Transcriptomics, molecular docking, and cross-resistance profiling of nobiletin in cancer cells and synergistic interaction with doxorubicin upon SOX5 transfection.
Nobiletin is a polymethoxylated flavone from citrus fruit peels. Among other bioactivities, it acts antioxidative, anti-inflammatory, neuroprotective, and cardiovascular-protective. Nobiletin exerts profound anticancer activity in vitro and in vivo but the underlying mechanisms are not well understood. The aim was to unravel the multiple modes of action against cancer cells by bioinformatic and transcriptomic techniques and their verification by molecular pharmacological methods. The in silico methods used were COMPARE analysis of transcriptomic data, signaling pathway analysis, transcription factor binding motif analysis in promoter sequences of target genes, and molecular docking. The in vitro methods used were resazurin assay, isobologram analysis, generation of stably SOX5-tranfected cells, and Western blotting. Nobiletin was cytotoxic against a wide range of cell lines from different tumor types, including diverse phenotypes to established anticancer drugs (e.g., P-glycoprotein, ABCB5, p53, EGFR). Cross-resistance profiling with 83 standard anticancer drugs revealed a correlation to antihormonal anticancer drugs, which can be explained by the phytoestrogenic features of nobiletin. Transcriptomic analysis showed that the responsiveness of tumor cells was predictable by their specific mRNA expression profile. Nobiletin bound to the transcription factor SOX5 in silico. SOX5 conferred resistance to the control drug doxorubicin but collateral sensitivity to nobiletin in HEK293 cells transfected with a lentiviral GFP-tagged pLOCORF-SOX5 vector. The combination of nobiletin and doxorubicin synergistically killed HEK293-SOX5 cells in isobologram analyses, implying attractive new treatment options. Nobiletin represents an interesting candidate for cancer therapy with broad-spectrum activity and multiple modes of action. The identification of novel targets (i.e., SOX5) may allow its use for targeted tumor therapy in individualized treatment protocols.


Examining the Effects of Gestational Physical Activity and Hofbauer Cell Polarization on Angiogenic Factors.
While gestational physical activity (PA) has demonstrated health benefits for both birthing parent and fetus, the mechanisms still need to be fully understood. Placental macrophages, or Hofbauer cells (HBCs), comprise a heterogenous population containing inflammatory (CD206-) and anti-inflammatory (CD206+) phenotypes. Similar to other tissue-resident macrophages (TRMs), HBCs are potential mediators of angiogenesis due to their secretion of both pro- and anti-angiogenic factors, including FGF2, VEGF, and SPRY2. While PA is associated with an increase in the proportion of VEGF- and FGF2-producing CD206+ macrophages in other tissues, the phenotypes producing FGF2, VEGF, and SPRY2 in the placenta and the associated relationships with gestational PA have not been studied. Using accelerometry, pregnant participants were classified as physically active or inactive in mid- and late-gestation. Term placenta tissue was collected at delivery and used for Western blotting and immunofluorescence to examine the protein expression of FGF2 and SPRY2, and to localize FGF2 in histological samples, respectively. Primary cultures of HBCs were used to examine the phenotypic differences in FGF2, SPRY2, and VEGF production. While no differences in the placental expression of SPRY2, total FGF2, or high-molecular-weight FGF2 were observed based on PA status, active individuals had significantly reduced levels of low-molecular-weight FGF2. Additionally, HBCs of all polarizations produce VEGF, FGF2, and SPRY2, and can form intercellular junctions and multinucleated giant cells. These findings suggest a possible relationship between PA and HBC-driven angiogenesis, providing an avenue for future exploration.


A clinical prospective randomized comparative study on ostyeosynthesis of mandibular anterior fractures following open reduction using lag screws and miniplates.
The aim of the present study was to compare fixation of mandibular anterior fractures following open reduction using lag screws or miniplates. This prospective study was conducted on 20 patients diagnosed with cases of displaced mandibular anterior fractures treated with open reduction and internal fixation. The patients were then randomly allocated to either of two groups - Group A: two 2.5 mm stainless steel lag screws were placed in 10 patients. Group B: two 2.5 mm miniplates were placed in 10 patients for the fixation of fractures. Subsequent follow-up was done on the 1st day, 1st, 4th, and 36th week postoperatively. During every follow-up, patient was assessed clinically for infection, malocclusion, loosening of plate/screw, malunion/nonunion, and masticatory efficiency. Radiographs (orthopantogram) were taken preoperative, 1st, 4th, and 36th postoperative week to compare the osteosynthesis between the two groups. Pain was objectively measured using a visual analog scale. The data collected was subjected to unpaired t-test and paired t-test for statistical analysis. It was found that lag screw placement was rapid in comparison of miniplate placement. 3rd month postoperative assessment revealed Lag screw group to have better biting efficiency, and better bone healing which was statistically significant when compared with miniplate group. Our study suggests that lag screw osteosynthesis can be advocated as a valid treatment modality in the management of mandibular symphysis and parasymphysis fractures.


Rapid 3D Refractive-Index Imaging of Live Cells in Suspension without Labeling Using Dielectrophoretic Cell Rotation.
A major challenge in the field of optical imaging of live cells is achieving rapid, 3D, and noninvasive imaging of isolated cells without labeling. If successful, many clinical procedures involving analysis and sorting of cells drawn from body fluids, including blood, can be significantly improved. A new label-free tomographic interferometry approach is presented. This approach provides rapid capturing of the 3D refractive-index distribution of single cells in suspension. The cells flow in a microfluidic channel, are trapped, and then rapidly rotated by dielectrophoretic forces in a noninvasive and precise manner. Interferometric projections of the rotated cell are acquired and processed into the cellular 3D refractive-index map. Uniquely, this approach provides full (360°) coverage of the rotation angular range around any axis, and knowledge on the viewing angle. The experimental demonstrations presented include 3D, label-free imaging of cancer cells and three types of white blood cells. This approach is expected to be useful for label-free cell sorting, as well as for detection and monitoring of pathological conditions resulting in cellular morphology changes or occurrence of specific cell types in blood or other body fluids.


An innate granuloma eradicates an environmental pathogen using Gsdmd and Nos2.
Granulomas often form around pathogens that cause chronic infections. Here, we discover an innate granuloma model in mice with an environmental bacterium called Chromobacterium violaceum. Granuloma formation not only successfully walls off, but also clears, the infection. The infected lesion can arise from a single bacterium that replicates despite the presence of a neutrophil swarm. Bacterial replication ceases when macrophages organize around the infection and form a granuloma. This granuloma response is accomplished independently of adaptive immunity that is typically required to organize granulomas. The C. violaceum-induced granuloma requires at least two separate defense pathways, gasdermin D and iNOS, to maintain the integrity of the granuloma architecture. This innate granuloma successfully eradicates C. violaceum infection. Therefore, this C. violaceum-induced granuloma model demonstrates that innate immune cells successfully organize a granuloma and thereby resolve infection by an environmental pathogen.


Effects of the protein environment on the spectral properties of tryptophan radicals in Pseudomonas aeruginosa azurin.
Many biological electron-transfer reactions involve short-lived tryptophan radicals as key reactive intermediates. While these species are difficult to investigate, the recent photogeneration of a long-lived neutral tryptophan radical in two Pseudomonas aeruginosa azurin mutants (Az48W and ReAz108W) made it possible to characterize the electronic, vibrational, and magnetic properties of such species and their sensitivity to the molecular environment. Indeed, in Az48W the radical is embedded in the hydrophobic core while, in ReAz108W it is solvent-exposed. Here we use density functional theory and multiconfigurational perturbation theory to construct quantum-mechanics/molecular-mechanics models of Az48W(•) and ReAz108W(•) capable of reproducing specific features of their observed UV-vis, resonance Raman, and electron paramagnetic resonance spectra. The results show that the models can correctly replicate the spectral changes imposed by the two contrasting hydrophobic and hydrophilic environments. Most importantly, the same models can be employed to disentangle the molecular-level interactions responsible for such changes. It is found that the control of the hydrogen bonding between the tryptophan radical and a single specific surface water molecule in ReAz108W(•) represents an effective means of spectral modulation. Similarly, a specific electrostatic interaction between the radical moiety and a Val residue is found to control the Az48W(•) excitation energy. These modulations appear to be mediated by the increase in nitrogen negative charge (and consequent increase in hydrogen bonding) of the spectroscopic D2 state with respect to the D0 state of the chromophore. Finally, the same protein models are used to predict the relaxed Az48W(•) and ReAz108W(•) D2 structures, showing that the effect of the environment on the corresponding fluorescence maxima must parallel that of D0 absorption spectra.


Effect of angiotensin II type 1 receptor blocker and angiotensin converting enzyme inhibitor on the intraocular growth factors and their receptors in streptozotocin-induced diabetic rats.
To investigate the effect of angiotensin II type 1 receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI) on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. Forty Sprague-Dawley rats were divided into 4 groups: control, diabetes mellitus (DM), candesartan-treated DM, and enalapril-treated DM (each group, n=10). After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/(kg·d)] and enalapril [ACEI, 10 mg/(kg·d)] were administered to rats orally for 4wk. Vascular endothelial growth factor (VEGF) and angiotensin II (Ang II) concentrations in the vitreous were measured using enzyme-linked immunosorbent assays, and VEGF receptor 2 and angiotensin II type 1 receptor (AT1R) levels were assessed at week 4 by Western blotting. Vitreous Ang II levels were significantly higher in the DM group and candesartan-treated DM group than in the control (P=0.04 and 0.005, respectively). Vitreous AT1R increased significantly in DM compared to the other three groups (P<0.007). Candesartan-treated DM rats showed higher vitreal AT1R concentration than the enalapril-treated DM group and control (P<0.001 and P=0.005, respectively). No difference in vitreous Ang II and AT1R concentration was found between the enalapril-treated DM group and control. VEGF and its receptor were below the minimum detection limit in all 4 groups. Increased Ang II and AT1R in the hyperglycemic state indicate activated the intraocular renin-angiotensin system, which is inhibited more effectively by systemic ACEI than systemic ARB.


