A DNA configuration switch was designed to fabricate a reversible and regenerable Raman-active substrate. The substrate is composed of an Au film and hairpin-shaped DNA strand (hot spot generation probes, HSGPs) labeled with dye-functionalized silver nanoparticle (AgNP). Another ssDNA that recognizes a specific trigger was used as an antenna. The HSGPs are immobilized on the Au film to draw the dye-functionalized AgNPs close to the Au surface and create an intense electromagnetic field. Hybridization of HSGP with the two arm segments of the antenna forms a triplex-stem structure to separate the dye-functionalized AgNP from the Au surface and cause a quenching of the Raman signal. Interaction with its trigger leads to release of the antenna from the triplex-stem structure, and the hairpin structure of the HSGP is restored, thereby creating an effective “off” to “on” state of the Raman signal. Nucleic acid sequence associated with the HIV-1 U5 long terminal repeat sequences and ATP are used as the triggers. The substrate shows excellent reversibility, reproducibility and controllability of SERS effects, which are significant requirements for practical SERS sensor applications.
Rare opportunistic (non-Candida, non-Cryptococcus) yeast bloodstream infections (ROYBSIs) are rare, even in cancer patients.
We retrospectively reviewed all episodes of ROYBSIs occurring from 1998 to 2010 in our cancer center.
Of 2984 blood cultures positive for Candida and non-Candida yeasts, 94 (3.1%) were positive for non-Candida yeasts, representing 41 ROYBSIs (incidence, 2.1 cases/100,000 patient-days). Catheter-associated fungemia occurred in 21 (51%) patients. Breakthrough ROYBSIs occurred in 20 (49%) patients. The yeast species distribution was Rhodotorula in 21 (51%) patients, Trichosporon in 8 (20%) patients, Saccharomyces cerevisiae in 8 (20%) patients, Geotrichum in 2 (5%) patients, Pichia anomala, and Malassezia furfur in 1 patient each. All tested Trichosporon, Geotrichum, and Pichia isolates were azole-susceptible, whereas the Rhodotorula isolates were mostly azole-resistant. We noted echinocandin nonsusceptibility (minimal inhibitory concentration ≥ 2 mg/L) in all but the S. cerevisiae isolates. Most of the isolates (28/33 [85%]) were susceptible to amphotericin B. The mortality rate in all patients at 30 days after ROYBSIs diagnosis was 34%. Multivariate survival analysis revealed increased risk of death in patients with S. cerevisiae infections (hazard ratio, 3.7), Geotrichum infections (hazard ratio, 111.3), or disseminated infections (hazard ratio, 33.4) and reduced risk in patients who had catheter removal (hazard ratio, 0.1).
ROYBSIs are uncommon in patients with cancer, and catheters are common sources of them. Half of the ROYBSIs occurred as breakthrough infections, and in vitro species-specific resistance to echinocandins and azoles was common. Disseminated infections resulted in the high mortality rate.
Non-Candida yeast; Cancer; Immunosuppression
Ginsenoside Rb1 (RB1), the most clinically effective constituent of ginseng, possesses a variety of biological activities. The objectives of this study were to investigate the protective effects of RB1 and its underlying mechanism on renal injury induced by intestinal ischemia-reperfusion (IIR) in mice. RB1 was administered prior to inducing IIR achieved by occluding the superior mesenteric artery for 45 min followed by 120 min of reperfusion. All-trans-retinoic acid (ATRA) was used as an inhibitor of NF-E2-related factor-2 (Nrf2) signaling. Adult male C57BL/6J mice were randomly divided into six groups: (1) sham group, (2) IIR group, (3) RB1 group, (4) sham + ATRA group, (5) IIR + ATRA group, and (6) RB1 + ATRA group. Intestinal histology and pathological injury score were observed. Intestinal mucosal injury was also evaluated by measuring serum diamine oxidase (DAO). Renal injury induced by IIR was characterized by increased levels of histological severity score, blood urea nitrogen (BUN), serum creatinine (Scr) and neutrophil gelatinase-associated lipocalin (NGAL), which was accompanied with elevated renal TUNEL-positive cells and the Bcl-2/Bax expression ratio. RB1 significantly reduced renal injury and apoptosis as compared with IIR group, which was reversed by ATRA treatment. Immunohistochemistry and Western blot analysis demonstrated that RB1 significantly upregulated the protein expression of heme oxygenase-1 (HO-1) and Nrf2, which were attenuated by ATRA treatment. Taken together, these results suggest that the protective effects of RB1 pretreatment against renal injury induced by IIR are associated with activation of the Nrf2/ anti-oxidant response element (ARE) pathway.
