonatal alloimmune thrombocytopenia: an observational cohort study of 43 cases from an international multicentre registry
Authors: Tiller Heidi , Kamphuis Marije M , Flodmark Olof , Papadogiannakis Nikos , David Anna L , Sainio Susanna , Koskinen Sinikka , Javela Kaija , Wikman Agneta Taune , Kekomaki Riitta , Kanhai Humphrey H H , Oepkes Dick , Husebekk Anne , Westgren Magnus
Published: March 2013

Objective

To characterise pregnancies where the fetus or neonate was diagnosed with fetal and neonatal alloimmune thrombocytopenia (FNAIT) and suffered from intracranial haemorrhage (ICH), with special focus on time of bleeding onset.

Design

Observational cohort study of all recorded cases of ICH caused by FNAIT from the international No IntraCranial Haemorrhage (NOICH) registry during the period 2001–2010.

Setting

13 tertiary referral centres from nine countries across the world.

Participants

37 mothers and 43 children of FNAIT pregnancies complicated by fetal or neonatal ICH identified from the NOICH registry was included if FNAIT diagnosis and ICH was confirmed.

Primary and secondary outcome measures

Gestational age at onset of ICH, type of ICH and clinical outcome of ICH were the primary outcome measures. General maternal and neonatal characteristics of pregnancies complicated by fetal/neonatal ICH were secondary outcome measures.

Results

From a total of 592 FNAIT cases in the registry, 43 confirmed cases of ICH due to FNAIT were included in the study. The majority of bleedings (23/43, 54%) occurred before 28 gestational weeks and often affected the first born child (27/43, 63%). One-third (35%) of the children died within 4 days after delivery. 23 (53%) children survived with severe neurological disabilities and only 5 (12%) were alive and well at time of discharge. Antenatal treatment was not given in most (91%) cases of fetal/neonatal ICH.

Conclusions

ICH caused by FNAIT often occurs during second trimester and the clinical outcome is poor. In order to prevent ICH caused by FNAIT, at-risk pregnancies must be identified and prevention and/or interventions should start early in the second trimester.
Survival transcriptome in the coenzyme Q10deficiency syndrome is acquired by epigenetic modifications: a modelling study for human coenzyme Q10deficiencies
Authors: Fernández-Ayala Daniel J M , Guerra Ignacio , Jiménez-Gancedo Sandra , Cascajo Maria V , Gavilán Angela , DiMauro Salvatore , Hirano Michio , Briones Paz , Artuch Rafael , De Cabo Rafael , Salviati Leonardo , Navas Plácido
Published: March 2013

Objectives

Coenzyme Q10(CoQ10) deficiency syndrome is a rare condition that causes mitochondrial dysfunction and includes a variety of clinical presentations as encephalomyopathy, ataxia and renal failure. First, we sought to set up what all have in common, and then investigate why CoQ10supplementation reverses the bioenergetics alterations in cultured cells but not all the cellular phenotypes.

Design Modelling study

This work models the transcriptome of human CoQ10deficiency syndrome in primary fibroblast from patients and study the genetic response to CoQ10treatment in these cells.

Setting

Four hospitals and medical centres from Spain, Italy and the USA, and two research laboratories from Spain and the USA.

Participants

Primary cells were collected from patients in the above centres.

Measurements

We characterised by microarray analysis the expression profile of fibroblasts from seven CoQ10-deficient patients (three had primary deficiency and four had a secondary form) and aged-matched controls, before and after CoQ10supplementation. Results were validated by Q-RT-PCR. The profile of DNA (CpG) methylation was evaluated for a subset of gene with displayed altered expression.

Results

CoQ10-deficient fibroblasts (independently from the aetiology) showed a common transcriptomic profile that promotes cell survival by activating cell cycle and growth, cell stress responses and inhibiting cell death and immune responses. Energy production was supported mainly by glycolysis while CoQ10supplementation restored oxidative phosphorylation. Expression of genes involved in cell death pathways was partially restored by treatment, while genes involved in differentiation, cell cycle and growth were not affected. Stably demethylated genes were unaffected by treatment whereas we observed restored gene expression in either non-methylated genes or those with an unchanged methylation pattern.

