bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple electrolyte disorders in a neurosurgical patient: solving the rebus
Authors: Corradetti Valeria , Esposito Pasquale , Rampino Teresa , Gregorini Marilena , Libetta Carmelo , Bosio Francesca , Valsania Teresa , Pattonieri Eleonora Francesca , Rocca Chiara , Bianzina Stefania , Dal Canton Antonio
Published: July 2013

Background

It is important to ensure an adequate sodium and volume balance in neurosurgical patients in order to avoid the worsening of brain injury.

Indeed, hyponatremia and polyuria, that are frequent in this patient population, are potentially harmful, especially if not promptly recognized.

Differential diagnosis is often challenging, including disorders, which, in view of similar clinical pictures, present very different pathophysiological bases, such as syndrome of inappropriate antidiuresis, cerebral/renal salt wasting syndrome and diabetes insipidus.

Case presentation

Here we present the clinical report of a 67-year-old man with a recent episode of acute subarachnoid haemorrhage, admitted to our ward because of severe hyponatremia, hypokalemia and huge polyuria.

We performed a complete workup to identify the underlying causes of these alterations and found a complex picture of salt wasting syndrome associated to primary polydipsia. The appropriate diagnosis allowed us to correct the patient hydro-electrolyte balance.

Conclusion

The comprehension of the pathophysiological mechanisms is essential to adequately recognize and treat hydro-electrolyte disorders, also solving the most complex clinical problems.
Wāhine hauora: linking local hospital and national health information datasets to explore maternal risk factors and obstetric outcomes of New Zealand Māori and non-Māori women in relation to infant respiratory admissions and timely immunisations
Authors: Filoche Sara , Garrett Susan , Stanley James , Rose Sally , Robson Bridget , Elley C Raina , Lawton Bev
Published: July 2013

Background

Significant health inequities exist around maternal and infant health for Māori, the indigenous people of New Zealand. The infants of Māori are more likely to die in their first year of life and also have higher rates of hospital admission for respiratory illnesses, with the greatest burden of morbidity being due to bronchiolitis in those under one year of age. Timely immunisations can prevent some respiratory related hospitalisations, although for Māori, the proportion of infants with age appropriate immunisations are lower than for non-Māori. This paper describes the protocol for a retrospective cohort study that linked local hospital and national health information datasets to explore maternal risk factors and obstetric outcomes in relation to respiratory admissions and timely immunisations for infants of Māori and non-Māori women.

Methods/Design

The study population included pregnant women who gave birth in hospital in one region of New Zealand between 1995 and 2009. Routinely collected local hospital data were linked via a unique identifier (National Health Index number) to national health information databases to assess rates of post-natal admissions and access to health services for Māori and non-Māori mothers and infants. The two primary outcomes for the study are: 1. The rates of respiratory hospitalisations of infants (≤ 1 yr of age) calculated for infants of both Māori and non-Māori women (for mothers under 20 years of age, and overall) accounting for relationship to parity, maternal age, socioeconomic deprivation index, maternal smoking status. 2. The proportion of infants with age appropriate immunisations at six and 12 months, calculated for both infants born to Māori women and infants born to non-Māori women, accounting for relationship to parity, maternal age, socioeconomic deprivation index, smoking status, and other risk factors.

Discussion

Analysis of a wide range of routinely collected health information in which maternal and infant data are linked will allow us to directly explore the relationship between key maternal factors and infant health, and provide a greater understanding of the causes of health inequalities that exist between the infants of Māori and non-Māori mothers.
Cost-effectiveness of MRI for breast cancer screening in BRCA1/2 mutation carriers
Authors: Pataky Reka , Armstrong Linlea , Chia Stephen , Coldman Andrew J , Kim-Sing Charmaine , McGillivray Barbara , Scott Jenna , Wilson Christine M , Peacock Stuart
Published: July 2013

Background

Women with mutations in BRCA1 or BRCA2 are at high risk of developing breast cancer and, in British Columbia, Canada, are offered screening with both magnetic resonance imaging (MRI) and mammography to facilitate early detection. MRI is more sensitive than mammography but is more costly and produces more false positive results. The purpose of this study was to calculate the cost-effectiveness of MRI screening for breast cancer in BRCA1/2 mutation carriers in a Canadian setting.

Methods

We constructed a Markov model of annual MRI and mammography screening for BRCA1/2 carriers, using local data and published values. We calculated cost-effectiveness as cost per quality-adjusted life-year gained (QALY), and conducted one-way and probabilistic sensitivity analysis.

Results

The incremental cost-effectiveness ratio (ICER) of annual mammography plus MRI screening, compared to annual mammography alone, was $50,900/QALY. After incorporating parameter uncertainty, MRI screening is expected to be a cost-effective option 86% of the time at a willingness-to-pay of $100,000/QALY, and 53% of the time at a willingness-to-pay of $50,000/QALY. The model is highly sensitive to the cost of MRI; as the cost is increased from $200 to $700 per scan, the ICER ranges from $37,100/QALY to $133,000/QALY.

