Professional development short scale: Measurement invariance, stability, and validity in Brazil and Angola.
Professional development is the vital process in the workplace that comprises the growth and maturation of knowledge, skills, and attitudes arising from formal and informal learning at work throughout one's life. The goal of this research was to present validity evidence and accuracy of the Professional Development Short Scale (PDSS) for different occupational categories. The research was conducted using four cross-sectional questionnaire surveys with convenience samples of different occupational categories (N = 2,547) in 41 cities throughout Brazil and Angola. The first study aimed to explore the factorial structure and internal consistency of the PDSS. The second study aimed to evaluate the cross-cultural validity and measurement invariance of the scale. The third study was to assess concurrent validity and predictive validity. The fourth study was to assess the test-retest reliability. The results indicated a one-factor structure, with six items for both countries' datasets. This research pointed out the validity of the PDSS as regards its convergence-discriminant pattern with the General Self-Efficacy and Job Self-Efficacy Scales, and also, the relationship of the PDSS with relevant constructs (Bases of Power/leadership styles, In-role performance, Job Satisfaction, and Career Promotion). In this study, we provide psychometric validity of the Professional Development Short Scale to offer it as a resource to measure the construct and allow researchers to apply it in research models easily integrated to other constructs. We covered several different incremental approaches to ensure the scale validity. Besides showing temporal stability to ensure it can be applied from time to time, as one dynamic construct should, we also indicated that social desirability did not influence the measurement of the PDSS. Furthermore, the results indicate that the effects of the method do not generate undue confusion on the scale. Thus, the psychometric properties of the PDSS allow for recommending the use of the scale in extensive studies. This scale therefore contributes to contemporary professional development literature through the comparison of the perceptions of professional development in different professional categories and by providing organizational researchers with a tool to evaluate the effects and predictors of such construct.


The short-term and long-term effects of radical prostatectomy on lower urinary tract symptoms.
We determined the long-term effect of radical prostatectomy on lower urinary tract symptoms. Between October 1, 2000 and January 30, 2003, 587 men underwent open radical retropubic prostatectomy. Of these men 453 completed the American Urological Association symptom index at baseline, and 12 and 48 months. Mean changes in American Urological Association total, voiding and storage symptom scores were ascertained between baseline and 12 months (short term), baseline and 48 months (long term), and between 12 and 48 months (natural history of lower urinary tract symptoms without a prostate). Symptom scores were ascertained independently for men with baseline mild vs moderate/severe lower urinary tract symptoms. Clinically and statistically significant short-term and long-term improvements were observed in mean American Urological Association total, storage and voiding symptom scores for men presenting with moderate/severe lower urinary tract symptoms. The previously reported progression of lower urinary tract symptoms in the general population of men older than 40 years was not observed in our patients with an absent prostate. The current study provides compelling evidence that radical prostatectomy prevents the progression of lower urinary tract symptoms in men with and without baseline clinically significant lower urinary tract symptoms. This beneficial effect of radical prostatectomy on the natural history of lower urinary tract symptoms should be considered when weighing the risks and benefit of the treatment option for localized prostate cancer.


A communication approach to drug use intervention.
A schema has been designed to enable intervention planners to more functionally select, and to more effectively utilize a communication model for drug use/misuse intervention which is suitable for the focus of their efforts and which meets the necessary demands of prevention, education, training, and information dissemination.


Potentiation of cisplatin-induced lipid peroxidation in kidney cortical slices by glutathione depletion.
Effects of cis-diamminedichloroplatinum II (cisplatin), an antitumor agent with a dose-limiting effect of nephrotoxicity, on lipid peroxides and glutathione (GSH) were examined in rat kidney cortical slices treated with or without diethylmaleate (DEM), a GSH depletor, in vitro. DEM (3 mM) decreased the GSH level to about 16% of the control with a concomitant increase in lipid peroxides after 90 min of incubation. The same effects were obtained with 1 mM cisplatin 90 min later. Cisplatin (1 mM) with DEM (2 mM) stimulated both the decrease in GSH and the increase in lipid peroxides 90 min after incubation. However, cisplatin with DEM markedly stimulated lipid peroxidation with a small effect on the GSH decrease by cisplatin alone 30 min after incubation, while each drug by itself did not affect lipid peroxidation. The antioxidants N,N'-diphenyl-p-phenylene-diamine (DPPD), promethazine, and ascorbic acid abolished cisplatin-induced lipid peroxidation in the presence of DEM. DPPD had no effect on the depletion of GSH caused by cisplatin and DEM. Ascorbic acid and promethazine caused only a slight return towards the control level. The results suggested that cisplatin-induced lipid peroxidation is due to another mechanism in addition to the GSH depletion caused by the antitumor drug.


Preoperative Location Of Parathyroid Adenomas In Primary Hyperparathyroidism: The Role of Cervical Doppler Ultrasound.
Parathyroid adenoma is the most frequent cause of primary hyperparathyroidism. In recent years, the preoperative location of parathyroid adenomas allowed minimally invasive surgical techniques that have become preferred over the traditional bilateral neck exploration. The more recent guidelines on this subject highlight the role of nuclear medicine imaging tests. The aim of this study was to review the current role of Doppler ultrasound (US) in assessing the preoperative location of parathyroid adenomas in patients with primary hyperparathyroidism. Retrospective study based on data from patients with primary hyperparathyroidism that underwent parathyroidectomy between January 2013 and January 2022 at the Centro Hospitalar Universitário Lisboa Central. Statistical analysis was performed with IBM SPSS Statistics, version 220.127.116.11®. Parathyroidectomy was performed in 171 patients (77.8% females) with primary hyperparathyroidism. Cervical Doppler ultrasound was the most performed test (64.3%, n = 110) for preoperative location and detected a suspicious lesion in 98 patients (89.1%). The preoperative location of the parathyroid adenomas was assessed through the Doppler ultrasound and was compared with the surgical reports and histological findings; a correct identification was made in 76 patients (77.6%). Doppler ultrasound slightly underestimated the mean adenoma size (18.1 ± 7.7 mm preoperative versus 22 ± 8.4 mm postoperative). Calcium, parathyroid hormone levels, adenoma size and concomitant presence of thyroid nodules did not affect the accuracy of Doppler ultrasound. Doppler ultrasound showed high diagnostic accuracy even in patients with nodular thyroid disease regardless of calcium and parathyroid hormone levels and adenoma size. Furthermore, its safety, affordability and availability should favor its use as first line test in primary hyperparathyroidism to assess the preoperative location of parathyroid adenomas.


Personalized Models of Human Atrial Electrophysiology Derived From Endocardial Electrograms.
Computational models represent a novel framework for understanding the mechanisms behind atrial fibrillation (AF) and offer a pathway for personalizing and optimizing treatment. The characterization of local electrophysiological properties across the atria during procedures remains a challenge. The aim of this work is to characterize the regional properties of the human atrium from multielectrode catheter measurements. We propose a novel method that characterizes regional electrophysiology properties by fitting parameters of an ionic model to conduction velocity and effective refractory period restitution curves obtained by a s1-s2 pacing protocol applied through a multielectrode catheter. Using an in-silico dataset we demonstrate that the fitting method can constrain parameters with a mean error of 21.9 ± 16.1% and can replicate conduction velocity and effective refractory curves not used in the original fitting with a relative error of 4.4 ± 6.9%. We demonstrate this parameter estimation approach on five clinical datasets recorded from AF patients. Recordings and parametrization took approx. 5 and 6 min, respectively. Models fitted restitution curves with an error of ~ 5% and identify a unique parameter set. Tissue properties were predicted using a two-dimensional atrial tissue sheet model. Spiral wave stability in each case was predicted using tissue simulations, identifying distinct stable (2/5), meandering and breaking up (2/5), and unstable self-terminating (1/5) spiral tip patterns for different cases. We have developed and demonstrated a robust and rapid approach for personalizing local ionic models from a clinically tractable.


Equiatomic AEAuX (AE=Ca-Ba, X=Al-In) Intermetallics: A Systematic Study of their Electronic Structure and Spectroscopic Properties.
The three intermetallic compounds SrAuGa, BaAuAl and BaAuGa were synthesised from the elements in niobium ampoules. The Sr compound crystallises in the orthorhombic KHg2 -type structure (Imma, a=465.6(1), b=771.8(2), c=792.6(2) pm, wR2 =0.0740, 324 F2 values, 13 variables), whereas the Ba compounds were both found to crystallise in the cubic non-centrosymmetric LaIrSi-type structure (P21 3, BaAuAl: a=696.5(1) pm; wR2 =0.0427, 446 F2 values, 12 variables; BaAuGa: a=693.49(4) pm, wR2 =0.0717, 447 F2 values, 12 variables). The samples were investigated by powder X-ray diffraction and their structures refined on the basis of single-crystal X-ray diffraction data. The title compounds, along with references from the literature (CaAuAl, CaAuGa, CaAuIn, and SrAuIn), were characterised further by susceptibility measurements and 27 Al and 71 Ga solid-state NMR spectroscopy. Theoretical calculations of the density of states (DOS) and the NMR parameters were used for the interpretation of the spectroscopic data. The electron transfer from the alkaline-earth metals and the group 13 elements onto the gold atoms was investigated through X-ray photoelectron spectroscopy (XPS), classifying these intermetallics as aurides.


Identification of a small tetraheme cytochrome c and a flavocytochrome c as two of the principal soluble cytochromes c in Shewanella oneidensis strain MR1.
Two abundant, low-redox-potential cytochromes c were purified from the facultative anaerobe Shewanella oneidensis strain MR1 grown anaerobically with fumarate. The small cytochrome was completely sequenced, and the genes coding for both proteins were cloned and sequenced. The small cytochrome c contains 91 residues and four heme binding sites. It is most similar to the cytochromes c from Shewanella frigidimarina (formerly Shewanella putrefaciens) NCIMB400 and the unclassified bacterial strain H1R (64 and 55% identity, respectively). The amount of the small tetraheme cytochrome is regulated by anaerobiosis, but not by fumarate. The larger of the two low-potential cytochromes contains tetraheme and flavin domains and is regulated by anaerobiosis and by fumarate and thus most nearly corresponds to the flavocytochrome c-fumarate reductase previously characterized from S. frigidimarina to which it is 59% identical. However, the genetic context of the cytochrome genes is not the same for the two Shewanella species, and they are not located in multicistronic operons. The small cytochrome c and the cytochrome domain of the flavocytochrome c are also homologous, showing 34% identity. Structural comparison shows that the Shewanella tetraheme cytochromes are not related to the Desulfovibrio cytochromes c(3) but define a new folding motif for small multiheme cytochromes c.