The discovery of topological insulators (TIs) has led to numerous exciting opportunities for studying topological states of quantum physics and for exploring spintronic applications due to the new physics arising from their robust metallic surface states. Here, we report the high-quality topological insulator (BixSb1−x)2Te3 thin films using a single van der Waals GaSe buffer layer. As a result, ultra-low surface carrier density of 1.3 × 1012 cm−2 and a high Hall mobility of 3100 cm2/Vs have been achieved for (Bi0.53Sb0.47)2Te3. The high-quality films enable us to observe quantum oscillations associated with the top and bottom surface states and to manipulate the Dirac electrons and bulk holes' conduction properties. The observation of the two surface states may lead to a path towards the implementation of TIs in spintronics.
In spite of much work on topological insulators (TIs), systematic experiments for TI/TI heterostructures remain absent. We grow a high quality heterostructure containing single quintuple layer (QL) of Bi2Se3 on 19 QLs of Bi2Te3 and compare its transport properties with 20 QLs Bi2Se3 and 20 QLs Bi2Te3. All three films are grown on insulating sapphire (0001) substrates by molecular beam epitaxy (MBE). In situ angle-resolved photoemission spectroscopy (ARPES) provides direct evidence that the surface state of 1 QL Bi2Se3/19 QLs Bi2Te3 heterostructure is similar to the surface state of the 20 QLs Bi2Se3 and different with that of the 20 QLs Bi2Te3. In ex situ transport measurements, the observed linear magnetoresistance (MR) and weak antilocalization (WAL) of the hybrid heterostructure are similar to that of the pure Bi2Se3 film and not the Bi2Te3 film. This suggests that the single Bi2Se3 layer on top of 19 QLs Bi2Te3 dominates its transport properties.
Mosaic Analysis with Double Markers (MADM) is a mouse genetic system that allows simultaneous gene knockout and fluorescent labeling of sparse, clonally-related cells within an otherwise normal mouse, thereby circumventing embryonic lethality problems and providing single-cell resolution for phenotypic analysis in vivo. The clonal efficiency of MADM is intrinsically low because it relies on Cre/loxP-mediated mitotic recombination between two homologous chromosomes rather than within the same chromosome, as in the case of conditional knockout (CKO). Although sparse labeling enhances in vivo resolution, the original MADM labels too few or even no cells when a low-expressing Cre transgene is used or a small population of cells is studied. Recently, we described the usage of a new system, MADM-ML, which contains three mutually exclusive, self-recognizing loxP variant sites as opposed to a single loxP site present in the original MADM system (referred to as MADM-SL in this paper). Here we carefully compared the recombination efficiency between MADM-SL and MADM-ML using the same Cre transgene, and found that the new system labels significantly more cells than the original system does. When we established mouse medulloblastoma models with both the original and the new MADM systems, we found that, while the MADM-SL model suffered from varied tumor progression and incomplete penetrance, the MADM-ML model had consistent tumor progression and full penetrance of tumor formation. Therefore MADM-ML, with its higher recombination efficiency, will broaden the applicability of MADM for studying many biological questions including normal development and disease modeling at cellular resolution in vivo.
Kidney transplant recipients are recognized as a vulnerable population that is at increased risk of adverse health outcomes. However, there have been few studies that have compared hospital-related morbidity of these patients to the general population, and how this differs with respect to time since transplantation. Such analyses are useful in estimating the health burden in this patient population.
We assembled a population-based Canadian cohort (excluding Quebec) of 6,116 kidney transplant recipients who underwent transplantation between 1 April 2001 and 31 December 2008. Record linkage was used to identify hospital discharge records of these patients from 1 April 2001 through 31 March 2009. Hospital discharges were tabulated across the main disease chapters of the ICD10, and person-years of follow-up were calculated across age and sex strata. Comparisons of hospital-related morbidity to the general population were made by using a standardized hospitalization ratio (SHR). For those who underwent transplantation in 2004, stratified analyses were performed to explore differences in hospital discharge rates both before and after transplantation.
