Catalytic ozone oxidation of benzene at low temperature over MnOx/Al-SBA-16 catalyst

The low-temperature catalytic ozone oxidation of benzene was investigated. In this study, Al-SBA-16 (Si/Al = 20) that has a three-dimensional cubic Im3m structure and a high specific surface area was used for catalytic ozone oxidation for the first time. Two different Mn precursors, i.e., Mn acetate and Mn nitrate, were used to synthesize Mn-impregnated Al-SBA-16 catalysts. The characteristics of these two catalysts were investigated by instrumental analyses using the Brunauer-Emmett-Teller method, X-ray diffraction, X-ray photoelectron spectroscopy, and temperature-programmed reduction. A higher catalytic activity was exhibited when Mn acetate was used as the Mn precursor, which is attributed to high Mn dispersion and a high degree of reduction of Mn oxides formed by Mn acetate than those formed by Mn nitrate

Implication of NOD1 and NOD2 for the Differentiation of Multipotent Mesenchymal Stem Cells Derived from Human Umbilical Cord Blood

Toll-like receptors (TLRs) and Nod-like receptors (NLRs) are known to trigger an innate immune response against microbial infection. Although studies suggest that activation of TLRs modulate the function of mesenchymal stem cells (MSCs), little is known about the role of NLRs on the MSC function. In this study, we investigated whether NOD1 and NOD2 regulate the functions of human umbilical cord blood-derived MSCs (hUCB-MSCs). The genes of TLR2, TLR4, NOD1, and NOD2 were expressed in hUCB-MSCs. Stimulation with each agonist (Pam3CSK4 for TLR2, LPS for TLR4, Tri-DAP for NOD1, and MDP for NOD2) led to IL-8 production in hUCB-MSC, suggesting the expressed receptors are functional in hUCB-MSC. CCK-8 assay revealed that none of agonist influenced proliferation of hUCB-MSCs. We next examined whether TLR and NLR agonists affect osteogenic-, adipogenic-, and chondrogenic differentiation of hUCB-MSCs. Pam3CSK4 and Tri-DAP strongly enhanced osteogenic differentiation and ERK phosphorylation in hUCB-MSCs, and LPS and MDP also slightly did. Treatment of U0126 (MEK1/2 inhibitor) restored osteogenic differentiation enhanced by Pam3CSK4. Tri-DAP and MDP inhibited adipogenic differentiation of hUCB-MSCs, but Pam3CSK4 and LPS did not. On chondrogenic differentiation, all TLR and NLR agonists could promote chondrogenesis of hUCB-MSCs with difference in the ability. Our findings suggest that NOD1 and NOD2 as well as TLRs are involved in regulating the differentiation of MSCs

Triple-negative breast cancer and PTEN (phosphatase and tensin homologue)loss are predictors of BRCA1 germline mutations in women with early-onset and familial breast cancer, but not in women with isolated late-onset breast cancer

Introduction: Given that breast cancers in germline BRCA1 carriers are predominantly estrogen-negative and triple-negative, it has been suggested that women diagnosed with triple-negative breast cancer (TNBC) younger than 50 years should be offered BRCA1 testing, regardless of family cancer characteristics. However, the predictive value of triple-negative breast cancer, when taken in the context of personal and family cancer characteristics, is unknown. The aim of this study was to determine whether TNBC is a predictor of germline BRCA1 mutations, in the context of multiple predictive factors.Methods: Germline mutations in BRCA1 and BRCA2 were analyzed by Sanger sequencing and multiple ligation-dependent probe amplification (MLPA) analysis in 431 women from the Malaysian Breast Cancer Genetic Study, including 110 women with TNBC. Logistic regression was used to identify and to estimate the predictive strength of major determinants. Estrogen receptor (ER) and phosphatase and tensin homologue (PTEN) status were assessed and included in a modified Manchester scoring method.Results: Our study in an Asian series of TNBC patients demonstrated that 27 (24.5%) of 110 patients have germline mutations in BRCA1 (23 of 110) and BRCA2 (four of 110). We found that among women diagnosed with breast cancer aged 36 to 50 years but with no family history of breast or ovarian cancer, the prevalence of BRCA1 and BRCA2 mutations was similar in TNBC (8.5%) and non-TNBC patients (6.7%). By contrast, in women diagnosed with breast cancer, younger than 35 years, with no family history of these cancers, and in women with a family history of breast cancer, the prevalence of mutations was higher in TNBC compared with non-TNBC (28.0% and 9.9%; P = 0.045; and 42.1% and 14.2%; P < 0.0001, respectively]. Finally, we found that incorporation of estrogen-receptor and TNBC status improves the sensitivity of the Manchester Scoring method (42.9% to 64.3%), and furthermore, incorporation of PTEN status further improves sensitivity (42.9% to 85.7%).Conclusions: We found that TNBC is an important criterion for highlighting women who may benefit from genetic testing, but that this may be most useful for women with early-onset breast cancer (35 years or younger) or with a family history of cancers. Furthermore, addition of TNBC and PTEN status improves the sensitivity of the Manchester scoring method and may be particularly important in the Asian context, where risk-assessment models underestimate the number of mutation carriers. © 2012 Phuah et al.; licensee BioMed Central Ltd