Errorless learning: reinforcement contingencies and stimulus control transfer in delayed prompting.
Delayed prompting can produce errorless discrimination learning. There is inherent in the procedure a disparity in reinforcement density which favors unprompted over prompted responses. We used three schedules of reinforcement to investigate the impact of reinforcement probability on transfer of stimulus control. One schedule of reinforcement was equal prior to and following a prompt (CRF/CRF), the second favored unprompted responses (CRF/FR3), and the third favored responses following the prompt (FR3/CRF). Experimental questions concerned the probability of errors, the probability of transfer, and the rate of transfer in the context of delayed prompting. Transfer was accelerated when reinforcement probability favored anticipatory responding. The schedule that favored prompted responses did not prevent a shift to unprompted responding. Errors were infrequent across procedures. Reinforcement probability contributes to but does not entirely determine transfer of stimulus control from a delayed prompt.


Annual Report to the Nation on the Status of Cancer, Part 1: National Cancer Statistics.
The American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, and North American Association of Central Cancer Registries collaborate to provide annual updates on cancer incidence and mortality and trends by cancer type, sex, age group, and racial/ethnic group in the United States. In this report, we also examine trends in stage-specific survival for melanoma of the skin (melanoma). Incidence data for all cancers from 2001 through 2017 and survival data for melanoma cases diagnosed during 2001-2014 and followed-up through 2016 were obtained from the Centers for Disease Control and Prevention- and National Cancer Institute-funded population-based cancer registry programs compiled by the North American Association of Central Cancer Registries. Data on cancer deaths from 2001 to 2018 were obtained from the National Center for Health Statistics' National Vital Statistics System. Trends in age-standardized incidence and death rates and 2-year relative survival were estimated by joinpoint analysis, and trends in incidence and mortality were expressed as average annual percent change (AAPC) during the most recent 5 years (2013-2017 for incidence and 2014-2018 for mortality). Overall cancer incidence rates (per 100 000 population) for all ages during 2013-2017 were 487.4 among males and 422.4 among females. During this period, incidence rates remained stable among males but slightly increased in females (AAPC = 0.2%, 95% confidence interval [CI] = 0.1% to 0.2%). Overall cancer death rates (per 100 000 population) during 2014-2018 were 185.5 among males and 133.5 among females. During this period, overall death rates decreased in both males (AAPC = -2.2%, 95% CI = -2.5% to -1.9%) and females (AAPC = -1.7%, 95% CI = -2.1% to -1.4%); death rates decreased for 11 of the 19 most common cancers among males and for 14 of the 20 most common cancers among females, but increased for 5 cancers in each sex. During 2014-2018, the declines in death rates accelerated for lung cancer and melanoma, slowed down for colorectal and female breast cancers, and leveled off for prostate cancer. Among children younger than age 15 years and adolescents and young adults aged 15-39 years, cancer death rates continued to decrease in contrast to the increasing incidence rates. Two-year relative survival for distant-stage skin melanoma was stable for those diagnosed during 2001-2009 but increased by 3.1% (95% CI = 2.8% to 3.5%) per year for those diagnosed during 2009-2014, with comparable trends among males and females. Cancer death rates in the United States continue to decline overall and for many cancer types, with the decline accelerated for lung cancer and melanoma. For several other major cancers, however, death rates continue to increase or previous declines in rates have slowed or ceased. Moreover, overall incidence rates continue to increase among females, children, and adolescents and young adults. These findings inform efforts related to prevention, early detection, and treatment and for broad and equitable implementation of effective interventions, especially among under resourced populations.


Mechanochemically Synthesized Prussian Blue for Efficient Removal of Cesium Ions from Aqueous Solutions.
The adsorptive removal of radioactive cesium [Cs(I)] is important for ensuring a clean aquatic environment. In this work, the adsorption of Cs(I) was carried out using Prussian blue (PB) prepared by mechanochemical synthesis. X-ray diffraction, Fourier-transform infrared spectroscopy, and field-emission scanning electron microscopy results indicated that PB had been successfully synthesized by mechanochemical synthesis. Thermogravimetric analysis, contact angle analysis, inductively coupled plasma atomic emission spectrometry, elemental analysis, and electrophoretic light scattering spectrophotometry confirmed that several defects were formed, explaining the principal mechanism for the efficient adsorption over PB prepared by mechanochemical synthesis. The superior adsorption properties toward Cs(I) make PB prepared by mechanochemical synthesis an attractive candidate material for the efficient, economical, and eco-friendly processes for purifying radioactive wastewater.


Alterations of cardiac innervation in evolving myocardial infarction and transplanted hearts. An anatomo-clinical reappraisal.
Debate regarding the alterations of the cardiac innervation in an evolving myocardial infarction and transplanted hearts is still raging and most studies are based on radionuclide uptake of neurotransmitters or on the evaluation of the cardiorespiratory reflex. The present investigation, upon human autoptic specimens of 57 infarcts and 8 cardiac transplants, was carried out with traditional neuropathology and modern molecular biology techniques. The specimens were selected for the identification of neurons, nerve fibers and their sheaths. First of all, these techniques confirmed the gross difference in the vulnerability of infarcted myocytes if compared with the local innervation, the metabolism of which is infinitely less oxygen-dependent than that of working myocardium (approximate quantitation below). Delicate technicalities of the traditional silver impregnation for nerves usually yield a large incidence of artifacts. Thereby, only perfect results (20% of cases), corroborated by parallel nerve sheath immunostaining (70% of cases), were retained and documented herein. In the meantime, acidosis and free radicals increase, while catabolite accumulation supervenes. These three factors threaten myocardial viability. Thereby, nervelets can be seen to survive the hyperacute phase of ischemia, but may be in part damaged by the successive granulocytic-macrophage inflammation enzyme lysis of the infarcted muscle. The delayed and incomplete anatomical neural damage is confirmed by the observation of preserved nerve sheaths and neural filaments surviving in postinfarction scars, almost devoid of myocardiocytes. The rich sympatho-vagal cardiac network might further provide alternative bypasses for post-infarct reinnervation. The functional implications of this process remain unclear.


Tricorrectional bunionectomy for correction of high intermetatarsal angles.
The authors propose the use of the tricorrectional bunionectomy as a viable procedure for correction of high intermetatarsal angles. The tricorrectional bunionectomy was performed on 39 patients (51 feet). All patients had intermetatarsal angles of 16 degrees or greater. The average follow-up period was 12.8 months. The authors believe this procedure is an excellent alternative to more disabling base osteotomies.


Landau Velocity for Collective Quantum Hall Breakdown in Bilayer Graphene.
Breakdown of the quantum Hall effect (QHE) is commonly associated with an electric field approaching the inter-Landau-level (LL) Zener field, the ratio of the Landau gap and the cyclotron radius. Eluded in semiconducting heterostructures, in spite of extensive investigation, the intrinsic Zener limit is reported here using high-mobility bilayer graphene and high-frequency current noise. We show that collective excitations arising from electron-electron interactions are essential. Beyond a noiseless ballistic QHE regime a large super-Poissonian shot noise signals the breakdown via inter-LL scattering. The breakdown is ultimately limited by collective excitations in a regime where phonon and impurity scattering are quenched. The breakdown mechanism can be described by a Landau critical velocity as it bears strong similarities with the roton mechanism of superfluids. In addition, we show that breakdown is a precursor of an electric-field induced QHE-metal transition.


Association of lean body mass with nutritional parameters and mortality in hemodialysis patients: A long-term follow-up clinical study.
This study aimed to evaluate the correlation between lean body mass (LBM) and nutritional status in hemodialysis (HD) patients to better predict their long-term prognosis. Anthropometric body measurements and biochemical parameters were recorded from 222 patients on maintenance hemodialysis (MHD) at the Shanghai Pudong Hospital Hemodialysis Center. LBM was calculated using the serum creatinine index (LBM-SCR), mid-arm muscle circumference (LBM-MAMC), and dominant-arm hand-grip strength (LBM-HGS). Patient mortality and hospitalization were observed after 24 months. LBMs measured from LBM-SCR and LBM-MAMC were associated with sex, body mass index (BMI), serum albumin, and serum creatinine (SCR) ( p < 0.05). Through three methods of LBM evaluation, low LBM was shown to be associated with a higher mortality in patients undergoing HD ( p < 0.05). In addition, the rate of hospitalization among these patients was significantly increased ( p < 0.05). Performing multivariate regression analysis using mortality and hospitalization as the dependent variable, we found LBM-SCR and LBM-HGS are strongly associated with hospitalization and mortality in HD patients, indicating LBM is an important factor in prediction of outcomes in those patients. LBM is associated with nutritional parameters in HD patients, and LBM-SCR, HGS, and MAMC are simple approaches for accurately predicting the patient's risk of hospitalization and/or death.


Tuning Exchange Coupling in a New Family of Nanocrystal-Based Granular Multiferroics Using an Applied Electric Field.
In this work, we demonstrate an experimental realization of a granular multiferroic composite, where the magnetic state of a nanocrystal array is modified by tuning the interparticle exchange coupling using an applied electric field. Previous theoretical models of a granular multiferroic composite predicted a unique magnetoelectric coupling mechanism, in which the magnetic spins of the ensemble are governed by interparticle exchange. The extent of these exchange interactions can be controlled by varying the local dielectric environment between grains. We specifically utilize the strong dielectric dependence of ferroelectric materials to modify the interparticle coupling of closely spaced magnetic nanoparticles using either a change in temperature or an electric field. This coupling modifies the ensemble magnetic coercivity and thus the superparamagnetic-to-ferromagnetic phase transition temperature. Through the use of two different ferroelectrics, our results suggest that this magnetoelectric coupling mechanism could be generalized as a new class of multiferroic material, applicable to a broad range of ferroelectric/magnetic nanocrystal composites.