Respiratory training in Spain.
Respiratory medicine is a varied specialty that encompasses a broad spectrum of diseases, specific diagnostic and treatment techniques, and both critical and chronic care patients. However, while in some countries is one of the most competitive specialties to get into, in Spain is one of the less popular options.


Effects of di-n-butyl phthalate on aerobic composting process of agricultural waste: Mainly based on bacterial biomass and community dynamics analysis.
Phthalic acid esters (PAEs) pollution has become a major environmental problem in agricultural waste composting. However, little information was available about the how the PAEs alter microbial processes during composting. This study investigated the effects of di-n-butyl phthalate (DBP) on bacterial biomass and community dynamics during composting. The results showed that a decreasing of DBP was observed from thermophilic phase and 43.26% of DBP was degraded after composting. The bacterial biomass and diversity during composting were reduced under DBP stress, so delaying the decomposition of organic matter. Moreover, the changes in bacterial community were observed since the thermophilic phase of DBP-contaminated composting. KEGG pathway analysis indicated that DBP stress decreased the relative abundance of the main metabolic pathways and inhibited compost maturation. Moreover, DBP stress had more significant correlation with the dominant bacteria. This work will expand the understanding of PAEs-contaminated organic waste composting and further control of PAEs pollutants.


[Treatment and challenges of bulevirtide in chronic hepatitis D].
In July of 2020, bulevirtide was conditionally approved for the treatment of adults with compensated chronic hepatitis D. Some clinical studies have evaluated the safety and efficacy of bulevirtide as a treatment option for chronic hepatitis D in recent years. Herein are presented a brief review and an outline.


Automatic continuous scanning and random-access switching of mid-infrared waves generated by difference-frequency mixing.
We report the rapid tuning of mid-infrared waves beyond 5 microm emitted in difference-frequency mixing with an electronically tuned dual-wavelength Ti:Al2O3 laser used as a pumping source. Simultaneous rapid tuning of the dual wavelengths, which satisfy phase matching in AgGaS2, allows rapid random access switching and continuous tuning of mid-infrared wavelengths. In random-access switching, the mid-infrared wavelength is tuned every pulse shot at a repetition rate of 1 kHz. Mid-infrared wavelengths continuously tuned from 5.2 to 7.2 microm, from 7.0 to 9.1 microm, and from 8.9 to 12.0 microm are achieved at phase-matched angles of 55 degrees, 50 degrees, and 45 degrees, respectively.


[Reference values for protein C activity in healthy adults in Mexico].
Protein C (pC) is a natural-occurring anticoagulant and its acquired or hereditary deficiency has been associated with thrombosis. For its screening, technics that appraise both its plasmatic concentration and biological activity are used. The quantitative deficiency is important, but some characteristics of pC activity (pCA) suggest an essential role of the functional deficiency. Because reference levels have not been previously described in Mexico, we report here the results of a pCA assessed by a chromogenic assay in 88 adult healthy mexican people between 15 and 69 years of age. The pCA values at the 2.5 and 97.5% percentiles in our population were 75 and 137% in normal plasma. Functional disorders of this protein have been described in the presence of normal pC quantitative levels and, therefore, there are individuals with low pC concentrations and a normal pCA without thrombosis. These data suggest that the pCA could be a more important screening test than the quantitative determination as the first step in the study of a possible deficiency state of protein C.


[Ankylosing spondylitis. Comparative trial of two non-steroidal anti-inflammatory agents: pirprofen and ketoprofen].
In this double blind, crossover trial, 40 patients with ankylosing spondylitis were treated during two successive periods of 4 weeks each with either pirprofen 800 mg/day or ketoprofen 300 mg/day administered orally in a randomized order. The efficacy of pirprofen and ketoprofen was comparable, the results, as assessed by the clinician, were excellent or satisfactory in 53% of both groups. Pirprofen was well tolerated by 71% of the patients and ketoprofen by 59%.


[HTLV-I associated interstitial pneumonia--a case report and bronchoalveolar lavage study].
A 70-year-old male was admitted to our hospital because of fever and dyspnea. The patient was seropositive for HTLV-I and ATL cells were seen in the peripheral blood in the percentage of 2-5. The proviral DNA was positive and the diagnosis of smoldering ATL was made. His chest X-ray film showed diffuse reticulo-nodular infiltrates in both lung fields. The lung tissue obtained by transbronchial lung biopsy showed the lymphocytic infiltrations in the alveolar septa and the submucosa of the bronchioles. Bronchoalveolar lavage (BAL) fluid showed an increased proportion of lymphocytes that consisted mainly of CD3+ DR+ cells and the CD4+/CD8+ ratio was 2.1 during exacerbation and 0.8 after steroid therapy. Anti-HTLV-I IgG and IgA antibodies were positive in both serum and BAL fluid by Western blotting method. It is suggested that T-lymphocyte alveolitis may occur in patients who are seropositive for HTLV-I and the immunological mechanism seems to be responsible.


The "other" side of labor reform: accounts of incarceration and resistance in the Straits Settlements penal system, 1825-1873.
The rhetoric surrounding the transportation of prisoners to the Straits Settlements and the reformative capacity of the penal labor regime assumed a uniform subject, an impoverished criminal, who could be disciplined and accordingly civilized through labor. Stamford Raffles, as lieutenant governor of Benkulen, believed that upon realizing the advantages of the new colony, criminals would willingly become settlers. These two colonial prerogatives of labor and population categorized transportees into laboring classes where their exploitation supposedly brought mutual benefit. The colonized was collectively homogenized as a class of laborers and evidence to the contrary, of politically challenging and resistant individuals was suppressed. This paper focuses on two prisoners who were incriminated during the anti-colonial rebellions of the mid-nineteenth century and were transported to the Straits Settlements. Nihal Singh, a political prisoner from Lahore, was incarcerated in isolation to prevent his martyrdom and denied the supposed benefits of labor reform. Conversely, Tikiri Banda Dunuwille, a lawyer from Ceylon was sent to labor in Melaka as a form of humiliation. Tikiri's many schemes to evade labor damned him in the eyes of the authorities. The personal histories of these two individuals expose how colonial penal policy recognized and manipulated individual differences during a time of rising anti-colonial sentiment. The experiences of these prisoners, the response of their communities and the voices of their descendents offer us a very different entry point into colonial penal history.


Identification of tumor immune infiltration-associated lncRNAs for improving prognosis and immunotherapy response of patients with non-small cell lung cancer.
Increasing evidence has demonstrated the functional relevance of long non-coding RNAs (lncRNAs) to immunity regulation and the tumor microenvironment in non-small cell lung cancer (NSCLC). However, tumor immune infiltration-associated lncRNAs and their value in improving clinical outcomes and immunotherapy remain largely unexplored. We developed a computational approach to identify an lncRNA signature (TILSig) as an indicator of immune cell infiltration in patients with NSCLC through integrative analysis for lncRNA, immune and clinical profiles of 115 immune cell lines, 187 NSCLC cell lines and 1533 patients with NSCLC. Then the influence of the TILSig on the prognosis and immunotherapy in NSCLC was comprehensively investigated. Computational immune and lncRNA profiling analysis identified an lncRNA signature (TILSig) consisting of seven lncRNAs associated with tumor immune infiltration. The TILSig significantly stratified patients into the immune-cold group and immune-hot group in both training and validation cohorts. These immune-hot patients exhibit significantly improved survival outcome and greater immune cell infiltration compared with immune-cold patients. Multivariate analysis revealed that the TILSig is an independent predictive factor after adjusting for other clinical factors. Further analysis accounting for TILSig and immune checkpoint gene revealed that the TILSig has a discriminatory power in patients with similar expression levels of immune checkpoint genes and significantly prolonged survival was observed for patients with low TILSig and low immune checkpoint gene expression implying a better response to immune checkpoint inhibitor (ICI) immunotherapy. Our finding demonstrated the importance and value of lncRNAs in evaluating the immune infiltrate of the tumor and highlighted the potential of lncRNA coupled with specific immune checkpoint factors as predictive biomarkers of ICI response to enable a more precise selection of patients.


Tongue-palate contact patterns for Japanese speakers with and without cleft lip and palate.
Purpose: Visual feedback therapy, using electropalatography (EPG), has been used to remedy residual articulation errors associated with cleft palate. The tongue-palate contact patterns of typical speakers without cleft palate are usually used as a model. However, it is questionable whether these model patterns are adequate for clients with repaired cleft palate, as their dento-palatal morphology is different from non-cleft speakers. The objective of this study was to investigate the differences in tongue-palate contact patterns between typical speakers with and without cleft palate.Method: EPG data were recorded for alveolar consonants in 15 participants with repaired unilateral cleft lip and palate (UCLP) whose speech was perceptually assessed as typical Japanese. The cumulative templates for each consonant were generated from the maximum contact frame; quantitative analyses (centre of gravity [CoG], variability index) were performed. Fifteen typical Japanese speakers without cleft served as a control group.Result: EPG patterns for each consonant were generally similar between groups. The CoG value of the UCLP group was significantly lower only for /s/. The average variability index was higher for every consonant but the comparisons did not reach significance.Conclusion: The typical tongue-palate contact patterns can be used as a model of visual feedback therapy.


Effects of a dried Bacillus subtilis culture on egg quality.
The effects of a dried Bacillus subtilis culture on the egg qualities of layers were studied. Nine hundred and sixty 25-wk-old Lohmann Brown layers were randomly divided into 5 groups with 192 layers in each group. Layers in group 1 were fed a control diet. The remaining groups received the control diet that contained either 20 mg of zinc bacitracin/kg and 4 mg of colistin sulfate/kg or 500, 1,000, or 1,500 mg of B. subtilis culture/ kg, respectively. The results showed improvements in egg production, feed consumption, and feed conversion (P < 0.05) of layers when 500 mg of B. subtilis culture/kg was added to the diets. The results also showed some special improvements in this group, including increases in eggshell thickness, yolk color, and Haugh unit, and decreases in yolk cholesterol concentration (P < 0.05). However, excessive doses of B. subtilis culture did not improve the performance of layers.