Conclusions

The cost-effectiveness of using MRI and mammography in combination to screen for breast cancer in BRCA1/2 mutation carriers is finely balanced. The sensitivity of the results to the cost of the MRI screen itself warrants consideration: in jurisdictions with higher MRI costs, screening may not be a cost-effective use of resources, but improving the efficiency of MRI screening will also improve cost-effectiveness.
Dolosigranulum pigrum keratitis: a three-case series
Authors: Sampo Magali , Ghazouani Oaufeh , Cadiou Dominique , Trichet Elodie , Hoffart Louis , Drancourt Michel
Published: July 2013

Background

Dolosigranulum pigrum is a commensal inhabitant of the upper respiratory tract suspected to be responsible for ocular infections but no well-described case of D. pigrum corneal infection has been reported. Herein culture and PCR-sequencing-based investigations of corneal scraping specimens confirmed D. pigrum keratitis in three patients.

Case presentation

Three elderly patients presented with unilateral keratitis. None was a corneal-contact lens wearer, one had previous cataract surgery and another suffered rheumatoid arthritis sicca syndrome. Culturing the corneal scraping specimen was positive for two cases and PCR-sequencing of bacterial 16S rDNA in the presence of negative controls identified D. pigrum in three cases. The two D. pigrum isolates were in-vitro susceptible to penicillin G, amoxicillin, doxycycline, rifampicin and gentamicin. In all cases, surgical treatment of corneal thinning was necessary, but corneal perforation occurred in two cases despite intensive antimicrobial treatment with ticarcillin, gentamicin and vancomycin or levofloxacin eye drops leading to enucleation in one case.

Conclusions

D. pigrum is the likely cause of corneal infection in three patients, with effective antibiotic treatment in two patients.
Eyelid-associated complications after autogenous fat injection for cosmetic forehead augmentation
Authors: Paik Ji-Sun , Cho Won-Kyung , Park Gyeong-Sin , Yang Suk-Woo
Published: July 2013

Background

We report two cases of unilateral upper eyelid swelling with multiple small lumps as an unusual complication of autogenous fat injection for cosmetic forehead augmentation.

Case presentation

Two female patients were referred to our clinic for unusual unilateral eyelid swelling, with multiple small lumps. The duration of symptoms differed in each case, but both patients had a history of autogenous fat injection for cosmetic forehead augmentation at a local plastic surgery clinic. The lumps were small (diameter 5 mm~10 mm), palpable, hard, and nonmobile, and were evaluated by magnetic resonance imaging (MRI). Lumps from the eyelids of two patients were excised under general anesthesia. All of the masses were located deeply and found near the superior orbital rim or lateral orbital rim. The lumps exhibited chronic inflammation with fibrosis. Some of the lumps showed foamy histiocytic aggregation and foreign body lipogranuloma, resulting from iatrogenic fat injection. After excision, all masses and swelling disappeared, and moderate ptotic eyelid or lagophthalmos of affected eyes also improved.

Conclusions

To our knowledge, eyelid swelling with multiple lumps in the eyelid is a very rare complication of autogenous fat injection for cosmetic forehead augmentation. This report should be helpful for ophthalmic clinicians who encounter these unusual symptoms.
Assessment of phytochemicals, antimicrobial and cytotoxic activities of extract and fractions from Fagonia olivieri (Zygophyllaceae)
Authors: Rashid Umbreen , Khan Muhammad Rashid , Jan Shumaila , Bokhari Jasia , Shah Naseer Ali
Published: July 2013

Background

In Pakistan Fagonia olivieri (Zygophyllaceae) is commonly used in the indigenous system of medicine for treatment of conditions like diabetes, cancer, fever, asthma, toothache, stomach troubles and kidney disorders. This study evaluated the crude methanol extract of F. olivieri (FOM) and its derived fractions for their antimicrobial and cytotoxic activities as well as the classes of phytochemical.

Methods

Dried powder of whole plant of F. olivieri was extracted with methanol (FOM) and the resultant was fractionated to give n-hexane fraction (FOH), chloroform fraction (FOC), ethyl acetate fraction (FOE), n-butanol fraction (FOB) and residual aqueous fraction (FOA). Methanol extract and its derived fractions were subjected to phytochemical screening using standard procedures. Also the extract and fractions were assayed for antibacterial, antifungal and cytotoxic activities using agar well diffusion technique, agar tube dilution method and brine shrimps lethality test, respectively.

Results

The results obtained for phytochemical analysis indicate the presence of saponins and alkaloids in all the tested extract and fractions while anthraquinones were not detected. The results showed that all the bacterial strains tested in this study were susceptible to at least one of the fractions tested. However, FOE and FOB were the best antibacterial fractions and showed antibacterial activity against maximum number of bacterial strains. The results showed that Escherichia coli was the most sensitive bacterium while Bordetella bronchiseptica and Enterobacter aerogenes were less susceptible against various fractions. Maximum percent inhibition for growth was recorded for the fungus Aspergillus flavus with FOE whereas growth of Aspergillus fumigatus and Fusarium solani was inhibited by FOM and its all derived fractions. Minimum LC50 (24.07 mg/L) for brine shrimp assay was recorded for FOE followed by LC50 of FOC (26.1 mg/L) and FOB (30.05 mg/L) whereas maximum LC50 was exhibited by FOH (1533 mg/L).