Motion style acupuncture treatment (MSAT) for acute low back pain with severe disability: a multicenter, randomized, controlled trial protocol

<p>Abstract</p> <p>Background</p> <p>Acupuncture is widely-used to treat patients with low back pain, despite insufficient evidence of the technique's efficacy for acute back pain. Motion style acupuncture treatment (MSAT) is a non-traditional acupuncture treatment requiring a patient to exercise while receiving acupuncture. In Korea, MSAT is used to reduce musculoskeletal pain and improve functional status. The study aims to evaluate the effect of MSAT on acute low back pain with severe disability.</p> <p>Methods/Design</p> <p>This study is a multicenter, randomized, active-controlled trial with two parallel arms. Participants with acute low back pain and severe functional disability, defined as an Oswestry Disability Index (ODI) value > 60%, will be randomly allocated to the acupuncture group and the nonsteroidal anti-inflammatory drug (NSAID) injection group. The acupuncture group will receive MSAT and the NSAID injection group will receive an intramuscular injection of diclofenac. All procedures will be limited to one session and the symptoms before and after treatment will be measured by assessors blinded to treatment allocation. The primary outcome will be measured at 30 minutes after treatment using the numerical rating scale (NRS) of low back pain while the patient is moving. Secondary outcomes will be measured at 30 minutes after treatment using the NRS of leg pain, ODI, patient global impression of change, range of motion (ROM) of the lumbar spine, and degrees of straight leg raising (SLR). Post-treatment follow-up will be performed to measure primary and secondary outcomes with the exception of ROM and SLR at 2, 4, and 24 weeks after treatment.</p> <p>Discussion</p> <p>The results of this trial will be discussed.</p> <p>Trial Registration</p> <p>ClinicalTrial.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01315561">NCT01315561</a></p

Prehospital critical care for out-of-hospital cardiac arrest: An observational study examining survival and a stakeholder-focused cost analysis

© 2016 The Author(s). Background: Survival rates from out-of-hospital cardiac arrest (OHCA) remain low, despite remarkable efforts to improve care. A number of ambulance services in the United Kingdom (UK) have developed prehospital critical care teams (CCTs) which attend critically ill patients, including OHCA. However, current scientific evidence describing CCTs attending OHCA is sparse and research to date has not demonstrated clear benefits from this model of care. Methods: This prospective, observational study will describe the effect of CCTs on survival from OHCA, when compared to advanced-life-support (ALS), the current standard of prehospital care in the UK. In addition, we will describe the association between individual critical care interventions and survival, and also the costs of CCTs for OHCA. To examine the effect of CCTs on survival from OHCA, we will use routine Utstein variables data already collected in a number of UK ambulance trusts. We will use propensity score matching to adjust for imbalances between the CCT and ALS groups. The primary outcome will be survival to hospital discharge, with the secondary outcome of survival to hospital admission. We will record the critical care interventions delivered during CCT attendance at OHCA. We will describe frequencies and aim to use multiple logistic regression to examine possible associations with survival. Finally, we will undertake a stakeholder-focused cost analysis of CCTs for OHCA. This will utilise a previously published Emergency Medical Services (EMS) cost analysis toolkit and will take into account the costs incurred from use of a helicopter and the proportion of these costs currently covered by charities in the UK. Discussion: Prehospital critical care for OHCA is not universally available in many EMS. In the UK, it is variable and largely funded through public donations to charities. If this study demonstrates benefit from CCTs at an acceptable cost to the public or EMS commissioners, it will provide a rationale to increase funding and service provision. If no clinical benefit is found, the public and charities providing these services can consider concentrating their efforts on other areas of prehospital care. Trial registration: ISRCTN registry ID ISRCTN18375201

Glucuronidation by UGT1A1 Is the Dominant Pathway of the Metabolic Disposition of Belinostat in Liver Cancer Patients

10.1371/journal.pone.0054522PLoS ONE81

Chromosomal Inversions between Human and Chimpanzee Lineages Caused by Retrotransposons