[Detection ofmethylated genes related to allergic rhinitis and establishment of methylation profile].
Objective:The aim of this study is to detect differentially methylated genes to allergic rhinitis (AR) based on methylation chip, and to analyze the relationship between DNA methylation and AR.Method:Illumina methylation chip were made by normal inferior turbinate mucous tissue obtained from patients(n=19) and healthy individuals(n=11). Detection of differential the sites of methylated genes, Gene Ontology enrichment, KEGG pathway enrichment database and literature search were used to analysis.Result:There were 94 aberrant methylation sites in patients with AR, including 51 hypermethylation sites (e.g. ST7,LCE2D,ATRIP genes) and 43 hypomethylation sites (e.g. PIK3CG, TLR6, IL-4 genes). The results of Gene Ontology enrichment and KEGG pathway enrichment indicates the DNA methylation has relative trend with AR, and DNA methylation of ST7, LCE2D, PIK3CG genes may be associated with AR, but the results of GO analysis and KEGG analysis were statistically significant. Moreover, literature search prompts that DNA methylation of TLR6 gene and IL-4 gene may be associated with AR.Conclusion:Varying degrees of methylated genes from inferior turbinate mucous tissue based on high-flux methylation chip hint gene methylation is an important cause of AR. The relationship between them needs further verification.


Biotribological evaluation of artificial disc arthroplasty devices: influence of loading and kinematic patterns during in vitro wear simulation.
Wear simulation is an essential pre-clinical method to predict the mid- and long-term clinical wear behavior of newly introduced devices for total disc arthroplasty. The main requirement of a suitable method for spinal wear simulation has to be the ability to distinguish between design concepts and allow for a direct comparison of predicate devices. The objective of our study was to investigate the influence of loading and kinematic patterns based on two different protocols for spinal wear simulation (ISO/FDIS 18192-1 (2006) and ASTM F2423-05). In vitro wear simulation was performed with six activ L lumbar artificial disc devices (Aesculap Tuttlingen, Germany). The applied kinematic pattern of movement was multidirectional for ISO (elliptic track) and unidirectional with a curvilinear shape for ASTM. Testing was done for 10 million cycles in the ISO loading mode and afterwards with the same specimens for 5 million cycles according to the ASTM protocol with a customized six-station servohydraulic spinal wear simulator (EndoLab Thansau, Germany). Gravimetrical and geometrical wear assessment, a slide track analysis correlated to an optical surface characterization, and an estimation of particle size and morphology were performed. The gravimetric wear rate for the first 10 million cycles was ISO(initial) = 2.7 +/- 0.3 mg/million cycles. During the ASTM test period (10-15 million cycles) a gravimetric wear rate of 0.14 +/- 0.06 mg/million cycles was estimated. The wear rates between the ISO and ASTM driven simulations differ substantially (approximately 20-fold) and statistical analysis demonstrates a significant difference (p < 0.001) between the test groups. The main explanation of divergency between ISO and ASTM driven wear simulations is the multidirectional pattern of movement described in the ISO document resulting in a cross-shear stress on the polyethylene material. Due to previous retrieval observations, it seems to be very unlikely that a lumbar artificial disc is loaded with a linear wear path.Testing according to ASTM F2423-05 with pure unidirectional motion does not reflect the kinematics of TDA patients' daily activities. Based on our findings it seems to be more reliable to predict the clinical wear behavior of an artificial disc replacement using the ISO/FDIS 18192-1 method.


Checklists to detect potential predatory biomedical journals: a systematic review.
The increase in the number of predatory journals puts scholarly communication at risk. In order to guard against publication in predatory journals, authors may use checklists to help detect predatory journals. We believe there are a large number of such checklists yet it is uncertain whether these checklists contain similar content. We conducted a systematic review to identify checklists that help to detect potential predatory journals and examined and compared their content and measurement properties. We searched MEDLINE, Embase, PsycINFO, ERIC, Web of Science and Library, and Information Science & Technology Abstracts (January 2012 to November 2018); university library websites (January 2019); and YouTube (January 2019). We identified sources with original checklists used to detect potential predatory journals published in English, French or Portuguese. Checklists were defined as having instructions in point form, bullet form, tabular format or listed items. We excluded checklists or guidance on recognizing "legitimate" or "trustworthy" journals. To assess risk of bias, we adapted five questions from A Checklist for Checklists tool a priori as no formal assessment tool exists for the type of review conducted. Of 1528 records screened, 93 met our inclusion criteria. The majority of included checklists to identify predatory journals were in English (n = 90, 97%), could be completed in fewer than five minutes (n = 68, 73%), included a mean of 11 items (range = 3 to 64) which were not weighted (n = 91, 98%), did not include qualitative guidance (n = 78, 84%), or quantitative guidance (n = 91, 98%), were not evidence-based (n = 90, 97%) and covered a mean of four of six thematic categories. Only three met our criteria for being evidence-based, i.e. scored three or more "yes" answers (low risk of bias) on the risk of bias tool. There is a plethora of published checklists that may overwhelm authors looking to efficiently guard against publishing in predatory journals. The continued development of such checklists may be confusing and of limited benefit. The similarity in checklists could lead to the creation of one evidence-based tool serving authors from all disciplines.


Impact of venous invasion on the efficacy of adjuvant chemotherapy in elderly patients with stage III colorectal cancer.
One of the reasons for the underuse of adjuvant chemotherapy in elderly patients with stage III colorectal cancer is a small survival benefit. This retrospective study sought to identify the predictive factors for elderly patients who could obtain a sufficient survival benefit. We reviewed the data of 1354 elderly patients (aged ≥70 years) with stage III colorectal cancer who underwent complete resection between January 1997 and December 2006. The efficacy of adjuvant chemotherapy was assessed, and the risk factors for recurrence were determined. The efficacy of adjuvant chemotherapy was also assessed after stratification for the above-mentioned risk factors for recurrence. There was a tendency for adjuvant chemotherapy to be effective in elderly patients (hazard ratio 0.84; 95% CI 0.70-1.01). Age, tumor location, pathology findings, tumor depth, venous invasion and lymph node metastasis were identified to be independent risk factors for recurrence by univariate and multivariate analyses. Among these factors, adjuvant chemotherapy was much effective in the elderly patients with high venous invasion (v2-3) (hazard ratio 0.69; 95% CI 0.52-0.91). High venous invasion (v2-3) was identified to be a predictive factor for elderly patients with stage III colorectal cancer who gained a sufficient survival benefit.


Electroencephalographic findings in children treated with cytotoxic agents.
106 EEG investigations were carried out in 17 children with various types of neoplastic disease without cerebral involvement during one or more courses of treatment with cytotoxic agents. EEGs were recorded before and 24 h after administration of the drugs. A transient slowing of the dominant frequency in the alpha-band by about 1 c/s and a decrease in the relative power of alpha-activity by 20-30% was observed in only 4 patients. These children did not receive the same antineoplastic treatment. 1 patient received very high dose methotrexate, 2 patients received vincristine combined with other cytotoxic agents, and the other patient received L-asparaginase. It is suggested that EEG changes in patients receiving intravenous cytotoxic treatment usually occur only where there is a preexisting impairment of the blood-cerebrospinal fluid barrier or the blood-brain barrier.


Tree species diversity promotes aboveground carbon storage through functional diversity and functional dominance.
The relationship between biodiversity and ecosystem function has increasingly been debated as the cornerstone of the processes behind ecosystem services delivery. Experimental and natural field-based studies have come up with nonconsistent patterns of biodiversity-ecosystem function, supporting either niche complementarity or selection effects hypothesis. Here, we used aboveground carbon (AGC) storage as proxy for ecosystem function in a South African mistbelt forest, and analyzed its relationship with species diversity, through functional diversity and functional dominance. We hypothesized that (1) diversity influences AGC through functional diversity and functional dominance effects; and (2) effects of diversity on AGC would be greater for functional dominance than for functional diversity. Community weight mean (CWM) of functional traits (wood density, specific leaf area, and maximum plant height) were calculated to assess functional dominance (selection effects). As for functional diversity (complementarity effects), multitrait functional diversity indices were computed. The first hypothesis was tested using structural equation modeling. For the second hypothesis, effects of environmental variables such as slope and altitude were tested first, and separate linear mixed-effects models were fitted afterward for functional diversity, functional dominance, and both. Results showed that AGC varied significantly along the slope gradient, with lower values at steeper sites. Species diversity (richness) had positive relationship with AGC, even when slope effects were considered. As predicted, diversity effects on AGC were mediated through functional diversity and functional dominance, suggesting that both the niche complementarity and the selection effects are not exclusively affecting carbon storage. However, the effects were greater for functional diversity than for functional dominance. Furthermore, functional dominance effects were strongly transmitted by CWM of maximum plant height, reflecting the importance of forest vertical stratification for diversity-carbon relationship. We therefore argue for stronger complementary effects that would be induced also by complementary light-use efficiency of tree and species growing in the understory layer.


Am I motivated to share knowledge for better innovative performance? An approach and avoidance framework.
Past research has long emphasized the critical roles of approach and avoidance motivation orientations in people's creative and innovative performance. However, it has generated mixed results and suggested the possibility of multiple pathways and mechanisms to explain these relationships. In this article, we first argue that employees' approach and avoidance motivation orientations are likely to guide their knowledge-sharing (KS) behaviors, which, in turn, influence their innovative performance. We differentiate between explicit and implicit KS and posit that approach motivation orientation is positively associated with both types of KS. In addition, we argue that while avoidance motivation orientation is positively related to explicit KS, it is negatively related to implicit KS. From a support-threat perspective, we also propose that perceived organizational support and psychological contract breach moderate the effects of approach and avoidance motivation orientations, respectively. We tested these relationships in a survey of 331 employees and their supervisors in two organizations in China. The results supported all of the hypothesized relationships, except for the relationship between avoidance motivation orientation and explicit KS, which was only significant when psychological contract breach was lower. These findings have both theoretical and practical implications. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Identification and nomenclature of the genus Penicillium.
Penicillium is a diverse genus occurring worldwide and its species play important roles as decomposers of organic materials and cause destructive rots in the food industry where they produce a wide range of mycotoxins. Other species are considered enzyme factories or are common indoor air allergens. Although DNA sequences are essential for robust identification of Penicillium species, there is currently no comprehensive, verified reference database for the genus. To coincide with the move to one fungus one name in the International Code of Nomenclature for algae, fungi and plants, the generic concept of Penicillium was re-defined to accommodate species from other genera, such as Chromocleista, Eladia, Eupenicillium, Torulomyces and Thysanophora, which together comprise a large monophyletic clade. As a result of this, and the many new species described in recent years, it was necessary to update the list of accepted species in Penicillium. The genus currently contains 354 accepted species, including new combinations for Aspergillus crystallinus, A. malodoratus and A. paradoxus, which belong to Penicillium section Paradoxa. To add to the taxonomic value of the list, we also provide information on each accepted species MycoBank number, living ex-type strains and provide GenBank accession numbers to ITS, β-tubulin, calmodulin and RPB2 sequences, thereby supplying a verified set of sequences for each species of the genus. In addition to the nomenclatural list, we recommend a standard working method for species descriptions and identifications to be adopted by laboratories working on this genus.


