Physico-chemical characteristics of the sulfated polysaccharides of the red microalgae Dixoniella grisea and Porphyridium aerugineum.
The sulfated polysaccharides of red microalgae have attracted increasing attention in recent years due to their unique rheological and bioactivities. Todate, most studies are devoted to the polysaccharide of the marine species Porphyridium sp., with limited information about that of the brackish water- Dixoniella grisea and the freshwater- Porphyridium aerugineum. We therefore conducted a comparative study of the two less explored sulfated polysaccharides, emphasizing their similarities and differences in composition, physical properties and biocompatibility. Both polysaccharides were found to be composed of 6-8 monosaccharides, predominantly xylose. Sulfur content was 0.8% for P. aerugineum and 1.6% for D. grisea. Solutions of both polysaccharides were highly viscous and exhibited shear thinning and weak gel behavior. Both were found to be stable in an alkaline environment, whereas in an acidic environment the viscosity of the polysaccharide of the brackish water species increased while that of the freshwater species decreased. Both exhibited a similar morphology, having a porous fibrous structure with a rough amorphous surface. By complementing previous studies on the Porphyridium sp. polysaccharide, we have established a sound basis for elucidating the structure/function relationships that in turn, will promote the development of innovative applications for the biotech industries for pharmaceutics, food and drug-delivery.


Palladium-catalyzed oxidative alkoxylation of alpha-alkenyl beta-diketones to form functionalized furans.
Treatment of 4-allyl-2,6-dimethyl-3,5-heptanedione with a catalytic amount of PdCl(2)(CH(3)CN)(2) (5 mol %) and a stoichiometric amount of CuCl(2) (2.2 equiv) in dioxane at 60 degrees C for 12 h formed 3-isobutyryl-2-isopropyl-5-methylfuran in 77% isolated yield. A number of alpha-alkenyl beta-diketones underwent oxidative alkoxylation under these conditions to form 2,3,5-trisubsituted furans in moderate to good yield.


Psychological morbidity in patients with facial and neck burns.
115 patients with facial and neck burns were assessed for the presence and severity of psychological morbidity. Various manifestations of such disorders and their predisposing factors are described. Countermeasures to ameliorate these disorders consist of early psychological intervention, which should be begun at the time of the patient's admission and continued-until the patient returns to society together with carefully planned treatment of the burn wounds, and skillful reconstructive surgery to correct the resultant disfigurements to attain a reasonably satisfactory cosmetic effect.


Increasing concentrations of phenol progressively affect anaerobic digestion of cellulose and associated microbial communities.
Performance stability is a key issue when managing anaerobic digesters. However it can be affected by external disturbances caused by micropollutants. In this study the influence of phenol on the methanization of cellulose was evaluated through batch toxicity assays. Special attention was given to the dynamics of microbial communities by means of automated ribosomal intergenic spacer analysis. We observed that, as phenol concentrations increased, the different steps of anaerobic cellulose digestion were unevenly and progressively affected, methanogenesis being the most sensitive: specific methanogenic activity was half-inhibited at 1.40 g/L of phenol, whereas hydrolysis of cellulose and its fermentation to VFA were observed at up to 2.00 g/L. Depending on the level of phenol, microbial communities resisted either through physiological or structural adaptation. Thus, performances at 0.50 g/L were maintained in spite of the microbial community's shift. However, the communities' ability to adapt was limited and performances decreased drastically beyond 2.00 g/L of phenol.


The disparity of indirect and direct zirconyl-gel assays for carcinoembryonic antigen.
Experience with the zirconyl phosphate gel (Z-gel) radioimmunoassays for plasma CEA levels below 20 ng/ml (the indirect method) and for levels greater than 20 ng/ml (the direct method) has shown that a disparity of values exists, caused by shifting from one assay to the other. This disparity is at least partially due to PCA-labile proteins reacting in the direct assay. It may be constant for individual patients but varies among patients. The magnitude of this disparity is independent of the CEA level (above 15 ng/ml).