Conclusion

These results indicated the use of F. olivieri to treat infections with emphasis to isolate and characterize the active principle responsible for antibacterial, antifungal and cytotoxic activities and its exploitation as therapeutic agent.
Biological evaluation of hydroxynaphthoquinones as anti-malarials
Authors: Schuck Desiree C , Ferreira Sabrina B , Cruz Laura N , da Rocha David R , Moraes Miriam S , Nakabashi Myna , Rosenthal Philip J , Ferreira Vitor F , Garcia Celia RS
Published: July 2013

Background

The hydroxynaphthoquinones have been extensively investigated over the past 50 years for their anti-malarial activity. One member of this class, atovaquone, is combined with proguanil in Malarone®, an important drug for the treatment and prevention of malaria.

Methods

Anti-malarial activity was assessed in vitro for a series of 3-alkyl-2-hydroxy-1,4-naphthoquinones (N1-N5) evaluating the parasitaemia after 48 hours of incubation. Potential cytotoxicity in HEK293T cells was assessed using the MTT assay. Changes in mitochondrial membrane potential of Plasmodium were measured using the fluorescent dye Mitrotracker Red CMXROS.

Results

Four compounds demonstrated IC50s in the mid-micromolar range, and the most active compound, N3, had an IC50 of 443 nM. N3 disrupted mitochondrial membrane potential, and after 1 hour presented an IC50ΔΨmit of 16 μM. In an in vitro cytotoxicity assay using HEK 293T cells N3 demonstrated no cytotoxicity at concentrations up to 16 μM.

Conclusions

N3 was a potent inhibitor of mitochondrial electron transport, had nanomolar activity against cultured Plasmodium falciparum and showed minimal cytotoxicity. N3 may serve as a starting point for the design of new hydroxynaphthoquinone anti-malarials.
Population pharmacokinetics of mefloquine, piperaquine and artemether-lumefantrine in Cambodian and Tanzanian malaria patients
Authors: Staehli Hodel Eva Maria , Guidi Monia , Zanolari Boris , Mercier Thomas , Duong Socheat , Kabanywanyi Abdunoor M , Ariey Frédéric , Buclin Thierry , Beck Hans-Peter , Decosterd Laurent A , Olliaro Piero , Genton Blaise , Csajka Chantal
Published: July 2013

Background

Inter-individual variability in plasma concentration-time profiles might contribute to differences in anti-malarial treatment response. This study investigated the pharmacokinetics of three different forms of artemisinin combination therapy (ACT) in Tanzania and Cambodia to quantify and identify potential sources of variability.

Methods

Drug concentrations were measured in 143 patients in Tanzania (artemether, dihydroartemisinin, lumefantrine and desbutyl-lumefantrine), and in 63 (artesunate, dihydroartemisinin and mefloquine) and 60 (dihydroartemisinin and piperaquine) patients in Cambodia. Inter- and intra-individual variabilities in the pharmacokinetic parameters were assessed and the contribution of demographic and other covariates was quantified using a nonlinear mixed-effects modelling approach (NONMEM®).

Results

A one-compartment model with first-order absorption from the gastrointestinal tract fitted the data for all drugs except piperaquine (two-compartment). Inter-individual variability in concentration exposure was about 40% and 12% for mefloquine. From all the covariates tested, only body weight (for all antimalarials) and concomitant treatment (for artemether only) showed a significant influence on these drugs’ pharmacokinetic profiles. Artesunate and dihydroartemisinin could not be studied in the Cambodian patients due to insufficient data-points. Modeled lumefantrine kinetics showed that the target day 7 concentrations may not be achieved in a substantial proportion of patients.

Conclusion

The marked variability in the disposition of different forms of ACT remained largely unexplained by the available covariates. Dosing on body weight appears justified. The concomitance of unregulated drug use (residual levels found on admission) and sub-optimal exposure (variability) could generate low plasma levels that contribute to selecting for drug-resistant parasites.
Establishment of patient-derived non-small cell lung cancer xenograft models with genetic aberrations within EGFR, KRAS and FGFR1: useful tools for preclinical studies of targeted therapies
Authors: Zhang Xu-chao , Zhang Jingchuan , Li Ming , Huang Xiao-sui , Yang Xue-ning , Zhong Wen-zhao , Xie Liang , Zhang Lin , Zhou Minhua , Gavine Paul , Su Xinying , Zheng Li , Zhu Guanshan , Zhan Ping , Ji Qunsheng , Wu Yi-long
Published: July 2013

Background

Patient-derived tumor xenograft models have been established and increasingly used for preclinical studies of targeted therapies in recent years. However, patient-derived non-small cell lung cancer (NSCLC) xenograft mouse models are relatively few in number and are limited in their degree of genetic characterization and validation. In this study, we aimed to establish a variety of patient-derived NSCLC models and characterize these for common genetic aberrations to provide more informative models for preclinical drug efficacy testing.

Methods

NSCLC tissues from thirty-one patients were collected and implanted into immunodeficient mice. Established xenograft models were characterized for common genetic aberrations, including detection of gene mutations within EGFR and KRAS, and genetic amplification of FGFR1 and cMET. Finally, gefitinib anti-tumor efficacy was tested in these patient-derived NSCLC xenograft models.