Anion dependence in the spin-crossover properties of a Fe(II) podand complex.
We report the syntheses, characterisations, and spin state behaviours of salts of the tripodal-ligated Fe(II) complex [FeL(6-OH)]X(2) (L(6-OH) = tris{4-[(6-methanol)-2-pyridyl]-3-aza-3-butenyl}amine, X = OTf(-) (1), Br(-) (2), I(-) (3), BPh(4)(-) (4)). Covalent linking of the ligand arms is imperative as a high-spin bis(tridentate) complex (5) is formed when a non-tethered ethyl iminopyridine ligand (L(2) = 4-[(6-methanol)-2-pyridyl]-3-aza-3-butenyl) is used. For salts 1-4, thermally-induced spin-crossover (SCO) is observed in the solid state, with dependence on anion and solvate molecules. Salts with larger anions show more complete SCO centred at higher temperatures (1 > 3 > 2); the triflate salt 1 (T(1/2) = 173 K) also shows the strongest cooperativity of the compounds examined. Hydrogen bonding appears to be critical to SCO in this family of salts: limiting interactions by use of tetraphenylborate produces a high-spin complex down to 5 K. In protic solvents such as methanol, spectra of [FeL(6-OH)](2+) are largely unchanged over a period of three days, but dissociate when interrogated with strong field bidentate ligands. Compounds 1-3, and 5 remain high spin in solution down to 180 K, consistent with the data obtained in the solid state.


Penicillin as empirical therapy for patients hospitalised with community acquired pneumonia at a Danish hospital.
We report on the outcome of a study of patients hospitalised with community acquired pneumonia (HCAP) at a Danish university hospital. In a retrospective study of 243 consecutive patients with radiographically verified HCAP, data on clinical and laboratory findings and outcome parameters were collected. Three groups were established according to the initial choice of antibiotic(s): penicillin only (n = 160); non-allergic patients starting broader spectrum therapy (n = 54); and patients with suspected penicillin allergy (n = 29). The overall mortality within three months was 12% and the readmission rate within three months was 20%. The three treatment groups were comparable with respect to most demographic and clinical criteria at baseline. No significant differences in outcome between the groups were found: the mortality was 12.5%, 13.0%, and 10.3%, respectively, p = 0.94, and the readmission rate 20.3%, 24.0%, and 14.8%, respectively; p = 0.63. Patients treated for community-acquired pneumonia at a Danish university hospital had clinical outcomes fully at height with findings from other countries, and half of the patients were successfully treated with penicillin monotherapy. No differences in clinical outcomes were documented between patients treated empirically with broad-spectrum therapy and penicillin monotherapy. Therefore, penicillin seems to be a reasonable first choice for initial therapy of HCAP in Denmark as in other regions with similar patterns of microbial pathogens and resistance.


Use of Continuous Exposure Variables when Examining Dose-Dependent Pharmacological Effects - Application to the Association between Exposure to Higher Statin Doses and the Incidence of Diabetes.
Many observational studies have found an association between the exposure to statins and the increased risk of diabetes, mostly through the use of intent-to-treat (ITT) like exposure measure (EM). ITT like EM may not adequately reflect the mechanism of action by which statins could cause diabetes. To determine if continuous EMs can more accurately reflect the mechanism of action by which statins and incidence of diabetes would be associated than ITT like EM. We obtained a cohort of 404,129 diabetes-free incident statin users from the Québec public drug insurance plan. Patients dispensed with a drug used in the treatment of diabetes or diagnosed with diabetes within 2-years follow-up were defined as cases. Controls were randomly matched to each case on the index date. Three EMs were tested. EM 1: exposure to a high versus low dose statin at baseline (ITT like); EM 2: cumulative standardized statin dose (cSSD) at the index date; and EM 3: cSSD in the 180 days prior to the index date. The optimal EM was selected based upon each model's Akaike's information criterion (AIC). Conditional logistic regressions were used to calculate conditional OR and model AIC. All three EMs identified an increased risk of diabetes among patients exposed to higher statin doses. Model AIC identified EM 3 as the best EM for this association. Our results indicate that higher statin doses increase the risk of diabetes but favour a cumulative reversible diabetogenic effect of statins.


Lessons to Learn for Adequate Targeted Therapy Development in Metastatic Colorectal Cancer Patients.
Insulin-like growth factor 1 receptor (IGF1R) is a receptor tyrosine kinase that regulates cell growth and proliferation. Upregulation of the IGF1R pathway constitutes a common paradigm shared with other receptor tyrosine kinases such as EGFR, HER2, and MET in different cancer types, including colon cancer. The main IGF1R signaling pathways are PI3K-AKT and MAPK-MEK. However, different processes, such as post-translational modification (SUMOylation), epithelial-to-mesenchymal transition (EMT), and microenvironment complexity, can also contribute to intrinsic and acquired resistance. Here, we discuss new strategies for adequate drug development in metastatic colorectal cancer patients.


Immune activation in lactating dams alters sucklings' brain cytokines and produces non-overlapping behavioral deficits in adult female and male offspring: A novel neurodevelopmental model of sex-specific psychopathology.
Early immune activation (IA) in rodents, prenatal through the mother or early postnatal directly to the neonate, is widely used to produce behavioral endophenotypes relevant to schizophrenia and depression. Given that maternal immune response plays a crucial role in the deleterious effects of prenatal IA, and lactation is a critical vehicle of immunological support to the neonate, we predicted that immune activation of the lactating dam will produce long-term abnormalities in the sucklings. Nursing dams were injected on postnatal day 4 with the viral mimic poly-I:C (4mg/kg) or saline. Cytokine assessment was performed in dams' plasma and milk 2h, and in the sucklings' hippocampus, 6h and 24h following poly-I:C injection. Male and female sucklings were assessed in adulthood for: a) performance on behavioral tasks measuring constructs considered relevant to schizophrenia (selective attention and executive control) and depression (despair and anhedonia); b) response to relevant pharmacological treatments; c) brain structural changes. Maternal poly-I:C injection caused cytokine alterations in the dams' plasma and milk, as well as in the sucklings' hippocampus. Lactational poly-I:C exposure led to sex-dimorphic (non-overlapping) behavioral abnormalities in the adult offspring, with male but not female offspring exhibiting attentional and executive function abnormalities (manifested in persistent latent inhibition and slow reversal) and hypodopaminergia, and female but not male offspring exhibiting despair and anhedonia (manifested in increased immobility in the forced swim test and reduced saccharine preference) and hyperdopaminergia, mimicking the known sex-bias in schizophrenia and depression. The behavioral double-dissociation predicted distinct pharmacological profiles, recapitulating the pharmacology of negative/cognitive symptoms and depression. In-vivo imaging revealed hippocampal and striatal volume reductions in both sexes, as found in both disorders. This is the first evidence for the emergence of long-term behavioral and brain abnormalities after lactational exposure to an inflammatory agent, supporting a causal link between early immune activation and disrupted neuropsychodevelopment. That such exposure produces schizophrenia- or depression-like phenotype depending on sex, resonates with notions that risk factors are transdiagnostic, and that sex is a susceptibility factor for neurodevelopmental psychopathologies.


1-Million droplet array with wide-field fluorescence imaging for digital PCR.
Digital droplet reactors are useful as chemical and biological containers to discretize reagents into picolitre or nanolitre volumes for analysis of single cells, organisms, or molecules. However, most DNA based assays require processing of samples on the order of tens of microlitres and contain as few as one to as many as millions of fragments to be detected. Presented in this work is a droplet microfluidic platform and fluorescence imaging setup designed to better meet the needs of the high-throughput and high-dynamic-range by integrating multiple high-throughput droplet processing schemes on the chip. The design is capable of generating over 1-million, monodisperse, 50 picolitre droplets in 2-7 minutes that then self-assemble into high density 3-dimensional sphere packing configurations in a large viewing chamber for visualization and analysis. This device then undergoes on-chip polymerase chain reaction (PCR) amplification and fluorescence detection to digitally quantify the sample's nucleic acid contents. Wide-field fluorescence images are captured using a low cost 21-megapixel digital camera and macro-lens with an 8-12 cm(2) field-of-view at 1× to 0.85× magnification, respectively. We demonstrate both end-point and real-time imaging ability to perform on-chip quantitative digital PCR analysis of the entire droplet array. Compared to previous work, this highly integrated design yields a 100-fold increase in the number of on-chip digitized reactors with simultaneous fluorescence imaging for digital PCR based assays.


A Systematic Review and Meta-analysis of Neuroimaging in Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD) Taking Attention-Deficit Hyperactivity Disorder (ADHD) Into Account.
Oppositional defiant disorder (ODD) and conduct disorder (CD) are common behavioural disorders in childhood and adolescence and are associated with brain abnormalities. This systematic review and meta-analysis investigates structural (sMRI) and functional MRI (fMRI) findings in individuals with ODD/CD with and without attention-deficit hyperactivity disorder (ADHD). Online databases were searched for controlled studies, resulting in 12 sMRI and 17 fMRI studies. In line with current models on ODD/CD, studies were classified in hot and cool executive functioning (EF). Both the meta-analytic and narrative reviews showed evidence of smaller brain structures and lower brain activity in individuals with ODD/CD in mainly hot EF-related areas: bilateral amygdala, bilateral insula, right striatum, left medial/superior frontal gyrus, and left precuneus. Evidence was present in both structural and functional studies, and irrespective of the presence of ADHD comorbidity. There is strong evidence that abnormalities in the amygdala are specific for ODD/CD as compared to ADHD, and correlational studies further support the association between abnormalities in the amygdala and ODD/CD symptoms. Besides the left precuneus, there was no evidence for abnormalities in typical cool EF related structures, such as the cerebellum and dorsolateral prefrontal cortex. Resulting areas are associated with emotion-processing, error-monitoring, problem-solving and self-control; areas associated with neurocognitive and behavioural deficits implicated in ODD/CD. Our findings confirm the involvement of hot, and to a smaller extent cool, EF associated brain areas in ODD/CD, and support an integrated model for ODD/CD (e.g. Blair, Development and Psychopathology, 17(3), 865-891, 2005).


