bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pulmonary melioidosis in Cambodia: A prospective study
Authors: Rammaert Blandine , Beauté Julien , Borand Laurence , Hem Sopheak , Buchy Philippe , Goyet Sophie , Overtoom Rob , Angebault Cécile , Te Vantha , Try Patrich Lorn , Mayaud Charles , Vong Sirenda , Guillard Bertrand 
Published: May 2011

Abstract

Background
Melioidosis is a disease caused by Burkholderia pseudomallei and considered endemic in South-East Asia but remains poorly documented in Cambodia. We report the first series of hospitalized pulmonary melioidosis cases identified in Cambodia describing clinical characteristics and outcomes.

Methods
We characterized cases of acute lower respiratory infections (ALRI) that were identified through surveillance in two provincial hospitals. Severity was defined by systolic blood pressure, cardiac frequency, respiratory rate, oxygen saturation and body temperature. B. pseudomallei was detected in sputum or blood cultures and confirmed by API20NE gallery. We followed up these cases between 6 months and 2 years after hospital discharge to assess the cost-of-illness and long-term outcome.

Results
During April 2007 - January 2010, 39 ALRI cases had melioidosis, of which three aged ≤2 years; the median age was 46 years and 56.4% were males. A close contact with soil and water was identified in 30 patients (76.9%). Pneumonia was the main radiological feature (82.3%). Eleven patients were severe cases. Twenty-four (61.5%) patients died including 13 who died within 61 days after discharge. Of the deceased, 23 did not receive any antibiotics effective against B. pseudomallei. Effective drugs that were available did not include ceftazidime. Mean total illness-related costs was of US$65 (range $25-$5000). Almost two-thirds (61.5%) incurred debt and 28.2% sold land or other belongings to pay illness-related costs.

Conclusions
The observed high fatality rate is likely explained by the lack or limited access to efficient antibiotics and under-recognition of the disease among clinicians, which led to inappropriate therapy.
Celastrol targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent cytotoxicity in tumor cells
Authors: Chen Guozhu , Zhang Xuhui , Zhao Ming , Wang Yan , Cheng Xiang , Wang Di , Xu Yuanji , Du Zhiyan , Yu Xiaodan 
Published: May 2011

Abstract

Background
Celastrol is an active ingredient of the traditional Chinese medicinal plant Tripterygium Wilfordii, which exhibits significant antitumor activity in different cancer models in vitro and in vivo; however, the lack of information on the target and mechanism of action of this compound have impeded its clinical application. In this study, we sought to determine the mode of action of celastrol by focusing on the processes that mediate its anticancer activity.

Methods
The downregulation of heat shock protein 90 (HSP90) client proteins, phosphorylation of c-Jun NH2-terminal kinase (JNK), and cleavage of PARP, caspase 9 and caspase 3 were detected by western blotting. The accumulation of reactive oxygen species (ROS) was analyzed by flow cytometry and fluorescence microscopy. Cell cycle progression, mitochondrial membrane potential (MMP) and apoptosis were determined by flow cytometry. Absorption spectroscopy was used to determine the activity of mitochondrial respiratory chain (MRC) complexes.

Results
Celastrol induced ROS accumulation, G2-M phase blockage, apoptosis and necrosis in H1299 and HepG2 cells in a dose-dependent manner. N-acetylcysteine (NAC), an antioxidative agent, inhibited celastrol-induced ROS accumulation and cytotoxicity. JNK phosphorylation induced by celastrol was suppressed by NAC and JNK inhibitor SP600125 (SP). Moreover, SP significantly inhibited celastrol-induced loss of MMP, cleavage of PARP, caspase 9 and caspase 3, mitochondrial translocation of Bad, cytoplasmic release of cytochrome c, and cell death. However, SP did not inhibit celastrol-induced ROS accumulation. Celastrol downregulated HSP90 client proteins but did not disrupt the interaction between HSP90 and cdc37. NAC completely inhibited celastrol-induced decrease of HSP90 client proteins, catalase and thioredoxin. The activity of MRC complex I was completely inhibited in H1299 cells treated with 6 μM celastrol in the absence and presence of NAC. Moreover, the inhibition of MRC complex I activity preceded ROS accumulation in H1299 cells after celastrol treatment.