Results

Ten passable patient-derived NSCLC xenograft models were established by implantation of NSCLC specimens of thirty-one patients into immunodeficient mice. Genetic aberrations were detected in six of the models, including one model with an EGFR activating mutation (Exon19 Del), one model with KRAS mutation, one model with both KRAS mutation and cMET gene amplification, and three models with FGFR1 amplification. Anti-tumor efficacy studies using gefitinib demonstrated that the EGFR activating mutation model had superior sensitivity and that the KRAS mutation models were resistant to gefitinib. The range of gefitinib responses in the patient-derived NSCLC xenograft models were consistent with the results reported from clinical trials. Furthermore, we observed that patient-derived NSCLC models with FGFR1 gene amplification were insensitive to gefitinib treatment.

Conclusions

Ten patient-derived NSCLC xenograft models were established containing a variety of genetic aberrations including EGFR activating mutation, KRAS mutation, and FGFR 1 and cMET amplification. Gefitinib anti-tumor efficacy in these patient-derived NSCLC xenografts containing EGFR and KRAS mutation was consistent with the reported results from previous clinical trials. Thus, data from our panel of patient-derived NSCLC xenograft models confirms the utility of these models in furthering our understanding of this disease and aiding the development of personalized therapies for NSCLC patients.
Clear cell renal cell carcinoma associated microRNA expression signatures identified by an integrated bioinformatics analysis
Authors: Chen Jiajia , Zhang Daqing , Zhang Wenyu , Tang Yifei , Yan Wenying , Guo Lingchuan , Shen Bairong
Published: July 2013

Background

Clear cell renal cell carcinoma (ccRCC) represents the most invasive and common adult kidney neoplasm. Mounting evidence suggests that microRNAs (miRNAs) are important regulators of gene expression. But their function in tumourigenesis in this tumour type remains elusive. With the development of high throughput technologies such as microarrays and NGS, aberrant miRNA expression has been widely observed in ccRCC. Systematic and integrative analysis of multiple microRNA expression datasets may reveal potential mechanisms by which microRNAs contribute to ccRCC pathogenesis.

Methods

We collected 5 public microRNA expression datasets in ccRCC versus non-matching normal renal tissues from GEO database and published literatures. We analyzed these data sets with an integrated bioinformatics framework to identify expression signatures. The framework incorporates a novel statistic method for abnormal gene expression detection and an in-house developed predictor to assess the regulatory activity of microRNAs. We then mapped target genes of DE-miRNAs to different databases, such as GO, KEGG, GeneGo etc, for functional enrichment analysis.

Results

Using this framework we identified a consistent panel of eleven deregulated miRNAs shared by five independent datasets that can distinguish normal kidney tissues from ccRCC. After comparison with 3 RNA-seq based microRNA profiling studies, we found that our data correlated well with the results of next generation sequencing. We also discovered 14 novel molecular pathways that are likely to play a role in the tumourigenesis of ccRCC.

Conclusions

The integrative framework described in this paper greatly improves the inter-dataset consistency of microRNA expression signatures. Consensus expression profile should be identified at pathway or network level to address the heterogeneity of cancer. The DE-miRNA signature and novel pathways identified herein could provide potential biomarkers for ccRCC that await further validation.
PRECISE - pregabalin in addition to usual care for sciatica: study protocol for a randomised controlled trial
Authors: Mathieson Stephanie , Maher Christopher G , McLachlan Andrew J , Latimer Jane , Koes Bart W , Hancock Mark J , Harris Ian , Day Richard O , Pik Justin , Jan Stephen , Billot Laurent , Lin Chung-Wei Christine
Published: July 2013

Background

Sciatica is a type of neuropathic pain that is characterised by pain radiating into the leg. It is often accompanied by low back pain and neurological deficits in the lower limb. While this condition may cause significant suffering for the individual, the lack of evidence supporting effective treatments for sciatica makes clinical management difficult. Our objectives are to determine the efficacy of pregabalin on reducing leg pain intensity and its cost-effectiveness in patients with sciatica.

Methods/Design

PRECISE is a prospectively registered, double-blind, randomised placebo-controlled trial of pregabalin compared to placebo, in addition to usual care. Inclusion criteria include moderate to severe leg pain below the knee with evidence of nerve root/spinal nerve involvement. Participants will be randomised to receive either pregabalin with usual care (n = 102) or placebo with usual care (n = 102) for 8 weeks. The medicine dosage will be titrated up to the participant’s optimal dose, to a maximum 600 mg per day. Follow up consultations will monitor individual progress, tolerability and adverse events. Usual care, if deemed appropriate by the study doctor, may include a referral for physical or manual therapy and/or prescription of analgesic medication. Participants, doctors and researchers collecting participant data will be blinded to treatment allocation. Participants will be assessed at baseline and at weeks 2, 4, 8, 12, 26 and 52. The primary outcome will determine the efficacy of pregabalin in reducing leg pain intensity. Secondary outcomes will include back pain intensity, disability and quality of life. Data analysis will be blinded and by intention-to-treat. A parallel economic evaluation will be conducted from health sector and societal perspectives.

Discussion

This study will establish the efficacy of pregabalin in reducing leg pain intensity in patients with sciatica and provide important information regarding the effect of pregabalin treatment on disability and quality of life. The impact of this research may allow the future development of a cost-effective conservative treatment strategy for patients with sciatica.