Differential effects of selenium on normal and neoplastic canine mammary cells.
Four different canine mammary tumor (CMT) cell lines and a nonneoplastic primary culture of mammary cells were examined for their in vitro responsiveness to selenium supplementation. These cell lines were found to vary in their metabolic response to increasing concentrations of selenium. Sensitivity to selenium, as sodium selenite, increased with increasing concentrations of this trace element in all of the neoplastic lines. These data also suggest that increasing the plating density of tumor cells further increases the sensitivity to selenium. A relatively selenium-sensitive cell line (CMT-13) and relatively insensitive cell line (CMT-11) were characterized on the basis of reduced growth resulting from selenium supplementation. Increasing the concentration of selenium to 0.75 microgram/ml depressed the growth of CMT-13 and CMT-11 cells by 75% and 11%, respectively, while no inhibition was observed in nonneoplastic cells. These cell lines also varied in their sensitivity to different forms of selenium. Selenodiglutathione was the most effective form of selenium examined that inhibited tumor cell growth. The sensitivity of the neoplastic lines was selenodiglutathione much greater than sodium selenite much greater than selenocystine greater than selenomethionine. None of the forms of selenium examined inhibited the growth of the nonneoplastic mammary cells in culture. Supplementation with sodium selenite (1 microgram Se per ml) for 60 min resulted in a dramatic depression in RNA biosynthesis in CMT-13, but not CMT-11 or nonneoplastic cells.


Reliable classification of two-class cancer data using evolutionary algorithms.
In the area of bioinformatics, the identification of gene subsets responsible for classifying available disease samples to two or more of its variants is an important task. Such problems have been solved in the past by means of unsupervised learning methods (hierarchical clustering, self-organizing maps, k-mean clustering, etc.) and supervised learning methods (weighted voting approach, k-nearest neighbor method, support vector machine method, etc.). Such problems can also be posed as optimization problems of minimizing gene subset size to achieve reliable and accurate classification. The main difficulties in solving the resulting optimization problem are the availability of only a few samples compared to the number of genes in the samples and the exorbitantly large search space of solutions. Although there exist a few applications of evolutionary algorithms (EAs) for this task, here we treat the problem as a multiobjective optimization problem of minimizing the gene subset size and minimizing the number of misclassified samples. Moreover, for a more reliable classification, we consider multiple training sets in evaluating a classifier. Contrary to the past studies, the use of a multiobjective EA (NSGA-II) has enabled us to discover a smaller gene subset size (such as four or five) to correctly classify 100% or near 100% samples for three cancer samples (Leukemia, Lymphoma, and Colon). We have also extended the NSGA-II to obtain multiple non-dominated solutions discovering as much as 352 different three-gene combinations providing a 100% correct classification to the Leukemia data. In order to have further confidence in the identification task, we have also introduced a prediction strength threshold for determining a sample's belonging to one class or the other. All simulation results show consistent gene subset identifications on three disease samples and exhibit the flexibilities and efficacies in using a multiobjective EA for the gene subset identification task.


Microfabricated devices: A new sample introduction approach to mass spectrometry.
Instrument miniaturization is one way of addressing the issues of sensitivity, speed, throughput, and cost of analysis in DNA diagnostics, proteomics, and related biotechnology areas. Microfluidics is of special interest for handling very small sample amounts, with minimal concerns related to sample loss and cross-contamination, problems typical for standard fluidic manipulations. Furthermore, the small footprint of these microfabricated structures leads to instrument designs suitable for high-density, parallel sample processing, and high-throughput analyses. In addition to miniaturized systems designed with optical or electrochemical detection, microfluidic devices interfaced to mass spectrometry have also been demonstrated. Instruments for automated sample infusion analysis are now commercially available, and microdevices utilizing chromatographic or capillary electrophoresis separation techniques are under development. This review aims at documenting the technologies and applications of microfluidic mass spectrometry for the analysis of proteomic samples.


[Epidemiology of scorpion envenomations in the pediatric service of the Agadez hospital center (Niger) in 1999].
In Agadez, northern Niger, envenomations due to scorpion sting is a major public health problem, ranking first among reasons for emergency admission to hospital and inducing significant mortality. In order to provide best medical care, improved knowledge of scorpion sting envenomation was required. From April to September 1999, we carried out a prospective, descriptive survey on the paediatric ward of the departmental hospital of Algadez. All children admitted to the ward for scorpion stings were included. Data was collected by questionnaire. Requested items were age, sex, type of scorpion, sting location, and clinical development. Over the 6 months of the survey, a total of 44 cases of scorpion sting were recorded on the ward. The majority of the cases (52%) were recorded in July. The main types of scorpion identified according to colour were black (18%), yellow (18%), and brown (5%). In 59% of the cases, the type of scorpion was not identified. 6-15 year-old children represented 50% of the cases. The lower limb was the main site of stings (66%). A majority of cases (52%) were admitted fewer than 30 minutes after the sting, and 30% between 30 minutes and 1 hour after the sting. The overall lethality rate was 23% (10/44). All the deaths occurred within 2 hours following the sting. Of all the deaths, 60% (6/10) occurred with 30 minutes after the sting. Our study has shown that scorpion stings remain a significant health problem in the area. As a consequence of our findings, we have introduced a new therapeutic protocol for the early case management.


[Catamnestic study of long-term prognosis in patients with acute kidney failure].
Of 250 patients who were haemodialyzed on account of an acute renal insufficiency during a period of 16 years 114 patients survived. A control of the course was performed in 105 patients. Altogether 34 patients dies after their discharge from hospital. Older age and acute renal insufficiency due to urological basic diseases or abscessing pyelonephrititides have clearly worse cumulative survival rates. The risk factors of chronic pyelonephritis and hypertension, respectively, are found in one third of the patients. The long-term prognosis after acute renal insufficiency can be improved by regular dispensary care.


Interaction and coordination geometries for Ag(I) in the two metal sites of hemocyanin.
111Ag(I) perturbed angular correlations of gamma-rays (PAC) has been used to investigate the binuclear metal site of 111Ag(I)-substituted Carcinus aestuarii deoxyhemocyanin. The studies have shown that apo-hemocyanin is able to bind 2 mol of Ag(I) per mol of protein and that the binding is specific for the metal ion sites. The PAC spectra show pronounced changes when the stoichiometry of Ag(I) to protein is increased from 0.1 to 2.0. These changes have been interpreted as evidence of interactions between the two sites in terms of a structural destabilization of the first occupied site caused by the occupation of the second site. The experimental data for the Ag(I)-substituted metal sites do not agree well with the three-coordinated structure found in the Cu(I) holo-protein. However, if a water molecule is included as a coordinating ligand in the Ag(I) metal site a successful interpretation of the experimental data can be obtained.


Bacterial community composition of biological degreasing systems and health risk assessment for workers.
Biological degreasing system is a new technology based on the degradation capabilities of microorganisms to remove oil, grease, or lubricants from metal parts. No data is available about the potential biological health hazards in such system. Thus, a health risk assessment linked to the bacterial populations present in this new degreasing technology is, therefore, necessary for workers. We performed both cultural and molecular approaches in several biological degreasing systems for various industrial contexts to investigate the composition and dynamics of bacterial populations. These biological degreasing systems did not work with the original bacterial populations. Indeed, they were colonized by a defined and restricted group of bacteria. This group replaced the indigenous bacterial populations known for degrading complex substrates. Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeruginosa, and Pantoea agglomerans were important members of the microflora found in most of the biological degreasing systems. These bacteria might represent a potential health hazard for workers.


Diagnosis and surgical treatment of carotid body tumor: A retrospective analysis of 58 patients.
The aim of the present study was to illustrate the diagnosis and treatment of carotid body tumor (CBT) based on our experience of previous patients. A total of 58 patients (62 lesions) with CBT who received surgery between October 2003 and October 2013 were included. In total, 17 lesions were categorized into Shamblin grade I, 33 were grade II, and 12 were grade III. Surgical resection of CBT was performed for 52 lesions, resection of CBT and the external carotid artery was performed for 9 lesions, and resection of CBT and the internal carotid artery was performed for 1 lesion. No hemiplegia was observed. Hoarseness and bucking were observed in 2 patients of Shamblin grade III, and were eliminated 1 month subsequent to the administration of hormone therapy and a nerve-nurturing strategy. No relapse or mortality was observed during the follow-up. In conclusion, surgical resection of CBT is recommended following diagnosis. The evaluation of imaging features and cerebral collateral circulation is important for treatment.


[Effects of 5-HT1A receptor antagonist on ethanol induced hypothermia and behavioral thermoregulatory response in rats].
To observe the effects of 5-HT1Areceptor antagonist p-MPI on ethanol induced hypothermia and behavioral ther-moregulatory response in rats. Core temperature and motor activities were monitored in undisturbed male SD rats using radioteleme-try. The behavioral thermoregulatory response and core temperature were monitored in rats using radiotelemetric temperature gradient apparatus. The rats were placed in a temperature gradient that permitted the selection of ambient temperature ranging from 15℃ to 40℃. Effect of ethanol (3 g/kg) and 5-HT1A receptor antagonist p-MPPI(1 mg/kg) on core temperature, motor activities, and the behavioral thermoregulatory re-sponse were observed in rats. ①Ethanol led to a rapid reduction in core temperature. The hypothermic responses were accompanied with a preference for cooler ambient temperature. ②5-HT1A receptor antagonist attenuated the hypothermia induced by ethanol, and accompa-nied with a selection for warmer ambient temperature. ①Behavioral thermoregulatory observations suggested that the ethanol could decrease the thermoregulatory set point,because rats treated with ethanol selected cooler ambient temperature facilitates the reduction in core temperature.②5-HT might be involved in ethanol-induced hypothermia and behavioral thermoregulatory response.