After excluding hospitalizations due to complications from transplantation, when compared to the general population, transplant recipients were approximately 6.4 (95% CI: 6.3, 6.5) times more likely to be hospitalized during follow-up. The SHRs were highest during the time periods proximate to transplantation, and then decreased to approximately a five-fold increase from 3 years post transplantation onwards. The largest disease-specific excesses were observed with infectious diseases and diseases of the endocrine system. Among those who underwent transplantation in 2004, the SHR decreased from 11.2 to 5.0 in the periods before and after surgery, respectively.
Our results indicate that, even more than 5-years post transplantation, there remains a more than six-fold difference in hospitalization rates relative to the general population. Additional work is needed to confirm these findings, and to develop strategies to reduce long-term morbidity in this patient population.
Cohort study; Kidney transplantation; Record linkage; Standardized hospitalization ratio
The forkhead box transcription factor Foxo3a has been implicated to play a critical role in various cancers by suppressing tumor growth. Recent studies have identified Foxo3a as a key regulator of Estrogen Receptor-α (ERα). In the present study, we examined the expression of Foxo3a, and investigated its clinical significance and correlation with ER and prognostic role in patients with breast cancer. Immunohistochemical analysis was performed on tumors from 70 breast cancer patients. Interpretable Foxo3a expression was analyzed along with major clinicopathologic variables, and a comparison was made with corresponding 5-year clinical follow-up data. Foxo3a protein expression correlated with ER positivity (P<0.001), histologic grade (1, 2) (P = 0.002), axillary lymph node negativity (P<0.001) and TNM stage (1, 2) (P<0.001). Moreover, the Kaplan-Meier survival curves of the study population showed that a high expression level of Foxo3a was significantly correlated with long-term survival (P<0.0001). In a multivariate analysis, Foxo3a expression was identified as a favorable independent prognostic factor in overall survival (P = 0.038). In conclusion, our results indicated that Foxo3a expression is a favorable prognostic marker in breast cancer. In addition, Foxo3a staining could potentially be used in patient stratification in conjunction with other prognostic markers.
Nemo-like kinase (NLK), a mediator of the Wnt signaling pathway, binds directly to c-Myb, leading to its phosphorylation, ubiquitination and proteasome-dependent degradation. NLK was significantly downregulated in the breast cancer tissues compared to corresponding normal tissues. NLK expression was negatively correlated with c-Myb expression. NLK suppressed proliferation, induced apoptosis and mediated c-Myb degradation in MCF-7 cells via a mechanism that seems to involve c-myc and Bcl2. These findings might provide a novel target for therapeutic intervention in patients with breast cancer.
AIM: To evaluate the clinical outcome of re-operation for recurrent abdominal liposarcoma following multidisciplinary team cooperation.
METHODS: Nineteen consecutive patients who had recurrent abdominal liposarcoma underwent re-operation by the retroperitoneal sarcoma team at our institution from May 2009 to January 2012. Patient demographic and clinical data were reviewed retrospectively. Multidisciplinary team discussions were held prior to treatment, and re-operation was deemed the best treatment. The categories of the extent of resection were as follows: gross total resection (GTR), palliative resection and partial resection. Surgical techniques were divided into discrete lesion resection and combined contiguous multivisceral resection (CMR). Tumor size was determined as the largest diameter of the specimen. Patients were followed up at approximately 3-monthly intervals. For survival analysis, a univariate analysis was performed using the Kaplan-Meier method, and a multivariate analysis was performed using the Cox proportional hazards model.
RESULTS: Nineteen patients with recurrent abdominal liposarcoma (RAL) underwent 32 re-operations at our institute. A total of 51 operations were reviewed with a total follow-up time ranging from 4 to 120 (47.4 ± 34.2) mo. The GTR rate in the CMR group was higher than that in the non-CMR group (P = 0.034). CMR was positively correlated with intra-operative bleeding (correlation coefficient = 0.514, P = 0.010). Six cases with severe postoperative complications were recorded. Patients with tumor sizes greater than 20 cm carried a significant risk of profuse intra-operative bleeding (P = 0.009). The ratio of a highly malignant subtype (dedifferentiated or pleomorphic) in recurrent cases was higher compared to primary cases (P = 0.027). Both single-factor survival using the Kaplan-Meier model and multivariate analysis using the Cox proportional hazards model showed that overall survival was correlated with resection extent and pathological subtype (P < 0.001 and P = 0.02), however, relapse-free interval (RFI) was only correlated with resection extent (P = 0.002).