Trial registration

ClinicalTrial.gov, ACTRN 12613000530729
SHP1-mediated cell cycle redistribution inhibits radiosensitivity of non-small cell lung cancer
Authors: Cao Rubo , Ding Qian , Li Pindong , Xue Jun , Zou Zhenwei , Huang Jing , Peng Gang
Published: July 2013

Background

Radioresistance is the common cause for radiotherapy failure in non-small cell lung cancer (NSCLC), and the degree of radiosensitivity of tumor cells is different during different cell cycle phases. The objective of the present study was to investigate the effects of cell cycle redistribution in the establishment of radioresistance in NSCLC, as well as the signaling pathway of SH2 containing Tyrosine Phosphatase (SHP1).

Methods

A NSCLC subtype cell line, radioresistant A549 (A549S1), was induced by high-dose hypofractionated ionizing radiations. Radiosensitivity-related parameters, cell cycle distribution and expression of cell cycle-related proteins and SHP1 were investigated. siRNA was designed to down-regulate SHP1expression.

Results

Compared with native A549 cells, the proportion of cells in the S phase was increased, and cells in the G0/G1 phase were consequently decreased, however, the proportion of cells in the G2/M phase did not change in A549S1 cells. Moreover, the expression of SHP1, CDK4 and CylinD1 were significantly increased, while p16 was significantly down-regulated in A549S1 cells compared with native A549 cells. Furthermore, inhibition of SHP1 by siRNA increased the radiosensitivity of A549S1 cells, induced a G0/G1 phase arrest, down-regulated CDK4 and CylinD1expressions, and up-regulated p16 expression.

Conclusions

SHP1 decreases the radiosensitivity of NSCLC cells through affecting cell cycle distribution. This finding could unravel the molecular mechanism involved in NSCLC radioresistance.
Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2
Authors: Wen Jiadi , Lopes Fátima , Soares Gabriela , Farrell Sandra A , Nelson Cara , Qiao Ying , Martell Sally , Badukke Chansonette , Bessa Carlos , Ylstra Bauke , Lewis Suzanne , Isoherranen Nina , Maciel Patricia , Rajcan-Separovic Evica
Published: July 2013

Background

Rare, recurrent genomic imbalances facilitate the association of genotype with abnormalities at the “whole body” level. However, at the cellular level, the functional consequences of recurrent genomic abnormalities and how they can be linked to the phenotype are much less investigated.

Method and results

We report an example of a functional analysis of two genes from a new, overlapping microdeletion of 2p13.2 region (from 72,140,702-72,924,626). The subjects shared intellectual disability (ID), language delay, hyperactivity, facial asymmetry, ear malformations, and vertebral and/or craniofacial abnormalities. The overlapping region included two genes, EXOC6B and CYP26B1, which are involved in exocytosis/Notch signaling and retinoic acid (RA) metabolism, respectively, and are of critical importance for early morphogenesis, symmetry as well as craniofacial, skeleton and brain development. The abnormal function of EXOC6B was documented in patient lymphoblasts by its reduced expression and with perturbed expression of Notch signaling pathway genes HES1 and RBPJ, previously noted to be the consequence of EXOC6B dysfunction in animal and cell line models. Similarly, the function of CYP26B1 was affected by the deletion since the retinoic acid induced expression of this gene in patient lymphoblasts was significantly lower compared to controls (8% of controls).

Conclusion

Haploinsufficiency of CYP26B1 and EXOC6B genes involved in retinoic acid and exocyst/Notch signaling pathways, respectively, has not been reported previously in humans. The developmental anomalies and phenotypic features of our subjects are in keeping with the dysfunction of these genes, considering their known role. Documenting their dysfunction at the cellular level in patient cells enhanced our understanding of biological processes which contribute to the clinical phenotype.
The impact of Hunter syndrome (mucopolysaccharidosis type II) on health-related quality of life
Authors: Raluy-Callado Mireia , Chen Wen-Hung , Whiteman David A H , Fang Juanzhi , Wiklund Ingela
Published: July 2013

Background

Hunter syndrome (mucopolysaccharidosis type II (MPS II)) is a rare metabolic disease that can severely compromise health, well-being and life expectancy. Little evidence has been published on the impact of MPS II on health-related quality of life (HRQL). The objective of this study was to describe this impact using the Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS) questionnaire and a range of standard validated questionnaires previously used in paediatric populations.

Methods

Clinical and demographic characteristics collected in a clinical trial and responses to four HRQL questionnaires completed both by patients and parents prior to enzyme replacement treatment were used. The association between questionnaire scores and clinical function parameters were tested using Spearman rank-order correlations. Results were compared to scores in other paediatric populations with chronic conditions obtained through a targeted literature search of published studies.

Results

Overall, 96 male patients with MPS II and their parents were enrolled in the trial. All parents completed the questionnaires and 53 patients above 12 years old also completed the self-reported versions. Parents’ and patients’ responses were analysed separately and results were very similar. Dysfunction according to the HS-FOCUS and the CHAQ was most pronounced in the physical function domains. Very low scores were reported in the Self Esteem and Family Cohesion domains in the CHQ and HUI3 disutility values indicated a moderate impact. Scores reported by patients and their parents were consistently lower than scores in the other paediatric populations identified (except the parent-reported Behaviour score); and considerably lower than normative values.