Conclusions

CoQ10deficiency induces a specific transcriptomic profile that promotes cell survival, which is only partially rescued by CoQ10supplementation.
Molecular biology of normal melanocytes and melanoma cells
Authors: Bandarchi Bizhan , Jabbari Cyrus Aleksandre , Vedadi Ali , Navab Roya
Published: March 2013

Malignant melanoma is one of the most aggressive malignancies in humans and is responsible for 60–80% of deaths from skin cancers. The 5-year survival of patients with metastatic malignant melanoma is about 14%. Its incidence has been increasing in the white population over the past two decades. The mechanisms leading to malignant transformation of melanocytes and melanocytic lesions are poorly understood. In developing malignant melanoma, there is a complex interaction of environmental and endogenous (genetic) factors, including: dysregulation of cell proliferation, programmed cell death (apoptosis) and cell-to-cell interactions. The understanding of genetic alterations in signalling pathways of primary and metastatic malignant melanoma and their interactions may lead to therapeutics modalities, including targeted therapies, particularly in advanced melanomas that have high mortality rates and are often resistant to chemotherapy and radiotherapy. Our knowledge regarding the molecular biology of malignant melanoma has been expanding. Even though several genes involved in melanocyte development may also be associated with melanoma cell development, it is still unclear how a normal melanocyte becomes a melanoma cell. This article reviews the molecular events and recent findings associated with malignant melanoma.
The role of amyloid β in the pathogenesis of Alzheimer's disease
Authors: Gilbert Barnabas James
Published: March 2013

The amyloid-β peptide (Aβ) is widely considered to be the major toxic agent in the pathogenesis of Alzheimer's disease, a condition which afflicts approximately 36 million people worldwide. Despite a plethora of studies stretching back over two decades, identifying the toxic Aβ species has proved difficult. Debate has centred on the Aβ fibril and oligomer. Despite support from numerous experimental models, important questions linger regarding the role of the Aβ oligomer in particular. It is likely a huge array of oligomers, rather than a single species, which cause toxicity. Reappraisal of the role of the Aβ fibril points towards a dynamic relationship with the Aβ oligomer within an integrated system, as supported by evidence from microglia. However, some continue to doubt the pathological role of amyloid β, instead proposing a protective role. If the field is to progress, all Aβ oligomers should be characterised, the nomenclature revised and a consistent experimental protocol defined. For this to occur, collaboration will be required between major research groups and innovative analytical tools developed. Such action must surely be taken if amyloid-based therapeutic endeavour is to progress.
The child's body without fluid: mother's knowledge and practices about hydration and rehydration in Salvador, Bahia, Brazil
Authors: Larrea-Killinger Cristina , Muñoz Araceli
Published: March 2013

Background

The aim of this article was to anthropologically analyse knowledge and practices about hydration and rehydration in a specific ethnographic context, where diverse therapies are combined to treat and take care of child diarrhoea as part of a wider social process that circumscribes transactions between self-care and biomedicine.

Methods

Ethnographic data from a qualitative study in the neighbourhood of Nova Constituinte (Salvador, Bahia) which was part of an interdisciplinary project aimed at epidemiologically evaluating an environmental sanitation programme. These data results from a series of in-depth interviews of 29 interviewees and field observations collected over two stages (1997/1998–2003/2004).

Results

Knowledge about hydration and rehydration is practical knowledge that demonstrates some of the cultural limits of dehydration in terms of the normality or pathology criteria related to child diarrhoea. This knowledge belongs to local interpretations, treatment experiences and the care that mothers provide in relation to their child's diarrhoea. We observed a process of medicalisation in the discourse about hydration and self-care.