[Epidemiological comparison between the new and the old diagnostic criteria for sepsis: a retrospective cohort study based on the database of Beijing Public Health Information System].
To describe and compare the epidemiology of Sepsis-1 and Sepsis-3 in Yuetan Subdistrict of Beijing, and to estimate the incidence of Sepsis-3 in China. A population-based cohort study was conducted. Through the database of Beijing Public Health Information System, the medical records of all adult residents hospitalized from July 1st, 2012 to June 30th, 2014 in Yuetan Subdistrict were reviewed. According to the clinical data of these patients, patients with Sepsis-1 and Sepsis-3 were enrolled in this analysis and the demographic characteristics of them were compared. Incidence and in-hospital mortality was calculated. Logistic regression method was used to analyze the risk factors of sepsis. Compared with non-septic patients with infections, patients with Sepsis-1 or Sepsis-3 were more likely to be male, older, had more comorbidities and lower body mass index (BMI), had more lower respiratory tract infections, more intra-abdominal infections and more blood flow infections, but had fewer urogenital tract infections, fewer upper respiratory tract infections, fewer gastrointestinal infections and fewer skin and soft tissue infections, and had pure prognosis with longer length of hospital stay [days, Sepsis-1 compared with non-Sepsis-1: 18 (10, 34) vs. 14 (9, 22), Sepsis-3 compared with non-Sepsis-3: 20 (11, 39) vs. 14 (9, 25)] and higher mortality [Sepsis-1 compared with non-Sepsis-1: 20.6% (353/1 716) vs. 2.5% (44/1 733), Sepsis-3 compared with non-Sepsis-3: 32.0% (299/935) vs. 3.9% (98/2 514), all P < 0.01]. Logistic regression analysis showed that male, elder (age ≥ 65 years old), low BMI, bed-rest state, and combined with cerebrovascular disease and hematological malignancies were risk factors for Sepsis-1 [all odds ratio (OR) > 1, all P < 0.05], while the male, elder (age ≥ 65 years old), low BMI, bed-rest state, and combined with cerebrovascular disease, rheumatic immune disease, malignant diseases of blood system and dementia were risk factors for Sepsis-3 (all OR > 1, all P < 0.05). Sepsis-3 was more common in males [OR = 1.19, 95% confidence interval (95%CI) was 1.01-1.40, P < 0.05] and elderly patients (age 65-84 years old: OR = 1.60, 95%CI was 1.28-1.99, P < 0.01; age ≥ 85 years old: OR = 1.76, 95%CI was 1.39-2.23, P < 0.01) as compared with Sepsis-1. After adjusted for gender and age, the standardized incidence of Sepsis-1 was 461 per 100 000 person-year, and that of Sepsis-3 was 236 per 100 000 person-year, with the standardized mortality of 79 per 100 000 person-year and 67 per 100 000 person-year, respectively, in Yuetan Subdistrict of Beijing. Corresponding to a speculative extrapolation of 4 856 532 new cases for Sepsis-1 and 2 487 949 new cases for Sepsis-3, there were 831 674 deaths and 700 437 deaths per year in China, respectively. Male, elder, more comorbidities and low BMI were risk factors for sepsis. The standardized incidence of Sepsis-3 in Yuetan Subdistrict of Beijing was 236 per 100 000 person-year, and speculated there were 2.5 million new cases of Sepsis-3 per year, resulting in more than 700 000 deaths in China. According to the diagnostic criterion of Sepsis-3, 2.36 million new cases per year were reduced, and the mortality was increased by 11.4%, as compared with the criterion of Sepsis-1.


On the chain flexibility of arabinoxylans and other beta-(1-->4) polysaccharides.
The recent paper by Dervilly-Pinel and co-workers (Carbohydr. Res. 2001, 330, 365-372) presents a complete macromolecular characterisation of a series of de-esterified arabinoxylans extracted and fractionated from wheat flour. From their measurements, they were able to extract parameters related to chain flexibility, such as the Mark-Houwink exponent a and the chain persistence length. However, the estimate they obtain for the latter parameter is rather larger than would be expected, since the arabinoxylan backbone is beta-(1-->4) like cellulose and the galactomannans. By treating their data in an alternative, but well accepted manner, we are able to obtain a lower value of persistence length, which agrees well with estimates for this parameter for cellulose, in the literature, and our own recent measurements for a series of differently substituted galactomannans. These results suggest that the parameters obtained may be applicable to other beta-(1-->4) polysaccharides.


Early amniotomy and early oxytocin for prevention of, or therapy for, delay in first stage spontaneous labour compared with routine care.
Caesarean section rates are over 20% in many developed countries. The main diagnosis contributing to the high rate in nulliparae is dystocia or prolonged labour. The present review assesses the effects of a policy of early amniotomy with early oxytocin administration for the prevention of, or the therapy for, delay in labour progress. To estimate the effects of early augmentation with amniotomy and oxytocin for prevention of, or therapy for, delay in labour progress on the caesarean birth rate and on indicators of maternal and neonatal morbidity. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15 February 2012), MEDLINE (1966 to 15 February 2012), EMBASE (1980 to 15 February 2012), CINAHL (1982 to 15 February 2012), MIDIRS (1985 to February 2012) and contacted authors for data from unpublished trials. Randomized and quasi-randomized controlled trials that compared oxytocin and amniotomy with expectant management. Three review authors extracted data independently. We stratified the analyses into 'Prevention Trials' and 'Therapy Trials' according to the status of the woman at the time of randomization. Participants in the 'Prevention Trials' were unselected women, without slow progress in labour, who were randomized to a policy of early augmentation or to routine care. In 'Treatment Trials' women were eligible if they had an established delay in labour progress. For this update, we have included a further two new clinical trials. This updated review includes 14 trials, randomizing a total of 8033 women. The unstratified analysis found early intervention with amniotomy and oxytocin to be associated with a modest reduction in the risk of caesarean section; however, the confidence interval (CI) included the null effect (risk ratio (RR) 0.89; 95% CI 0.79 to 1.01; 14 trials; 8033 women). In prevention trials, early augmentation was associated with a modest reduction in the number of caesarean births (RR 0.87; 95% CI 0.77 to 0.99; 11 trials; 7753). A policy of early amniotomy and early oxytocin was associated with a shortened duration of labour (average mean difference (MD) - 1.28 hours; 95% CI -1.97 to -0.59; eight trials; 4816 women). Sensitivity analyses excluding four trials with a full package of active management did not substantially affect the point estimate for risk of caesarean section (RR 0.87; 95% CI 0.73 to 1.05; 10 trials; 5165 women). We found no other significant effects for the other indicators of maternal or neonatal morbidity. In prevention trials, early intervention with amniotomy and oxytocin appears to be associated with a modest reduction in the rate of caesarean section over standard care.


Cervical length measured before delivery and the success rate of vaginal birth after cesarean (VBAC).
To test the hypothesis that measuring cervical length (CL) close to the time of delivery is a predictor of successful vaginal birth following a cesarean. A prospective longitudinal study included women with singleton pregnancies at 38-41 weeks, who previously underwent a cesarean, and who were interested in trial of labor. Patients who did not have a spontaneous onset of labor were induced at 41 weeks' gestation. CL measurements were performed prior to labor by transvaginal ultrasound, recorded, and blinded from the caring physicians. Vaginal birth was achieved in 63/105 (60%) of patients participating in the study. The mode of delivery significantly correlated with CL, Bishop score, and previous obstetrical history. When multivariate analysis was performed, only CL and previous obstetrical history correlated significantly with mode of delivery. In the subgroup of patients with no previous vaginal delivery, only CL had a significant correlation with mode of delivery. The ROC curve demonstrated a high prediction of vaginal delivery by CL for the entire study group and for the subgroup of patients with no previous vaginal delivery (AUC = 0.8, p < .0001). CL measurement after 36 weeks has a high predictive accuracy for a successful vaginal birth after cesarean.


Bronchial artery embolization as a treatment of hemoptysis induced by pulmonary metastasis from malignant melanoma.
Lung metastasis is a rare cause of hemoptysis. Bronchial artery embolization is an effective intervention for treatment of hemoptysis with various underlying etiologies. A 28-year-old man with a known history of malignant melanoma in the neck from 6 years ago and lung metastasis from 1 year ago referred to the Emergency Department of our teaching hospital with the chief complaint of hemoptysis. Chest x-ray and pulmonary CT-scan showed multiple pulmonary nodules with different sizes in both lung parenchyma. The patient's hemoptysis did not resolve completely in spite of appropriate medical treatment. The patient was then referred to the endovascular unit of the vascular department in our hospital and underwent bilateral bronchial artery embolization. With this procedure his symptoms resolved completely and he was discharged after a week.


Cues for the identification of pain in nursing home residents.
The aim of this section of a larger study was to identify the range of cues from which pain was inferred for a sample of residents with various levels of cognitive impairment in 15 UK nursing homes. Sixty-five nursing home staff and 36 informal carers of the 113 residents were interviewed. There was extensive use of body movements, facial expressions, and verbal and vocal cues and a considerable degree of interpretation of cues was used. There was little difference between the types of cue used by formal and informal carers, although informal carers tended to identify more of all types. There were differences in cues identified according to level of cognitive impairment, in particular, the interpretation of body movements. A simple model of the interaction between cognitive deficit, cue type and level of cue interpretation was proposed.


Coexistence of Cu(ii) and Cu(i) in Cu ion-doped zeolitic imidazolate frameworks (ZIF-8) for the dehydrogenative coupling of silanes with alcohols.
Recently, metal-ion-doped zeolitic imidazolate frameworks have gained considerable attention for their structure tailorability and potential catalytic applications. Herein, Cu ion-doped ZIF-8 nanocrystals were successfully prepared by the mechanical grinding of Cu(NO3)2, ZnO and 2-methylimidazole (HMeIM) using ethanol as an additive. In contrast to the general view that only Cu(ii) is present in Cu-doped ZIF-8, we found the coexistence of Cu(ii) and Cu(i) in this material, which was supported by XPS and X-ray induced Auger electron spectroscopy (XAES) characterizations. Moreover, ethanol might have acted as a reducer to induce the reduction of Cu(ii) during synthesis. Due to the mixed valency of Cu ions, the Cu ion-doped ZIF-8 nanocrystals showed excellent catalytic performance in the dehydrogenative coupling of silanes with alcohols.


Emdogain-regulated gene expression in palatal fibroblasts requires TGF-βRI kinase signaling.
Genome-wide microarrays have suggested that Emdogain regulates TGF-β target genes in gingival and palatal fibroblasts. However, definitive support for this contention and the extent to which TGF-β signaling contributes to the effects of Emdogain has remained elusive. We therefore studied the role of the TGF-β receptor I (TGF-βRI) kinase to mediate the effect of Emdogain on palatal fibroblasts. Palatal fibroblasts were exposed to Emdogain with and without the inhibitor for TGF-βRI kinase, SB431542. Emdogain caused 39 coding genes to be differentially expressed in palatal fibroblasts by microarray analysis (p<0.05; >10-fold). Importantly, in the presence of the TGF-βRI kinase inhibitor SB431542, Emdogain failed to cause any significant changes in gene expression. Consistent with this mechanism, three independent TGF-βRI kinase inhibitors and a TGF-β neutralizing antibody abrogated the increased expression of IL-11, a selected Emdogain target gene. The MAPK inhibitors SB203580 and U0126 lowered the impact of Emdogain on IL-11 expression. The data support that TGF-βRI kinase activity is necessary to mediate the effects of Emdogain on gene expression in vitro.