Relationship of right and left ventricular negative diastolic pressures, hypercontractility, and relief of outflow tract obstructions.
Continuous postoperative right and left ventricular diastolic pressures were measured in 12 consecutive patients undergoing pulmonic valvotomy and in 13 consecutive patients undergoing membranectomy and myectomy for discrete subaortic stenosis. All 25 patients had positive preoperative diastolic ventricular pressures. Negative ventricular diastolic pressure was detected immediately postoperatively in all 25. The lowest left ventricular negative diastolic pressure was -38 mm Hg, and the lowest right ventricular negative diastolic pressure was -28 mm Hg. Intravenous administration of volume (blood) reduced the right ventricular negative diastolic pressure significantly (from -14.8 +/- 9.2 to -6.4 +/- 6.8 mm Hg, p less than 0.001) and decreased right ventricular rate of pressure rise from 1100 +/- 320 to 380 +/- 180. Left ventricular negative diastolic pressure was not significantly affected (from -17 +/- 11 to -14.7 +/- 11 mm Hg). Left ventricular negative diastolic pressure disappeared spontaneously 6 to 9 hours postoperatively in association with a spontaneous decrease of left ventricular rate of pressure rise (from 3450 +/- 610 to 2100 +/- 660 mm Hg/sec). We conclude that negative right and left ventricular pressures are common findings immediately after surgical relief of outflow obstructions. Hypercontractility is the main reason for these phenomena. Volume load reduces the right ventricular negative diastolic pressure, but has insignificant effect on left ventricular negative diastolic pressure. The pathogenesis of the hypercontractility is discussed.


Comparative Effectiveness of Hepatic Artery Based Therapies for Unresectable Colorectal Liver Metastases: A Meta-Analysis.
Patients with unresectable Colorectal Liver Metastases (CRLM) are increasingly being managed using Hepatic Artery Based Therapies (HAT), including Hepatic Arterial Infusion (HAI), Radioembolization (RE), and Transcatheter Arterial Chemoembolization (TACE). Limited data is available on the comparative effectiveness of these options. We hypothesized that outcomes in terms of survival and toxicity were equivalent across the three strategies. A meta-analysis was performed using a prospectively registered search strategy at PROSPERO (CRD42013003861) that utilized studies from PubMed (2003-2013). Primary outcome was median overall survival (OS). Secondary outcomes were treatment toxicity, tumor response, and conversion of the tumor to resectable. Additional covariates included prior or concurrent systemic therapy. Of 491 studies screened, 90 were selected for analyses-52 (n = 3,000 patients) HAI, 24 (n = 1,268) RE, 14 (n = 1,038) TACE. The median OS (95% CI) for patients receiving HAT in the first-line were RE 29.4 vs. HAI 21.4 vs. TACE 15.2 months (p = 0.97, 0.69 respectively). For patients failing at least one line of prior systemic therapy, the survival outcomes were TACE 21.3 (20.6-22.4) months vs. HAI 13.2 (12.2-14.2) months vs. RE 10.7 (9.5-12.0). Grade 3-4 toxicity for HAT alone was 40% in the HAI group, 19% in the RE group, and 18% in the TACE groups, which was increased with the addition of systemic chemotherapy. Level 1 evidence was available in 5 studies for HAI, 2 studies for RE and 1 for TACE. HAI, RE, and TACE are equally effective in patients with unresectable CRLM with marginal differences in survival.


Prognostic Value Of Preoperative Systemic Inflammatory Biomarkers In Patients With Gallbladder Cancer And The Establishment Of A Nomogram.
Preoperative systemic inflammatory biomarkers, including neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) have been developed to predict patient outcome in several types of carcinomas. The aim of this study was to investigate the potential prognostic value of NLR, dNLR, PLR, and LMR, and establish a prognostic nomogram in postoperative GBC patients who underwent radical cholecystectomy. 169 GBC patients were retrospectively enrolled in the present study. ROC curve analysis was used to determine the optimal cut-off values of systemic inflammatory biomarkers. The prognostic value of those biomarkers was investigated according to the Kaplan-Meier method and Cox regression model. A relevant prognostic nomogram was established. Results showed that NLR, dNLR, PLR, and LMR were significantly associated with overall survival (OS); whereas, NLR and LMR were retained as independent indicators. Based on these independent predictors including tumor differentiation, T stage, N stage, CEA, NLR, and LMR, a nomogram was generated with an accuracy of 0.801. Based on our findings, the predictive nomogram could accurately predict individualized survival probability of postoperative GBC patients, and might support clinicians in treatment optimization and clinical decision-making.