CONCLUSION: Close follow-up should be conducted in patients with RAL. Early re-operation for relapse is preferred and gross resection most likely prolongs the RFI.
Overall survival; Recurrent abdominal liposarcoma; Relapse-free interval
Neuromyelitis optica (NMO) shows various brain magnetic resonance imaging (MRI) abnormalities with recurrent central nervous system (CNS) attacks, although predominantly affecting the spinal cord and optic nerve. However, NMO with extensive involvement of the brain has infrequently been studied. We investigated the clinical, radiographic features and immunomodulating changes of NMO patients with extensive brain lesions (EBLs) in China.
NMO patients (including 16 NMO patients with EBLs and 53 NMO patients without EBLs) hospitalized during January 2006 and February 2010 were recruited and analyzed retrospectively. Data of clinical characteristics, magnetic resonance imaging (MRI) features, laboratory abnormalities, treatment details and outcomes were analyzed. All the patients received the follow-up visits for two years.
EBLs in NMO were classified into four categories according to their respective MRI characteristics: 1) Tumefactive-like lesions (n=4, 25%); 2) Acute disseminated encephalomyelitis (ADEM)-like lesions (n=6, 37.5%); 3) Multiple sclerosis (MS)-like lesions (n=5, 31.25%); 4) Posterior reversible encephalopathy syndrome (PRES)-like lesions (n=1, 6.25%). NMO patients with EBLs had higher rates of encephalopathy symptoms (37.5% vs. 5.6%, p = 0.004), homonymous hemianopia (18.8% vs. 0%, p = 0.011) and AQP4 seropositivity (100% vs. 69.8%, p = 0.008) than NMO patients without EBLs (NEBLs). Immunomodulating changes (including the levels of C3, C4, ESR and CRP) were significantly higher in patients with EBLs than those without EBLs. The relapse times in EBLs during the follow-up period were more frequent than those happened in NEBLs (1.88 ± 0.30 vs. 1.23 ± 0.14, p = 0.04). The EDSS scores in EBLs patients were also much higher than those in NEBLs throughout all the whole visits of follow-up.
The presence of EBLs in NMO may indicate a higher diseases activity and portend a worse prognosis. CRP is a useful marker in monitoring diseases activity. Systemic inflammation may be crucial to the formation of EBLs in NMO.
Aquaporin-4; Complement; C-reactive Protein; Erythrocyte sedimentation rate; Extensive brain lesions; Magnetic resonance imaging; Neuromyelitis optica
Certain types of the Human Papillomavirus (HPV) are sexually transmitted and highly associated with development of cervical dysplasia and cervical cancer but the distribution of HPV infection in the North, particularly amongst First Nations, Metis, and Inuit peoples, is little known. The purposes of the study are to identify the prevalence of type-specific HPV infections and the association of different HPV types with cervical dysplasia among women in Northern Canada.
This was a cross-sectional study with attendants of the routine or scheduled Pap testing program in the Northwest Territories (NWT), Nunavut, Labrador and Yukon, Canada. Approximately half of each sample was used for Pap test and the remaining was used for HPV genotyping using a Luminex-based method. Pap test results, HPV types, and demographic information were linked for analyses.
Results from 14,598 specimens showed that HPV infection was approximately 50% higher among the Aboriginal than the non-Aboriginal population (27.6% vs. 18.5%). Although the most common HPV type detected was HPV 16 across region, the prevalence of other high risk HPV types was different. The age-specific HPV prevalence among Aboriginal showed a ‘U’ shape which contrasted to non-Aboriginal. The association of HPV infection with cervical dysplasia was similar in both Aboriginal and non-Aboriginal populations.
The HPV prevalence was higher in Northern Canada than in other Areas in Canada. The prevalence showed a higher rate of other high risk HPV infections but no difference of HPV 16/18 infections among Aboriginal in comparison with non-Aboriginal women. This study provides baseline information on HPV prevalence that may assist in surveillance and evaluation systems to track and assess HPV vaccine programs.
