bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of metabolic syndrome (MetS) in Chinese subjects gradually increased with impaired glucose homeostasis: a multicenter, clinical based, cross-sectional study
Authors: Xiang Yufei , Huang Gan , Zhou Weidong , Che Zhihong , Zhou Pengcheng , Zhou Zhiguang 
Published: August 2012

Abstract

Background
Metabolic Syndrome (MetS) is a high risk factor for Cardiovascular Diseases (CVD). We estimated to investigate how MetS prevalence by glucose homeostasis varies across different age and gender groups.

Methods
We studied 9257 Chinese subjects over the age of 15 years in two cross-sectional surveys in 2006. With oral glucose tolerance test (OGTT) test, 2341 subjects were normal glucose tolerance (NGT), and 5448 were diagnosed as having type 2 diabetes (T2D). All other 1468 subjects were considered to be impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) subjects. Diabetes was diagnosis by WHO99 criteria. We used modified NCEP-III criteria for the diagnosis of MetS.

Results
The prevalences of MetS in the male NGT, IFG/IGT and T2D groups were 25.9% (404/1559), 65.6% (769/1172), and 73.5% (2483/3376), respectively. The prevalences of MetS in the female NGT, IFG/IGT and T2D groups were 13.4% (105/782), 51.0% (151/296), and 75.4% (1563/2072), respectively. The prevalence of MetS in the male IFG/IGT group gradually decreased from 73.26% to 41.08% in subjects over the age of 30 years. The prevalence of MetS in the female IFG/IGT group gradually increased from 30% to 75% with aging.

Conclusions
The prevalence of MetS in subjects with different glucose tolerances in China was high and gradually increased with impaired glucose homeostasis both in males and females.
Molecular cloning and functional characterization of an ATP-binding cassette transporter OtrC from Streptomyces rimosus
Authors: Yu Lan , Yan Xiangyun , Wang Long , Chu Ju , Zhuang Yingping , Zhang Siliang , Guo Meijin 
Published: August 2012

Abstract

Background
The otrC gene of Streptomyces rimosus was previously annotated as an oxytetracycline (OTC) resistance protein. However, the amino acid sequence analysis of OtrC shows that it is a putative ATP-binding cassette (ABC) transporter with multidrug resistance function. To our knowledge, none of the ABC transporters in S. rimosus have yet been characterized. In this study, we aimed to characterize the multidrug exporter function of OtrC and evaluate its relevancy to OTC production.

Results
In order to investigate OtrC’s function, otrC is cloned and expressed in E. coli The exporter function of OtrC was identified by ATPase activity determination and ethidium bromide efflux assays. Also, the susceptibilities of OtrC-overexpressing cells to several structurally unrelated drugs were compared with those of OtrC-non-expressing cells by minimal inhibitory concentration (MIC) assays, indicating that OtrC functions as a drug exporter with a broad range of drug specificities. The OTC production was enhanced by 1.6-fold in M4018 (P = 0.000877) and 1.4-fold in SR16 (P = 0.00973) duplication mutants, while it decreased to 80% in disruption mutants (P = 0.0182 and 0.0124 in M4018 and SR16, respectively).

Conclusions
The results suggest that OtrC is an ABC transporter with multidrug resistance function, and plays an important role in self-protection by drug efflux mechanisms. This is the first report of such a protein in S. rimosus, and otrC could be a valuable target for genetic manipulation to improve the production of industrial antibiotics.
A novel, lactase-based selection and strain improvement strategy for recombinant protein expression in Kluyveromyces lactis
Authors: Krijger Jorrit-Jan , Baumann Jan , Wagner Melanie , Schulze Katja , Reinsch Christian , Klose Thomas , Onuma Osita F , Simon Claudia , Behrens Sven-Erik , Breunig Karin D 
Published: August 2012

Abstract

Background
The Crabtree-negative yeast species Kluyveromyces lactis has been established as an attractive microbial expression system for recombinant proteins at industrial scale. Its LAC genes allow for utilization of the inexpensive sugar lactose as a sole source of carbon and energy. Lactose efficiently induces the LAC4 promoter, which can be used to drive regulated expression of heterologous genes. So far, strain manipulation of K. lactis by homologous recombination was hampered by the high rate of non-homologous end-joining.