Conclusion
We identified ROS as the key intermediate for celastrol-induced cytotoxicity. JNK was activated by celastrol-induced ROS accumulation and then initiated mitochondrial-mediated apoptosis. Celastrol induced the downregulation of HSP90 client proteins through ROS accumulation and facilitated ROS accumulation by inhibiting MRC complex I activity. These results identify a novel target for celastrol-induced anticancer activity and define its mode of action.
The rise in narghile (shisha, hookah) waterpipe tobacco smoking: A qualitative study of perceptions of smokers and non smokers
Authors: Nakkash Rima T , Khalil Joanna , Afifi Rema A 
Published: May 2011

Abstract

Background
The prevalence of waterpipe tobacco smoking (WTS) in the Middle East region and worldwide is increasing. There is evidence to indicate both short term and long term health effects of WTS, resulting in the issuance of an advisory note by the World Health Organization.

Methods
This research aimed at gaining an in-depth understanding of the factors contributing to the rise in WTS in Lebanon. Qualitative focus groups (25) and in-depth interviews (9) were conducted with adults in Lebanon in 2007. Participants were recruited to represent diversity in smoking status, gender, age groups and urban/rural residence. The interviews and focus groups were thematically analyzed, and recurrent themes noted and summarized.

Results
The main themes identified were availability, affordability, innovation, influence of media, lack of a policy framework, and the sensory characteristics evoked from WTS. Men and women, smokers and non-smokers, and younger and older participants differed in their emphases on the above themes. These themes, though specific to waterpipe, are similar to themes manipulated by the cigarette industry, and eventually controlled through tobacco control policies.

Conclusions
Understanding reasons behind the rise in waterpipe tobacco use is important if appropriate prevention, cessation, and policy interventions are to be formulated. Strict adherence to the FCTC is warranted, with careful and vigilant attention that all tobacco products are covered by laws in both high as well as middle to lower income countries.
Chronic virus infections supress atopy but not asthma in a set of children from a large latin american city: a cross-section study
Authors: Veiga Rafael V , Cunha Sergio S , Dattoli Vitor CC , Cruz Álvaro C , Cooper Phillip J , Rodrigues Laura C , Barreto Maurício L , Alcantara-Neves Neuza M 
Published: May 2011

Abstract

Background
The prevalence of allergic diseases has increased over recent decades in affluent countries, but remains low in rural populations and some non-affluent countries. An explanation for these trends is that increased exposure to infections may provide protection against the development of allergy. In this work we investigated the association between exposure to viral infections in children living in urban Brazil and the prevalence of atopy and asthma.

Methods
School age children living in poor neighborhoods in the city of Salvador were studied. Data on asthma symptoms and relevant risk factors were obtained by questionnaire. Skin prick tests (SPTs) were performed to seven aeroallergens, and specific IgE was measured to four of these. Viral infections were determined by the presence of specific IgG in serum to Herpes simplex (HSV), Herpes zoster (HZV), Epstein-Barr (EBV), and Hepatitis A (HAV) viruses.

Results
A total of 644 (49.7%) children had at least one allergen-specific IgE> 0.35 kU/L and 489 (37.7%) had specific IgE> 0.70 kU/L. A total of 391 (30.2%) children were skin test positive (SPT+), and 295 (22.8%) children were asthmatic. The seroprevalence of viral infections was 88.9% for EBV, 55.4% for HSV, 45.5% for VZV and 17.5% for HAV. Negative associations were observed between SPT+ and HSV (OR = 0.64, CI = 0.51, 0.82) and EBV (OR = 0.63, CI = 0.44, 0.89) infections, but no associations were seen between viral infections and the presence of allergen-specific IgE or asthma.

Conclusion
These data do not support previous data showing a protective effect of HAV against atopy, but did show inverse associations between SPT+ (but not specific IgE+) and infections with HSV and EBV. These findings suggest that different viral infections may protect against SPT+ in different settings and may indicate an immunoregulatory role of such infections on immediate hypersensitivity responses. The data provide no support for a protective effect of viral infections against asthma in this population.
Misleading measures in Vitamin D analysis: A novel LC-MS/MS assay to account for epimers and isobars
Authors: Shah Iltaf , James Ricky , Barker James , Petroczi Andrea , Naughton Declan P 
Published: May 2011

Abstract

Background
Recently, the accuracies of many commercially available immunoassays for Vitamin D have been questioned. Liquid chromatography tandem mass spectrometry (LC- MS/MS) has been shown to facilitate accurate separation and quantification of the major circulating metabolite 25-hydroxyvitamin-D3 (25OHD3) and 25-hydroxyvitamin-D2 (25OHD2) collectively termed as 25OHD. However, among other interferents, this method may be compromised by overlapping peaks and identical masses of epimers and isobars, resulting in inaccuracies in circulating 25OHD measurements. The aim of this study was to develop a novel LC-MS/MS method that can accurately identify and quantitate 25OHD3 and 25OHD2 through chromatographic separation of 25OHD from its epimers and isobars.