Human papillomavirus; Prevalence; Pap abnormality; Northern region
Tumor-specific antigens (TSAs) are central elements in the immune control of cancers. To systematically explore the TSA genome, we developed a computational technology called Heterogeneous Expression Profile Analysis (HEPA), which can identify genes relatively uniquely expressed in cancer cells in contrast to normal somatic tissues. Rating human genes by their HEPA score enriched for clinically useful TSA genes, nominating candidate targets whose tumor-specific expression was verified by RT-PCR. Coupled with HEPA, we designed a novel assay termed Protein A/G based Reverse Serological Evaluation (PARSE) for quick detection of serum autoantibodies against an array of putative TSA genes. Remarkably, highly tumor-specific autoantibody responses against seven candidate targets were detected in 4–11% of patients, resulting in distinctive autoantibody signatures in lung and stomach cancers. Interrogation of a larger cohort of 149 patients and 123 healthy individuals validated the predictive value of the autoantibody signature for lung cancer. Together, our results establish an integrated technology to uncover a cancer-specific antigen genome offering a reservoir of novel immunological and clinical targets.
Tumor specific antigen; TSA; Gene expression profiling; New algorithims; Immunodiagnosis; Autoantibody signatures
Gestational diabetes mellitus (GDM) has been shown to be associated with high risk of diabetes in offspring. However, the mechanisms involved and the possibilities of transgenerational transmission are still unclear. We intercrossed male and female adult control and first-generation offspring of GDM (F1-GDM) mice to obtain the second-generation (F2) offspring in four groups: C♂-C♀, C♂-GDM♀, GDM♂-C♀, and GDM♂-GDM♀. We found that birth weight significantly increased in F2 offspring through the paternal line with impaired glucose tolerance (IGT). Regardless of birth from F1-GDM with or without IGT, high risk of IGT appeared as early as 3 weeks in F2 offspring and progressed through both parental lineages, especial the paternal line. IGT in male offspring was more obvious than that in females, with parental characteristics and sex-specific transmission. In both F1 and F2 offspring of GDM, the expression of imprinted genes Igf2 and H19 was downregulated in pancreatic islets, caused by abnormal methylation status of the differentially methylated region, which may be one of the mechanisms for impaired islet ultrastructure and function. Furthermore, altered Igf2 and H19 gene expression was found in sperm of adult F1-GDM, regardless of the presence of IGT, indicating that changes of epigenetics in germ cells contributed to transgenerational transmission.
Squamous cell carcinomas (SCC) are sun-induced skin cancers that are particularly numerous and aggressive in immunosuppressed individuals. SCC evade immune detection at least in part by down-regulating E-selectin on tumor vessels, thereby restricting entry of skin homing T cells into tumors. We find that nitric oxide potently suppresses E-selectin expression on human endothelial cells and that SCC are infiltrated by nitric oxide-producing iNOS+ CD11b+ CD33+ CD11c− HLA-DR− myeloid-derived suppressor cells (MDSC). MDSC from SCC produced NO, TGFβ and arginase and inhibited endothelial E-selectin expression in vitro. MDSC from SCC expressed the chemokine receptor CCR2 and tumors expressed the CCR2 ligand HBD3, suggesting CCR2-HBD3 interactions may contribute to MDSC recruitment to SCC. Treatment of SCC in vitro with the iNOS inhibitor L-NNA induced E-selectin expression at levels comparable to imiquimod-treated SCC undergoing immunologic destruction. Our results suggest that local production of NO in SCC may impair vascular E-selectin expression. We show that MDSC are critical producers of NO in SCC and that NO inhibition restores vascular E-selectin expression, potentially enhancing T cell recruitment. iNOS inhibitors and other therapies that reduce NO production may therefore be effective in the treatment of SCC and their premalignant precursor lesions actinic keratoses.