Alcohol-related road traffic accidents: promoting a lower alcohol strategy.
Impairment is the result of unpredictable genetic variation, coexisting disease, or drug interaction, and is modified by hepatic metabolism. The introduction of alcohol tsars and alcohol health workers in trauma centres would capitalise on the 'teachable moment' (when the conceptual link between drinking and its consequences can be demonstrated at a time when the consequences are obvious) to prevent recurring injuries and to lower alcohol intake. Accident fatalities have reached a plateau and the only way of reducing them further is to lower the European legal limit of blood alcohol concentration to a harmonised 50 mg/100 ml.


Diagnosis, pathogenesis and treatment of inclusion body myositis.
We provide an update of progress gained from research into sporadic inclusion body myositis (s-IBM). Most research on s-IBM has focused on the inflammatory reaction or the accumulation of pathological proteins in vacuolated muscle fibres. The inflammatory reaction is characterized by clonal expansions of lymphocytes, predominantly CD8 cytotoxic T cells, which invade and destroy muscle fibres. That costimulatory molecules have been identified demonstrates that muscle fibres can act as antigen presenting cells, and the expression of various chemokines in muscle indicates their importance in the immunopathogenesis of s-IBM. The region of interest for a susceptibility gene in the major histocompatibility complex has been narrowed, and for the first time it has been demonstrated that a chronic viral infection can trigger the inflammatory process leading to s-IBM. The nature of the accumulated material associated with the vacuoles has been extensively investigated over the past few years. Amyloid-beta and phosphorylated tau protein in intracellular inclusions are a characteristic finding in s-IBM, which may lead to calcium dyshomeostasis and endoplasmic reticulum stress. The proteasomal system is upregulated, including immunoproteasomes. 'Molecular misreading' leading to ubiquitin mRNA mutations and accumulation of pathological ubiquitin in muscle fibres may be associated with proteasomal dysfunction. There is still no efficient treatment for s-IBM, but the effects of new, more specific immunotherapies have begun to be explored. Recent findings indicate that both inflammatory reaction and abnormal protein accumulation are important for the pathogenesis in s-IBM. The link between them continues to await elucidation.


Contamination of germfree animals with intestinal Crohn tissue. A preliminary report.
The preliminary results of one of a series of prospective studies in the investigation of a possible transmissible agent in Crohn's disease are presented. Filtered human Crohn tissue homogenates was inoculated into eight germfree Sprague-Dawley rats, to test the reproducibility of recent reports suggesting a transmissible agent in regional ileitis. No histological changes were evident after 150 days, and no changes were observed in animals inoculated with non-Crohn tissue homogenates.


[The role of ticks and small mammals in propagation of Borrelia burgdorferi and Babesia microti].
In the present article, the role of ticks and small mammals in the epidemiology of Borrelia burgdorferi and Babesia microti is reviewed. Contrary to other European countries, the zoonotic reservoir of both potogens in Poland is unknown. In particular a preliminary analysis of B. burgdorferi and B. microti infections of rodents in District of Mazury Lake is presented.


[Attenuated psychosis syndrome: A new diagnostic category for further study in DSM-5].
In recent years an increasing number of studies focus on the issue of early diagnosis and intervention. At the same time, a large number of special service units for early psychosis have been established around the world especially in Australia, USA, UK, Germany etc. Recently, similar units operate in Greece also. The Diagnostic Manual of Mental Disorders of the American Psychiatric Association in its latest edition in 2013 (DSM-5), introduced the category "Attenuated Psychosis Syndrome" (APS) for people with early psychotic experiences in the section: "Conditions for further study '. This new category has specific criteria and describes a situation, in which a person displays psychotic symptoms in an attenuated form, with quite unaffected reality testing, but not qualifying a diagnosis of schizophrenic spectrum. The clinical expression of APS should be differentiated with several well known psychiatric disorders such as: brief psychotic disorder, schizotypal personality disorder, major depression with psychotic features, adolescence adjustment disorders, drug use, etc. The "Attenuated Psychosis Syndrome" occurs mainly in adolescence and in young adulthood. The mean percentage of transition to psychosis for these individuals is estimated at 36%, three years after the onset of initial symptoms, while the risk of transition to psychosis, although smaller, seems to remain up to ten years later. For some other individuals, transition to other psychiatric disorders occurs, such as depression with psychotic elements, or bipolar disorder, while a significant number of them will not transmit to even more serious disorders. At the biological level, studies focused in brain's neuroimaging, suggest significant volumetric differences among people at high risk for psychosis who later develop psychosis compared to those who don't, while studies of psychophysiological indicators or / and genetic markers show promising results for the identification of relevant parameters indicating the transition to psychosis. Αlthough an heterogeneous population, people with APS, show significant difficulties in social, professional and cognitive level, that should be therapeutically addressed. In an attempt to improve the clinical status of these individuals, to delay or even to prevent a psychotic episode, a series of interventions have been used by psychiatrists. These interventions include: (a) administration of drugs, especially atypical antipsychotics or antidepressants in low dosage, (b) administration of non-pharmaceutical supplements (e.g. omega-3 ), (c) psychotherapeutic interventions, mainly cognitive behavior therapy and (d) a combination of the above. Many questions need to be answered such as, the period of therapeutic intervention, identification of indicators (biological or/and clinical) that may determine the most suited for the APS individuals therapeutic interventions or, that may foresee, to prevent the transition to psychosis. Thus, the continuation of research in populations of APS individuals in multiple levels is necessary.


Testicular needle aspiration: Is it a safe method for breeding soundness evaluation in bulls?
The aim of this study was to evaluate the impact of successive bovine testicular punctures using different needle sizes. Fifteen bulls were submitted to testicular needle aspiration (TNA) in the left and right testis using 18-gauge (40×12mm) or 22-gauge (25×7mm) needles, respectively, once every 30 days. Animals were randomly divided into three groups, which were submitted to bilateral orchiectomy two days after the last puncture. Group 1 (G1): only one puncture (n=5); Group 2 (G2): three consecutive punctures in a period of three months (n=5); Group 3 (G3): six consecutive punctures in a period of 6 months (n=5). Fragments from the medial portion of the testicular parenchyma were excised and fixed in Bouin's fluid for histological analysis. No differences were observed in the percentage of seminiferous tubules degeneration between G1, G2 and G3 (P>0.05). Higher amounts of erythrocyte were found in G1 and G2 groups compared to G3, in the intra- and intertubular tissue (P<0.05). There was no interaction between the needle gauge and the occurrence of testicular damage in animals submitted to one (G1) or three (G2) punctures. However, a higher percentage of tubular degeneration was associated to 18-gauge compared to 22-gauge fine needles in G3. In conclusion, multiple testicular needle aspiration can be safely conducted using fine needles. Large needles are recommended only for a single TNA, since multiple punctures may result in increased tubular degeneration and compromise testicular architecture and functionality.


Layered gadolinium-based nanoparticle as a novel delivery platform for microRNA therapeutics.
Specific expression patterns of microRNA (miRNA) molecules have been linked to cancer initiation, progression, and metastasis. The accumulating evidence for the role of oncogenic or tumor-suppressing miRNAs identified the need for nano-scaled platform that can help deliver nucleotides to modulate miRNAs. Here we report the synthesis of novel layered gadolinium hydroxychloride (LGdH) nanoparticles, a member of the layered double hydroxide (LDH) family, with physiochemical properties suitable for cell uptake and tracing via magnetic resonance (MR) imaging. As a proof of concept, we demonstrate the inhibition of mature miRNA-10b in metastatic breast cancer cell line using LGdH nanoparticle as a delivery platform. Through characterization analysis, we show that nanoparticles are easily and stably loaded with anti-miRNA oligonucleotides (AMO) and efficiently penetrate cell membranes. We demonstrate that AMOs delivered by LGdH nanoparticles remain functional by inducing changes in the expression of its downstream effector and by curbing the invasive properties. Furthermore, we demonstrate the traceability of LGdH nanoparticles via T1 weighted MR imaging. LGdH nanoparticles, which are biocompatible with cells in vitro, provide a promising multifunctional platform for microRNA therapeutics through their diagnostic, imaging, and therapeutic potentials.


The CD95 type I/type II model.
CD95 (APO-1/Fas) has become the prototype of a death domain containing receptor and is the best studied member of the death receptors that activate the extrinsic apoptosis pathway. This pathway is initiated by recruitment and activation of caspase-8, an initiator caspase, in the death-inducing signaling complex (DISC) followed by direct cleavage of downstream effector caspases. In contrast, the intrinsic apoptosis pathway starts from within the cell either by direct activation of caspases or through intracellular changes such as DNA damage resulting in the release of a number of pro-apoptotic factors from the intermembrane space of mitochondria. The release of these factors results in the activation of another initiator caspase, caspase-9, and ultimately in the activation of effector caspases in a protein complex called the apoptosome. In recent years, it has become apparent that there is cross talk between the extrinsic and intrinsic pathway. In the death receptor pathway of apoptosis induction, the best characterized connection between the two pathways is the Bcl-2 family member Bid which translocates to mitochondria after cleavage by caspase-8 causing pro-apoptotic changes. Cells that die through CD95 without help from mitochondria are called Type I cells, whereas cells in which CD95-mediated death relies mostly on the intrinsic pathway are called Type II. This review focuses on recent developments in the delineation of the biochemistry and the physiological function of the two CD95 pathways.


Penetration of host cell membranes by adenovirus 2.
Highly purified human adenovirus type 2 directly penetrated the plasma membranes of KB cells. The process of membrane penetration resulted in the appearance of large numbers of adenovirions free in the cytoplasm of the infected cells. The virions underwent a morphological change as they penetrated the cell surface. Penetration of the plasma membranes and the accompanying alteration in virion morphology was dependent on a function associated with the intact cells, because neither event occurred when purified virions were added to isolated cell membranes. Inactivation of the adenovirions with heat or antibodies before inoculation of the cells reduced the infectivity of the virus population and prevented the appearance of virions free in the cytoplasm. The inactivation of the virions did not significantly reduce the number of virus particles which were found in cell vacuoles and pinocytotic vesicles.