Methods
A positive ion electrospray ionisation (ESI) LC-MS/MS method was used in the Multiple Reaction Monitoring (MRM) mode for quantification. It involved i) liquid-liquid extraction, ii) tandem columns (a high resolution ZORBAX C18 coupled to an ULTRON chiral, with guard column and inlet filter), iii) Stanozolol-D3 as internal standard, and iv) identification via ESI and monitoring of three fragmentation transitions. To demonstrate the practical usefulness of our method, blood samples were collected from 5 healthy male Caucasian volunteers; age range 22 to 37 years and 25OHD2, 25OHD3 along with co-eluting epimers and analogues were quantified.

Results
The new method allowed chromatographic separation and quantification of 25OHD2, 25OHD3, along with 25OHD3 epimer 3-epi-25OHD3 and isobars 1-α-hydroxyvitamin-D3 (1αOHD3), and 7-α-hydroxy-4-cholesten-3-one (7αC4). The new assay was capable of detecting 0.25 ng/mL of all analytes in serum.

Conclusions
To our knowledge, this is the first specific, reliable, reproducible and robust LC-MS/MS method developed for the accurate detection of 25OHD (Vitamin D). The method is capable of detecting low levels of 25OHD3 and 25OHD2 together with chromatographic separation from the co-eluting epimers and isobars and circumvents other instrumental/analytical interferences. This analytical method does not require time-consuming derivatisation and complex extraction techniques and could prove very useful in clinical studies.
Confounders in the assessment of the renal effects associated with low-level urinary cadmium: an analysis in industrial workers
Authors: Haddam Nahida , Samira Sekkal , Dumont Xavier , Taleb Abdesselem , Lison Dominique , Haufroid Vincent , Bernard Alfred 
Published: May 2011

Abstract

Background
Associations of proteinuria with low-level urinary cadmium (Cd) are currently interpreted as the sign of renal dysfunction induced by Cd. Few studies have considered the possibility that these associations might be non causal and arise from confounding by factors influencing the renal excretion of Cd and proteins.

Methods
We examined 184 healthy male workers (mean age, 39.5 years) from a zinc smelter (n = 132) or a blanket factory (n = 52). We measured the concentrations of Cd in blood (B-Cd) and the urinary excretion of Cd (U-Cd), retinol-binding protein (RBP), protein HC and albumin. Associations between biomarkers of metal exposure and urinary proteins were assessed by simple and multiple regression analyses.

Results
The medians (interquartile range) of B-Cd (μg/l) and U-Cd (μg/g creatinine) were 0.80 (0.45-1.16) and 0.70 (0.40-1.3) in smelter workers and 0.66 (0.47-0.87) and 0.55 (0.40-0.90) in blanket factory workers, respectively. Occupation had no influence on these values, which varied mainly with smoking habits. In univariate analysis, concentrations of RBP and protein HC in urine were significantly correlated with both U-Cd and B-Cd but these associations were substantially weakened by the adjustment for current smoking and the residual influence of diuresis after correction for urinary creatinine. Albumin in urine did not correlate with B-Cd but was consistently associated with U-Cd through a relationship, which was unaffected by smoking or diuresis. Further analyses showed that RBP and albumin in urine mutually distort their associations with U-Cd and that the relationship between RBP and Cd in urine was almost the replicate of that linking RBP to albumin

Conclusions
Associations between proteinuria and low-level urinary Cd should be interpreted with caution as they appear to be largely driven by diuresis, current smoking and probably also the co-excretion of Cd with plasma proteins.
Prostaglandin E2 binding peptide screened by phage displaying: a new therapeutic strategy in rheumatoid arthritis
Authors: Yan Dongmei , Han Weiwei , Bai Qinzhu , Zhao Xiangfeng , Han Xiao , Du Bairong , Zhu Xun 
Published: May 2011

Abstract

Objective
To investigate the therapeutic potential and mechanism of action of the mimotope of PGE2 receptor EP4 (PBP, named by our team) screened by phage displaying technique in the treatment of adjuvant-induced arthritis (AA).