This paper describes progress on formulating a national asbestos profile for the country of Vietnam. The Center of Asbestos Resource, Vietnam, formulated a National Profile on Asbestos-related Occupational Health, with due reference to the International Labor Organization/World Health Organization National Asbestos Profile. The Center of Asbestos Resource was established by the Vietnamese Health Environment Management Agency and the National Institute of Labor Protection, with the support of the Australian Agency for International Development, as a coordinating point for asbestos-related issues in Vietnam. Under the National Profile on Asbestos-related Occupational Health framework, the Center of Asbestos Resource succeeded in compiling relevant information for 15 of the 18 designated items outlined in the International Labor Organization/World Health Organization National Asbestos Profile, some overlaps of the information items notwithstanding. Today, Vietnam continues to import and use an average of more than 60,000 metric tons of raw asbestos per year. Information on asbestos-related diseases is limited, but the country has begun to diagnose mesothelioma cases, with the technical cooperation of Japan. As it stands, the National Profile on Asbestos-related Occupational Health needs further work and updating. However, we envisage that the National Profile on Asbestos-related Occupational Health will ultimately facilitate the smooth transition to an asbestos-free Vietnam.
asbestos; asbestos-related diseases; ILO/WHO National Asbestos Profile; ILO/WHO; Vietnam
Pathogenic Neisseria meningitidis isolates contain a polysaccharide capsule that is the main virulence determinant for this bacterium. Thirteen capsular polysaccharides have been described, and nuclear magnetic resonance spectroscopy has enabled determination of the structure of capsular polysaccharides responsible for serogroup specificity. Molecular mechanisms involved in N. meningitidis capsule biosynthesis have also been identified, and genes involved in this process and in cell surface translocation are clustered at a single chromosomal locus termed cps. The use of multiple names for some of the genes involved in capsule synthesis, combined with the need for rapid diagnosis of serogroups commonly associated with invasive meningococcal disease, prompted a requirement for a consistent approach to the nomenclature of capsule genes. In this report, a comprehensive description of all N. meningitidis serogroups is provided, along with a proposed nomenclature, which was presented at the 2012 XVIIIth International Pathogenic Neisseria Conference.
Neisseria meningitidis; capsule; serogroup; bacteria; nomenclature
The Phosphate transporter 1 (PHT1) gene family has crucial roles in phosphate uptake, translocation, remobilization, and optimization of metabolic processes using of Pi. Gene duplications expand the size of gene families, and subfunctionalization of paralog gene pairs is a predominant tendency after gene duplications. To date, experimental evidence for the evolutionary relationships among different paralog gene pairs of a given gene family in soybean is limited.
All potential Phosphate transporter 1 genes in Glycine max L. (GmPHT1) were systematically analyzed using both bioinformatics and experimentation. The soybean PHT1 genes originated from four distinct ancestors prior to the Gamma WGT and formed 7 paralog gene pairs and a singleton gene. Six of the paralog gene pairs underwent subfunctionalization, and while GmPHT1;4 paralog gene experienced pseudogenization. Examination of long-term evolutionary changes, six GmPHT1 paralog gene pairs diverged at multiple levels, in aspects of spatio-temporal expression patterns and/or quanta, phosphates affinity properties, subcellular localization, and responses to phosphorus stress.
These characterized divergences occurred in tissue- and/or development-specific modes, or conditional modes. Moreover, they have synergistically shaped the evolutionary rate of GmPHT1 family, as well as maintained phosphorus homeostasis at cells and in the whole plant.
Phosphate transporter 1; Gene duplication; Gene divergence; Phosphorus homeostasis; Evolution; Glycine max L.
Arterial calcification is a significant cardiovascular risk factor in hemodialysis patients. A series of factors are involved in the process of arterial calcification; however, the relationship between malnutrition and arterial calcification is still unclear.
68 hemodialysis patients were enrolled in this study. Nutrition status was evaluated using modified quantitative subjective global assessment (MQSGA). Related serum biochemical parameters were measured. And the radial artery samples were collected during the arteriovenous fistula surgeries. Hematoxylin/eosin stain was used to observe the arterial structures while Alizarin red stain to observe calcified depositions and classify calcified degree. The expressions of bone morphogenetic protein 2 (BMP2) and matrix Gla protein (MGP) were detected by immunohistochemistry and western blot methods.
66.18% hemodialysis patients were malnutrition. In hemodialysis patients, the calcified depositions were mainly located in the medial layer of the radial arteries and the expressions of BMP2 and MGP were both increased in the calcified areas. The levels of serum albumin were negatively associated with calcification score and the expressions of BMP2 and MGP. While MQSGA score, serum phosphorus and calcium × phosphorus product showed positive relationships with calcification score and the expressions of BMP2 and MGP.