Predictors of clinical outcomes in space-occupying cerebellar infarction undergoing suboccipital decompressive craniectomy.
Despite current clinical guidelines recommending suboccipital decompressive craniectomy (SDC) in cerebellar infarction when patients present with neurological deterioration, the precise definition of neurological deterioration remains unclear and accurate timing of SDC can be challenging. The current study aimed at characterizing whether clinical outcomes can be predicted by the GCS score immediately prior to SDC and whether higher GCS scores are associated with better clinical outcomes. In a single-center, retrospective analysis of 51 patients treated with SDC for space-occupying cerebellar infarction, clinical and imaging data were evaluated at the time points of symptom onset, hospital admission, and preoperatively. Clinical outcomes were measured by the mRS. Preoperative GCS scores were stratified into three groups (GCS, 3-8, 9-11, and 12-15). Univariate and multivariate Cox regression analyses were performed using clinical and radiological parameters as predictors of clinical outcomes. In cox regression analysis GCS scores of 12-15 at surgery were significant predictors of positive clinical outcomes (mRS, 1-2). For GCS scores of 3-8 and 9-11, no significant increase in proportional hazard ratios was observed. Negative clinical outcomes (mRS, 3-6) were associated with infarct volume above 6.0 cm3, tonsillar herniation, brainstem compression, and a preoperative GCS score of 3-8 [HR, 2.386 (CI, 1.160-4.906); p = 0.018]. Our preliminary findings suggest that SDC should be considered in patients with infarct volumes above 6.0 cm3 and with GCS between 12 and 15, as these patients may show better long-term outcomes than those in whom surgery is delayed until a GCS score below 11.


Small-caliber endobronchial ultrasonic videoscope: successful transesophageal and transgastric FNA after failed passage of a standard ultrasonic endoscope.
EUS-guided tissue acquisition is a valuable technique. Obstructing lesions of the oropharynx or esophagus may preclude passage of a standard echoendoscope. In the past this has prevented EUS-guided tissue sampling. The recently introduced small-caliber ultrasonic bronchovideoscope (developed for endobronchial ultrasound) may allow EUS-guided FNA in this setting. Our purpose was to assess the possible use of the ultrasonic bronchovideoscope to perform upper GI EUS in patients where passage of standard EUS scope was unsuccessful. A descriptive case series. A tertiary referral center. Two patients were evaluated after failure of passage of a standard echoendoscope (1 with congenital narrowing of the esophageal inlet, 1 with postoperative deformity). In both cases, sonographic visualization of the lesion of concern was achieved and FNA was performed successfully. The ultrasonic bronchovideoscope may be a valuable tool to perform FNA of mediastinal and GI lesions in situations when a standard ultrasonic endoscope cannot be passed because of luminal narrowing.


Evaluation of the genotoxic potential of cypermethrin, chlorpyrifos and their subsequent mixture, on cultured bovine lymphocytes.
Cypermethrin (CYP) and chlorpyrifos (CPF) are insecticides/parasiticides used in the production of fruits, vegetables and beef cattle. These substances or their metabolites are frequently reported as residues in food, whose consumption in a diet implies a genotoxic risk. The potential for chronic toxicity of CYP and CPF is unclear, and only a few genotoxicological evaluations based on their mixture have been performed. The aim of this study was to evaluate the genotoxic potential of CYP, CPF and CYP + CPF in five concentrations, from 5.9 to 175 μg/mL, on bovine lymphocytes. By means of the cytokinesis-block micronucleus cytome assay, a decrease in the cell proliferation index was observed (r = -0.89 p = 0.04); and also an increase in the frequencies of binucleated cells (BN) with micronuclei (BNMn) (r = 0.93, p = 0.02) and BN with nuclear buds (BNBud) (r = 0.778 p = 0.04), depending on the concentrations of CPF. An increase in BNMn frequencies was observed as a function of CYP concentrations (r = 0.89, p = 0.04) and also of the CYP + CPF mix (r = 0.99, p = 0.008). CYP caused greater genotoxic damage (BNMn) than CPF and the mixture on bovine lymphocytes. Cells with simultaneous presentation of micronuclei and nuclear buds were detected, as well as cells with irregular nuclei, something never previously reported, whose origin and significance should be investigated. The genotoxic effect of chlorpyrifos, cypermethrin and their mixture on bovine lymphocytes was observed. We recognized the value of the use of primary bovine cultures, animal species adjacent to man in the food chain, for genotoxicity studies.