Results
Selection for growth on lactose was applied to target the insertion of heterologous genes downstream of the LAC4 promoter into the K. lactis genome and found to yield high numbers of positive transformants. Concurrent reconstitution of the β-galactosidase gene indicated the desired integration event of the expression cassette, and β-galactosidase activity measurements were used to monitor gene expression for strain improvement and fermentation optimization. The system was particularly improved by usage of a cell lysis resistant strain, VAK367-D4, which allowed for protein accumulation in long-term fermentation. Further optimization was achieved by increased gene dosage of KlGAL4 encoding the activator of lactose and galactose metabolic genes that led to elevated transcription rates. Pilot experiments were performed with strains expressing a single-chain antibody fragment (scFvox) and a viral envelope protein (BVDV-E2), respectively. scFvox was shown to be secreted into the culture medium in an active, epitope-binding form indicating correct processing and protein folding; the E2 protein could be expressed intracellularly. Further data on the influence of protein toxicity on batch fermentation and potential post-transcriptional bottlenecks in protein accumulation were obtained.

Conclusions
A novel Kluyveromyces lactis host-vector system was developed that places heterologous genes under the control of the chromosomal LAC4 promoter and that allows monitoring of its transcription rates by β-galactosidase measurement. The procedure is rapid and efficient, and the resulting recombinant strains contain no foreign genes other than the gene of interest. The recombinant strains can be grown non-selectively in rich medium and stably maintained even when the gene product exerts protein toxicity.
Deaths due to Plasmodium knowlesi malaria in Sabah, Malaysia: association with reporting as Plasmodium malariae and delayed parenteral artesunate
Authors: Rajahram Giri S , Barber Bridget E , William Timothy , Menon Jayaram , Anstey Nicholas M , Yeo Tsin W 
Published: August 2012

Abstract

Background
The simian parasite Plasmodium knowlesi is recognized as a common cause of severe and fatal human malaria in Sabah, Malaysia, but is morphologically indistinguishable from and still commonly reported as Plasmodium malariae, despite the paucity of this species in Sabah. Since December 2008 Sabah Department of Health has recommended intravenous artesunate and referral to a general hospital for all severe malaria cases of any species. This paper reviews all malaria deaths in Sabah subsequent to the introduction of these measures. Reporting of malaria deaths in Malaysia is mandatory.

Methods
Details of reported malaria deaths during 2010-2011 were reviewed to determine the proportion of each Plasmodium species. Demographics, clinical presentations and management of severe malaria caused by each species were compared.

Results
Fourteen malaria deaths were reported, comprising seven Plasmodium falciparum, six P. knowlesi and one Plasmodium vivax (all PCR-confirmed). Of the six P. knowlesi deaths, five were attributable to knowlesi malaria and one was attributable to P. knowlesi-associated enterobacter sepsis. Patients with directly attributable P. knowlesi deaths (N = 5) were older than those with P. falciparum (median age 51 [IQR 50-65] vs 22 [IQR 9-55] years, p = 0.06). Complications in fatal P. knowlesi included respiratory distress (N = 5, 100%), hypotension (N = 4, 80%), and renal failure (N = 4, 80%). All patients with P. knowlesi were reported as P. malariae by microscopy. Only two of five patients with severe knowlesi malaria on presentation received immediate parenteral anti-malarial treatment. The patient with P. vivax-associated severe illness did not receive parenteral treatment. In contrast six of seven patients with severe falciparum malaria received immediate parenteral treatment.

Conclusion

Plasmodium knowlesi was responsible, either directly or through gram-negative bacteraemia, for almost half of malaria deaths in Sabah. Patients with severe non-falciparum malaria were less likely to receive immediate parenteral therapy. This highlights the need in Sabah for microscopically diagnosed P. malariae to be reported as P. knowlesi to improve recognition and management of this potentially fatal species. Clinicians need to be better informed of the potential for severe and fatal malaria from non-falciparum species, and the need to treat all severe malaria with immediate intravenous artesunate.
The extravascular compartment of the bone marrow: a niche for Plasmodium falciparum gametocyte maturation?
Authors: Farfour Eric , Charlotte Frédéric , Settegrana Catherine , Miyara Makoto , Buffet Pierre 
Published: August 2012

Abstract

Background

Plasmodium falciparum immature gametocytes accumulate in the bone marrow, but their exact location in this tissue remains unclear.