Methods
Freund's complete adjuvant-induced arthritis was induced in Wistar rats. At the first clinical sign of disease, mice were given with daily injections of PBP or saline for 21 days. Disease progression was monitored by measurement of paw swelling. Inflammation and joint destruction were assessed histologically. The IL-1β and TNF-α were studied by ELISA in the ankle steeps of arthritis model. The degree of proliferation and apoptosis of synoviocytes of RA patients were assessed by CCK-8 kit and Annexin⊠-FITC/PI respectively.

Results
PBP-treated animals displayed significantly less cartilage and bone destruction than model controls. Tumor necrosis factor α and IL-1β expression were reduced after PBP treatment. The proliferation and apoptosis of synoviocytes of RA patients were influenced by PBP.

Conclusions
The data support the view that PBP is a potential therapy for RA that may help to diminish both joint inflammation and destruction. And the activities of PBP are related with the effect on synoviocytes directly.
Comparative proteomics analysis of proteins expressed in the I-1 and I-2 internodes of strawberry stolons
Authors: Fang Xianping , Ma Huasheng , Lu Dezhao , Yu Hong , Lai Wenguo , Ruan Songlin 
Published: May 2011

Abstract

Background
Strawberries (Fragaria ananassa) reproduce asexually through stolons, which have strong tendencies to form adventitious roots at their second node. Understanding how the development of the proximal (I-1) and distal (I-2) internodes of stolons differ should facilitate nursery cultivation of strawberries.

Results
Herein, we compared the proteomic profiles of the strawberry stolon I-1 and I-2 internodes. Proteins extracted from the internodes were separated by two-dimensional gel electrophoresis, and 164 I-1 protein spots and 200 I-2 protein spots were examined further. Using mass spectrometry and database searches, 38 I-1 and 52 I-2 proteins were identified and categorized (8 and 10 groups, respectively) according to their cellular compartmentalization and functionality. Many of the identified proteins are enzymes necessary for carbohydrate metabolism and photosynthesis. Furthermore, identification of proteins that interact revealed that many of the I-2 proteins form a dynamic network during development. Finally, given our results, we present a mechanistic scheme for adventitious root formation of new clonal plants at the second node.

Conclusions
Comparative proteomic analysis of I-1 and I-2 proteins revealed that the ubiquitin-proteasome pathway and sugar-hormone pathways might be important during adventitious root formation at the second node of new clonal plants.
Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity
Authors: Bhakta Sushma J , Shang Liang , Prince Jessica L , Claiborne Daniel T , Hunter Eric 
Published: May 2011

AbstractBackgroundThe gp41 component of the Human Immunodeficiency Virus (HIV) envelope glycoprotein (Env) contains a long cytoplasmic domain (CD) with multiple highly conserved tyrosine (Y) and dileucine (LL) motifs. Studies suggest that the motifs distal to major endocytosis motif (Y712HRL), located at residues 712-715 of Env, may contribute to Env functionality in the viral life cycle. In order to examine the biological contribution of these motifs in the biosynthesis, transport, and function of Env, we constructed two panels of mutants in which the conserved Y- and LL-motifs were sequentially substituted by alternative residues, either in the presence or absence of Y712. Additional mutants targeting individual motifs were then constructed.ResultsAll mutant Envs, when expressed in the absence of other viral proteins, maintained at least WT levels of Env surface staining by multiple antibodies. The Y712mutation (Y712C) contributed to at least a 4-fold increase in surface expression for all mutants containing this change. Sequential mutagenesis of the Y- and LL-motifs resulted in a generally progressive decrease in Env fusogenicity. However, additive mutation of dileucine and tyrosine motifs beyond the tyrosine at residue 768 resulted in the most dramatic effects on Env incorporation into virions, viral infectivity, and virus fusion with target cells.ConclusionsFrom the studies reported here, we show that mutations of the Y- and LL-motifs, which effectively eliminate the amphipathic nature of the lytic peptide 2 (LLP2) domain or disrupt YW and LL motifs in a region spanning residues 795-803 (YWWNLLQYW), just C-terminal of LLP2, can dramatically interfere with biological functions of HIV-1 Env and abrogate virus replication. Because these mutant proteins are expressed at the cell surface, we conclude that tyrosine and di-leucine residues within the cytoplasmic domain of gp41 play critical roles in HIV-1 replication that are distinct from that of targeting the plasma membrane.
A336C/A336T/T337C variations in HBV core gene and spontaneous hepatitis B e antigen loss in chronic hepatitis B patients
Authors: Fan Wen , Huang Lu , zhou Zhiming , Li Yirong 
Published: May 2011