Conclusions

This study describes the impact on HRQL in patients with MPS II and provides a broader context by comparing it with that of other chronic paediatric diseases. Physical function and the ability to perform day-to-day activities were the most affected areas and a considerable impact on the psychological aspects of patients’ HRQL was also found, with a higher level of impairment across most dimensions (particularly Pain and Self Esteem) than that of other paediatric populations. Such humanistic data provide increasingly important support for establishing priorities for health care spending, and as a component of health economic analysis.
Synthesis and structure−activity relationship of 8-substituted protoberberine derivatives as a novel class of antitubercular agents
Authors: Li Ying-Hong , Fu Hai-Gen , Su Feng , Gao Li-Mei , Tang Sheng , Bi Chong-Wen , Li Yu-Huan , Wang Yan-Xiang , Song Dan-Qing
Published: July 2013

Background

The emergence of multi-drug resistant tuberculosis (MDR-TB) has heightened the need for new chemical classes and innovative strategies to tackle TB infections. It is urgent to discover new classes of molecules without cross-resistance with currently used antimycobacterial drugs.

Results

Eighteen new 8-substituted protoberberine derivatives were synthesized and evaluated for their anti-mycobacterial activities against Mycobacterium tuberculosis (M. tuberculosis) strain H37Rv. Among them, compound 7g was the most effective antitubercular agent with minimum inhibitory concentration (MIC) of 0.5 μg/mL. Moreover, it also afforded a potent antitubercular effect against clinically isolated MDR strains of M. tuberculosis with MICs ranging from 0.25 to 1.0 μg/mL, suggesting a novel mode of action.

Conclusions

The structure−activity relationship (SAR) analysis revealed that introduction of a substituent at the 8-position in pseudoprotoberberine, especially an n-decyl, could significantly enhance the anti-TB activity. We consider 8-n-decylberberines to be a novel family of anti-tubercular agents with an advantage of inhibiting MDR strains of M. tuberculosis.
Molecular profiling supports the role of epithelial-to-mesenchymal transition (EMT) in ovarian cancer metastasis
Authors: Lili Loukia N , Matyunina Lilya V , Walker L DeEtte , Wells Stephen L , Benigno Benedict B , McDonald John F
Published: July 2013

Background

While metastasis ranks among the most lethal of all cancer-associated processes, on the molecular level, it remains one of the least well understood. One model that has gained credibility in recent years is that metastasizing cells at least partially recapitulate the developmental process of epithelial-to-mesenchymal transition (EMT) in their transit from primary to metastatic sites. While experimentally supported by cell culture and animal model studies, the lack of unambiguous confirmatory evidence in cancer patients has led to persistent challenges to the model’s relevance in humans.

Methods

Gene expression profiling (Affymetrix, U133) was carried out on 14 matched sets of primary (ovary) and metastatic (omentum) ovarian cancer (serous adenocarcinoma) patient samples. Hierarchical clustering and functional pathway algorithms were used in the data analysis.

Results

While histological examination reveled no morphological distinction between the matched sets of primary and metastatic samples, gene expression profiling clearly distinguished two classes of metastatic samples. One class displayed expression patterns statistically indistinguishable from primary samples isolated from the same patients while a second class displayed expression patterns significantly different from primary samples. Further analyses focusing on genes previously associated with EMT clearly distinguished the primary from metastatic samples in all but one patient.

Conclusion

Our results are consistent with a role of EMT in most if not all ovarian cancer metastases and demonstrate that identical morphologies between primary and metastatic cancer samples is insufficient evidence to negate a role of EMT in the metastatic process.
Breakfast: a multidisciplinary approach
Authors: Affinita Antonio , Catalani Loredana , Cecchetto Giovanna , De Lorenzo Gianfranco , Dilillo Dario , Donegani Giorgio , Fransos Lucia , Lucidi Fabio , Mameli Chiara , Manna Elisa , Marconi Paolo , Mele Giuseppe , Minestroni Laura , Montanari Massimo , Morcellini Mario , Rovera Giuseppe , Rotilio Giuseppe , Sachet Marco , Zuccotti Gian Vincenzo
Published: July 2013

Background

The role of breakfast as an essential part of an healthy diet has been only recently promoted even if breakfast practices were known since the Middle Age. The growing scientific evidences on this topic are extremely sector-based nevertheless breakfast could be regarded from different point of views and from different expertises. This approach, that take into account history, sociology, anthropology, medicine, psychology and pedagogy, is useful to better understand the value of this meal in our culture. The aim of this paper was to analyse breakfast-related issues based on a multidisciplinary approach with input by specialists from different fields of learning.

Discussion

Breakfast is now recommended as part of a diet because it is associated with healthier macro- and micronutrient intakes, body mass index and lifestyle. Moreover recent studies showed that breakfast improves cognitive function, intuitive perception and academic performance. Research demonstrates the importance of providing breakfast not only to children but in adults and elderly too. Although the important role breakfast plays in maintaining the health, epidemiological data from industrialised countries reveal that many individuals either eat a nutritionally unhealthy breakfast or skip it completely.