Organometallic complexes with biological molecules. XVIII. Alkyltin(IV) cephalexinate complexes: synthesis, solid state and solution phase investigations.
Dialkyltin(IV) and trialkyltin(IV) complexes of the deacetoxycephalo-sporin-antibiotic cephalexin [7-(d-2-amino-2-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid] (Hceph) have been synthesized and investigated both in solid and solution phase. Analytical and thermogravimetric data supported the general formula Alk(2)SnOHceph(.)H(2)O and Alk(3)Snceph(.)H(2)O (Alk=Me, n-Bu), while structural information has been gained by FT-IR, (119)Sn Mössbauer and (1)H, (13)C, (119)Sn NMR data. In particular, IR results suggested polymeric structures both for Alk(2)SnOHceph(.)H(2)O and Alk(3)Snceph(.)H(2)O. Moreover, cephalexin appears to behave as monoanionic tridentate ligand coordinating the tin(IV) atom through ester-type carboxylate, as well as through beta-lactam carbonyl oxygen atoms and the amino nitrogen donor atoms in Alk(2)SnOHceph(.)H(2)O complexes. On the basis of (119)Sn Mössbauer spectroscopy it could be inferred that tin(IV) was hexacoordinated in such complexes in the solid state, showing skew trapezoidal configuration. As far as Alk(3)Sn(IV)ceph(.)H(2)O derivatives are concerned, cephalexin coordinated the Alk(3)Sn moiety through the carboxylate acting as a bridging bidentate monoanionic group. Again, (119)Sn Mössbauer spectroscopy led us to propose a trigonal configuration around the tin(IV) atom, with R(3)Sn equatorial disposition and bridging carboxylate oxygen atoms in the axial positions. The nature of the complexes in solution state was investigated by using (1)H, (13)C and (119)Sn NMR spectroscopy. Finally, the cytotoxic activity of organotin(IV) cephalexinate derivatives has been tested using two different chromosome-staining techniques Giemsa and CMA(3), towards spermatocyte chromosomes of the mussel Brachidontes pharaonis (Mollusca: Bivalvia). Colchicinized-like mitoses (c-mitoses) on slides obtained from animals exposed to organotin(IV) cephalexinate compounds, demonstrated the high mitotic spindle-inhibiting potentiality of these chemicals. Moreover, structural damages such as "chromosome achromatic lesions", "chromosome breakages" and "chromosome fragments" have been identified through a comparative analysis of spermatocyte chromosomes from untreated specimens (negative controls) and specimens treated with the organotin(IV) complexes.


Argon-plasma-induced ultrathin thermal grafting of thermoresponsive pNIPAm coating for contractile patterned human SMC sheet engineering.
A new method for ultrathin grafting of pNIPAm on PDMS surfaces is introduced that employs plasma activation of the surface followed by thermal polymerization. This method is optimized for human primary SMC attachment and subsequent intact cell sheet detachment by lowering the temperature. The contractile gene expression of the cells showed that the contractile phenotype of the SMCs which is induced by aligning the cells through micropatterning is more preserved after thermoresponsive cell sheet detachment in contrast with enzymatic detachment. Given its simplicity and low cost, this thermoresponsive grafting method can be utilized for engineering patterned cell sheets for future bottom-up tissue engineering techniques.


Provider perspectives on the utility of a colorectal cancer screening decision aid for facilitating shared decision making.
Decision aids for colorectal cancer (CRC) screening have been shown to enable patients to identify a preferred screening option, but the extent to which such tools facilitate shared decision making (SDM) from the perspective of the provider is less well established. Our goal was to elicit provider feedback regarding the impact of a CRC screening decision aid on SDM in the primary care setting. Cross-sectional survey. Primary care providers participating in a clinical trial evaluating the impact of a novel CRC screening decision aid on SDM and adherence. Perceptions of the impact of the tool on decision-making and implementation issues. Twenty-nine of 42 (71%) eligible providers responded, including 27 internists and two nurse practitioners. The majority (>60%) felt that use of the tool complimented their usual approach, increased patient knowledge, helped patients identify a preferred screening option, improved the quality of decision making, saved time and increased patients' desire to get screened. Respondents were more neutral is their assessment of whether the tool improved the overall quality of the patient visit or patient satisfaction. Fewer than 50% felt that the tool would be easy to implement into their practices or that it would be widely used by their colleagues. Decision aids for CRC screening can improve the quality and efficiency of SDM from the provider perspective but future use is likely to depend on the extent to which barriers to implementation can be addressed.


