bluuebunny/crossref_metadata_2025 huggingface dataset:
Global burden of chronic pulmonary aspergillosis complicating sarcoidosis
Authors: Denning David W. , Pleuvry Alex , Cole Donald C.
Published: June 2012

Chronic pulmonary aspergillosis (CPA) may complicate pulmonary sarcoidosis. We re-estimated the global burden of sarcoidosis and the burden of CPA complicating sarcoidosis.

We searched the literature and reference lists of retrieved papers to identify all published sarcoidosis incidence and prevalence data. We estimated the frequency of CPA from 11 papers relating to >3,000 patients with sarcoidosis to derive CPA patient numbers. We applied an annual attrition rate of 15% (range 10–25%) to estimate the global burden of CPA.

We estimate that the annual incidence of sarcoidosis is 344,000 patients worldwide and the prevalence is ∼1,238,000 cases, distributed as follows: 165,979 in Europe, 224,000 in the Americas, 492,892 in Africa, 80,023 in the Eastern Mediterranean, 41,660 in the West Pacific and 234,010 in Southeast Asia. CPA complicates sarcoidosis in 3–12% of cases. Using a 6% frequency, we estimate a global burden of 71,907 (range 35,954–143,815 (3–12%)) CPA cases complicating sarcoidosis, with 24% and 37% of cases estimated to be present in the Americas and Africa, because of the higher incidence of sarcoidosis in black people.

As CPA responds to long-term antifungal therapy, which may prevent life-threatening haemoptysis, screening periodically for CPA in those with pulmonary sarcoidosis may be important, especially in patients requiring corticosteroid therapy.
Generalized set-valued variational-like inclusions involving "Equation missing" -η-cocoercive operator in Banach spaces
Authors: Ahmad Rais , Dilshad Mohd , Wong Mu-Ming , Yao Jen-Chin
Published: June 2012

The aim of this paper is to introduce a new

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-η-cocoercive operator and its resolvent operator. We study some of the properties of

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-η-cocoercive operator and prove the Lipschitz continuity of resolvent operator associated with

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-η-cocoercive operator. Finally, we apply the techniques of resolvent operator to solve a generalized set-valued variational-like inclusion problem in Banach spaces. Our results are new and generalize many known results existing in the literature. Some examples are given in support of definition of

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-η-cocoercive operator.

MSC:47H19, 49J40.
Non-typeable Haemophilus influenzae decreases cilia beating via protein kinase C epsilon
Authors: Bailey Kristina L , LeVan Tricia D , Yanov Daniel A , Pavlik Jaqueline A , DeVasure Jane M , Sisson Joseph H , Wyatt Todd A
Published: June 2012

Background

Haemophilus influenzae infection of the nasal epithelium has long been associated with observations of decreased nasal ciliary beat frequency (CBF) and injury to the ciliated epithelium. Previously, we have reported that several agents that slow CBF also have the effect of activating protein kinase C epsilon (PKCϵ) activity in bronchial epithelial cells. The subsequent auto-downregulation of PKCϵ or the direct inhibition of PKCϵ leads to the specific detachment of the ciliated cells. METHODS: Primary cultures of ciliated bovine bronchial epithelial cells were exposed to filtered conditioned media supernatants from non-typeable H. influenzae (NTHi) cultures. CBF and motile points were measured and PKCϵ activity assayed.

Results

NTHi supernatant exposure significantly and rapidly decreased CBF in a dose-dependent manner within 10 minutes of exposure. After 3 hours of exposure, the number of motile ciliated cells significantly decreased. Direct measurement of PKCϵ activity revealed a dose-dependent activation of PKCϵ in response to NTHi supernatant exposure. Both CBF and PKCϵ activity changes were only observed in fresh NTHi culture supernatant and not observed in exposures to heat-inactivated or frozen supernatants.

Conclusions

Our results suggest that CBF slowing observed in response to NTHi is consistent with the stimulated activation of PKCϵ. Ciliated cell detachment is associated with PKCϵ autodownregulation.
RUNX2 tandem repeats and the evolution of facial length in placental mammals
Authors: Pointer Marie A , Kamilar Jason M , Warmuth Vera , Chester Stephen G B , Delsuc Frédéric , Mundy Nicholas I , Asher Robert J , Bradley Brenda J
Published: June 2012

Background

When simple sequence repeats are integrated into functional genes, they can potentially act as evolutionary ‘tuning knobs’, supplying abundant genetic variation with minimal risk of pleiotropic deleterious effects. The genetic basis of variation in facial shape and length represents a possible example of this phenomenon. Runt-related transcription factor 2 (RUNX2), which is involved in osteoblast differentiation, contains a functionally-important tandem repeat of glutamine and alanine amino acids. The ratio of glutamines to alanines (the QA ratio) in this protein seemingly influences the regulation of bone development. Notably, in domestic breeds of dog, and in carnivorans in general, the ratio of glutamines to alanines is strongly correlated with facial length.

Results

In this study we examine whether this correlation holds true across placental mammals, particularly those mammals for which facial length is highly variable and related to adaptive behavior and lifestyle (e.g., primates, afrotherians, xenarthrans). We obtained relative facial length measurements and RUNX2 sequences for 41 mammalian species representing 12 orders. Using both a phylogenetic generalized least squares model and a recently-developed Bayesian comparative method, we tested for a correlation between genetic and morphometric data while controlling for phylogeny, evolutionary rates, and divergence times. Non-carnivoran taxa generally had substantially lower glutamine-alanine ratios than carnivorans (primates and xenarthrans with means of 1.34 and 1.25, respectively, compared to a mean of 3.1 for carnivorans), and we found no correlation betweenRUNX2sequence and face length across placental mammals.