Conclusions

Unlike rehydration, hydration is structural to self-care processes. While the former constitutes a way of alleviating diarrhoea, the latter is a type of care centred on healing. The difference between these practices does not lie in the type of remedies used but in the meaning attributed to them and the way they are combined.
Infectious disease control in the Ionian Islands during the British Protection (1815–1864)
Authors: Tsiamis Costas , Thalassinou E , Poulakou-Rebelakou E , Anogiatis-Pelé D , Hatzakis A
Published: March 2013

This review presents the medical and social role of British military doctors in the formation of the British sanitary campaign in the Ionian Islands during the period 1815–1864. They were the core of a health system based on the old sanitary model of the Venetian Republic, which was the former ruler of the region. The British innovation and reorganisation of the old lazarettos (a quarantine system for maritime travellers), the new marine sanitary procedures, the determination of quarantine duration for major infectious diseases along with the introduction of the vaccination system resulted in a satisfactory defence against epidemics in Greece during the 19th century. The British military physicians applied and established West European medical ideas, as well as the principles of preventive medicine, for the first time in the Greek territory and this is a historical example of a successful sanitary campaign based on the experience of military physicians and their collaboration with civilian physicians.
Military treatment of splenic injury in the era of non-operative management
Authors: Mossadegh Somayyeh , Midwinter M , Sapsford W , Tai N
Published: March 2013

Objectives

Management of blunt splenic injury (BSI) in battlefield casualties is controversial. Splenectomy is the traditional treatment, as setting the conditions for selective non-operative management (SNOM) is difficult in the operational environment. On mature operations, it may be feasible to adopt a more conservative approach and manage the patient according to civilian protocols. The aim of this study was to document the contemporary practice of deployed military surgeons when dealing with BSI and to compare this against a matched cohort of civilian BSI patients.

Method

The Joint Theatre Trauma Registry held at the Royal Centre for Defence Medicine, Birmingham, was thoroughly examined to yield patients with BSI. The study encompassed a 55-month period ending September 2009. Data abstracted included patient demographics, injury epidemiology, grade of splenic injury, treatment and outcome. These data were compared with a registry database from a UK civilian major trauma centre.

Result

Of 1516 military trauma patients, 16 (1%) had a splenic injury, of which five were excluded either because of fatalities due to overwhelming injury or penetrating trauma. The remaining 11 had a blunt component. Median (IQR) injury severity score (ISS) was 17 (15–21). Nine underwent a splenectomy with median (IQR) ISS of 17 (12–18). Of this group, organ injury grades were documented in 10 patients (four Grade V injuries, three Grade IV and three Grade II). All patients survived surgery. There were no complications in survivors as a result of splenic conservation in the military group. Data from the civilian major trauma centre database showed 160 (2%) patients sustained a splenic injury, of which 131 (82%) had a blunt mechanism, 43/160 (27%) and 9/160 (6%) patients underwent splenectomy and angio-embolisation, respectively.

Conclusions

Patients with BSI, an uncommon finding in combat casualties, are occasionally selected for conservative management, contrary to previous military surgical paradigms but in keeping with the civilian shift to SNOM. Guidelines to clarify the place of SNOM are required to assist surgical decision making on deployed operations.
An unusual case of anaemia and lymphadenopathy in a soldier on deployment
Authors: O'Shea M K , Gregg R , Naylor J
Published: March 2013

We describe the case of a British soldier, originally from southeast Africa, who presented to the British military hospital in Helmand Province, southern Afghanistan, with a history of constitutional upset, profound anaemia and diffuse lymphadenopathy with hepatosplenomegaly. Following evacuation to the UK investigations revealed a rare (and a not so rare) diagnosis. This case raises a number of questions regarding the population at risk, the prevalence of endemic diseases in this population and laboratory capabilities in the deployed setting.
Patient reported outcome measures in military patients with shoulder instability
Authors: Middleton Simon , Guyver P , Boyd M , Brinsden M
Published: March 2013

Objectives

The Oxford Shoulder Instability Score (OSIS) is a measure of functional impairment of the upper limb, but it is unclear how it translates into military patients where lower scores, implying higher function, may still be insufficient to meet the increased demands of military service and necessitating surgery. This study aimed to compare OSIS in military and civilian patients undergoing shoulder stabilisation surgery.

Methods

We undertook a prospective, blinded cohort-controlled study with a null hypothesis that there was no difference in the Oxford Instability Scores between military and civilian patient groups. 40 patients were required in each group. A prospective clinical data base (iParrot, ByResults, Oxford, UK) was interrogated for consecutive patients undergoing shoulder stabilisation surgery at a single centre. The senior author—blinded to the outcome score—matched patients according to age, gender and diagnosis. Statistical analysis showed the data to be normally distributed and a paired samples t test was used to compare the two groups.