A simple six-step guide to National-Scale Hypertension Control Program implementation.
Hypertension is the leading single preventable risk factor for death worldwide, and most of the disease burden attributed to hypertension weighs on low-and middle-income countries. Effective large-scale public health hypertension control programs are needed to control hypertension globally. National programs can follow six important steps to launch a successful national-scale hypertension control program: establish an administrative structure and survey current resources, select a standard hypertension treatment protocol, ensure supply of medication and blood pressure devices, train health care workers to measure blood pressure and control hypertension, implement an information system for monitoring patients and the program overall, and enroll and monitor patients with phased program expansion. Resolve to Save Lives, an initiative of global public health organization Vital Strategies, and its partners organized these six key steps and materials into a structured, stepwise guide to establish best practices in hypertension program design, launch, maintenance, and scale-up.


[Off-label therapy from the perspective of the medical insurance service].
The assessment of off-label medications is one of the most common reasons for assessment of drugs for individual patients in the German medical services. Tension is not uncommon because of great expectations of patients and doctors on the one hand and the requirements of the law on the other. They often do not match. Even if there is a medically justified off-label use the road to drug approval is principally via the authorities with tested efficacy and safety in order not to deprive the patient of the protection of the Pharmaceuticals Act. The jurisdiction has approved criteria for reimbursement by the statutory health insurance only in clearly defined exception and one requirement is that there are no alternative forms of treatment. For serious diseases this is based on the evidence of drug approval; however, for immediately life-threatening situations a very low evidence level is sufficient.


Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homeostasis.
Hematopoietic stem cells (HSCs) balance self-renewal and differentiation to maintain hematopoietic fitness throughout life. In steady-state conditions, HSC exhaustion is prevented by the maintenance of most HSCs in a quiescent state, with cells entering the cell cycle only occasionally. HSC quiescence is regulated by retinoid and fatty-acid ligands of transcriptional factors of the nuclear retinoid X receptor (RXR) family. Herein, we show that dual deficiency for hematopoietic RXRα and RXRβ induces HSC exhaustion, myeloid cell/megakaryocyte differentiation, and myeloproliferative-like disease. RXRα and RXRβ maintain HSC quiescence, survival, and chromatin compaction; moreover, transcriptome changes in RXRα;RXRβ-deficient HSCs include premature acquisition of an aging-like HSC signature, MYC pathway upregulation, and RNA intron retention. Fitness loss and associated RNA transcriptome and splicing alterations in RXRα;RXRβ-deficient HSCs are prevented by Myc haploinsufficiency. Our study reveals the critical importance of RXRs for the maintenance of HSC fitness and their protection from premature aging.


p73 function is inhibited by tumor-derived p53 mutants in mammalian cells.
The p53 tumor suppressor protein, found mutated in over 50% of all human tumors, is a sequence-specific transcriptional activator. Recent studies have identified a p53 relative, termed p73. We were interested in determining the relative abilities of wild-type and mutant forms of p53 and p73alpha and -beta isoforms to transactivate various p53-responsive promoters. We show that both p73alpha and p73beta activate the transcription of reporters containing a number of p53-responsive promoters in the p53-null cell line H1299. However, a number of significant differences were observed between p53 and p73 and even between p73alpha and p73beta. Additionally, a Saccharomyces cerevisiae-based reporter assay revealed a broad array of transcriptional transactivation abilities by both p73 isoforms at 37 degreesC. Recent data have shown that p73 can associate with p53 by the yeast two-hybrid assay. When we examined complex formation in transfected mammalian cells, we found that p73alpha coprecipitates with mutant but not wild-type p53. Since many tumor-derived p53 mutants are capable of inhibiting transactivation by wild-type p53, we tested the effects of two representative hot-spot mutants (R175H and R248W) on p73. By cotransfecting p73alpha along with either p53 mutant and a p53-responsive reporter, we found that both R175H and R248W reduces the transcriptional activity of p73alpha. This decrease in transcriptional activity is correlated with the reduced ability of p73alpha to promote apoptosis in the presence of tumor-derived p53 mutants. Our data suggest the possibility that in some tumor cells, an outcome of the expression of mutant p53 protein may be to interfere with the endogenous p73 protein.