The historical, bio-psychological and educational value of breakfast in our culture is extremely important and should be recognized and stressed by the scientific community. Efforts should be done to promote this practice for the individual health and well-being.
Beyond intracranial pressure: optimization of cerebral blood flow, oxygen, and substrate delivery after traumatic brain injury
Authors: Bouzat Pierre , Sala Nathalie , Payen Jean-François , Oddo Mauro
Published: July 2013

Monitoring and management of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is a standard of care after traumatic brain injury (TBI). However, the pathophysiology of so-called secondary brain injury, i.e., the cascade of potentially deleterious events that occur in the early phase following initial cerebral insult—after TBI, is complex, involving a subtle interplay between cerebral blood flow (CBF), oxygen delivery and utilization, and supply of main cerebral energy substrates (glucose) to the injured brain. Regulation of this interplay depends on the type of injury and may vary individually and over time. In this setting, patient management can be a challenging task, where standard ICP/CPP monitoring may become insufficient to prevent secondary brain injury. Growing clinical evidence demonstrates that so-called multimodal brain monitoring, including brain tissue oxygen (PbtO2), cerebral microdialysis and transcranial Doppler among others, might help to optimize CBF and the delivery of oxygen/energy substrate at the bedside, thereby improving the management of secondary brain injury. Looking beyond ICP and CPP, and applying a multimodal therapeutic approach for the optimization of CBF, oxygen delivery, and brain energy supply may eventually improve overall care of patients with head injury. This review summarizes some of the important pathophysiological determinants of secondary cerebral damage after TBI and discusses novel approaches to optimize CBF and provide adequate oxygen and energy supply to the injured brain using multimodal brain monitoring.
What Should I Do and What Was I Thinking? Philosophical Examples and the Uses of the Literary
Authors: Ferguson Frances
Published: July 2013

Philosophers frequently attempt to achieve clarity about particular problems in moral philosophy both by modeling specific hypothetical cases very exactly and by turning to literature for examples. Ferguson here relies on some of the work of Bernard Williams, Donald Davidson, and Candace Vogler to treat their various suggestions about moral problems and how literature might serve them. In particular, she observes that each of these philosophers suggests how modern moral thought, which Williams sees as dominated by a progressivist account of its own history, arrives at less comprehensive clarity than it sometimes claims to do. She further notices how far their views take comfort from aspects of literature that do not revolve around the promulgation of readerly omniscience that attaches to the novel in modernity.
The Literary Example in Moral Philosophy Today
Authors: Small Helen
Published: July 2013

The standard claim made for literary examples in moral philosophy is that they assist moral reasoning by offering appropriately complex descriptions of the conditions under which moral decisions are made or might plausibly be made. This essay offers a critical examination of that claim, exploring the attractions of literary exemplarity for moral philosophy of several kinds since the 1960s but also the constrained terms under which the invitation to deep reflectiveness is permitted to operate. The essay then considers why many recent moral philosophers (with the partial exception of Bernard Williams) have preferred quasi- or faux-literary examples, developing a kind of stripped-down or gestural literariness that offers the benefits of just enough, not too much, complexity.
A Matter of Light and Shade: Fiction and Criticism in R. K. Narayan’s Malgudi
Authors: Basu Manisha
Published: July 2013

This essay reads exemplary instances of the fictional work of Indian novelist R. K. Narayan (1906-2001) as expressions of critical anachronism in a world literary marketplace that, despite claiming diversity as a global, even transcendental, value, remains committed to both the uniformity of literature as a conceptual form and the ubiquity of national models of cultural production. Narayan’s fictional world very deftly brings to light a plethora of verbal and textual practices—whether they be the calligraphy of the signboard painter (The Painter of Signs) or the discourse of a “little magazine” (Mr. Sampath)—that have their own modes of authorization and circulation distinct from the increasingly universal molar institution of literature. It is these dispersed textualities that sustain the nameless, ad hoc relationships that make the human aggregations of Narayan’s imaginary town of Malgudi as something other than microcosms of national-civilizational wholes. Inextricably intertwined with his elaboration of such radically experimental human relationships is a syntax of love that is an extension of the intimacy between Narayan’s craftsmen characters and the practice of their crafts but is not founded in templates of belonging—national, civilizational, familial, or conjugal. My argument ends with the idea that for Narayan, this conceptualization of love generates critical practice as a function of the kind of curiosity that, armed with the force of fictional possibilities, has the strength to imagine different realities and possibilities under the most difficult political circumstances.
Climate influences thermal balance and water use in African and Asian elephants: physiology can predict drivers of elephant distribution
Authors: Dunkin Robin C. , Wilson Dinah , Way Nicolas , Johnson Kari , Williams Terrie M.
Published: July 2013