Gene pool variation and phylogenetic relationships of an indigenous northeast Italian grapevine collection revealed by nuclear and chloroplast SSRs.
A germplasm safeguard programme was set up with 19 grapevine varieties considered as indigenous to northeastern Italy. To better estimate how genetic structure can be used to obtain a conservation perspective of local varieties, genetic variability was examined at 30 nuclear and 3 chloroplast polymorphic microsatellite loci in the native varieties plus 7 European cultivars taken as reference. The genetic profiles of all the cultivars were searched for possible parentage relationships and several suspected cases of the same variety having different names were investigated. The alleles shared at the loci suggest a parent-offspring relationship between Merlot and Cabernet Franc, 'Gruaja' and 'Negrara Veronese', and Marzemina Nera and Marzemina Bianca. Alleles at the 30 nuclear loci are consistent with Raboso Veronese being the progeny of Marzemina Bianca and Raboso Piave. Chloroplast-specific haplotypes were singled out for the first time in this indigenous germplasm and should be considered typical of the region. It is hypothesized that there are many specific haplotypes for the local varieties due to a past contribution of wild grapevine to the cultivated gene pool. The majority of investigated cultivars were demonstrated to constitute an independent source of genetic variation, and therefore a possible valuable resource of genetic traits for breeders.


Multi-Object Tracking with Correlation Filter for Autonomous Vehicle.
Multi-object tracking is a crucial problem for autonomous vehicle. Most state-of-the-art approaches adopt the tracking-by-detection strategy, which is a two-step procedure consisting of the detection module and the tracking module. In this paper, we improve both steps. We improve the detection module by incorporating the temporal information, which is beneficial for detecting small objects. For the tracking module, we propose a novel compressed deep Convolutional Neural Network (CNN) feature based Correlation Filter tracker. By carefully integrating these two modules, the proposed multi-object tracking approach has the ability of re-identification (ReID) once the tracked object gets lost. Extensive experiments were performed on the KITTI and MOT2015 tracking benchmarks. Results indicate that our approach outperforms most state-of-the-art tracking approaches.


The Mi1000 CONCERTO PIN cochlear implant: An evaluation of its safety and stability in adults and children.
Conclusion The study demonstrates the medium-term stability and safety of the CONCERTO PIN cochlear implant. The use of the CONCERTO PIN proved to be suitable for the use of a surgical technique without the need for suture fixation and resulted in short surgery duration and a low medium-term complication rate. Objective The primary aim was to provide data on medium-term safety and stability of the CONCERTO PIN cochlear implant in adults and children, and to collect feedback on the surgical technique used, which involved no drilling and no suture fixation. The secondary aim was to analyze surgery duration. Methods Implantation was performed using minimally invasive surgery. During surgery, data on the surgical procedure was collected by the attending surgeons or a designee. Safety and stability of the CONCERTO PIN were assessed at first fitting (1 month after implantation) and 6 months after first fitting. Results Ninety-nine patients were implanted with a CONCERTO PIN implant and one patient with a CONCERTO implant. The CONCERTO PIN implants implanted during this study were immobilized by pins and a tight periosteal pocket. The mean (± SD) surgery duration was 27:52 (± 9:19) min.


Efficacy of the Small Step Program in a Randomized Controlled Trial for Infants under 12 Months Old at Risk of Cerebral Palsy (CP) and Other Neurological Disorders.
The objective was to evaluate the effects of the Small Step Program on general development in children at risk of cerebral palsy (CP) or other neurodevelopmental disorders. A randomized controlled trial compared Small Step with Standard Care in infants recruited at 4-9 months of corrected age (CA). The 35-week intervention targeted mobility, hand use, and communication during distinct periods. The Peabody Developmental Motor Scales2ed (PDMS-2) was the primary outcome measure. For statistical analysis, a general linear model used PDMS-2 as the main outcome variable, together with a set of independent variables. Thirty-nine infants were randomized to Small Step (n = 19, age 6.3 months CA (1.62 SD)) or Standard Care (n = 20, age 6.7 months CA (1.96 SD)). Administering PDMS-2 at end of treatment identified no group effect, but an interaction between group and PDMS-2 at baseline was found (p < 0.02). Development was associated with baseline assessments in the Standard Care group, while infants in the Small Step group developed independent of the baseline level, implying that Small Step helped the most affected children to catch up by the end of treatment. This result was sustained at 2 years of age for PDMS-2 and the PEDI mobility scale.


Inflammatory myofibroblastic tumor involving lung and brain in a 10-year-old boy: a case report.
Inflammatory myofibroblastic tumors are rare tumors of unknown etiology, composed of proliferating myofibroblasts and accompanying lymphoplasmacytic infiltration. A 10-year-old boy who developed inflammatory myofibroblastic tumors in the lung as well as the brain is described. Surgery and radiation therapy were not feasible. The authors review the current literature and treatment options.


Intergenerational instability and marked anticipation in SCA-17.
The authors describe an Italian family with autosomal dominant ataxia, dementia, psychiatric and extrapyramidal features, epilepsy, mild sensorimotor axonal neuropathy, and MRI findings of cerebral and cerebellar atrophy. A child had a distinctive presentation with onset at 3 years, growth retardation, fast progression, and early death. Molecular analysis demonstrated an expanded CAG/CAA repeat in the TBP gene (SCA-17). The repeat size was 66 triplets in the child and 53 in all the other patients.


Nutrition and multiple gestation.
Multiple pregnancy represents a state of magnified nutritional requirements, resulting in a greater nutrient drain on maternal resources and an accelerated depletion of nutritional reserves. The accelerated starvation which occurs in pregnancy is exaggerated with a multiple gestation, particularly during the second half of pregnancy, with more rapid depletion of glycogen stores and resultant metabolism of fat between meals and during an overnight fast. A reduced glucose stream from mother to fetus results in slower fetal growth, smaller birth size, as well as a higher risk of preterm labor and preterm birth. For this reason, diet therapy with a diabetic regimen of 20% of calories from protein, 40% of calories from carbohydrate, and 40% of calories from fat may be particularly useful. Iron-deficiency anemia has also been linked to preterm delivery and other adverse pregnancy outcomes. Mobilization of maternal iron stores, in addition to an adequate amount and pattern of gestational weight gain (including BMI-specific weight gain goals by 20 and 28 weeks gestation), has been associated with significantly better fetal growth and longer gestations in twin pregnancies. Supplementation with calcium, magnesium, and zinc, as well as multivitamins and essential fatty acids may also reduce pregnancy complications and improve postnatal health for infants born from a multiple gestation. Diet therapy for women pregnant with multiples is an important component of effective prenatal care.


Higher-Order Topology of the Axion Insulator EuIn_{2}As_{2}.
Based on first-principles calculations and symmetry analysis, we propose that EuIn_{2}As_{2} is a long-awaited axion insulator with antiferromagnetic (AFM) long-range order. Characterized by the parity-based invariant Z_{4}=2, the topological magnetoelectric effect is quantized with θ=π in the bulk, with a band gap as large as 0.1 eV. When the staggered magnetic moments of the AFM phase are along the a or b axis, it is also a topological crystalline insulator phase with gapless surface states emerging on (100), (010), and (001) surfaces. When the magnetic moments are along the c axis, both the (100) and (001) surfaces are gapped, and the material can also be viewed as a high-order topological insulator with one-dimensional chiral states existing on the hinges between those gapped surfaces. We have calculated both the topological surface states and the hinge state in different phases of the system, respectively, which can be detected by angle-resolved photoemission spectroscopy or STM experiments.


Childhood overweight and obesity in Bariloche, Argentina: Beyond eating habits and physical activity.
The incidence of overweight and obesity is alarming worldwide. In Argentina, multifactorial studies are scarce despite the high rates of childhood overweight and obesity (OW/OB). In this study we assessed the prevalence of childhood OW/OB and the associated risk factors from a multicausal perspective: we analyzed sleep habits, screen use, chronic stress in children and their caregivers, social relationship problems, eating habits, and physical activity. Of the 397 first and seventh graders who completed the questionnaires, 41% had childhood OW/OB. In children with obesity, a lower level of physical activity, a lower consumption of protective foods, a higher risk for sleep disorders, higher levels of chronic stress (in both children and their caregivers), and higher rates of peer rejection were observed. Widespread use of screens before bedtime was noted in most children. This study evidences the diversity of factors associated with childhood OW/OB and highlights the convenience of a multidimensional approach to address it. In addition, the results of this study suggest the need to consider lifestyle habits as a preventive and therapeutic strategy for the management of OW/OB from early stages.


Treatment outcomes of drug-resistant tuberculosis in the Netherlands, 2005-2015.
Since in low incidence TB countries population migration and complex treatment of drug-resistant tuberculosis (DR-TB) patients are major issues, we aimed to analyse patient risk factors associated with the incidence of poor outcome of TB treatment among DR-TB patients in the Netherlands. This retrospective cohort study included adult patients with confirmed DR-TB treated from 2005 to 2015. We obtained data from a nationwide exhaustive registry of tuberculosis patients in the Netherlands. Predictors for unsuccessful TB treatment (defaulted and failed treatment) and TB-associated mortality were analysed using multivariate logistic regression. Among 10,303 registered TB patients, 545 patients with DR-TB were analysed. Six types of DR-TB were identified from the included patients, i.e. isoniazid mono- or poly-resistance (68%); rifampicin mono- or poly-resistance (3.1%); pyrazinamide mono-resistance (8.3%); ethambutol mono-resistance (0.1%); multidrug-resistance (18.9%); and extensively drug-resistance (0.7%). The majority of patients were foreign-born (86%) and newly diagnosed TB (89%) patients. The cumulative incidence of unsuccessful treatment and mortality were 5 and 1%, respectively. Among all DR-TB cases, patients with Multi Drug-Resistant Tuberculosis (MDR-TB) (OR 4.43; 95%CI 1.70-11.60) were more likely to have unsuccessful treatment, while miliary and central nervous system TB (OR 15.60; 95%CI 2.18-111.52) may also be predictors for TB mortality. Additionally, patients with substance abuse and homelessness tend to have unsuccessful treatment. In recent years, we identified a low incidence of DR-TB as well as the poor outcome of DR-TB treatment. The majority of cases were primary drug-resistant and foreign-born. To further improve treatment outcome, special attention should be given to the high-risk DR-TB patients.