Temporal phenotyping by mining healthcare data to derive lines of therapy for cancer.
Lines of therapy (LOT) derived from real-world healthcare data not only depict real-world cancer treatment sequences, but also help define patient phenotypes along the course of disease progression and therapeutic interventions. The sequence of prescribed anticancer therapies can be defined as temporal phenotyping resulting from changes in morphological (tumor staging), biochemical (biomarker testing), physiological (disease progression), and behavioral (physician prescribing and patient adherence) parameters. We introduce a novel methodology that is a two-part approach: 1) create an algorithm to derive patient-level LOT and 2) aggregate LOT information via clustering to derive temporal phenotypes, in conjunction with visualization techniques, within a large insurance claims dataset. We demonstrated the methodology using two examples: metastatic non-small cell lung cancer and metastatic melanoma. First, we generated a longitudinal patient cohort for each cancer type and applied a set of rules to derive patient-level LOT. Then the LOT algorithm outputs for each cancer type were visualized using Sankey plots and K-means clusters based on durations of LOT and of gaps in therapy between LOT. We found differential distribution of temporal phenotypes across clusters. Our approach to identify temporal patient phenotypes can increase the quality and utility of analyses conducted using claims datasets, with the potential for application to multiple oncology disease areas across diverse healthcare data sources. The understanding of LOT as defining patients' temporal phenotypes can contribute to continuous health learning of disease progression and its interaction with different treatment pathways; in addition, this understanding can provide new insights that can be applied by tailoring treatment sequences for the patient phenotypes who will benefit.


Development of the cochlea.
The cochlea, a coiled structure located in the ventral region of the inner ear, acts as the primary structure for the perception of sound. Along the length of the cochlear spiral is the organ of Corti, a highly derived and rigorously patterned sensory epithelium that acts to convert auditory stimuli into neural impulses. The development of the organ of Corti requires a series of inductive events that specify unique cellular characteristics and axial identities along its three major axes. Here, we review recent studies of the cellular and molecular processes regulating several aspects of cochlear development, such as axial patterning, cochlear outgrowth and cellular differentiation. We highlight how the precise coordination of multiple signaling pathways is required for the successful formation of a complete organ of Corti.


[Assessment of nutritional status in children with atopic dermatitis].
There has been described some exacerbating factors for atopic dermatitis, including foods. Several investigations have reported controversial results about the influence of foods on atopic dermatitis. But there is scarce information about the nutritional status of patients with atopic dermatitis. To characterize the nutritional condition in a sample of children with atopic dermatitis in Old Havana, Cuba. In this descriptive study, were included 60 children, aged between 2 and 14 years, with the diagnosis of atopic dermatitis from the Allergy Department in the municipality Havana, from January to April of 2008. For every patient we evaluated anthropometrics, biochemical and immunologic measurements, as well the frequency of meals ingestion and the types of foods. We found that 83.3% of the patients were younger than 6 years, with a slight prevalence of females (53.3%). Ninety-seven percent of the children had a normal height for its age and 48.3% had a normal weight for their height, and 20% of the patients had malnutrition. It was detected mild and moderate anemia in 63.3%. The daily frequency of taking breakfast was carried out in 55%, the lunch in 100% and dinner in 95%. The products of regular consumption are carbohydrates, candies nd sodas in 76.6%. Fish and shellfish are consumed only for 16% of the patients. In the studied sample of children with atopic dermatitis we found a high prevalence of malnutrition associated with poor dietary habits. Breast milk feeding was related to a less malnutrition percentage in children with atopic dermatitis.


[Acute liver failure caused by paracetamol: should treatment with N-acetylcysteine be prolonged?].
Some cases of paracetamol-induced acute hepatic failure may require liver transplantation but the present shortage of graft urges the search for an alternate therapeutic approach. A 17 year-old girl was admitted for sleepingness and vomiting after about 15 hours of voluntary but denied absorption of paracetamol. Plasma paracetamol concentration was 120 mg/l; factors VII+X level were 55% and factor V 106%. The patient was given IV N-acetylcysteine, 150 mg/kg/30 min, then 50 mg/kg/4 hours. Further decrease in facteur VII level led to pursue administration of N-acetylcysteine (total dose: 350 mg/kg/2 hours). While indication of liver transplantation was considered, clinical and laboratory findings definitely improved. N-acetylcysteine may be effective even if administered late. Repeated determination of factor VII could be a good means for managing such a severe condition.