Conclusions

Results of our diverse comparative phylogenetic analyses indicate that QA ratio does not consistently correlate with face length across the 41 mammalian taxa considered. Thus, although RUNX2 might function as a ‘tuning knob’ modifying face length in carnivorans, this relationship is not conserved across mammals in general.
Phylogeography of Camellia taliensis (Theaceae) inferred from chloroplast and nuclear DNA: insights into evolutionary history and conservation
Authors: Liu Yang , Yang Shi-xiong , Ji Peng-zhang , Gao Li-zhi
Published: June 2012

Background

As one of the most important but seriously endangered wild relatives of the cultivated tea,Camellia taliensisharbors valuable gene resources for tea tree improvement in the future. The knowledge of genetic variation and population structure may provide insights into evolutionary history and germplasm conservation of the species.

Results

Here, we sampled 21 natural populations from the species' range in China and performed the phylogeography ofC. taliensisby using the nuclearPALgene fragment and chloroplastrpl32-trnLintergenic spacer. Levels of haplotype diversity and nucleotide diversity detected atrpl32-trnL(h = 0.841;π = 0.00314) were almost as high as atPAL(h = 0.836;π = 0.00417). Significant chloroplast DNA population subdivision was detected (GST = 0.988;NST = 0.989), suggesting fairly high genetic differentiation and low levels of recurrent gene flow through seeds among populations. Nested clade phylogeographic analysis of chlorotypes suggests that population genetic structure inC. taliensishas been affected by habitat fragmentation in the past. However, the detection of a moderate nrDNA population subdivision (GST = 0.222;NST = 0.301) provided the evidence of efficient pollen-mediated gene flow among populations and significant phylogeographical structure (NST > GST;P < 0.01). The analysis ofPALhaplotypes indicates that phylogeographical pattern of nrDNA haplotypes might be caused by restricted gene flow with isolation by distance, which was also supported by Mantel’s test of nrDNA haplotypes (r = 0.234,P < 0.001). We found that chlorotype C1 was fixed in seven populations of Lancang River Region, implying that the Lancang River might have provided a corridor for the long-distance dispersal of the species.

Conclusions

We found thatC. taliensisshowed fairly high genetic differentiation resulting from restricted gene flow and habitat fragmentation. This phylogeographical study gives us deep insights into population structure of the species and conservation strategies for germplasm sampling and developingin situconservation of natural populations.
Whole-genome in-silico subtractive hybridization (WISH) - using massive sequencing for the identification of unique and repetitive sex-specific sequences: the example of Schistosoma mansoni
Authors: Portela Julien , Grunau Christoph , Cosseau Céline , Beltran Sophie , Dantec Christelle , Parrinello Hugues , Boissier Jérôme
Published: June 2012

Background

Emerging methods of massive sequencing that allow for rapid re-sequencing of entire genomes at comparably low cost are changing the way biological questions are addressed in many domains. Here we propose a novel method to compare two genomes (genome-to-genome comparison). We used this method to identify sex-specific sequences of the human blood fluke Schistosoma mansoni.

Results

Genomic DNA was extracted from male and female (heterogametic) S. mansoni adults and sequenced with a Genome Analyzer (Illumina). Sequences are available at the NCBI sequence read archive http://www.ncbi.nlm.nih.gov/Traces/sra/ under study accession number SRA012151.6. Sequencing reads were aligned to the genome, and a pseudogenome composed of known repeats. Straightforward comparative bioinformatics analysis was performed to compare male and female schistosome genomes and identify female-specific sequences. We found that the S. mansoni female W chromosome contains only few specific unique sequences (950 Kb i.e. about 0.2% of the genome). The majority of W-specific sequences are repeats (10.5 Mb i.e. about 2.5% of the genome). Arbitrarily selected W-specific sequences were confirmed by PCR. Primers designed for unique and repetitive sequences allowed to reliably identify the sex of both larval and adult stages of the parasite.

Conclusion

Our genome-to-genome comparison method that we call "whole-genome in-silico subtractive hybridization" (WISH) allows for rapid identification of sequences that are specific for a certain genotype (e.g. the heterogametic sex). It can in principle be used for the detection of any sequence differences between isolates (e.g. strains, pathovars) or even closely related species.
Elucidation of the molecular envenomation strategy of the cone snail Conus geographus through transcriptome sequencing of its venom duct
Authors: Hu Hao , Bandyopadhyay Pradip K , Olivera Baldomero M , Yandell Mark
Published: June 2012

Background

The fish-hunting cone snail, Conus geographus, is the deadliest snail on earth. In the absence of medical intervention, 70% of human stinging cases are fatal. Although, its venom is known to consist of a cocktail of small peptides targeting different ion-channels and receptors, the bulk of its venom constituents, their sites of manufacture, relative abundances and how they function collectively in envenomation has remained unknown.