Malnutrition is prevalent in hemodialysis patients and is associated with arterial calcification and the expressions of BMP2 and MGP in calcified radial arteries. Malnutrition may be a new inducer candidate for arterial calcification in hemodialysis patients.
Arterial calcification; Hemodialysis; Malnutrition; Bone morphogenetic protein 2; Matrix Gla protein
To examine the prevalence and factors affecting activity-limiting injuries (ALI) in individuals and in the Canadian population; to estimate the short and long term impact on health status and well-being because of ALI in Canada from 1994 to 2006 using the Canadian National Population Health Survey (NPHS).
The NPHS is a randomised longitudinal cohort study with biennial interviews, with information on age, sex, education, marital status, income, residence, height and weight to self-perceived health status, healthcare utilisation and medication use in addition to ALI.
The study population was a random sample of male and female participants 20 years and older from 10 provinces and three territories in Canada.
Primary and secondary outcome measures
Logistic regression models were used to assess the potential impact of ALI on individuals and on the Canadian population. The interviews 2 years before and 2 years after the ALI were compared to examine long-term effects, and the McNemar test option in SAS was used for the matched analysis.
The immediate impacts of ALI were pain, disability and disruption of regular life. Long-term effects in patients were chronic pain and increased medical doctor visits. Population impact included a considerable increase in healthcare access and cost. The odds ratios (OR) for the 20–39 age group compared with those 60+ was 2.2; 95% CI 1.8 to 2.7, while the OR associated with male participants was 1.4; 95% CI 1.1 to 1.6. Individuals consuming nine or more alcoholic drinks per week were also significantly more likely to report an ALI (OR, 1.5; 95% CI 1.3 to 1.8).
The findings from this study illustrated the immediate and long-term impact of individuals and population level injuries in Canada. Injury control policies should aim to prevent the number of injuries, fatalities as well as the consequences among survivors.
Background and methods:
In this report, layered microporous titanate nanowire scaffolds (TiNWs) were constructed via a hydrothermal route and then decorated with anatase nanocrystals (ANs@TiNWs) by immersion in TiCl4 solution. The diameter and specific surface area of the ANs@TiNWs was measured. The TiNWs and ANs@TiNWs were then compared for their ability to adsorb protein and adhere to MG63 cells.
The diameter and specific surface area of the ANs@TiNWs were significantly larger than for TiNWs, and the ANs@TiNWs had an enhanced protein-adsorbing effect. It was found that the MG63 cells were less able to adhere to the flat titanium substrate than the TiNWs and ANs@TiNWs, and that this cell-repellant ability was greater with ANs@TiNWs. Other MG63 cell functions, proliferation in particular, were also inhibited by ANs@TiNWs.
ANs@TiNWs show a high protein adsorption and cell-repellant capacity which would be useful in drug delivery.
protein adsorption; antiadhesion; nanotopography; drug delivery
MicroRNAs (miRNAs) have been shown to be dysregulated in virus-related cancers; however, miRNA regulation of virus-related cancer development and progression remains poorly understood. Here, we report that miR-148a is repressed by hepatitis B virus (HBV) X protein (HBx) to promote cancer growth and metastasis in a mouse model of hepatocellular carcinoma (HCC). Hematopoietic pre–B cell leukemia transcription factor–interacting protein (HPIP) is an important regulator of cancer cell growth. We used miRNA target prediction programs to identify miR-148a as a regulator of HPIP. Expression of miR-148a in hepatoma cells reduced HPIP expression, leading to repression of AKT and ERK and subsequent inhibition of mTOR through the AKT/ERK/FOXO4/ATF5 pathway. HBx has been shown to play a critical role in the molecular pathogenesis of HBV-related HCC. We found that HBx suppressed p53-mediated activation of miR-148a. Moreover, expression of miR-148a was downregulated in patients with HBV-related liver cancer and negatively correlated with HPIP, which was upregulated in patients with liver cancer. In cultured cells and a mouse xenograft model, miR-148a reduced the growth, epithelial-to-mesenchymal transition, invasion, and metastasis of HBx-expressing hepatocarcinoma cells through inhibition of HPIP-mediated mTOR signaling. Thus, miR-148a activation or HPIP inhibition may be a useful strategy for cancer treatment.