Results

110 patients were required to provide a matched cohort of 40 in each group (70 male, 10 female subjects). Age distribution was 16–19 years (n=6); 20–24 years (n=28); 25–29 (n=16); 30–34 (n=12); 35–49 (n=12); and 40–44 (n=6). 72 patients (90%) had polar group 1 instability and eight patients (10%) had polar group 2 instability. The mean OSIS in the civilian group was 17.25 and in the military group 18.25. There was no statistical difference between the two groups (p=0.395).

Conclusions

This study supports the use of the OSIS to assess military patients with shoulder instability and monitor the progress of their condition.
Trauma treatment in a Role 1 medical facility in Afghanistan
Authors: Vedel Pernille Nygaard , Helsø I , Jørgensen H L , Lauritzen J Bruun , Nissen L Ravnborg
Published: March 2013

Background

Most of the emergency care delivered in Afghanistan is currently provided by the military sector and non-governmental organisations. Main Operating Base (MOB) Price in Helmand Province has a small medical centre and due to its location provides critical care to civilians and military casualties and this article describes the patterns in trauma patient care at the MOB Price medical centre regarding the types of patients and injuries.

Materials and methods

The study population consists of 64 consecutive critically injured patients treated in MOB Price during a 4-month period from September to December 2010. The outcomes were battle-related injuries, treatment received before arriving to MOB Price, types of injury and treatment.

Results

There were 35 civilians (12 children and 23 adults), 28 Afghan National Security Forces and one International Security Assistance Force soldier; they were divided into three groups (civilian adults, civilian children and military). 22% of the patients suffered fragmentation injuries and civilians were more likely to incur fragment injury than military personnel (OR (95% CI) 7.04 (1.4 to 34.8)). Regarding intubation, there was a trend towards more civilians needing it than military personnel and significantly more children than adults underwent intubation (OR (95% Cl) 51 (5.2 to 498.5)). Gunshot wounds (GSW) occurred in 30% of the patients. Civilians patients had a lower OR for GSWs than military patients (OR (95% CI) 0.35 (0.1 to 1.1)). Other trends in injury types and treatment were apparent but did not reach significance due to the small number of patients.

Conclusions

Both civilians and military personnel benefitted from the in-theatre Role 1 medical facility treatment. The most frequent injuries were fragmentation damage and GSW.
Transfemoral venous approach for Onyx embolization of anterior fossa dural arteriovenous fistulae
Authors: Spiotta Alejandro M , Hawk Harris , Kellogg Ryan T , Turner Raymond D , Chaudry M Imran , Turk Aquilla S
Published: March 2013

Background

Dural arteriovenous fistulae (dAVF) of the anterior fossa have a malignant course since they exclusively drain into cortical frontal veins and warrant aggressive treatment. Classically, these lesions have been treated with microsurgical clipping of the fistulous connection. We describe a transvenous approach for Onyx embolization of these lesions that relies on distal venous access using a flexible new-generation guide catheter.

Methods

A retrospective review was performed of all patients with an anterior fossa dAVF treated at the Medical University of South Carolina since 2010. Charts, procedural records, angiographic images and follow-up were reviewed. Three patients were identified.

Results

Transfemoral venous access and distal transvenous sinus access was obtained in a retrograde fashion to at least the level of the right transverse sinus. Once a distal guide catheter position was obtained within the venous sinus system, a microcatheter was advanced into the predominant draining anterior frontal cortical vein in preparation for embolization. Onyx 34 embolization was then initiated from this position with the objective of achieving penetration across the vascular shunt.

Conclusions

Our experience demonstrates that transvenous Onyx embolization offers an effective and safe alternative to the classic neurosurgical treatment of anterior fossa dAVF.
Diagnosis algorithm for leptospirosis in dogs: disease and vaccination effects on the serological results
Authors: Andre‐Fontaine G.
Published: March 2013