Development of professional competence via self-instructional units.
In recent years, self-instructional teaching methods have come under criticism from educators, much of it warranted. But when self-instructional materials are written by experienced educators who teach the topic and are developed within a versatile process using a proven format, they are extremely valuable teaching aids. We discuss here the results of a grant project funded by W. K. Kellogg Foundation and describe the process used at Kettering Medical Center's School of Medical Technology to develop and produce over 100 self-instructional units. We also discuss potential uses of self-instructional units in professional continuing education programs and suggest ways self-instructional units might be used to promote interdisciplinary health care and expansion of professional knowledge banks. This project confirmed that professions can create their own educational materials through the independent efforts of their members.


Prevention of delayed vasospasm by an endothelin ETA receptor antagonist, BQ-123: change of ETA receptor mRNA expression in a canine subarachnoid hemorrhage model.
The authors investigated the roles of endothelin (ET)-1 and the ETA receptor in the pathogenesis of delayed cerebral vasospasm following subarachnoid hemorrhage (SAH). A study was made of the preventive effect of a novel ETA receptor antagonist, BQ-123, on vasospasm and the expression of the ETA receptor messenger ribonucleic acid (mRNA) using a canine two-hemorrhage SAH model. Continuous intrathecal administration of BQ-123 (5 x 10(-6) mol/day) prevented narrowing of the basilar artery on Day 7 after SAH in 97.6% of cases in the study group versus 70.7% of cases in the control group (p < 0.05). While expression of the mRNA-coding ETA receptor was not detected in the control animals, it markedly increased on Day 3 after SAH and was also detected on Day 7. The results suggest that endothelin-1 and the ETA receptor participate in the pathogenesis of delayed cerebral vasospasm following SAH.


Strength of the repulsive part of the interatomic potential determines fragility in metallic liquids.
The dynamical behaviour of liquids is frequently characterized by the fragility, which can be defined from the temperature dependence of the shear viscosity, η (ref. ). For a strong liquid, the activation energy for η changes little with cooling towards the glass transition temperature, Tg. The change is much greater in fragile liquids, with the activation energy becoming very large near Tg. While fragility is widely recognized as an important concept-believed, for example, to play an important role in glass formation-the microscopic origin of fragility is poorly understood. Here, we present new experimental evidence showing that fragility reflects the strength of the repulsive part of the interatomic potential, which can be determined from the steepness of the pair distribution function near the hard-sphere cutoff. On the basis of an analysis of scattering data from ten different metallic alloy liquids, we show that stronger liquids have steeper repulsive potentials.


The relationship between CD5-expressing B lymphocytes and serologic abnormalities in rheumatoid arthritis patients and their relatives.
The influence of genetic factors on the expression of CD5+ B lymphocytes and their relationship to a broad spectrum of autoantibodies was investigated in a study of 12 patients with rheumatoid arthritis (RA) and 52 of their healthy first-degree relatives. The proportion of CD5+ B cells was significantly higher in RA patients (mean +/- SEM 23.9 +/- 2.7%) compared with that in their relatives (18.3 +/- 1.1%, P less than 0.05) and compared with that in a group of healthy control subjects (16.1 +/- 1.8%; P less than 0.05). Much more striking, however, were the high levels of CD5+ B cells found in the patients and their relatives in 5 of the families studied. Increases in total immunoglobulin levels and autoantibody levels were frequently observed in RA patients (approximately 20-40%) and their relatives (approximately 10-20%). Furthermore, a statistically significant correlation (P less than 0.01) between IgM rheumatoid factor and the percentage of B lymphocytes expressing CD5 was observed.


The Roles of Mitochondrial SIRT4 in Cellular Metabolism.
Sirtuins comprise a family of nicotinamide adenine dinucleotide (NAD+)-dependent lysine deacylases that regulate the life span, aging, and metabolism. Seven sirtuin family members (SIRT1-7) have been identified in mammals, including humans. Despite the indispensable role of mitochondrial sirtuin 4 (SIRT4) in metabolic regulation, the primary enzymatic activity of SIRT4 remains enigmatic. SIRT4 possesses ADP-ribosyltransferase, lipoamidase and deacylase activities. Interestingly, the enzymatic activities and substrates of SIRT4 vary in different tissues and cells. SIRT4 inhibits insulin secretion in pancreatic β cells and regulates insulin sensitivity as a deacylase in the pancreas. SIRT4 represses fatty acid oxidation (FAO) in muscle and liver cells differently. SIRT4 has also been identified as a mitochondrial-localized tumor suppressor. A comprehensive understanding of the enzymology of SIRT4 in metabolism is essential for developing novel therapeutic agents for human metabolic diseases. This review will update the roles of SIRT4 in cellular and organismal metabolic homeostasis.


Skin ulceration induced by kerosene injection.
This article describes 2 patients with skin ulceration induced by kerosene injection. This is an unusual cause of ulceration, which could not be documented in the literature. The article also outlines the appropriate management of these cases, which should be considered true surgical emergencies.


[Atypical presentation of syringocystoadenoma papilliferum].
Syringocystoadenoma papilliferum is benign adnexal tumor derived from the sweat glands that is located in the head and neck in 70-80% of patients, and commonly presents as a papule or a solitary nodule. We report a case of syringocystoadenoma papilliferum with an atypical presentation given its location in the thigh and the peculiar histologic features, unrepresentative of this entity.


Organic Persistent Luminescent Materials: Ultralong Room-Temperature Phosphorescence and Multicolor-Tunable Afterglow.
Organic persistent luminescent materials have attracted special attention due to their significant applications in optoelectronics, sensors, and security technology areas. In this work, a series of organic compounds (1-4) with twisted electron donor-acceptor structures are successfully designed and synthesized, and then the resultant compounds are dissolved in methyl methacrylate (MMA), and afterward, in situ polymerization realizes single-molecular organic room-temperature phosphorescent (RTP) materials (P1-P4). All RTP materials show long lifetime, especially P2 exhibits ultralong lifetime of 1.51 s. When the compounds are grown into single crystals, multicolor-tunable afterglow is obtained at different delay times due to the dual emission of phosphorescence and delayed fluorescence, which is promising to be applied in high-level anticounterfeiting.


Prevalence and Predictors of Home Use of Glucometers in Diabetic Patients.
Self-monitoring of blood glucose (SMBG) is a critical component of diabetes care. However, it has been shown that use of glucometers in developing countries such as Pakistan is limited. The aim of this study was to determine the frequency of glucometer usage in the urban diabetic population of Karachi and to identify variables that influenced the likelihood of practice of SMBG. A cross-sectional study was conducted among 567 adult diabetic patients selected at random from the out-patient departments of multiple healthcare institutions in Karachi categorized into two settings; Government and Private. Non-diabetics, patients having gestational diabetes, diabetes insipidus and Cushing's syndrome and terminally ill patients were excluded. Pearson Chi-square and Mann-Whitney U test were applied as the primary statistical method. Prevalence of home glucometer usage was 59% (n= 331). High socioeconomic status (p < 0.001), receiving care from private institutions (p < 0.001), higher education (p < 0.001), a family history of diabetes (p =0.001), awareness regarding diabetes (p < 0.001), having diabetes for > five years (p <0.001), and managing diabetes via pharmacological interventions (p <0.001) (versus diet and exercise) were significant positive predictors of glucometer usage. Our study demonstrates the increasing trend in use of SMBG. Lack of awareness and cost of glucometers were reported to be the main reasons for not practicing SMBG. Given these factors are easily modifiable, government subsidized initiatives and awareness programs can result in a successful public health strategy to promote SMBG.


[Vena cava agenesia presented as incarcerated groin hernia].
The case describes a 45-year-old man with a rare finding of vena cava agenesia presented as incarcerated groin hernia. From childhood the patient had developed dilatation of subcutaneous veins with establishment of aneurismal dilatation in the lower right side of the abdomen and groin. The patient was submitted with severe abdominal pain in the lower right side. The case describes the difficulties of an initially incorrect radiological diagnosis of incarcerated groin hernia and the discrepancy of the clinical findings. The case stresses the importance of a thorough evaluation of each patient.


Pudendal Nerve Block With Liposomal Bupivacaine for Sacrospinous Ligament Suspension.
Pudendal nerve block has been frequently used as a pain management modality for vaginal prolapse surgery. However, studies investigating its efficacy and the type of anesthetic used have had conflicting results. This study aimed to evaluate the effect of intraoperative pudendal nerve block with liposomal bupivacaine on postoperative pain after sacrospinous ligament suspension surgery. In this single-blinded randomized controlled trial, 83 women undergoing sacrospinous ligament suspension were randomized to receive either intraoperative pudendal nerve block with liposomal bupivacaine or no block. Participants recorded their pain level on postoperative days (PODs) 1-3 and 7, the number of pain medication pills consumed, and the quality of their recovery using a validated questionnaire. There were no significant differences in pain scores between the groups on POD 1 and POD 3: 5 (2-6.25) versus 5.5 (4-8; P = 0.058) and 4 (1-6) versus 5 (2-7; P = 0.146), respectively. On POD 2, the overall pain score was statistically different between the groups, with the block group having lower interquartile ranges. This difference, however, was not clinically significant: 5 (1.75-5) versus 5 (3.25-7.75; P = 0.023). In the subset of participants who underwent a concomitant midurethral sling procedure, POD 2 and POD3 pain scores were significantly lower in those who received the block: 3 (1-5) versus 6 (5-8; P = 0.006) for POD 2 and 3 (1-5) versus 5 (3.250-7; P = 0.042) for POD 3. There were no significant differences in pain medication consumption or the quality of recovery scores. Pudendal nerve block with liposomal bupivacaine did not result in significant differences in postoperative pain after sacrospinous ligament suspension, except in those participants who underwent a concomitant midurethral sling procedure.