The long interspersed element-1 (LINE-1 or L1) and Alu elements are the most abundant mobile elements comprising 21% and 11% of the human genome, respectively. Since the divergence of human and chimpanzee lineages, these elements have vigorously created chromosomal rearrangements causing genomic difference between humans and chimpanzees by either increasing or decreasing the size of genome. Here, we report an exotic mechanism, retrotransposon recombination-mediated inversion (RRMI), that usually does not alter the amount of genomic material present. Through the comparison of the human and chimpanzee draft genome sequences, we identified 252 inversions whose respective inversion junctions can clearly be characterized. Our results suggest that L1 and Alu elements cause chromosomal inversions by either forming a secondary structure or providing a fragile site for double-strand breaks. The detailed analysis of the inversion breakpoints showed that L1 and Alu elements are responsible for at least 44% of the 252 inversion loci between human and chimpanzee lineages, including 49 RRMI loci. Among them, three RRMI loci inverted exonic regions in known genes, which implicates this mechanism in generating the genomic and phenotypic differences between human and chimpanzee lineages. This study is the first comprehensive analysis of mobile element bases inversion breakpoints between human and chimpanzee lineages, and highlights their role in primate genome evolution

Amitriptyline-Mediated Cognitive Enhancement in Aged 3×Tg Alzheimer's Disease Mice Is Associated with Neurogenesis and Neurotrophic Activity

Approximately 35 million people worldwide suffer from Alzheimer's disease (AD). Existing therapeutics, while moderately effective, are currently unable to stem the widespread rise in AD prevalence. AD is associated with an increase in amyloid beta (Aβ) oligomers and hyperphosphorylated tau, along with cognitive impairment and neurodegeneration. Several antidepressants have shown promise in improving cognition and alleviating oxidative stress in AD but have failed as long-term therapeutics. In this study, amitriptyline, an FDA-approved tricyclic antidepressant, was administered orally to aged and cognitively impaired transgenic AD mice (3×TgAD). After amitriptyline treatment, cognitive behavior testing demonstrated that there was a significant improvement in both long- and short-term memory retention. Amitriptyline treatment also caused a significant potentiation of non-toxic Aβ monomer with a concomitant decrease in cytotoxic dimer Aβ load, compared to vehicle-treated 3×TgAD controls. In addition, amitriptyline administration caused a significant increase in dentate gyrus neurogenesis as well as increases in expression of neurosynaptic marker proteins. Amitriptyline treatment resulted in increases in hippocampal brain-derived neurotrophic factor protein as well as increased tyrosine phosphorylation of its cognate receptor (TrkB). These results indicate that amitriptyline has significant beneficial actions in aged and damaged AD brains and that it shows promise as a tolerable novel therapeutic for the treatment of AD

Sporangiospore Size Dimorphism Is Linked to Virulence of Mucor circinelloides

Mucor circinelloides is a zygomycete fungus and an emerging opportunistic pathogen in immunocompromised patients, especially transplant recipients and in some cases otherwise healthy individuals. We have discovered a novel example of size dimorphism linked to virulence. M. circinelloides is a heterothallic fungus: (+) sex allele encodes SexP and (−) sex allele SexM, both of which are HMG domain protein sex determinants. M. circinelloides f. lusitanicus (Mcl) (−) mating type isolates produce larger asexual sporangiospores that are more virulent in the wax moth host compared to (+) isolates that produce smaller less virulent sporangiospores. The larger sporangiospores germinate inside and lyse macrophages, whereas the smaller sporangiospores do not. sexMΔ mutants are sterile and still produce larger virulent sporangiospores, suggesting that either the sex locus is not involved in virulence/spore size or the sexP allele plays an inhibitory role. Phylogenetic analysis supports that at least three extant subspecies populate the M. circinelloides complex in nature: Mcl, M. circinelloides f. griseocyanus, and M. circinelloides f. circinelloides (Mcc). Mcc was found to be more prevalent among clinical Mucor isolates, and more virulent than Mcl in a diabetic murine model in contrast to the wax moth host. The M. circinelloides sex locus encodes an HMG domain protein (SexP for plus and SexM for minus mating types) flanked by genes encoding triose phosphate transporter (TPT) and RNA helicase homologs. The borders of the sex locus between the three subspecies differ: the Mcg sex locus includes the promoters of both the TPT and the RNA helicase genes, whereas the Mcl and Mcc sex locus includes only the TPT gene promoter. Mating between subspecies was restricted compared to mating within subspecies. These findings demonstrate that spore size dimorphism is linked to virulence of M. circinelloides species and that plasticity of the sex locus and adaptations in pathogenicity have occurred during speciation of the M. circinelloides complex