Perioperative anticoagulation practices for pediatric liver transplantation.
Despite continued advancements in perioperative care for pediatric liver transplant (LT), graft-threatening vascular occlusion events including hepatic artery thrombosis (HAT) and portal vein thrombosis (PVT) remain a source of significant morbidity and mortality. Perioperative anticoagulation is commonly used for the prevention of HAT and PVT, but evidence-based guidelines are lacking. The goals of this survey were to determine the frequency of use of an anticoagulation protocol and to describe variation in anticoagulation practices among pediatric LT centers. The study consisted of an online survey distributed to members of SPLIT. The survey focused on institutional anticoagulation practices employed to reduce the incidence of graft and life-threatening vascular occlusion events. Responses were received from 31 of 39 SPLIT centers. All respondents report using anticoagulation after pediatric LT, and approximately 90% have institutional anticoagulation protocols. Subgroup analysis of high volume pediatric LT centers revealed similar variability in anticoagulation patterns. All participating SPLIT centers reported the use of post-transplant anticoagulation and nearly all use a protocol. However, there is marked variability in the type and dose of anticoagulation as well as the timing of initiation and duration of therapy across centers.


Light-dependent attenuation of phycoerythrin gene expression reveals convergent evolution of green light sensing in cyanobacteria.
The colorful process of chromatic acclimation allows many cyanobacteria to change their pigmentation in response to ambient light color changes. In red light, cells produce red-absorbing phycocyanin (PC), whereas in green light, green-absorbing phycoerythrin (PE) is made. Controlling these pigment levels increases fitness by optimizing photosynthetic activity in different light color environments. The light color sensory system controlling PC expression is well understood, but PE regulation has not been resolved. In the filamentous cyanobacterium Fremyella diplosiphon UTEX 481, two systems control PE synthesis in response to light color. The first is the Rca pathway, a two-component system controlled by a phytochrome-class photoreceptor, which transcriptionally represses cpeCDESTR (cpeC) expression during growth in red light. The second is the Cgi pathway, which has not been characterized. We determined that the Cgi system also regulates PE synthesis by repressing cpeC expression in red light, but acts posttranscriptionally, requiring the region upstream of the CpeC translation start codon. cpeC RNA stability was comparable in F. diplosiphon cells grown in red and green light, and a short transcript that included the 5' region of cpeC was detected, suggesting that the Cgi system operates by transcription attenuation. The roles of four predicted stem-loop structures within the 5' region of cpeC RNA were analyzed. The putative stem-loop 31 nucleotides upstream of the translation start site was required for Cgi system function. Thus, the Cgi system appears to be a unique type of signal transduction pathway in which the attenuation of cpeC transcription is regulated by light color.


Lifetime personal cigarette smoking and risk of young-onset breast cancer by subtype among non-Hispanic Black and White women in the Young Women's Health History Study.
To evaluate the association between lifetime personal cigarette smoking and young-onset breast cancer (YOBC; diagnosed <50 years of age) risk overall and by breast cancer (BC) subtype, and whether risk varies by race or socioeconomic position (SEP). Data are from the Young Women's Health History Study (YWHHS), a population-based case-control study of non-Hispanic Black (NHB) and White (NHW) women, ages 20-49 years (n = 1812 cases, n = 1381 controls) in the Los Angeles County and Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) registry areas, 2010-2015. Lifetime personal cigarette smoking characteristics and YOBC risk by subtype were examined using sample-weighted, multivariable-adjusted polytomous logistic regression. YOBC risk associated with ever versus never smoking differed by subtype (Pheterogeneity = 0.01) with risk significantly increased for Luminal A (adjusted odds ratio [aOR] 1.34; 95% confidence interval [CI] 1.06-1.68) and HER2-type (aOR 1.97; 95% CI 1.23-3.16), and no association with Luminal B or Triple Negative subtypes. Additionally, ≥30 years since smoking initiation (versus never) was statistically significantly associated with an increased risk of Luminal A (aOR 1.55; 95% CI 1.07-2.26) and HER2-type YOBC (aOR 2.77; 95% CI 1.32-5.79), but not other subtypes. In addition, among parous women, smoking initiated before first full-term pregnancy (versus never) was significantly associated with an increased risk of Luminal A YOBC (aOR 1.45; 95% CI 1.11-1.89). We observed little evidence for interactions by race and SEP. Findings confirm prior reports of a positive association between cigarette smoking and Luminal A YOBC and identify a novel association between smoking and HER2-type YOBC.


[Dream interpretation and experimental dream research: a comparison].
Since the discovery of REM sleep, many experimental studies have focused on dream recall, dream function and dream analysis in the sleep laboratory. The present article gives an overview of the results of experimental dream research and tries to evaluate the relevance of these results for psychoanalytical dream theory. Two theories originating from psychophysiological dream research are discussed in detail and compared with formulations stemming from psychoanalytical oriented dream theory.


Sedentary behavior: understanding and influencing adults' prolonged sitting time.
Too much sitting is now understood to be a health risk that is additional to, and distinct from, too little exercise. There is a rapidly-accumulating evidence on relationships of prolonged sedentary time and patterns of sedentary time with cardio-metabolic risk biomarkers and health outcomes. There is, however, the need to gather dose-response evidence and develop a broader understanding of the set of mechanisms linking sedentary behavior to health outcomes. In addition to the further understanding of the associated health risks, there is a new health-behavior, and epidemiological and experimental research agenda to be pursued, which include measurement studies; understanding the relevant determinants-particularly environmental determinants of sedentary behavior; and, developing effective interventions. A broad-based body of evidence is needed to inform the research-translation agenda-identifying and developing the future public health initiatives, environmental and policy changes and clinical guidelines that may be required.


Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli.
In an effort to decrease deaths from gram-negative bacteremia and endotoxin shock, we treated bacteremic patients with human antiserum to endotoxin (lipopolysaccharide) core. Antiserum was prepared by vaccinating healthy men with heat-killed Escherichia coli J5; this mutant lacks lipopolysaccharide oligosaccharide side chains, so that the core, which is nearly identical to that of most other gram-negative bacteria, is exposed for antibody formation. In a randomized controlled trial, patients were given either J5 antiserum or preimmune control serum intravenously, near the onset of illness. The number of deaths in the bacteremic patients was 42 of 109 (39 per cent) in controls and 23 of 103 (22 per cent) in recipients of J5 antiserum (P = 0.011). In those with profound shock, mortality was 30 of 39 (77 per cent) in controls and 18 of 41 (44 per cent) in recipients of J5 antiserum (P = 0.003). We conclude that human antiserum to the lipopolysaccharide core can substantially reduce deaths from gram-negative bacteremia.


Serum Levels of Albumin and Prealbumin Do Not Correlate With Nutrient Delivery in Surgical Intensive Care Unit Patients.
Serum albumin and prealbumin levels, may be more strongly associated with inflammation than with nutrient delivery. Their predictive value has not been extensively described in surgical intensive care unit (ICU) patients. We analyzed a registry of adult surgical ICU patients receiving enteral nutrition. Subjects with at least 1 serum albumin, prealbumin, or C-reactive protein (CRP) level were included. Demographic, nutrition, and clinical outcome data were collected. A total 252 subjects were included. A subset had serial measurements: albumin (n = 194), prealbumin (n = 13), CRP (n = 9), white blood cell (WBC) (n = 131), and neutrophil-lymphocyte ratio (NLR) (n = 86). Serum albumin level was inversely correlated with all 3 inflammatory biomarkers (CRP, ρ = -0.24, P <0.02; WBC, ρ = -0.15, P <0.001; and NLR, ρ = -0.26, P < 0.001). Change in serum albumin level was inversely correlated with change in NLR (ρ = -0.22, P = 0.044) but not with CRP or WBC. Admission serum albumin level was significantly higher in nourished vs. moderately and/or severely malnourished patients (3.2 [2.7-3.7] vs. 2.7 [2.3-3.0], P = 0.004). Admission serum prealbumin level was significantly higher in nourished vs. moderately and/or severely malnourished patients (9 [7-12] vs. 4 [3-5], P = 0.001). Serum albumin level was inversely correlated with Charlson Comorbidity Index (ρ = 0.20, P = 0.001). Calorie and/or protein delivery in the ICU was not correlated with changes in serum albumin or prealbumin levels. In the ICU, initial serum albumin levels and serial trends are inversely correlated with inflammation. Although initial serum albumin levels are reflective of baseline nutrition status, neither serum albumin level nor serum prealbumin level trends correlate with calorie or protein deficits and should not be used to assess adequacy of nutrition delivery.


[Atypical clinical presentation of autoimmune polyglandular syndrome type 4].
Autoimmune polyglandular syndromes (APS) are rarely diagnosed conditions characterised by the combination of two or more autoimmune endocrinopathies and nonendocrine autoimmunopathies. They comprise a wide spectrum of autoimmune disorders, differing in the immunologic features of their pathogenesis. Based on their clinical manifestation, APS are divided into four different types. Primary hypoparathyroidism is characteristic for APS type 1, the major disease components of which are adrenal insufficiency, hypoparathyroidism, and candidiasis. However, the literature is sparse regarding the presence of hypoparathyroidism in the remaining types of APS. In our article, we present a case of a young female with primary hypoparathyroidism and a family history of autoimmune disorders who after several years developed type 1 diabetes. She also had anti-transglutaminase and anti-parietal cell antibodies. This constellation of two endocrine disorders and non-endocrine abnormalities led to the diagnosis of APS type 4. We show in details diagnostic and treatment strategies undertaken in our patient and their impact on the course of APS.


An immunohistochemical approach to the differential diagnosis of renal tumors.
Renal neoplasms comprise several distinct clinicopathologic entities with potential prognostic and the rapeutic differences. Although careful morphologic examination using sections stained with hematoxylin and eosin will allow for the correct diagnosis in the majority of cases, there is sufficient overlap between several entities such that ancillary techniques may be necessary to arrive at the correct diagnosis. In routine diagnostic surgical pathology practice of renal tumors, immunohistochemistry is the foremost ancillary technique. Using an approach based on common histologic patterns (tumors with clear cytoplasm, granular cytoplasm, tubulopapillary architecture, spindle cell morphology, small round-cell morphology, and infiltrating poorly differentiated carcinoma), we will discuss the utility of immunohistochemistry in the differential diagnosis of renal neoplasms. In recent years, needle biopsies from renal masses are being increasingly performed. In these small biopsies, the entire range of cytoarchitectural features that are generally necessary to make a diagnosis may not be fully appreciated. Immunohistochemistry may be helpful in this setting to narrow the differential diagnosis or to arrive at a definitive diagnosis. Finally, the use of immunohistochemistry for the confirmation of metastatic renal cell carcinoma presenting at distant sites will be discussed. Panels of immunohistochemical stains are proposed for different settings, including renal cell carcinoma (RCC) marker, CD10, and vimentin to suggest renal origin of a metastatic tumor, and markers to aid in subclassification of RCC, including parvalbumin and c-kit for chromophobe RCC, and cytokeratin 7 and alpha-methyl-acyl-CoA racemase for papillary RCC.