Leptospirosis is a common disease in dogs, despite their current vaccination. Vet surgeons may use a serological test to verify their clinical observations. The gold standard is the Microscopic Agglutination Test (MAT). After infection, the dog produces agglutinating antibodies against the lipopolyosidic antigens shared by the infectious strain but also, after vaccination, against the lipopolyosidic antigens shared by the serovars used in the bacterins (Leptospira species serovars Icterohaemorrhagiae and Canicola in most countries). MATs were performed in a group of 102 healthy field dogs and a group of 6 Canicola‐challenged dogs. A diagnosis algorithm was constructed based on age, previous vaccinations, kinetics of the agglutinating antibodies after infection or vaccination and the delay after onset of the disease. This algorithm was applied to 169 well‐documented sera (clinical and vaccine data) from 272 sick dogs with suspected leptospirosis. Totally, 102 dogs were vaccinated according to the usual vaccination scheme and 30 were not vaccinated. Leptospirosis was confirmed by MAT in 37/102 (36.2 per cent) vaccinated dogs and remained probable in 14 others (13.7 per cent), thus indicating the permanent exposure of dogs and the weakness of the protection offered by the current vaccines to pathogenic Leptospira.
COMBINATION OF HETEROGENEOUS EEG FEATURE EXTRACTION METHODS AND STACKED SEQUENTIAL LEARNING FOR SLEEP STAGE CLASSIFICATION
Authors: HERRERA L. J. , FERNANDES C. M. , MORA A. M. , MIGOTINA D. , LARGO R. , GUILLEN A. , ROSA A. C.
Published: March 2013

This work proposes a methodology for sleep stage classification based on two main approaches: the combination of features extracted from electroencephalogram (EEG) signal by different extraction methods, and the use of stacked sequential learning to incorporate predicted information from nearby sleep stages in the final classifier. The feature extraction methods used in this work include three representative ways of extracting information from EEG signals: Hjorth features, wavelet transformation and symbolic representation. Feature selection was then used to evaluate the relevance of individual features from this set of methods. Stacked sequential learning uses a second-layer classifier to improve the classification by using previous and posterior first-layer predicted stages as additional features providing information to the model. Results show that both approaches enhance the sleep stage classification accuracy rate, thus leading to a closer approximation to the experts' opinion.
A STUDY OF CITY TRAFFIC IN AFTERNOON RUSH HOURS
Authors: ÁVALOS EDGAR , HUANG D. W. , HUANG W. N.
Published: March 2013

The traffic of vehicles from downtown to suburban areas is investigated numerically. We propose a cellular automaton to simulate the traffic of vehicles within a city regulated by traffic lights. Both traffic flow and travel time are presented and we discuss some strategies to optimize these quantities.
CONDITIONAL MATCHING PRECLUSION FOR (n,k)-STAR GRAPHS
Authors: CHENG EDDIE , LIPTÁK LÁSZLÓ
Published: March 2013

The matching preclusion number of an even graph G, denoted by mp (G), is the minimum number of edges whose deletion leaves the resulting graph without perfect matchings. The conditional matching preclusion number of an even graph G, denoted by mp 1(G), is the minimum number of edges whose deletion leaves the resulting graph with neither perfect matchings nor isolated vertices. The class of (n,k)-star graphs is a popular class of interconnection networks for which the matching preclusion number and the classification of the corresponding optimal solutions were known. However, the conditional version of this problem was open. In this paper, we determine the conditional matching preclusion for (n,k)-star graphs as well as classify the corresponding optimal solutions via several new results. In addition, an alternate proof of the results on the matching preclusion problem will also be given.
STRUCTURAL DYNAMICS OF ELECTRONIC SYSTEMS
Authors: SUHIR E.
Published: March 2013

The published work on analytical ("mathematical") and computer-aided, primarily finite-element-analysis (FEA) based, predictive modeling of the dynamic response of electronic systems to shocks and vibrations is reviewed. While understanding the physics of and the ability to predict the response of an electronic structure to dynamic loading has been always of significant importance in military, avionic, aeronautic, automotive and maritime electronics, during the last decade this problem has become especially important also in commercial, and, particularly, in portable electronics in connection with accelerated testing of various surface mount technology (SMT) systems on the board level. The emphasis of the review is on the nonlinear shock-excited vibrations of flexible printed circuit boards (PCBs) experiencing shock loading applied to their support contours during drop tests. At the end of the review we provide, as a suitable and useful illustration, the exact solution to a highly nonlinear problem of the dynamic response of a "flexible-and-heavy" PCB to an impact load applied to its support contour during drop testing.