Results

We have used transcriptome sequencing to systematically elucidate the contents the C. geographus venom duct, dividing it into four segments in order to investigate each segment’s mRNA contents. Three different types of calcium channel (each targeted by unrelated, entirely distinct venom peptides) and at least two different nicotinic receptors appear to be targeted by the venom. Moreover, the most highly expressed venom component is not paralytic, but causes sensory disorientation and is expressed in a different segment of the venom duct from venoms believed to cause sensory disruption. We have also identified several new toxins of interest for pharmaceutical and neuroscience research.

Conclusions

Conus geographus is believed to prey on fish hiding in reef crevices at night. Our data suggest that disorientation of prey is central to its envenomation strategy. Furthermore, venom expression profiles also suggest a sophisticated layering of venom-expression patterns within the venom duct, with disorientating and paralytic venoms expressed in different regions. Thus, our transcriptome analysis provides a new physiological framework for understanding the molecular envenomation strategy of this deadly snail.
Characterization of Mycobacterium tuberculosis Beijing isolates from the Mediterranean area
Authors: Alonso M , Alonso Rodriguez N , Garzelli C , Martínez Lirola M , Herranz M , Samper S , Ruiz Serrano MJ , Bouza E , García de Viedma D
Published: June 2012

Background

The Beijing lineage ofMycobacterium tuberculosisis causing concern due to its global distribution and its involvement in severe outbreaks. Studies focused on this lineage are mainly restricted to geographical settings where its prevalence is high, whereas those in other areas are scarce. In this study, we analyze Beijing isolates in the Mediterranean area, where this lineage is not prevalent and is mainly associated with immigrant cases.

Results

Only 1% (N = 26) of the isolates from two population-based studies in Spain corresponded to Beijing strains, most of which were pan-susceptible and from Peruvian and Ecuadorian patients. Restriction fragment length polymorphism typing with the insertion sequence IS6110identified three small clusters (2-3 cases). Mycobacterial interspersed repetitive unit-variable number tandem repeat typing (MIRU-15) offered low discriminatory power, requiring the introduction of five additional loci. A selection of the Beijing isolates identified in the Spanish sample, together with a sample of Beijing strains from Italy, to broaden the analysis context in the Mediterranean area, were assayed in an infection model with THP-1 cells. A wide range of intracellular growth rates was observed with only two isolates showing an increased intracellular replication, in both cases associated with contained production of TNF-α. No correlation was observed between virulence and the Beijing phylogenetic group, clustered/orphan status, or resistance. The Beijing strain responsible for extensive spread on Gran Canaria Island was also identified in Madrid, but did not lead to secondary cases and did not show high infectivity in the infection model.

Conclusions

The Beijing lineage in our area is a non-homogeneous family, with only certain highly virulent representatives. The specific characterization of Beijing isolates in different settings could help us to accurately identify the virulent representatives before making general assumptions about this lineage.
Cloning, expression and characterization of an aryl-alcohol dehydrogenase from the white-rot fungus Phanerochaete chrysosporium strain BKM-F-1767
Authors: Yang Dong-Dong , François Jean Marie , de Billerbeck Gustavo M
Published: June 2012

Background

The white-rot fungus Phanerochaete chrysosporium is among the small group of fungi that can degrade lignin to carbon dioxide while leaving the crystalline cellulose untouched. The efficient lignin oxidation system of this fungus requires cyclic redox reactions involving the reduction of aryl-aldehydes to the corresponding alcohols by aryl-alcohol dehydrogenase. However, the biochemical properties of this enzyme have not been extensively studied. These are of most interest for the design of metabolic engineering/synthetic biology strategies in the field of biotechnological applications of this enzyme.

Results

We report here the cloning of an aryl-alcohol dehydrogenase cDNA from the white-rot fungus Phanerochaete chrysosporium, its expression in Escherichia coli and the biochemical characterization of the encoded GST and His6 tagged protein. The purified recombinant enzyme showed optimal activity at 37°C and at pH 6.4 for the reduction of aryl- and linear aldehydes with NADPH as coenzyme. NADH could also be the electron donor, while having a higher Km (220 μM) compared to that of NADPH (39 μM). The purified recombinant enzyme was found to be active in the reduction of more than 20 different aryl- and linear aldehydes showing highest specificity for mono- and dimethoxylated Benzaldehyde at positions 3, 4, 3,4 and 3,5. The enzyme was also capable of oxidizing aryl-alcohols with NADP + at 30°C and an optimum pH of 10.3 but with 15 to 100-fold lower catalytic efficiency than for the reduction reaction.

Conclusions

In this work, we have characterized the biochemical properties of an aryl-alcohol dehydrogenase from the white-rot fungus Phanerochaete chrysosporium. We show that this enzyme functions in the reductive sense under physiological conditions and that it displays relatively large substrate specificity with highest activity towards the natural compound Veratraldehyde.
Characterization of non-host resistance in broad bean to the wheat stripe rust pathogen
Authors: Cheng Yulin , Zhang Hongchang , Yao Juanni , Wang Xiaojie , Xu Jinrong , Han Qingmei , Wei Guorong , Huang Lili , Kang Zhensheng
Published: June 2012

Background

Non-host resistance (NHR) confers plant species immunity against the majority of microbial pathogens and represents the most robust and durable form of plant resistance in nature. As one of the main genera of rust fungi with economic and biological importance, Puccinia infects almost all cereals but is unable to cause diseases on legumes. Little is known about the mechanism of this kind of effective defense in legumes to these non-host pathogens.