Methods
The stage and deposition pattern of gametocytes was analysed on histological sections of a bone marrow sample collected in a patient with subacute P. falciparum malaria.

Results
A majority (89%) of immature stages II to IV gametocytes and a minority (29%) of mature stage V gametocytes were observed in extravascular spaces.

Discussion and conclusion
These observations represent a valuable step towards understanding sequestration patterns of P. falciparum gametocytes and may ultimately lead to novel transmission-blocking interventions.
IFN-γ-induced increase in the mobility of MHC class II compartments in astrocytes depends on intermediate filaments
Authors: Vardjan Nina , Gabrijel Mateja , Potokar Maja , Švajger Urban , Kreft Marko , Jeras Matjaž , de Pablo Yolanda , Faiz Maryam , Pekny Milos , Zorec Robert 
Published: August 2012

AbstractBackgroundIn immune-mediated diseases of the central nervous system, astrocytes exposed to interferon-γ (IFN-γ) can express major histocompatibility complex (MHC) class II molecules and antigens on their surface. MHC class II molecules are thought to be delivered to the cell surface by membrane-bound vesicles. However, the characteristics and dynamics of this vesicular traffic are unclear, particularly in reactive astrocytes, which overexpress intermediate filament (IF) proteins that may affect trafficking. The aim of this study was to determine the mobility of MHC class II vesicles in wild-type (WT) astrocytes and in astrocytes devoid of IFs.MethodsThe identity of MHC class II compartments in WT and IF-deficient astrocytes 48 h after IFN-γ activation was determined immunocytochemically by using confocal microscopy. Time-lapse confocal imaging and Alexa Fluor546-dextran labeling of late endosomes/lysosomes in IFN-γ treated cells was used to characterize the motion of MHC class II vesicles. The mobility of vesicles was analyzed using ParticleTR software.ResultsConfocal imaging of primary cultures of WT and IF-deficient astrocytes revealed IFN-γ induced MHC class II expression in late endosomes/lysosomes, which were specifically labeled with Alexa Fluor546-conjugated dextran. Live imaging revealed faster movement of dextran-positive vesicles in IFN-γ-treated than in untreated astrocytes. Vesicle mobility was lower in IFN-γ-treated IF-deficient astrocytes than in WT astrocytes. Thus, the IFN-γ-induced increase in the mobility of MHC class II compartments is IF-dependent.ConclusionsSince reactivity of astrocytes is a hallmark of many CNS pathologies, it is likely that the up-regulation of IFs under such conditions allows a faster and therefore a more efficient delivery of MHC class II molecules to the cell surface. In vivo, such regulatory mechanisms may enable antigen-presenting reactive astrocytes to respond rapidly and in a controlled manner to CNS inflammation.
Pathological femoral fractures due to osteomalacia associated with adefovir dipivoxil treatment for hepatitis B: a case report
Authors: Tanaka Motoyuki , Setoguchi Takao , Ishidou Yasuhiro , Arishima Yoshiya , Hirotsu Masataka , Saitoh Yoshinobu , Nakamura Shunsuke , Kakoi Hironori , Nagano Satoshi , Yokouchi Masahiro , Kamizono Junichi , Komiya Setsuro 
Published: August 2012

Abstract
We present a case of a 62-year-old man who underwent total hip arthroplasty for treatment of pathologic femoral neck fracture associated with adefovir dipivoxil-induced osteomalacia. He had a 13-month history of bone pain involving his shoulders, hips, and knee. He received adefovir dipivoxil for treatment of lamivudine-resistant hepatitis B virus infection for 5 years before the occurrence of femoral neck fracture. Orthopedic surgeons should be aware of osteomalacia and pathological hip fracture caused by drug-induced renal dysfunction, which results in Fanconi’s syndrome.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1600344696739249
Mass spectrometry quantification of clusterin in the human brain
Authors: Chen Junjun , Wang Meiyao , Turko Illarion V 
Published: August 2012

Abstract

Background
The multifunctional glycoprotein clusterin has been associated with late-onset Alzheimer’s disease (AD). Further investigation to define the role of clusterin in AD phenotypes would be aided by the development of techniques to quantify level, potential post-translational modifications, and isoforms of clusterin. We have developed a quantitative technique based on multiple reaction monitoring (MRM) mass spectrometry to measure clusterin in human postmortem brain tissues.