Neurochemical and behavioral effects of N-ethyl-acetylcholine aziridinium chloride in mice.
N-ethyl-choline aziridinium (ECA) and N-ethyl-acetylcholine aziridinium (EAA) were shown to be inhibitors of high affinity choline uptake in vitro (IC50 = 0.4 microM and 1.5 microM, respectively), and intraventricular administration showed that EAA was more selective in its inhibition of hippocampal choline uptake in vivo. EAA significantly reduced the activity of choline acetyltransferase in the hippocampus 3 to 28 days following intraventricular infusion, but not in the striatum or parahippocampal cortex. Neither muscarinic receptor binding nor glutamic acid decarboxylase activity were affected in any of the three brain regions. EAA (12 or 16 nanomoles, intraventricular) significantly impaired memory performance of mice in a radial arm maze when tested two weeks after treatment. A subgroup analysis implicated long-term reference memory as the mechanism disrupted.


Activation of aldehyde dehydrogenase 2 protects ethanol-induced osteonecrosis of the femoral head in rat model.
Osteonecrosis of the femoral head (ONFH) is a devastating disease characterized by destructive bone structures, enlarged adipocyte accumulation and impaired vascularization. The aldehyde dehydrogenase 2 (ALDH 2) is the limiting enzyme for ethanol metabolism with many physiological functions. The aim was investigated the potential protective role of activated ALDH 2 by Alda-1 for ethanol-induced ONFH. The ethanol-induced ONFH in rat was performed to explore the protective of Alda-1 by various experimental methods. Subsequently, the effect of Alda-1 and ethanol on the osteogenic and adipogenic differentiation was investigated via multiple cellular and molecular methods. Finally, the effect of Alda-1 and ethanol on the neo-vascularization was detected in Human umbilical vein endothelial cells (HUVECs) and ONFH model. Firstly, radiographical and pathological measurements indicated that alda-1 protected ethanol-induced ONFH. Moreover, ethanol significantly inhibited the proliferation and osteogenic differentiation of BMSCs, whereas Alda-1 could distinctly rescue it by PI3K/AKT signalling. Secondly, ethanol remarkably promoted the lipid vacuoles formation of BMSCs, while Alda-1 significantly retarded it on BMSCs by AMPK signalling pathway. Finally, ethanol significantly inhibited proliferation and growth factor level resulting in reduced angiogenesis, whereas Alda-1 could rescue the effect of ethanol. Additionally, Alda-1 significantly reduced the occurrence of ONFH and promoted vessel number and distribution in alcoholic ONFH. Alda-1 activation of ALDH 2 was highly demonstrated to protect ethanol-induced ONFH by triggering new bone formation, reducing adipogenesis and stimulating vascularization.


Impact of older age on the long-term survival in living-donor liver transplantation: A propensity score matching analysis.
Prevalence of the end-stage liver disease in the elderly patients indicating a liver transplantation (LT) has been increasing. There is no universally accepted upper age limit for LT candidates but the functional status of older patients is important in pre-LT evaluation. This study aimed to examine the impact of older age on survival after living donor liver transplantation (LDLT). A total of 171 LDLT recipients were assessed in two groups: age ≥65 and < 65. To eliminate selection bias propensity score matching (PSM) was performed, and 56 of 171 recipients were included in this study. There were 20 recipients in the older group and 36 in the younger. The 1-, 3-, and 5-year survival rates were 65.0%, 60.0%, and 60.0% in group 1; 88.9%, 84.7%, and 71.4% in group 2, respectively. The 1-year survival was significantly lower in the older recipients; however, overall survival rates were similar between the groups. Of the 56 recipients, 15 (27%) deaths were observed in overall, and 11 (20%) in 1-year follow-up. The univariate regression analysis after PSM revealed that MELD score affected 1- year survival and the multivariate analysis revealed that age ≥65 years and MELD score were the predictors of 1-year survival. At first sight, before PSM, survival appeared to be worse for older recipients. However, we have shown that there were confounding effects of clinical variables in the preliminary evaluation. After the elimination of this bias with PSM, This study highlights that older recipients have similar outcomes as youngers in LDLT for long-term survival.


Low impact to fixed cell processing aiming transmission electron microscopy.
In cell culture, cell structures suffer strong impact due to centrifugation during processing for electron microscope observation. In order to minimise this effect, a new protocol was successfully developed. Using conventional reagents and equipments, it took over one week, but cell compression was reduced to none or the lowest deformation possible.