A higher incidence of cervical cancer and human papillomavirus (HPV) infection has been reported in northern Canada and in First Nation, Métis and Inuit women, with some evidence to suggest that the HPV type distribution in these populations may be different from the rest of Canada.
The objective of this study was to measure the HPV type prevalence in Labrador women to determine if significant differences in HPV types could reduce the effectiveness of HPV vaccination.
The prevalence of HPV types was determined in 1,370 women presenting for routine pap screening in Labrador between February and November 2010. Cervical cytology and HPV genotyping were performed on the same liquid-based cytology specimens.
The overall prevalence of HPV was 21.4%; cytological abnormalities were found in 8.8% of the participants. HPV 16 and 18 were the most common high-risk HPV types. These two types were found in 52.4% of high-grade lesions. The prevalence in HPV infections was comparable across the Labrador regions.
The present results support the potential effectiveness of the HPV immunization program in Labrador.
human papillomavirus; cervical cancer; aboriginal populations; prevalence
Non-traumatic rhabdomyolysis is a rare complication of acute pancreatitis. One of the major risk factors of both acute pancreatitis and rhabdomyolysis is alcohol abuse. However, only a few studies have reported the prognosis and association of severe acute pancreatitis (SAP) and rhabdomyolysis in alcohol abuse patients. In the present study, we report two cases presenting with SAP complicated by rhabdomyolysis following high-dose alcohol intake. The disease onset, clinical manifestations, laboratory data, diagnosis and treatment procedure of each patient were recorded, and the association with rhabdomyolysis was analyzed. Alcohol consumption was the most predominant cause of SAP and rhabdomyolysis in these patients. SAP-related rhabdomyolysis was primarily induced by the toxicity associated with pancreatic necrosis. The laboratory tests revealed that the concentration of serum creatine kinase (CK) and myoglobin increased and acute renal failure symptoms were present, which provided an exact diagnosis for SAP-induced rhabdomyolysis. Rhabdomyolysis and subsequent hypermyoglobinuria severely impaired kidney function and aggravated hypocalcemia. The therapy of early stage SAP complicated by rhabdomyolysis involved liquid resuscitation support. When first stage treatment fails, blood purification should be performed immediately. Both patients developed multiple organ failure (MOF) and succumbed to the disease. Considering the two cases presented, we conclude that alcohol-related SAP complicated by rhabdomyolysis may have a poor clinical prognosis.
alcohol abuse; severe acute pancreatitis; rhabdomyolysis
Minocycline-rifampin-impregnated central venous catheters (M/R CVCs) have been shown to be efficacious in reducing catheter-related bloodstream infections (CRBSI) and inhibiting the biofilm adherence of resistant Gram-positive and Gram-negative pathogens, with the exception of Pseudomonas aeruginosa and Candida spp. To expand the spectrum of antimicrobial activity, a novel second-generation M/R catheter was developed by adding chlorhexidine (CHX-M/R). CVCs and peripherally inserted central catheters (PICCs) were impregnated with CHX-M/R and compared with first-generation M/R catheters, CHX-silver sulfadiazine-treated CVCs (CHX/SS-CVCs), chlorhexidine-treated PICCs, and uncoated catheters. A biofilm catheter colonization model was used to assess the efficacy of catheters against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), P. aeruginosa, Candida albicans, and Candida glabrata. CHX-M/R-impregnated CVCs were the only antimicrobial catheters that completely inhibited the biofilm colonization of all resistant bacterial and fungal organisms tested at all time intervals, and they were significantly superior to uncoated catheters (all P values were ≤0.003). Furthermore, CHX-M/R-coated CVCs had a significantly more effective and prolonged (up to 3 weeks) antimicrobial activity against MRSA and P. aeruginosa than M/R, CHX/SS, and uncoated CVCs (P < 0.0001). Similarly, CHX-M/R-coated PICCs were also superior to M/R-coated and CHX-coated PICCs in preventing biofilms of MRSA, VRE, P. aeruginosa, and Candida species (P value = 0.003 for all). Our study shows that novel CHX-M/R-coated catheters have unique properties in completely inhibiting biofilm colonization of MRSA, VRE, P. aeruginosa, and fungi in a manner superior to that of M/R- and chlorhexidine-treated catheters.