Abstract

Background
A336C/A336T/T337C variations in HBV core gene were demonstrated to relate to the decreases in serum HBV DNA levels and HBV replication in chronic hepatitis B patients. Usually the drastic decrease in serum HBV DNA levels correlates with spontaneous HBeAg loss during the course of chronic HBV infection. The aim of the present study was to investigate whether there was correlation between A336C/A336T/T337C variations and spontaneous HBeAg loss

Methodology/Principal Findings
A modified PCR-RFLP assay and ELISA were adopted to determine A336C/A336T/T337C variations and serum HBeAg levels in chronic hepatitis B patients without any antiviral therapy, respectively, whereas G1896A variation and HBV genotype were detected using Taqman-PCR assay. RFLP pattern C, E, G, C/G mixture and a new pattern C' were found in this study. A336C/A336T/T337C variations occurred in 40/166(24.1%) chronic hepatitis B patients. Chi-square test showed that C336/T336/C337 variants was more frequent in chronic hepatitis B patients with A1896 variants than those with the wild type G1896 (χ2 = 4.7, P = 0.03), and moreover, patients with C336/T336/C337 variants had a significantly lower HBeAg-positive percentage than those with the wild type A336/T337. Binary logistic regression identified genotype B (OR = 4.1, 95%CI = 1.8-9.2, P = 0.001), the presence of C336/T336/C337 variants (OR = 3.2, 95%CI = 1.2-8.5, P = 0.02) and A1896 variants (OR = 7.8, 95%CI = 3.3-18.5, P < 0.001) as independent factors associated with spontaneous HBeAg loss.

Conclusion/Significance
A336C/A336T/T337C were naturally occurring polymorphisms in HBV core gene, and moreover, the presence of C336/T336/C337 variants was first demonstrated to be an independent factor associating with spontaneous HBeAg loss in chronic hepatitis B patients.
Antinociceptive Effect of Cyclic Phosphatidic Acid and Its Derivative on Animal Models of Acute and Chronic Pain
Authors: Kakiuchi Yasutaka , Nagai Jun , Gotoh Mari , Hotta Harumi , Murofushi Hiromu , Ogawa Tomoyo , Ueda Hiroshi , Murakami-Murofushi Kimiko 
Published: May 2011

Background: Cyclic phosphatidic acid (cPA) is a structural analog of lysophosphatidic acid (LPA), but possesses different biological functions, such as the inhibition of autotaxin (ATX), an LPA-synthesizing enzyme. As LPA is a signaling molecule involved in nociception in the peripheral and central systems, cPA is expected to possess analgesic activity. We characterized the effects of cPA and 2-carba-cPA (2ccPA), a chemically stable cPA analog, on acute and chronic pain. Results: (1) The systemic injection of 2ccPA significantly inhibited somato-cardiac and somato-somatic C-reflexes but not the corresponding A-reflexes in anesthetized rats. (2) 2ccPA reduced sensitivity measured as the paw withdrawal response to electrical stimulation applied to the hind paws of mice through the C-fiber, but not Aδ or Aβ. (3) In mice, pretreatment with 2ccPA dose-dependently inhibited the second phase of formalin-induced licking and biting responses. (4) In mice, pretreatment and repeated post-treatments with 2ccPA significantly attenuated thermal hyperalgesia and mechanical allodynia following partial ligation of the sciatic nerve. (5) In rats, repeated post-treatments with 2ccPA also significantly attenuated thermal hyperalgesia and mechanical allodynia following chronic sciatic nerve constriction. Conclusions: Our results suggest that cPA and its stable analog 2ccPA inhibit chronic and acute inflammation-induced C-fiber stimulation, and that the central effects of 2ccPA following repeated treatments attenuate neuropathic pain.