Results

In this study, the basis of NHR in broad bean (Vicia faba L.) against the wheat stripe rust pathogen, Puccinia striiformis f. sp. tritici (Pst), was characterized. No visible symptoms were observed on broad bean leaves inoculated with Pst. Microscopic observations showed that successful location of stomata and haustoria formation were significantly reduced in Pst infection of broad bean. Attempted infection induced the formation of papillae, cell wall thickening, production of reactive oxygen species, callose deposition and accumulation of phenolic compounds in plant cell walls. The few Pst haustoria that did form in broad bean cells were encased in reactive oxygen and callose materials and those cells elicited cell death. Furthermore, a total of seven defense-related genes were identified and found to be up-regulated during the Pst infection.

Conclusions

The results indicate that NHR in broad bean against Pst results from a continuum of layered defenses, including basic incompatibility, structural and chemical strengthening of cell wall, posthaustorial hypersensitive response and induction of several defense-related genes, demonstrating the multi-layered feature of NHR. This work also provides useful information for further determination of resistance mechanisms in broad bean to rust fungi, especially the adapted important broad bean rust pathogen, Uromyces viciae-fabae, because of strong similarity and association between NHR of plants to unadapted pathogens and basal resistance of plants to adapted pathogens.
Impact of community-acquired paediatric rotavirus gastroenteritis on family life: data from the REVEAL study
Authors: Van der Wielen Marie , Giaquinto Carlo , Gothefors Leif , Huelsse Christel , Huet Frédéric , Littmann Martina , Maxwell Melanie , Talayero José MP , Todd Peter , Vila Miguel T , Cantarutti Luigi , Van Damme Pierre ,   the REVEAL Study Group
Published: June 2012

Background

Rotavirus is the leading cause of acute gastroenteritis (AGE) and the most frequent cause of severe diarrhoea in children aged less than 5 years. Although the epidemiology of rotavirus gastroenteritis (RVGE) is well documented, there are few data on the impact of RVGE on the families of affected children.

Methods

Data associated with the burden of RVGE, including number of working days lost, levels of parental stress, the need for alternative childcare arrangements and additional nappies used, were extracted from questionnaires completed by parents of children participating in a prospective, multicentre, observational study (Rotavirus gastroenteritis Epidemiology and Viral types in Europe Accounting for Losses in public health and society, REVEAL), conducted during 2004-2005 in selected areas of Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom to estimate the incidence of RVGE in children aged less than 5 years seeking medical care as a result of AGE.

Results

1102 children with RVGE were included in the present analysis. The proportion of RVGE cases that required at least one parent or other person to be absent from work was 39%-91% in the hospital setting, 44%-64% in the emergency department, and 20%-64% in primary care. Self-reported levels of parental stress were generally high (mean stress levels, ≥ 5 on a 10-point visual analogue scale). Additional childcare arrangements were required in up to 21% of RVGE episodes. The mean number of nappies used per day during RVGE episodes was approximately double that used when the child was not ill.

Conclusions

Paediatric RVGE cases cause disruption to families and parental stress. The burden of RVGE on children and their families could be substantially reduced by routine rotavirus vaccination of infants.
One third of middle ear effusions from children undergoing tympanostomy tube placement had multiple bacterial pathogens
Authors: Holder Robert C , Kirse Daniel J , Evans Adele K , Peters Timothy R , Poehling Katherine A , Swords W Edward , Reid Sean D
Published: June 2012

Background

Because previous studies have indicated that otitis media may be a polymicrobial disease, we prospectively analyzed middle ear effusions of children undergoing tympanostomy tube placement with multiplex polymerase chain reaction for four otopathogens.

Methods

Middle ear effusions from 207 children undergoing routine tympanostomy tube placement were collected and were classified by the surgeon as acute otitis media (AOM) for purulent effusions and as otitis media with effusion (OME) for non-purulent effusions. DNA was isolated from these samples and analyzed with multiplex polymerase chain reaction for Haemophilus influenzae, Streptococcus pneumoniae, Alloiococcus otitidis, and Moraxella catarrhalis.

Results

119 (57%) of 207 patients were PCR positive for at least one of these four organisms. 36 (30%) of the positive samples indicated the presence of more than one bacterial species. Patient samples were further separated into 2 groups based on clinical presentation at the time of surgery. Samples were categorized as acute otitis media (AOM) if pus was observed behind the tympanic membrane. If no pus was present, samples were categorized as otitis media with effusion (OME). Bacteria were identified in most of the children with AOM (87%) and half the children with OME (51%, p < 0.001). A single bacterial organism was detected in middle ear effusions from children with AOM more often than those with OME (74% versus 33%, p < 0.001). Haemophilus influenzae was the predominant single organism and caused 58% of all AOM in this study. Alloiococcus otitidis and Moraxella catarrhalis were more frequently identified in middle ear effusions than Streptococcus pneumoniae.

Conclusions

Haemophilus influenzae, Streptococcus pneumoniae, Alloiococcus otitidis, and Moraxella catarrhalis were identified in the middle ear effusions of some patients with otitis media. Overall, we found AOM is predominantly a single organism infection and most commonly from Haemophilus influenzae. In contrast, OME infections had a more equal distribution of single organisms, polymicrobial entities, and non-bacterial agents.
An unsupervised machine learning method for assessing quality of tandem mass spectra
Authors: Lin Wenjun , Wang Jianxin , Zhang Wen-Jun , Wu Fang-Xiang
Published: June 2012

Background

In a single proteomic project, tandem mass spectrometers can produce hundreds of millions of tandem mass spectra. However, majority of tandem mass spectra are of poor quality, it wastes time to search them for peptides. Therefore, the quality assessment (before database search) is very useful in the pipeline of protein identification via tandem mass spectra, especially on the reduction of searching time and the decrease of false identifications. Most existing methods for quality assessment are supervised machine learning methods based on a number of features which describe the quality of tandem mass spectra. These methods need the training datasets with knowing the quality of all spectra, which are usually unavailable for the new datasets.