Results
A stable isotope-labeled concatenated peptide (QconCAT) bearing selected peptides from clusterin was expressed with an in vitro translation system and purified. This clusterin QconCAT was validated for use as an internal standard for clusterin quantification using MRM mass spectrometry. Measurements were performed on the human postmortem frontal and temporal cortex from control and severe AD cases. During brain tissues processing, 1% SDS was used in the homogenization buffer to preserve potential post-translational modifications of clusterin. However, MRM quantifications in the brain did not suggest phosphorylation of Thr393, Ser394, and Ser396 residues reported for clusterin in serum. MRM quantifications in the frontal cortex demonstrated significantly higher (P < 0.01) level of clusterin in severe AD group (39.1 ± 9.1 pmol/mg tissue protein) in comparison to control group (25.4 ± 4.4 pmol/mg tissue protein). In the temporal cortex, the clusterin levels were not significantly different, 29.0 ± 7.9 pmol/mg tissue protein and 28.0 ± 8.4 pmol/mg tissue protein in control and severe AD groups, respectively.

Conclusions
The proposed protocol is a universal quantitative technique to assess expression level of clusterin. It is expected that application of this protocol to quantification of various clusterin isoforms and potential post-translational modifications will be helpful in addressing the role of clusterin in AD.
Flexibility of EF-hand motifs: structural and thermodynamic studies of Calcium Binding Protein-1 from Entamoeba histolytica with Pb2+, Ba2+, and Sr2+
Authors: Kumar Shivesh , Ahmad Ejaz , Kumar Sanjeev , Khan Rizwan Hasan , Gourinath Samudrala 
Published: August 2012

Abstract

Background
EF-hand proteins can be activated by the binding of various heavy metals other than calcium, and such complexes can disturb the calcium-signaling pathway and cause toxicity and disease causing state. So far, no comprehensive study has been done to understand different heavy metals binding to calcium signaling proteins.

Results
In this work, the flexibility of the EF-hand motifs are examined by crystallographic and thermodynamic studies of binding of Pb2+, Ba2+ and Sr2+ to Calcium Binding Protein-1 from Entamoeba histolytica (EhCaBP1). The structures of the EhCaBP1- heavy metal complexes are found to be overall similar, nevertheless specific differences in metal coordination, and small differences in the coordination distances between the metal and the ligands in the metal binding loop. The largest such distances occur for the Ba2+- EhCaBP1 complex, where two bariums are bound with partial occupancy at the EF2 motif. Thermodynamic studies confirm that EhCaBP1 has five binding sites for Ba2+ compared to four binding sites for the other metals. These structures and thermodynamic studies reveal that the EF-hand motifs can accommodate several heavy atoms with similar binding affinities. The binding of Ca2+ to the 1st, 2nd and 4th sites and the binding of Ba2+ to the 1st, 2nd, 4th and 5th sites are both enthalpically and entropically driven, whereas the binding of Sr2+ to the 1st, 2nd and 4th sites are simply enthalpy driven, interestingly in agreement with ITC data, Sr2+ do not coordinate with water in this structure. For all the metals, binding to the 3rd site is only entropy driven.

Conclusion
Energetically, Ca2+ is preferred in three sites, while in one site Ba2+ has better binding energy. The Sr2+-coordination in the EF hand motifs is similar to that of the native Ca2+ bound structure, except for the lack of water coordination. Sr2+ coordination seems to be a pre-formed in nature since all seven coordinating atoms are from the protein itself, which also correlates with entropy contributions in Sr2+ binding. These findings improve our understanding of metal association with calcium binding proteins and of metal induced conformational changes.
Gene-expression profiling of microdissected breast cancer microvasculature identifies distinct tumor vascular subtypes
Authors: Pepin François , Bertos Nicholas , Laferrière Julie , Sadekova Svetlana , Souleimanova Margarita , Zhao Hong , Finak Greg , Meterissian Sarkis , Hallett Michael T , Park Morag 
Published: August 2012

Abstract
Introduction
Angiogenesis represents a potential therapeutic target in breast cancer. However, responses to targeted antiangiogenic therapies have been reported to vary among patients. This suggests that the tumor vasculature may be heterogeneous and that an appropriate choice of treatment would require an understanding of these differences.

Methods
To investigate whether and how the breast tumor vasculature varies between individuals, we isolated tumor-associated and matched normal vasculature from 17 breast carcinomas by laser-capture microdissection, and generated gene-expression profiles. Because microvessel density has previously been associated with disease course, tumors with low (n = 9) or high (n = 8) microvessel density were selected for analysis to maximize heterogeneity for this feature.