Elephant movement patterns in relation to surface water demonstrate that they are a water-dependent species. Thus, there has been interest in using surface water management to mitigate problems associated with localized elephant overabundance. However, the physiological mechanisms underlying the elephant's water dependence remain unclear. Although thermoregulation is likely an important driver, the relationship between thermoregulation, water use and climate has not been quantified. We measured skin surface temperature of and cutaneous water loss from 13 elephants (seven African, 3768±642 kg; six Asian, 3834±498 kg) and determined the contribution of evaporative cooling to their thermal and water budgets across a range of air temperatures (8–33°C). We also measured respiratory evaporative water loss and resting metabolic heat production on a subset of elephants (N=7). The rate of cutaneous evaporative water loss ranged between 0.31 and 8.9 g min−1 m−2 for Asian elephants and 0.26 and 6.5 g min−1 m−2 for African elephants. Simulated thermal and water budgets using climate data from Port Elizabeth, South Africa, and Okaukuejo, Namibia, suggested that the 24-h evaporative cooling water debt incurred in warm climates can be more than 4.5 times that incurred in mesic climates. This study confirms elephants are obligate evaporative coolers but suggests that classification of elephants as water dependent is insufficient given the importance of climate in determining the magnitude of this dependence. These data highlight the potential for a physiological modeling approach to predicting the utility of surface water management for specific populations.
Aerobic scope measurements of fishes in an era of climate change: respirometry, relevance and recommendations
Authors: Clark Timothy D. , Sandblom Erik , Jutfelt Fredrik
Published: July 2013

Measurements of aerobic scope [the difference between minimum and maximum oxygen consumption rate ( and , respectively)] are increasing in prevalence as a tool to address questions relating to fish ecology and the effects of climate change. However, there are underlying issues regarding the array of methods used to measure aerobic scope across studies and species. In an attempt to enhance quality control before the diversity of issues becomes too great to remedy, this paper outlines common techniques and pitfalls associated with measurements of , and aerobic scope across species and under different experimental conditions. Additionally, we provide a brief critique of the oxygen- and capacity-limited thermal tolerance (OCLTT) hypothesis, a concept that is intricately dependent on aerobic scope measurements and is spreading wildly throughout the literature despite little evidence for its general applicability. It is the intention of this paper to encourage transparency and accuracy in future studies that measure the aerobic metabolism of fishes, and to highlight the fundamental issues with assuming broad relevance of the OCLTT hypothesis.
Activation of the immune defence of the freshwater snailLymnaea stagnalisby different immune elicitors
Authors: Seppälä Otto , Leicht Katja
Published: July 2013

Understanding the outcomes of host–parasite interactions in nature is in high demand as parasites and pathogens are important for several ecological and evolutionary processes. Ecological immunology (ecoimmunology) has a key role in reaching this goal because immune defence is the main physiological barrier against infections. To date, ecoimmunological studies largely lean on measuring constitutive immune defences (components of defence that are always active). However, understanding the role of inducible components of immune function is important as the immune system is largely an inducible defence. Measuring such defences can be complicated as different parasites may activate different immune cascades, and expression of different immune traits may not be independent. We examined the suitability of different immune activation techniques for the freshwater snail Lymnaea stagnalis. By experimentally challenging snails with different immune elicitors [injection with snail saline (i.e. wounding), lyophilized Escherichia coli cells, lyophilized Micrococcus lysodeikticus cells, healthy snail gonad, and trematode-infected snail gonad; maintenance in microorganism-enriched water] and measuring phenoloxidase-like and antibacterial activity of their haemolymph, we found increased immune activity against some immune elicitors, but also decreased activity. Our findings suggest potentially complicated relationships among immune traits, and propose suitable techniques for ecological studies in this study system.
X-ray motion analysis of the vertebral column during the startle response in striped bass,Morone saxatilis
Authors: Nowroozi B. N. , Brainerd E. L.
Published: July 2013

Whole-body stiffness has a substantial impact on propulsive wave speed during axial undulatory locomotion in fishes. The connective tissues of the vertebral column may contribute to body stiffness, but without mechanical and kinematic analysis it is unclear whether the in vivo range of motion of intervertebral joints (IVJs) is great enough to stress IVJ tissues, thus generating stiffness. The present study used 2D videoradiography and 3D X-ray reconstruction of moving morphology (XROMM) to quantify vertebral kinematics during the startle response in striped bass (Morone saxatilis). X-ray video revealed two distinct patterns of bending: pattern I begins in the abdominal region and then proceeds to maximum IVJ angles in the caudal region, whereas pattern II begins in the cervical region and proceeds to maximum IVJ angles in the abdominal and then the caudal joints. In pattern II bends, the cervical joints exhibit a greater in vivo range of motion than previously reported in other species. XROMM analysis of caudal IVJs suggests primarily lateral bending: mean axial and dorsoventral rotations were less than 2 deg and inconsistent across 51 sequences analyzed from five individuals, whereas mean maximum lateral bending angles were 10.4±3.57 deg. These angles, combined with previous investigations of mechanical properties, reveal that the maximum angles all occur within the neutral zone of bending, indicating that little stress is experienced about the joint. This suggests that the IVJs of striped bass are quite compliant and likely do not contribute significantly to whole-body stiffness or elastic recoil during swimming in vivo.
Hydrophobic Surface Based on Microtexture of Ag Nanoparticle/POSS Nanocomposite Film
Authors: Watanabe Akira , Qin Gang , Cheng Chung-Wei , Shen Wei-Chin , Chu Ching-I
Published: July 2013

A new class of nanohybrids consisting of metal nanoparticles and polyhedral oligomeric silsesquioxane (POSS) showed the formation of a unique surface microtexture such as a fern-like fractal pattern. A silver macropore film was formed by heat treatment of silver nanoparticle (Ag nanoparticle) aggregates around the POSS crystal as a relief. A new method to fabricate a hydrophobic metal surface based on surface texturing was provided.