Results

This study proposes an unsupervised machine learning method for quality assessment of tandem mass spectra without any training dataset. This proposed method estimates the conditional probabilities of spectra being high quality from the quality assessments based on individual features. The probabilities are estimated through a constraint optimization problem. An efficient algorithm is developed to solve the constraint optimization problem and is proved to be convergent. Experimental results on two datasets illustrate that if we search only tandem spectra with the high quality determined by the proposed method, we can save about 56 % and 62% of database searching time while losing only a small amount of high-quality spectra.

Conclusions

Results indicate that the proposed method has a good performance for the quality assessment of tandem mass spectra and the way we estimate the conditional probabilities is effective.
A framework for personalized medicine: prediction of drug sensitivity in cancer by proteomic profiling
Authors: Kim Dong-Chul , Wang Xiaoyu , Yang Chin-Rang , Gao Jean X
Published: June 2012

Background

The goal of personalized medicine is to provide patients optimal drug screening and treatment based on individual genomic or proteomic profiles. Reverse-Phase Protein Array (RPPA) technology offers proteomic information of cancer patients which may be directly related to drug sensitivity. For cancer patients with different drug sensitivity, the proteomic profiling reveals important pathophysiologic information which can be used to predict chemotherapy responses.

Results

The goal of this paper is to present a framework for personalized medicine using both RPPA and drug sensitivity (drug resistance or intolerance). In the proposed personalized medicine system, the prediction of drug sensitivity is obtained by a proposed augmented naive Bayesian classifier (ANBC) whose edges between attributes are augmented in the network structure of naive Bayesian classifier. For discriminative structure learning of ANBC, local classification rate (LCR) is used to score augmented edges, and greedy search algorithm is used to find the discriminative structure that maximizes classification rate (CR). Once a classifier is trained by RPPA and drug sensitivity using cancer patient samples, the classifier is able to predict the drug sensitivity given RPPA information from a patient.

Conclusion

In this paper we proposed a framework for personalized medicine where a patient is profiled by RPPA and drug sensitivity is predicted by ANBC and LCR. Experimental results with lung cancer data demonstrate that RPPA can be used to profile patients for drug sensitivity prediction by Bayesian network classifier, and the proposed ANBC for personalized cancer medicine achieves better prediction accuracy than naive Bayes classifier in small sample size data on average and outperforms other the state-of-the-art classifier methods in terms of classification accuracy.
Back mobility and interincisor distance ranges in racially diverse North American healthy children and relationship to generalized hypermobility
Authors: Woolston Sophie L , Beukelman Timothy , Sherry David D
Published: June 2012

Background

Given the dearth of normal values, we conducted a cross-sectional study of North American racially diverse children to determine normal values of interincisor distance and lower spine flexion.

Methods

Demographs of 307 children aged 5–17 seeking treatment emergency care were obtained along with interincisor distance measured by incisor tooth-to-tooth gap, lower spine flexion measured by the Schober and modified Schober measurements, popliteal extension, hypermobility (Beighton) score, weight and height.

Results

Normal range of motion values for the Schober was a mean of 14.3 cm (95% confidence interval (CI) was 11.2 to 17. cm) and the mean modified Schober’s was 21.6 cm (95% CI 18.4 cm to 24.8 cm). Retained lumbar lordosis on forward flexion was observed in 33%. Back mobility was associated with body mass index (BMI), popliteal angle, and Beighton score but not sex, race or retained lordosis. The mean interincisor distance measurement was 47 mm (95% CI 35 mm to 60 mm) and was associated with height and BMI but not sex, race, or Beighton score.

Conclusion

Normal values for lower back range of motion and interincisor distance were obtained which are needed in pediatric rheumatologic clinics and do not significantly vary as to race or sex. Retained lordosis on forward flexion is a normal variant. Hamstring tightness, hypermobility and BMI need to be considered when ascertaining back mobility.
In vivo USPIO Magnetic Resonance Imaging Shows That Minocycline Mitigates Macrophage Recruitment to a Peripheral Nerve Injury
Authors: Ghanouni Pejman , Behera Deepak , Xie Jin , Chen Xiaoyuan , Moseley Michael , Biswal Sandip
Published: June 2012

Background:

Minocycline has proven anti-nociceptive effects, but the mechanism by which minocycline delays the development of allodynia and hyperalgesia after peripheral nerve injury remains unclear. Inflammatory cells, in particular macrophages, are critical components of the response to nerve injury. Using ultrasmall superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI) to monitor macrophage trafficking, the purpose of this project is to determine whether minocycline modulates macrophage trafficking to the site of nerve injury in vivo and, in turn, results in altered pain thresholds.