Results
We identified differences between tumor and normal vasculature, and we describe two subtypes present within tumor vasculature. These subtypes exhibit distinct gene-expression signatures that reflect features including hallmarks of vessel maturity. Potential therapeutic targets (MET, ITGAV, and PDGFRβ) are differentially expressed between subtypes. Taking these subtypes into account has allowed us to derive a vascular signature associated with disease outcome.

Conclusions
Our results further support a role for tumor microvasculature in determining disease progression. Overall, this study provides a deeper molecular understanding of the heterogeneity existing within the breast tumor vasculature and opens new avenues toward the improved design and targeting of antiangiogenic therapies.
Primary prevention of cardiovascular disease using validated risk scores: A systematic review
Authors: Willis Andrew , Davies Melanie , Yates Thomas , Khunti Kamlesh 
Published: August 2012

Objectives The high prevalence of cardiovascular disease (CVD) and the increased cost of treatment have prompted strategies for the primary prevention of CVD in the UK to move towards the use of validated CVD risk scores to identify individuals at the highest risk. There are no reviews evaluating the effectiveness of this strategy as a means of reducing CVD risk or mortality. This review summarizes current evidence for and against the use of validated CVD risk scores for the primary prevention of CVD. Design We utilized an in depth search strategy to search MEDLINE, EMBASE and the Cochrane database of clinical trials, expert opinions were sought and reference lists of identified studies and relevant reviews were checked. Due to a lack of homogeneity in outcomes and risk scores used it was not possible to conduct a meta-analysis of the identified studies. Setting The majority of included trials were carried out in a primary care setting. 2 trials were carried out in North America, 2 in Scandinavia and 1 in the UK. Participants 31,651 participants in total were recruited predominantly from a primary care setting. Participants were aged 18-65 years old and were free from CVD at baseline. Main outcome measures Outcome measures used in the included studies were change in validated CVD risk score and CVD/All-cause mortality. Results We identified 16 papers which matched the inclusion criteria reporting 5 unique trials. Due to a lack of homogeneity in outcomes and risk scores used it was not possible to conduct a meta-analysis of the identified studies. Only one study reported a significant difference in risk score at follow up and one study reported a significant difference in total mortality, however significant differences in individual risk factors were reported by the majority of identified studies. Conclusions This review demonstrates the potential for multifactorial interventions aimed at individuals selected by CVD risk scores for lowering CVD risk and mortality. However, the majority of studies in this area do not provide an intensity of intervention which is sufficient in significantly reducing CVD mortality or validated CVD risk.
Hip precautions after hemiarthroplasty: what is happening in the UK and at what cost?
Authors: Fox R , Halliday R , Barnfield S , Roxburgh J , Dunford J , Chesser TJS 
Published: August 2012

INTRODUCTION The aim of this study was to observe current practice of the use of hip precautions following hemiarthroplasty for hip fractures in England and to audit the cost of hip precautions in this patient group. METHODS A telephone review was undertaken of all units identified by the National Hip Fracture Database as receiving centres for hip fractures across England to ascertain current practice in the use of hip precautions. A prospective audit of occupational therapy (OT) practice including the cost of equipment provision and OT time was carried out locally. RESULTS All 174 units in England were successfully contacted. Practice varied between centres but hip precautions were in use at 78% of centres. Prior to stopping hip precautions at the local hospital, we audited the costs associated with their use. Mean equipment costs per patient decreased by £12 (from £49 to £37, range: £0–£83) and mean OT time per patient decreased by 1.5 hours (from 8 hours to 6.5 hours, range: 1–22 hours) following removal of hip precaution guidelines. A mean of 0.25 days' discharge delay (range: 0–4 days) due to equipment provision was identified prior to removing hip precautions with no discharge delay following. CONCLUSIONS This study has highlighted the variation in practice across the country and inconsistency with the advice published by the British Orthopaedic Association and British Geriatrics Society in the ‘Blue Book’ (The Care of Patients with Fragility Fracture). Hip precautions are unnecessary after hemiarthroplasty, cost money both in therapist time and equipment provision and increase the length of hospital stay. Nevertheless, they continue to be used by three-quarters of trauma hospitals in England.