[Spectral luminescence studies of cells stained with acrichine derivatives].
Excitation and fluorescence spectra are given of quinacrine derivative solutions, of buccal epithelium cell nuclei, of peripheral blood cells, and of isolated chromosomes treated with propyl-quinacrine mustard. It is confirmed that the differential cell treatment with quinacrine derivates may be observed in aqueous solutions only. Data obtained allow us to give some recommendations for employment of optimal filters and dichroic beam-splitters in the fluorescence microscopy of chromosomes treated with quinacrine derivatives.


Rydberg gas theory of a glow discharge plasma: III. Formation, occupied state distributions, free energy, and kinetic control.
It has been suggested that Rydberg gas atoms are involved in conducting electricity through a steady state flowing afterglow (FAG) discharge plasma (R. S. Mason, D. J. Mitchell and P. M. Dickinson, Phys. Chem. Chem. Phys., 2010, DOI: ). From known properties of Rydberg atoms, a statistical model is developed here to find the distribution of levels (principal quantum number n) occupied in such a hypothetical Rydberg gas. It behaves non-ideally at positive column plasma densities, predicting 30 < n < 150, peaking at n approximately = 85. These values depend on assumptions concerning the power of n dependency of 'pressure ionization' and the free charge density. The occupied states are very long-lived and almost completely separated from the low n states by the low probability of intermediate levels. The effects of Rydberg gas (N(R)) and free charge densities are examined. The gas can exist in a deep free energy well (> 120 kJ mol(-1) below ionisation level when 10(10) < or = N(R) < or = 10(11) atoms cm(-3)) but this is approximately 11 kJ mol(-1) higher than that of the equivalent free ion-electron gas; therefore if it exists in preference to the classical form of the plasma, it is controlled by kinetic factors. A mechanism is suggested by which this could occur. Thus, whilst ionization by high energy electron impact occurs at the Cathode Fall-Negative Glow (NG) boundary as usual, excitation of Rydberg atoms becomes more probable, by electrons slowed by collision and deceleration at the opposite NG-Positive Column (PC) plasma boundary. The atoms become stabilized after passing into the PC, by collisionally induced (nlm) mixing of states and the removal of free charge by charge transfer (and hence the passage of electric current through the Rydberg gas). The coupling of Rydberg states with the ionization continuum is poor; therefore, if the rate of their charge transfer is greater than that of their ionization, the Rydberg gas will remain relatively charge free and hence stable when it is conducting a current. When applied to the FAG plasma, the model provides a self-consistent interpretive framework for all its electrical, mass spectrometric and chemical behaviour. The effect on the optical spectroscopy of these plasmas is considered briefly.


Informatics-based medical procedure assistance during space missions.
Currently, paper-based and/or electronic together with telecommunications links to Earth-based physicians are used to assist astronaut crews perform diagnosis and treatment of medical conditions during space travel. However, these have limitations, especially during long duration missions in which telecommunications to earth-based physicians can be delayed. We describe an experimental technology called GuideView in which clinical guidelines are presented in a structured, interactive, multi-modal format and, in each step, clinical instructions are provided simultaneously in voice, text, pictures video or animations. An example application of the system to diagnosis and treatment of space Decompression Sickness is presented. Astronauts performing space walks from the International Space Station are at risk for decompression sickness because the atmospheric pressure of the Extra-vehicular Activity space- suit is significantly less that that of the interior of the Station.


Two sisters in the same dress: Heliconius cryptic species.
Sister species divergence and reproductive isolation commonly results from ecological adaptation. In mimetic Heliconius butterflies, shifts in colour pattern contribute to pre- and post-mating reproductive isolation and are commonly correlated with speciation. Closely related mimetic species are therefore not expected, as they should lack several important sources of reproductive isolation. Here we present phenotypic, behavioral and genetic evidence for the coexistence of two sympatric 'cryptic' species near Florencia in the eastern Andes of Colombia that share the same orange rayed colour pattern. These represent H. melpomene malleti and a novel taxon in the H. cydno group, here designated as novel race of Heliconius timareta, Heliconius timareta florencia. No-choice mating experiments show that these sympatric forms have strong assortative mating ( approximately 96%) despite great similarity in colour pattern, implying enhanced divergence in pheromonal signals. We hypothesize that these species might have resulted from recent convergence in colour pattern, perhaps facilitated by hybrid introgression of wing pattern genes.


Perfusion index in newborns with CHD without clinical signs of hypoperfusion and heart failure: comparison with healthy newborns.
Peripheral perfusion index has been proposed as a possible method for detecting circulatory impairment. We aimed to determine the normal range of peripheral perfusion index in healthy newborns and compare it with that of newborns with CHD. Right-hand saturation and right-hand peripheral perfusion index levels were recorded, and physical examination and echocardiography were performed in newborns who were 0-28 days old and whom were evaluated in our paediatric cardiology outpatient clinic. The saturation and peripheral perfusion index levels of newborns with normal heart anatomy and function were compared with those of newborns with CHD. Out of 358 newborns (238 mature and 75 premature) enrolled in the study, 39 had CHD (20 mild CHD, 13 moderate CHD, and 6 severe CHD), of which 29 had CHD with left-to-right shunting, 5 had obstructive CHD, and 5 had cyanotic CHD. No newborn had clinical signs of hypoperfusion or heart failure, such as prolonged capillary refill, weakened pulses, or coldness of extremities. Peripheral perfusion index level was median (interquartile range) 1.7 (0.6) in healthy newborns, 1.8 (0.7) in newborns with mild CHD, and 1.8 (0.4) in newborns with moderate and severe CHD, and there was no significant difference between the groups regarding peripheral perfusion index level. Peripheral perfusion index remains unchanged in newborns with CHD without the clinical signs of hypoperfusion or heart failure. Larger studies with repeated peripheral perfusion index measurements can determine how valuable this method will be in the follow-up of newborns with CHD.


The value of hyoscine butylbromide in pelvic MRI.
To evaluate the effect of hyoscine butylbromide (HBB) on image quality and lesion and organ visualization in pelvic magnetic resonance imaging (MRI) MATERIALS AND METHODS: A prospective, ethically approved study was undertaken of 47 patients attending for pelvic MRI at a cancer centre. T2-weighted transverse and sagittal sequences were performed before and after intravenous injection of 20 mg HBB. Three radiologists independently scored anonymized image series for overall image quality, visualization of pelvic lesions and visualization of individual pelvic organs. Statistical analysis was performed to assess improvements in radiologists' scores post-HBB administration. Radiologists also assessed pre-HBB administration T1-weighted images for degree of bowel peristalsis to determine whether this could predict improvement in post-HBB T2-weighted image scores. Side effects of HBB were recorded using a patient questionnaire. Radiologists' scores for image quality and lesion visualization were significantly higher on the post-HBB administration T2-weighted series (p<0.0005). Scores for the visualization of the bladder, rectum, pelvic bowel, prostate, and seminal vesicles (all p<0.0005), cervix (p=0.019) and vagina (p=0.0001) were also significantly higher post-HBB administration. Scores for the degree of peristalsis on T1-weighted images were not related to improvement in image quality or lesion visualization on T2-weighted images post-HBB administration. Side effects of HBB were mild and self-limiting. Intravenous HBB administration improves image quality and lesion visualization in oncological pelvic MRI and is recommended for routine use.


Growth-regulating functions of human papillomavirus early gene products in cervical cancer cells acting dominant over enhanced epidermal growth factor receptor expression.
Squamous cell carcinomas of the human anogenital tract are usually associated with infection of specific types of human papillomaviruses (HPV 16, 18, 31, 33, 35). The intracellular concentration of human papillomavirus early gene products E6 and E7 has been directly linked to the proliferative capacity of cervical cancer cells. Since the expression rate of epidermal growth factor receptor correlates to growth properties in squamous carcinoma cell lines, it has been presumed that human papillomavirus early genes influence cell growth via enhanced epidermal growth factor receptor expression. This hypothesis implies that growth regulation by epidermal growth factor receptor overexpression dominates over a growth-regulatory influence of human papillomavirus early gene products in squamous carcinoma cells. To test this hypothesis epidermal growth factor receptor expression was analyzed in various clones of the C4-1 cervical cancer cell line which, upon dexamethasone treatment, express either increased or decreased levels of human papillomavirus 18 early gene products. In C4-1 clones expressing reduced levels of viral E6/E7 gene products upon glucocorticoid treatment expression of epidermal growth factor receptor was the same as in those clones displaying increased levels of papillomavirus proteins under identical culture conditions. The growth rate of the cells correlated with the level of viral gene products rather than with the expression of epidermal growth factor receptor. These findings suggest that unregulated overexpression of epidermal growth factor receptor is not the dominant mechanism of growth control in papillomavirus-positive carcinoma cells. Other, yet unknown pathways associated with papillomavirus early genes are essentially involved in growth control mechanisms of human cervical cancer cells.


Office procedures for quantitative assessment of olfactory function.
Despite the importance of the sense of smell for establishing the flavor of foods and beverages, as well as protecting against environmental dangers, this primary sensory system is commonly ignored by the rhinologist. In this article basic issues related to practical measurement of olfactory function in the clinic are described and examples of the application of the two most common paradigms for such measurement--odor identification and detection--are presented. A listing is made of the 27 olfactory tests currently used clinically, along with their strengths and weaknesses. A brief review of common nasosinus-related disorders for which quantitative olfactory testing has been performed is provided. Although many psychophysical tests are available for quantifying olfactory loss, it is apparent that a number are limited in terms of practicality, sensitivity, and reliability. In general, sensitivity and reliability are positively correlated with test length. Given the strengths of the more reliable forced-choice pyschophysical tests and the limitations of electrophysiological tests, the common distinction between "subjective" and "objective" tests is misleading and should not be used. Complete recovery of olfactory function, as measured quantitatively, rarely follows surgical or medical interventions in patients with rhinosinusitis. Given the availability of practical clinical olfactory tests, the modern rhinologist can easily quantify cranial nerve (CN) I function. The application of such tests has led to a new understanding of the effects of nasal disease on olfactory function. Except in cases of total or near-total nasal obstruction, olfactory and airway patency measures usually are unrelated, in accord with the concept that rhinosinusitis primarily influences olfactory function by apoptotic pathological changes within the olfactory neuroepithelium.