Results:

Animal experiments were approved by Stanford IACUC. A model of neuropathic pain was created using the Spared Nerve Injury (SNI) model that involves ligation of the left sciatic nerve in the left thigh of adult Sprague–Dawley rats. Animals with SNI and uninjured animals were then injected with/without USPIOs (300 μmol/kg IV) and with/without minocycline (50 mg/kg IP). Bilateral sciatic nerves were scanned with a volume coil in a 7 T magnet 7 days after USPIO administration. Fluid-sensitive MR images were obtained, and ROIs were placed on bilateral sciatic nerves to quantify signal intensity. Pain behavior modulation by minocycline was measured using the Von Frey filament test. Sciatic nerves were ultimately harvested at day 7, fixed in 10% buffered formalin and stained for the presence of iron oxide-laden macrophages. Behavioral measurements confirmed the presence of allodynia in the neuropathic pain model while the uninjured and minocycline-treated injured group had significantly higher paw withdrawal thresholds (p<0.011). Decreased MR signal is observed in the SNI group that received USPIOs (3.3+/−0.5%) compared to the minocycline-treated SNI group that received USPIOs (15.2+/−4.5%) and minocycline-treated group that did not receive USPIOs (41.2 +/−2.3%) (p<0.04). Histology of harvested sciatic nerve specimens confirmed the presence USPIOs at the nerve injury site in the SNI group without minocycline treatment.

Conclusion:

Animals with neuropathic pain in the left hindpaw show increased trafficking of USPIO-laden macrophages to the site of sciatic nerve injury. Minocycline to retards the migration of macrophages to the nerve injury site, which may partly explain its anti-nociceptive effects. USPIO-MRI is an effective in vivo imaging tool to study the role of macrophages in the development of neuropathic pain.
Incorporating breath holding and image guidance in the adjuvant gastric cancer radiotherapy: a dosimetric study
Authors: Hu Weigang , Ye Jinsong , Wang Jiazhou , Xu Qing , Zhang Zhen
Published: June 2012

Background

The respiratory related target motion and setup error will lead to a large margin in the gastric radiotherapy. The purpose of this study is to investigate the dosimetric benefit and the possibility of incorporating the breath-hold (BH) technique with online image-guided radiotherapy in the adjuvant gastric cancer radiotherapy.

Methods

Setup errors and target motions of 22 post-operative gastric cancer patients with surgical clips were analyzed. Clips movement was recorded using the digital fluoroscopics and the probability distribution functions (pdf) of the target motions were created for both the free breathing (FB) and BH treatment. For dosimetric comparisons, two intensity-modulated radiotherapy (IMRT) treatment plans, i.e. the free breathing treatment plan (IMRTFB) and the image-guided BH treatment plan (IMRTIGBH) using the same beam parameters were performed among 6 randomly selected patients. Different margins for FB and BH plans were derived. The plan dose map was convoluted with various pdfs of the setup errors and the target motions. Target coverage and dose to organs at risk were compared and the dose-escalation probability was assessed.

Results

The mean setup errors were 1.2 mm in the superior-inferior (SI), 0.0 mm in the left-right (LR), and 1.4 mm in the anterior-posterior (AP) directions. The mean target motion for the free breathing (vs. BH) was 11.1 mm (vs. 2.2 mm), 1.9 mm (vs. 1.1 mm), and 5.5 mm (vs. 1.7 mm) in the SI, LR, and AP direction, respectively. The target coverage was comparable for all the original plans. IMRTIGBH showed lower dose to the liver compared with IMRTFB (p = 0.01) but no significant difference in the kidneys. Convolved IMRTIGBH showed better sparing in kidneys (p < 0.01) and similar in liver (p = 0.08).

Conclusions

Combining BH technique with online image guided IMRT can minimize the organ motion and improve the setup accuracy. The dosimetric comparison showed the dose could be escalated to 54 Gy without increasing the critical organs toxicities, although further clinical data is needed.
In-vivo glenohumeral translation and ligament elongation during abduction and abduction with internal and external rotation
Authors: Massimini Daniel F , Boyer Patrick J , Papannagari Ramprasad , Gill Thomas J , Warner Jon P , Li Guoan
Published: June 2012

Study Design

Basic Science. To investigate humeral head translations and glenohumeral ligament elongation with a dual fluoroscopic imaging system.

Background

The glenohumeral ligaments are partially responsible for restraining the humeral head during the extremes of shoulder motion. However, in-vivo glenohumeral ligaments elongation patterns have yet to be determined. Therefore, the objectives of this study were to 1) quantify the in-vivo humeral head translations and glenohumeral ligament elongations during functional shoulder positions, 2) compare the inferred glenohumeral ligament functions with previous literature and 3) create a baseline data of healthy adult shoulder glenohumeral ligament lengths as controls for future studies.

Methods

Five healthy adult shoulders were studied with a validated dual fluoroscopic imaging system (DFIS) and MR imaging technique. Humeral head translations and the superior, middle and inferior glenohumeral ligaments (SGHL, MGHL, IGHL) elongations were determined.

Results

The humeral head center on average translated in a range of 6.0mm in the anterior-posterior direction and 2.5mm in the superior-inferior direction. The MGHL showed greater elongation over a broader range of shoulder motion than the SGHL. The anterior-band (AB)-IGHL showed maximum elongation at 90° abduction with maximum external rotation. The posterior-band (PB)-IGHL showed maximum elongation at 90° abduction with maximum internal rotation.