Fluorescent staining of glycoproteins on polyvinylidene difluoride membrane with 8-aminonaphthalene-1,3,6-trisulfonate.
Here, we describe a simple and sensitive method that allows fluorescent detection of glycoproteins on polyvinylidene difluoride (PVDF) membrane. We used periodic acid oxidation of carbohydrate chains of glycoproteins and fluorescent labeling with 8-aminonaphthalene-1,3,6-trisulfonate (AN-TS) by reductive amination. We developed an additional method to enhance the ability of PVDF to absorb glycoproteins by using non-glycoprotein lectin, such as wheat germ agglutinin (WGA), as a link between the PVDF membrane and glycoproteins, resulting in considerably increased detection sensitivity to glycoproteins.


Presence of hepatitis E virus in sewage in Northern India: frequency and seasonal pattern.
Outbreaks of acute hepatitis E, associated with consumption of contaminated drinking water, are frequent in India. Sewage is a major source for contamination of surface water. Data on the presence of hepatitis E virus (HEV) in sewage in India are limited. The aim of this study was to look for the presence of HEV RNA in concentrates of sewage specimens collected from a major open sewage drain in Lucknow, India during August 2004 to July 2006, by the polymerase chain reaction, using primers specific for human HEV (genotype 1) or Indian swine HEV (genotype 4). Of the 192 sewage specimens tested, 79 (41%) showed presence of human HEV RNA. The positivity rate was higher during the second year (52/103 [51%]) than during the first year (27/89 [30%]; P = 0.005). The seasonal pattern of HEV RNA positivity was as follows: winter months (November to February): 28 of 61 (46%); summer months (March to June): 36 of 66 (55%); and, monsoon months (July to October) 15 of 65 (23%). There was no reported outbreak of hepatitis E in the city during the study period. Swine HEV RNA was not detected in any of the 69 specimens tested. Repeat testing confirmed the reproducibility of the results. In addition, nucleic acid sequencing of six sewage isolates showed that these belonged to HEV genotype 1. The study suggests that HEV infection and fecal viral excretion may be common in HEV-endemic regions throughout the year even during non-epidemic periods.


The effect of calmodulin antagonists on hyperthermic cell killing and the development of thermotolerance.
The role of calmodulin (CaM) in hyperthermic cell killing, and the development of thermotolerance in rat 13762NF mammary adenocarcinoma cells, was investigated by using the CaM antagonists W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide] and W-13 [N-(4-aminobutyl)-2-chloro-naphthalenesulphonamide] and their less active analogues W-5 [N-(6-aminohexyl)-1-naphthalenesulphonamide] and W-12 [N-(4-aminobutyl)-2-naphthalenesulphonamide]. The CaM antagonists W-7 and W-13 potentiated 43 degrees C cell killing (and the less active analogues did not) at a concentration compatible with CaM inhibition, thus hyperthermic perturbation of CaM-regulated processes may contribute to cellular lethality. The potentiation of hyperthermic killing by antagonists appeared to be temperature-dependent, sensitizing much more effectively to 43 degrees C than to 42 degrees C killing. The effect may be related to differing primary mechanisms of hyperthermic killing activated at the two temperatures, or simply to differences in incorporation or localization of the antagonists. The presence of the CaM antagonists throughout fractionated 42 degrees C or 43 degrees C heating, or during continuous 42 degrees C heating, did not significantly inhibit or potentiate the triggering and development of thermotolerance or alter the rates of heat stress protein (HSP) synthesis. Studies using CaM-agarose isolation of CaM-binding proteins indicated that binding of some HSP to CaM-agarose occurred and was Ca2+-dependent. The specificity and physiological relevance of these HSP binding to CaM was not clear, since their affinity was not high in these cells. Presumably W-7 would perturb any physiologically relevant CaM-protein interactions in cells but W-7 concentrations that reduced HSP and other protein binding to CaM-agarose columns by 50 per cent or more, had no effect on thermotolerance development in cells. These observations, combined with the studies that showed little effect of CaM antagonists on HSP synthesis at concentrations which potentiated cell killing, suggested that events leading to triggering or developing thermotolerance were not strongly dependent on any putative HSP binding to CaM. These studies also suggest some targets of hyperthermic cell killing at 43 degrees C are different from those that lead to the triggering and development of thermotolerance.


Inorganic nanovehicle for potential targeted drug delivery to tumor cells, tumor optical imaging.
In this work, an inorganic multifunctional nanovehicle was tailored as a carrier to deliver anticancer drug for tumor optical imaging and therapy. The nanovehicle could be used as a dually targeted drug nanovehicle by bonded magnetical (passive) and folic acid (active) targeting capabilities. In addition, it was developed using rhodamine 6G (R6G) as a fluorescence reagent, and an α-zirconium phosphate nanoplatform (Zr(HPO4)2·H2O, abbreviated as α-ZrP) as the anticancer drug nanovehicle. The novel drug-release system was designed and fabricated by intercalation of α-ZrP with magnetic Fe3O4 nanoparticles and anticancer drug 5-fluorouracil (5-FU), followed by reacting with a folate acid-chitosan-rhodamine6G (FA-CHI-R6G) complex, and then α-ZrP intercalated with Fe3O4 nanoparticles and 5-fluorouracil (5-FU) was successfully encapsulated into chitosan (CHI). The resultant multifunctional drug delivery system was characterized by scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray analysis, photoluminescence spectra, magnetometry, fluorescence microscopy imaging studies and other characterization methods. Simultaneously, the drug release in vitro on the obtained nanocomposites that exhibited a sustained release behavior was carried out in buffer solution at 37 °C, which demonstrated clearly that the nanocomposites shown a sustained release behavior. Meanwhile, cell culture experiments also indicated that the drug-release system had the potential to be used as an dually targeted drug nanovehicle into the tumor cells.


Laboratory performance of alternating pressure air mattresses component and sequelae.
The performance of three different alternating pressure air mattresses with different geometries of air cell were compared (Nimbus 3, Heritage, Tamora Plus), using simple performance indices based on pressure mapping. The aim of this study was to examine the effect on performance of elevating the backrest and thigh section of the bed into sitting position. Ten healthy volunteers of various sizes were pressure-mapped over the full pressure cycle on three alternating pressure air mattresseses with differing cell geometries. This was then repeated with the beds profiled to a sitting position. Performance of the alternating pressure air mattresses in terms of their ability to redistribute pressure dynamically was assessed in the different positions. The different alternating pressure air mattresses performed similarly with the bed in the lying flat position, but smaller cells appeared to be more effective in the sitting position. A conclusion was made that cell geometry may have an effect on the ability of the mattress to achieve alternating behaviour in the sitting position.


Focal adhesion kinase and reactive oxygen species contribute to the persistent fibrotic phenotype of lesional scleroderma fibroblasts.
Fibrotic diseases such as SSc (systemic sclerosis, scleroderma) are characterized by the abnormal presence of the myofibroblast, a specialized type of fibroblast that overexpresses the highly contractile protein α-smooth muscle actin. Myofibroblasts display excessive adhesive properties and hence exert a potent mechanical force. We aim to identify the precise contribution of adhesive signalling, which requires integrin-mediated activation of focal adhesion kinase (FAK)/src, to fibrogenic gene expression in normal and fibrotic SSc fibroblasts. We subject either FAK wild-type and knockout fibroblasts or normal and SSc fibroblasts treated with FAK/src inhibitors to real-time polymerase chain, western blot, cell migration and collagen gel contraction analyses. FAK operates downstream of both integrin β1 and reactive oxygen species (ROS) to promote the expression of genes involved in matrix production and remodelling, including CCN2, α-smooth muscle actin and type I collagen. Blocking either FAK/src with PP2 or ROS with N-acetyl cysteine alleviates the elevated contractile and migratory capability of lesional SSc dermal fibroblasts. Excessive adhesive signalling is intimately involved with the fibrotic phenotype of lesional SSc fibroblasts; blocking adhesive signalling or ROS generation may be beneficial in controlling the fibrosis observed in SSc.


The significance of grafting collagen on polycaprolactone composite scaffolds: processing-structure-functional property relationship.
The study concerns processing-structure-functional property relationship in organic-inorganic hybrid scaffolds based on grafted collagen for bone tissue engineering. Biodegradable polyester, polycaprolactone (PCL) and nanohydroxyapatite were used to fabricate three-dimensional porous scaffolds by adopting a combination of solvent casting, particulate leaching, and polymer leaching approaches. The PCL scaffold was subsequently surface modified by chemical bonding of 1,6-hexanediamine to the ester groups of PCL to introduce free NH2 groups. The introduction of NH2 groups as active sites enabled immobilization of biocompatible macromolecule, collagen, on the aminolyzed PCL via a cross-linking agent, glutaraldehyde. The osteoblasts' functions, notably cell adhesion, proliferation, and mineralization, were favorably modulated because of the chemical interaction between Arg-Gly-Asp domains in collagen molecule and integrin receptor in the cell membrane. The study underscores the significance of grafting collagen on PCL-nHA scaffold in modulating cellular activity and biological functions expanding its current use in soft tissue engineering to hard tissue regeneration.


Binding of serum albumin on tumor cells and characterization of the albumin binding protein.
The binding of bovine (BSA) and human serum albumin (HSA) to the surface of human and mouse tumor cells in vitro was examined by flow cytometry using monoclonal antibodies against these albumins. Both isologous and heterologous types of albumin bound firmly on several lines of human and mouse tumor cells. The cell-bound albumin was removable by protease (actinase) treatment or by culture in albumin-free medium for more than 2 days, but not by simple washing. The amount of albumin capable of binding to the tumor cell surface differed among the 9 tumor cell lines tested. As determined with radioiodinated BSA, about 2.6 x 10(6) BSA molecules/cell could bind to MDA-MB-453 human mammary cancer cells, which exhibit high binding capacity as to BSA. A unique peptide having a molecular weight of 18 kDa was detected on gel electrophoresis in extracts of tumor cells or normal aortic endothelial cells which had been treated with radioiodinated, photocross-linker-labeled BSA or HSA, followed by UV-irradiation. This peptide was also immuno-precipitated with an anti-BSA or anti-HSA monoclonal antibody. With both methods, the yield of the peptide was decreased by previous addition of an excess amount of unlabeled BSA or HSA. These findings indicated that the 18-kDa peptide expressed on both normal aortic endothelial cells and tumor cells is a principal serum albumin-binding protein, and that this protein binds both BSA and HSA.