Structural characterization of the cell division cycle in Strigomonas culicis, an endosymbiont-bearing trypanosomatid.
Strigomonas culicis (previously referred to as Blastocrithidia culicis) is a monoxenic trypanosomatid harboring a symbiotic bacterium, which maintains an obligatory relationship with the host protozoan. Investigations of the cell cycle in symbiont harboring trypanosomatids suggest that the bacterium divides in coordination with other host cell structures, particularly the nucleus. In this study we used light and electron microscopy followed by three-dimensional reconstruction to characterize the symbiont division during the cell cycle of S. culicis. We observed that during this process, the symbiotic bacterium presents different forms and is found at different positions in relationship to the host cell structures. At the G1/S phase of the protozoan cell cycle, the endosymbiont exhibits a constricted form that appears to elongate, resulting in the bacterium division, which occurs before kinetoplast and nucleus segregation. During cytokinesis, the symbionts are positioned close to each nucleus to ensure that each daughter cell will inherit a single copy of the bacterium. These observations indicated that the association of the bacterium with the protozoan nucleus coordinates the cell cycle in both organisms.


Treatment of the blast crisis of chronic myelogenous leukemia with 5-azacitidine and VP-16-213.
Twenty-seven patients with chronic myelogenous leukemia in blast crisis were treated with a combination of 5-azacitidine (150 mg/m2/day iv in 3 divided doses x 5 days) and VP-16-213 (75 mg/m2/day x 5). No patient had lymphoid histology, and terminal transferase was not present in the 12 patients tested. One complete and 15 partial responses (58% response rate) were seen, with a median survival of 231 days for responders and 73 days for patients who failed to achieve a partial response (P = 0.008). The overall survival was 161 days (range, 20-316+). Moderately severe nausea and vomiting, muscle aches, and mucositis (two patients) were the major side effects, although toxic effects tended to decrease with subsequent courses and many patients could be treated on an outpatient basis. These results compare favorably with other results in this refractory disorders and suggest that 5-azacitidine and VP-16-213 be studied further, either in higher doses or in combination with other agents, in therapy for chronic myelogenous leukemia in blast crisis.


5-Aza-2'-deoxycytidine induces cytotoxicity in BGC-823 cells via DNA methyltransferase 1 and 3a independent of p53 status.
The DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-Aza-CdR) has therapeutic value for the treatment of cancer. However, the mechanism by which 5-Aza-CdR induces antineoplastic activity is not clear. The efficacy of 5-Aza-CdR on the contribution of gene reactivation by demethylation and enzyme-DNA adduct formation is an important unresolved question. The aim of this study was to explore the mechanism of the effect of 5-Aza-CdR on human gastric cancer growth. Human BGC-823 cells were treated with different concentrations of 5-Aza-CdR for different durations. Cell viability, DNA damage and gene expression were determined. The results showed that 5-Aza-CdR at low concentrations induced inhibition of gastric cancer BGC-823 cell proliferation as well as increased apoptosis caused by DNA damage. For the first time, we demonstrated that 5-Aza-CdR-induced cytotoxicity against BGC-823 cells was predominantly regulated via upregulation of DNA methyltransferase 1, 3a and partially via reactivation of RUNX3, which was independent of p53 status and its ability to activate p21Waf1/Cip1 expression. To our knowledge, this is the first demonstration of p53-independent 5-Aza-CdR action on DNA methyltransferases and demethylation. These results strongly provide the preclinical rationale for the clinical evaluation of 5-Aza-CdR to improve patient outcome in gastric cancer.


Bite force and dental implant treatment: a short review.
Dental implants are placed endosseously, and the bone is the ultimate bearer of the occlusal load. Patients are not uniform in the maximum bite force they can generate. The occlusal biting load in the posterior jaw is usually about three times of that found in the anterior. It is possible for supporting implants to be overloaded by the patients' biting force, resulting in bone loss and failure of the fixture. Bite force measurement may be an important parameter when planning dental implant treatment. Some patients can generate extreme biting loads that may cause a luxation of the fixture and subsequent loss of osseointegration. A patient with low biting force may be able to have a successful long-term outcome even with poor anatomical bone qualities. Patients with a high bite force capability may have an increased risk for late component fracture or implant failure. There is no correlation of any bite force value that would indicate any overload of a given implant in a given osseous site. Nonetheless, after bite force measurement, a qualitative judgement may be made by the clinician for the selection of an implant diameter and length and prosthetic design.


Tetrodotoxin suppresses thermal hyperalgesia and mechanical allodynia in a rat full thickness thermal injury pain model.
Burn injuries have been identified as the primary cause of injury in 5% of U.S. military personnel evacuated from Operations Iraqi Freedom and Enduring Freedom. Severe burn-associated pain is typically treated with opioids such as fentanyl, morphine, and methadone. Side effects of opioids include respiratory depression, cardiac depression, decrease in motor and cognitive function, as well as the development of hyperalgesia, tolerance and dependence. These effects have led us to search for novel analgesics for the treatment of burn-associated pain in wounded combat service members. Tetrodotoxin (TTX) is a selective voltage-gated sodium channel blocker currently in clinical trials as an analgesic. A phase 3 clinical trial for cancer-related pain has been completed and phase 3 clinical trials on chemotherapy-induced neuropathic pain are planned. It has also been shown in mice to inhibit the development of chemotherapy-induced neuropathic pain. TTX was originally identified as a neurotoxin in marine animals but has now been shown to be safe in humans at therapeutic doses. The antinociceptive effects of TTX are thought to be due to inhibition of Na(+) ion influx required for initiation and conduction of nociceptive impulses. One TTX sensitive sodium channel, Nav1.7, has been shown to be essential in lowering the heat pain threshold after burn injuries. To date, the analgesic effect of TTX has not been tested in burn-associated pain. Male Sprague-Dawley rats were subjected to a full thickness thermal injury on the right hind paw. TTX (8 μg/kg) was administered once a day systemically by subcutaneous injection beginning 3 days post thermal injury and continued through 7 days post thermal injury. Thermal hyperalgesia and mechanical allodynia were assessed 60 and 120 min post injection on each day of TTX treatment. TTX significantly reduced thermal hyperalgesia at all days tested and had a less robust, but statistically significant suppressive effect on mechanical allodynia. These results suggest that systemic TTX may be an effective, rapidly acting analgesic for battlefield burn injuries and has the potential for replacing or reducing the need for opioid analgesics.


Educational mobility and weight gain over 13 years in a longitudinal study of young women.
Limited evidence exists about the role of education and own educational mobility on body weight trajectory. A better understanding of how education influences long term weight gain can help us to design more effective health policies. Using random effects models, the association between i) highest education (n = 10 018) and ii) educational mobility over a 9 year period (n = 9 907) and weight gain was analysed using five waves of data (over 13 years) from the Australian Longitudinal Study on Women's Health 1973-78 cohort (from 18-23 years to 31-36 years). Highest educational attainment was inversely associated with weight at baseline and weight gain over 13 years. Compared to high educated women, those with a low (12 years or less) or intermediate (trade/certificate/diploma) education, respectively, weighed an additional 2.6 kg (95% CI:1.9 to 3.1) and 2.5 kg (95% CI:1.9 to 3.3) at baseline and gained an additional 3.9 kg (95% CI:2.6 to 5.2) and 3.1 kg (95% CI:2.6 to 3.9) over 13 years. Compared to women who remained with a low education, women with the greatest educational mobility had similar baseline weight to the women who already had a high education at baseline (2.7 kg lighter (95% CI:-3.7 to -1.8) and 2.7 kg lighter (95% CI:-3.4 to -1.9), respectively) and similarly favourable weight gain (gaining 3.1 kg less (95% CI:-4.0 to -2.21) and 4.2 kg less (95% CI:-4.8 to -3.4) over the 13 years, respectively). While educational attainment by mid-thirties was positively associated with better weight management, women's weight was already different in young adult age, before their highest education was achieved. These findings highlight a potential role of early life factors and personality traits which may influence both education and weight outcomes.


Tracking Health Inequalities from High School to Midlife.
Educational gradients in health status, morbidity, and mortality are well established, but which aspects of schooling produce those gradients is only partially understood. We draw on newly available data from the midlife follow-up of the High School and Beyond sophomore cohort to analyze the relationship between students' level of coursework in high school and their long-term health outcomes. We additionally evaluate the mediating roles of skill development, postsecondary attendance and degree attainment, and occupational characteristics. We find that students who took a medium- to high-level course of study in high school have better self-reported health and physical functioning in midlife, even net of family background, adolescent health, baseline skills, and school characteristics. The association partially operates through pathways into postsecondary education. Our findings have implications for both educational policy and research on the educational gradient in health.


Convenient One-Pot Synthesis of Kynurenic Acid Ethyl Ester and Exploration to Direct Synthesis of Neuroprotective Kynurenic Acid and Amide Derivatives.
Kynurenic acid (KYNA) is an endogenous molecule, which is a non-selective antagonist of ionotropic glutamate receptors and has been found to have neuroprotective activity. A supplement of KYNA may be applicable for the treatment of neurodegenerative disease, but it does not cross the blood-brain barrier due to its polar nature. Therefore, its different esters and amide derivatives were explored as a prodrug, which can cross blood-brain barrier and transform into KYNA in situ. However, many esters and amide derivatives of KYNA are synthesized via coupling reaction or multi-step synthesis using different organic or metallic catalysts. Herein, we developed a novel one-pot, catalyst-free, convenient synthesis of KYNA ethyl esters using aniline and diethyl acetylene dicarboxylate in DMF under heating. We also explored the synthesis of KYNA and KYNA amide derivative in a simple manner with overall good yields via hydrolysis and condensation, respectively.