Discussion

The results demonstrated that the humeral head translated statistically more in the anterior-posterior direction than the superior-inferior direction (p = 0.01), which supports the concept that glenohumeral kinematics are not ball-in-socket mechanics. The AB-IGHL elongation pattern makes it an important static structure to restrain anterior subluxation of the humeral head during the externally rotated cocking phase of throwing motion. These data suggest that in healthy adult shoulders the ligamentous structures of the glenohumeral joint are not fully elongated in many shoulder positions, but function as restraints at the extremes of glenohumeral motion. Clinically, these results may be helpful in restoring ligament anatomy during the treatment of anterior instability of the shoulder.
Robinsoniella peoriensis infection following surgery for scoliosis: a case report
Authors: Cassir Nadim , Laget Laurine , Renvoisé Aurélie , Gennari Jean-Marie , Drancourt Michel
Published: June 2012

Introduction

Robinsoniella peoriensis was recently identified as a Gram-positive, spore-forming, anaerobic bacillus originally isolated from swine manure storage pits. Seven isolates have been subsequently reported from human sources.

Case presentation

We report the case of an infection caused by R. peoriensis in a 45-year-old Caucasian woman after posterior instrumentation correction of idiopathic thoracolumbar scoliosis. The identification was made by culture of samples inoculated onto blood agar and chocolate agar and was confirmed by 16 S ribosomal ribonucleic acid gene sequencing.

Conclusions

We discuss similar cases suggesting that R. peoriensis is responsible for health care-associated infections with the colonic flora as a potential source of infection.
Comparison of the dosimetries of 3-dimensions Radiotherapy (3D-RT) with linear accelerator and intensity modulated radiotherapy (IMRT) with helical tomotherapy in children irradiated for neuroblastoma
Authors: Beneyton Violaine , Niederst Claudine , Vigneron Céline , Meyer Philippe , Becmeur François , Marcellin Luc , Lutz Patrick , Noel Georges
Published: June 2012

Background

Intensity modulated radiotherapy is an efficient radiotherapy technique to increase dose in target volumes and decrease irradiation dose in organs at risk. This last objective is mainly relevant in children. However, previous results suggested that IMRT could increase low dose, factor of risk for secondary radiation induced cancer. This study was performed to compare dose distributions with 3D-radiotherapy (3D-RT) and IMRT with tomotherapy (HT) in children with neuroblastoma. Seven children with neuroblastoma were irradiated. Treatment plans were calculated for 3D-RT, and for HT. For the volume of interest, the PTV-V95% and conformity index were calculated. Dose constraints of all the organs at risk and integral dose were compared.

Results

The conformity index was statistically better for HT than for 3D-RT. PTV-V95% constraint was reached in 6 cases with HT compared to 2 cases with 3D-RT. For the ipsilateral kidney of the tumor, the V12 Gy constraint was reached for 3 patients with both methods. The values were lower with HT than with 3D-RT in two cases and higher in one case. The threshold was not reached for one patient with either technique, but the value was lower with HT than with 3D-RT. For the contralateral kidney of the tumors, the V12 Gy constraint was reached for all patients with both methods. The values were lower with HT than with 3D-RT in 5 of 7 children, equal in one patient and higher in one patient. The organ-at-risk volumes receiving low doses were significantly lower with 3D-RT but larger for the highest doses, compared to those irradiated with HT. The integral doses were not different.

Conclusions

IMRT with HT allows a better conformity treatment, a more frequently acceptable PTV-V95% than 3D-RT and, concomitantly, a better shielding of the kidneys. The integral doses are comparable between both techniques but consideration of differences in dose distribution between the two techniques, for the organs at risk, has to be taken in account when validating treatment.
Cytoreduction surgery reduces systemic myeloid suppressor cell populations and restores intratumoral immunotherapy effectiveness
Authors: Predina Jarrod D , Kapoor Veena , Judy Brendan F , Cheng Guanjun , Fridlender Zvi Gregory , Albelda Steven M , Singhal Sunil
Published: June 2012

Background

Multiple immunotherapy approaches have improved adaptive anti-tumor immune responses in patients with early stage disease; however, results have been less dramatic when treating patients with late stage disease. These blunted responses are likely due to a host of factors, including changes in the tumor microenvironment and systemic immunosuppressive features, which accompany advanced tumor states. We hypothesized that cytoreductive surgery could control these immunosuppressive networks and restore the potency of immunotherapy in advanced disease scenarios.

Methods

To test these hypotheses, two representative intratumoral immunotherapies (an adenoviral vector encoding a suicide gene, AdV-tk, or a type-I interferon, Ad.IFNα) were tested in murine models of lung cancer. Cytoreductive surgery was performed following treatment of advanced tumors. Mechanistic underpinnings were investigated using flow cytometry, in vivo leukocyte depletion methods and in vivo tumor neutralization assays.

Results

AdV-tk and Ad.IFNα were effective in treating early lung cancers, but had little anti-tumor effects in late stage cancers. Interestingly, in late stage scenarios, surgical cytoreduction unmasked the anti-tumor potency of both immunotherapeutic approaches. Immune mechanisms that explained restoration in anti-tumor immune responses included increased CD8 T-cell trafficking and reduced myeloid derived suppressor cell populations.

Conclusion

This study demonstrates that surgical resection combined with immunotherapy may be a rational therapeutic option for patients with advanced stage cancer.
Testing for amphetamine-type stimulant (ATS) use to ascertain validity of self-reported ATS use among young female sex workers in Cambodia
Authors: Kab Vannda , Evans Jennifer , Sansothy Neth , Stein Ellen , Claude-Couture Marie , Maher Lisa , Page Kimberly
Published: June 2012

Objective

To assess concordance between self-reported amphetamine-type stimulant (ATS) use and toxicology results among young female sex workers (FSW) in Phnom Penh, Cambodia.