Extracellular ATP signaling via P2X(4) receptor and cAMP/PKA signaling mediate ATP oscillations essential for prechondrogenic condensation.
Prechondrogenic condensation is the most critical process in skeletal patterning. A previous study demonstrated that ATP oscillations driven by Ca(2+) oscillations play a critical role in prechondrogenic condensation by inducing oscillatory secretion. However, it remains unknown what mechanisms initiate the Ca(2+)-driven ATP oscillations, mediate the link between Ca(2+) and ATP oscillations, and then result in oscillatory secretion in chondrogenesis. This study has shown that extracellular ATP signaling was required for both ATP oscillations and prechondrogenic condensation. Among P2 receptors, the P2X(4) receptor revealed the strongest expression level and mediated ATP oscillations in chondrogenesis. Moreover, blockage of P2X(4) activity abrogated not only chondrogenic differentiation but also prechondrogenic condensation. In addition, both ATP oscillations and secretion activity depended on cAMP/PKA signaling but not on K(ATP) channel activity and PKC or PKG signaling. This study proposes that Ca(2+)-driven ATP oscillations essential for prechondrogenic condensation is initiated by extracellular ATP signaling via P2X(4) receptor and is mediated by cAMP/PKA signaling and that cAMP/PKA signaling induces oscillatory secretion to underlie prechondrogenic condensation, in cooperation with Ca(2+) and ATP oscillations.


Prenatal Diagnosis and Genetic Counseling of a Maternally Inherited Chromosome 15q11.2q13.1 Duplication in a Chinese Family.
Maternally inherited chromosomal duplications in the region of 15q11.2q13.1 have been associated with neurodevelopmental disorders and other clinical manifestations. Prenatal diagnosis of such duplications is crucial for providing accurate genetic counseling and guiding clinical management decisions. This study aims to present the prenatal diagnosis and genetic counseling of a maternally inherited 15q11.2q13.1 duplication. A 38-year-old gravida 1, para 0 woman underwent amniocentesis at 16 weeks of gestation due to advanced maternal age. Karyotype analysis was performed on cultured amniocytes, and chromosomal microarray analysis (CMA) was conducted on uncultured amniocytes. The karyotype analysis of the cultured amniocytes revealed a normal karyotype of 46, XX. CMA identified a 4.21 Mb maternally inherited chromosomal duplication in the region of 15q11.2q13.1 (arr[GRCh37]15q11.2q13.1(23,894,550_28,107,154)x3). Copy number variants (CNVs) and unbalanced chromosomal abnormalities (UBCA) identified in prenatal cases require careful consideration and accurate interpretation to determine their potential harm or harmlessness compared to the norm. The combination of prenatal ultrasound, karyotype analysis, CMA, and genetic counseling proves helpful in the prenatal diagnosis of CNVs and UBCA.


Expression of stathmin/op18 as a significant prognostic factor for cervical carcinoma patients.
Stathmin (Oncoprotein18), a ubiquitous and highly conserved 19-kDa cytosolic phosphoprotein, has been reported to play a critical role in mitosis and possibly other cellular processes, which is associated with tumor carcinogenesis and development. The purpose of this study was to examine the involvement of stathmin in human cervical carcinogenesis and to evaluate its prognostic significance in human cervical carcinoma. Using semiquantitative RT-PCR and Western blotting, we detected the expression of stathmin in human normal cervical epithelial cell line, immortalized cervical epithelial cell lines, and cervical carcinoma cell lines. Additionally, we also detected the expression of stathmin protein in 15 cases of cervical carcinoma tissues and adjacent non-carcinomous margin tissues. Furthermore, specimens from 148 patients with different grade and stage cervical carcinoma were investigated by immunohistochemistry for stathmin expression. Correlations between the expression of stathmin and various clinicopathological factors were studied, while statistical analyses were performed to evaluate prognostic and diagnostic associations. The levels of stathmin mRNA and protein expression were significantly higher in cervical carcinoma cells and immortalized cervical epithelial cells than in normal cervical epithelial cells (P < 0.05). Moreover, Western blotting revealed high stathmin protein expression in 73.3% (11/15) cervical carcinoma tissues, while stathmin were overexpressed in tumor tissues as compared with adjacent non-carcinomous margin samples (P = 0.017). In addition, immunohistochemical staining revealed stathmin immunoreactivity in 81.1% (120/148) of cervical carcinoma tissues and high stathmin expression was significantly correlated with clinical stage (P = 0.006), T classification (P = 0.012), regional lymph node metastasis (P = 0.005) and hematogenous metastasis (P = 0.021). Kaplan-Meier analysis showed that high stathmin positivity was significantly associated with a shorter survival time (P < 0.001). Clinical stage (P = 0.0022), T classification (P = 0.0035), regional lymph node (P = 0.0008) or hematogenous metastasis (P = 0.0015) were also associated with survival time. Furthermore, by Cox multivariate analysis, only lymph node (P = 0.0052) or hematogenous metastasis (P = 0.0046) maintained their significance as independent prognostic factors, although stathmin was not an independent prognostic factor (risk ratio: 1.45; P = 0.0624). Stathmin expression correlates with cervical carcinogenesis and tumor progression. This molecule is a valuable prognostic marker in patients with cervical carcinoma.


Melatonin mediates selenium-induced tolerance to cadmium stress in tomato plants.
Both selenium (Se) and melatonin reduce cadmium (Cd) uptake and mitigate Cd toxicity in plants. However, the relationship between Se and melatonin in Cd detoxification remains unclear. In this study, we investigated the influence of three forms of Se (selenocysteine, sodium selenite, and sodium selenate) on the biosynthesis of melatonin and the tolerance against Cd in tomato plants. Pretreatment with different forms of Se significantly induced the biosynthesis of melatonin and its precursors (tryptophan, tryptamine, and serotonin); selenocysteine had the most marked effect on melatonin biosynthesis. Furthermore, Se and melatonin supplements significantly increased plant Cd tolerance as evidenced by decreased growth inhibition, photoinhibition, and electrolyte leakage (EL). Se-induced Cd tolerance was compromised in melatonin-deficient plants following tryptophan decarboxylase (TDC) gene silencing. Se treatment increased the levels of glutathione (GSH) and phytochelatins (PCs), as well as the expression of GSH and PC biosynthetic genes in nonsilenced plants, but the effects of Se were compromised in TDC-silenced plants under Cd stress. In addition, Se and melatonin supplements reduced Cd content in leaves of nonsilenced plants, but Se-induced reduction in Cd content was compromised in leaves of TDC-silenced plants. Taken together, our results indicate that melatonin is involved in Se-induced Cd tolerance via the regulation of Cd detoxification.


Factor analysis of body measurements in Arabian horses.
Data of 13 body measurements have been analysed from 166 Arabian horses, 123 mares and 43 stallions, ranging from 49 to 298 months of age, belonging to Alzahraa stud, Cairo, Egypt. General linear model was used to study age and gender effects on these measures. Gender was a significant source of variation for most studied traits, but not for neck girth, cannon bone circumference of fore and hind legs, and pastern girth of fore and hind legs. Age significantly affected pastern girths of fore and hind legs and cannon bone circumference of fore legs, while there was no significant effect on the other measurements. Pearson correlations, adjusted for age effect, between measurements were estimated and ranged from 0.02 to 0.84 for mares and from -0.05 to 0.90 for stallions. Factor analysis with promax rotation for each gender was carried out to derive fewer independent common factors. Three factors were extracted which accounted for 66% and 67% of the total variance in mares and stallions respectively. The first, second and third factors in mares tended to describe body thickness, leg thickness and general size respectively; whereas in stallions they tended to differentiate among general size, leg thickness and body thickness respectively. The three extracted factors for each gender determine the main sources of shared variability that control body conformation in Arabian horses. These factors could be considered in selection programmes to acquire highly coordinated bodies in pure Arabian horses with fewer measurements.


Behavioural Changes in Dementia and their Impact on Professional Caregivers: A Grounded Theory Approach.
The present study aimed to explore the impact that changes in behavioural symptoms of people living with dementia have on professional caregiver and resident relationships. A total of 21 interviews were carried out with professional caregivers of people living with dementia. A grounded theory approach was used to investigate everyday experiences of provision of professional care in dementia settings, focussing specifically on the effect of behavioural change on such relationships. A core category emerged from this analysis: 'Developing behaviour in dementia impacts relationships on a personal and professional level'. Professionals have recognized as part of their everyday practice an eventual deterioration in relationships between themselves as professional caregivers and the residents, but also between the residents and their family members and among residents themselves. Importantly, understanding patients' behaviour and behavioural change was identified as a crucial factor to achieve and sustain good relationships between professionals and residents suffering with dementia.


Simplified qPCR method for detecting excessive mtDNA damage induced by exogenous factors.
Damage to mitochondrial DNA (mtDNA) is a meaningful biomarker for evaluating genotoxicity of drugs and environmental toxins. Existing PCR methods utilize long mtDNA fragments (∼8-10kb), which complicates detecting exact sites of mtDNA damage. To identify the mtDNA regions most susceptible to damage, we have developed and validated a set of primers to amplify ∼2kb long fragments, while covering over 95% of mouse mtDNA. We have modified the detection method by greatly increasing the enrichment of mtDNA, which allows us solving the problem of non-specific primer annealing to nuclear DNA. To validate our approach, we have determined the most damage-susceptible mtDNA regions in mice treated in vivo and in vitro with rotenone and H2O2. The GTGR-sequence-enriched mtDNA segments located in the D-loop region were found to be especially susceptible to damage. Further, we demonstrate that H2O2-induced mtDNA damage facilitates the relaxation of mtDNA supercoiled conformation, making the sequences with minimal damage more accessible to DNA polymerase, which, in turn, results in a decrease in threshold cycle value. Overall, our modified PCR method is simpler and more selective to the specific sites of damage in mtDNA.


Enhanced thermal stability of a polymer solar cell blend induced by electron beam irradiation in the transmission electron microscope.
We show by in situ microscopy that the effects of electron beam irradiation during transmission electron microscopy can be used to lock microstructural features and enhance the structural thermal stability of a nanostructured polymer:fullerene blend. Polymer:fullerene bulk-heterojunction thin films show great promise for use as active layers in organic solar cells but their low thermal stability is a hindrance. Lack of thermal stability complicates manufacturing and influences the lifetime of devices. To investigate how electron irradiation affects the thermal stability of polymer:fullerene films, a model bulk-heterojunction film based on a thiophene-quinoxaline copolymer and a fullerene derivative was heat-treated in-situ in a transmission electron microscope. In areas of the film that exposed to the electron beam the nanostructure of the film remained stable, while the nanostructure in areas not exposed to the electron beam underwent large phase separation and nucleation of fullerene crystals. UV-vis spectroscopy shows that the polymer:fullerene films are stable for electron doses up to 2000kGy.