Methods

Cross-sectional data from the Young Women’s Health Study-2 (YWHS-2), a prospective study of HIV and ATS use among young (15 to 29 years) FSW in Phnom Penh, Cambodia, was analyzed. The YWHS-2 assessed sociodemographic characteristics, HIV serology, HIV risk, and ATS use by self-report and urine toxicology testing at each quarterly visit, the second of which provided data for this assessment. Outcomes include sensitivity, specificity, positive- and negative predictive values (overall and stratified by age), sex-work setting, and HIV status.

Results

Among 200 women, prevalence of positive toxicology screening for ATS use was 14% (95% confidence interval [CI], 9.2, 18.9%) and concurrent prevalence of self-reported ATS was 15.5% (95% CI, 10.4, 20.6%). The sensitivity and specificity of self-reported ATS use compared to positive toxicology test results was 89.3% (25/28), and 96.5% (166/172), respectively. The positive predictive value of self-reported ATS use was 80.6% (25/31); the negative predictive value was 98.2% (166/169). Some differences in concordance between self-report and urine toxicology results were noted in analyses stratified by age group and sex-work setting but not by HIV status.

Conclusion

Results indicate a high prevalence of ATS use among FSW in Phnom Penh, Cambodia, and high concordance between self-reported and toxicology-test confirmed ATS use.
Mental health outcomes in HIV and childhood maltreatment: a systematic review
Authors: Spies Georgina , Afifi Tracie O , Archibald Sarah L , Fennema-Notestine Christine , Sareen Jitender , Seedat Soraya
Published: June 2012

Background

High rates of childhood maltreatment have been documented in HIV-positive men and women. In addition, mental disorders are highly prevalent in both HIV-infected individuals and victims of childhood maltreatment. However, there is a paucity of research investigating the mental health outcomes associated with childhood maltreatment in the context of HIV infection. The present systematic review assessed mental health outcomes in HIV-positive individuals who were victims of childhood maltreatment.

Methods

A systematic search of all retrospective, prospective, or clinical trial studies assessing mental health outcomes associated with HIV and childhood maltreatment. The following online databases were searched on 25–31 August 2010: PubMed, Social Science Citation Index, and the Cochrane Library (the Cochrane Central Register of Controlled Trials and the Cochrane Developmental, Psychosocial and Learning Problems, HIV/AIDS, and Depression, Anxiety and Neurosis registers).

Results

We identified 34 studies suitable for inclusion. A total of 14,935 participants were included in these studies. A variety of mixed mental health outcomes were reported. The most commonly reported psychiatric disorders among HIV-positive individuals with a history of childhood maltreatment included: substance abuse, major depressive disorder, and posttraumatic stress disorder. An association between childhood maltreatment and poor adherence to antiretroviral regimens was also reported in some studies.

Conclusion

A broad range of adult psychopathology has been reported in studies of HIV-infected individuals with a history of childhood maltreatment. However, a direct causal link cannot be well established. Longer term assessment will better delineate the nature, severity, and temporal relationship of childhood maltreatment to mental health outcomes.
Prediction of cardiac arrest in critically ill patients presenting to the emergency department using a machine learning score incorporating heart rate variability compared with the modified early warning score
Authors: Ong Marcus Eng Hock , Lee Ng Christina Hui , Goh Ken , Liu Nan , Koh Zhi Xiong , Shahidah Nur , Zhang Tong Tong , Fook-Chong Stephanie , Lin Zhiping
Published: June 2012

Introduction

A key aim of triage is to identify those with high risk of cardiac arrest, as they require intensive monitoring, resuscitation facilities, and early intervention. We aim to validate a novel machine learning (ML) score incorporating heart rate variability (HRV) for triage of critically ill patients presenting to the emergency department by comparing the area under the curve, sensitivity and specificity with the modified early warning score (MEWS).

Methods

We conducted a prospective observational study of critically ill patients (Patient Acuity Category Scale 1 and 2) in an emergency department of a tertiary hospital. At presentation, HRV parameters generated from a 5-minute electrocardiogram recording are incorporated with age and vital signs to generate the ML score for each patient. The patients are then followed up for outcomes of cardiac arrest or death.

Results

From June 2006 to June 2008 we enrolled 925 patients. The area under the receiver operating characteristic curve (AUROC) for ML scores in predicting cardiac arrest within 72 hours is 0.781, compared with 0.680 for MEWS (difference in AUROC: 0.101, 95% confidence interval: 0.006 to 0.197). As for in-hospital death, the area under the curve for ML score is 0.741, compared with 0.693 for MEWS (difference in AUROC: 0.048, 95% confidence interval: -0.023 to 0.119). A cutoff ML score ≥ 60 predicted cardiac arrest with a sensitivity of 84.1%, specificity of 72.3% and negative predictive value of 98.8%. A cutoff MEWS ≥ 3 predicted cardiac arrest with a sensitivity of 74.4%, specificity of 54.2% and negative predictive value of 97.8%.

Conclusion

We found ML scores to be more accurate than the MEWS in predicting cardiac arrest within 72 hours. There is potential to develop bedside devices for risk stratification based on cardiac arrest prediction.