Red blood cells: Supercarriers for drugs, biologicals, and nanoparticles and inspiration for advanced delivery systems.
Red blood cells (RBCs) constitute a unique drug delivery system as a biologic or hybrid carrier capable of greatly enhancing pharmacokinetics, altering pharmacodynamics (for example, by changing margination within the intravascular space), and modulating immune responses to appended cargoes. Strategies for RBC drug delivery systems include internal and surface loading, and the latter can be performed both ex vivo and in vivo. A relatively new avenue for RBC drug delivery is their application as a carrier for nanoparticles. Efforts are also being made to incorporate features of RBCs in nanocarriers to mimic their most useful aspects, such as long circulation and stealth features. RBCs have also recently been explored as carriers for the delivery of antigens for modulation of immune response. Therefore, RBC-based drug delivery systems represent supercarriers for a diverse array of biomedical interventions, and this is reflected by several industrial and academic efforts that are poised to enter the clinical realm.


Detection of elements responsible for stage- and tissue-specific expression of mouse Sry using an in vitro Cre/loxP system.
We have successfully specified essential sequences of the 5' upstream region for the stage- and tissue-specific expression of mouse Sry by using an in vitro Cre/loxP system. Sry/Cre plasmids carrying Sry 5' sequences of various sizes were transfected into the primary cultured cells from different tissues of CAG/loxP/CAT/loxP/LacZ transgenic fetuses on 11.5-day post coitus (dpc) or 13.5-dpc. Stage- and tissue-specific regulation of Sry expression was disrupted by the deletion of positions 7549-7660 (from -0.4 to -0.5 kb region). In vitro transcription assay also suggested that the region contains element(s) responsible for stage- and tissue-specific expression of mouse Sry. SRY promoter of Shiba goat (Capra hircus var Shiba), a native Japanese miniature goat, showed the tissue-specific activity in the cells from urogenital ridges of the male mouse, but not in the cells from female mice, indicating a possibly different mechanism among species in the regulation of Sry expression.


Mobile phone dependency and sleep quality in college students during COVID-19 outbreak: the mediating role of bedtime procrastination and fear of missing out.
The purpose of this study was to investigate the associations between mobile phone dependency, bedtime procrastination, FoMO, and sleep quality among college students during the COVID-19 outbreak. Specifically, we examined whether bedtime procrastination and FoMO mediate the relationship between mobile phone dependency and sleep quality. A total of 881 college students completed an online survey in May 2022 in Shanghai, China. Mobile Phone Involvement Questionnaire, Bedtime Procrastination Scale, Fear of Missing Out Scale and Pittsburgh Sleep Quality Index were used to assess mobile phone dependency, bedtime procrastination, fear of missing out, and sleep quality, respectively. Multiple linear regression and mediation analysis were conducted. The correlation analyses indicated mobile phone dependency was positively associated with fear of missing out, bedtime procrastination, and poor sleep quality among college students. The structural equation modeling analyses revealed that mobile phone dependency had significant indirect effects on sleep quality through bedtime procrastination (indirect effect: 0.030, 95%CI: 0.022-0.041) and fear of missing out (indirect effect: 0.013, 95%CI: 0.003-0.023). The findings indicated that bedtime procrastination and fear of missing out are mediators mediating the relationship between mobile phone dependency with sleep quality. Bedtime procrastination and fear of missing out should be considered as potential intervention targets for reducing mobile phone dependency and improving sleep quality in college students.


Juvenile hormone modifies larvae and silk gland development in Bombyx mori.
Topical application of a Juvenile Hormone Analogue (ZR 515) during the first half of the first half of the last (fifth) larval instar of Bombyx mori induces a prolongation of this instar and increases larvae weight and silk secretion. Later treatment can lead to an extra larval molt. Moreover, the hormone analogue stops either the development or the secretory activity of the silk gland, depending on the period of treatments. When Juvenile Hormone is administered at the beginning of the fifth instar, silk gland growth as well as RNA and protein syntheses are first inhibited and later resumed and amplified. Finaly silk production increases up to 150 per cent of controls. One of the primarly effects of treatments seems to be RNA synthesis. Thus Juvenile Hormone analogue application could be a new tool for studying RNA transcription and/or processing.


α2-antiplasmin positively regulates endothelial-to-mesenchymal transition and fibrosis progression in diabetic nephropathy.
Diabetic nephropathy (DN), is microvascular complication of diabetes causes to kidney dysfunction and renal fibrosis. It is known that hyperglycemia and advanced glycation end products (AGEs) produced by hyperglycemic condition induce myofibroblast differentiation and endothelial-to-mesenchymal transition (EndoMT), and exacerbate fibrosis in DN. Recently, we demonstrated that α2-antiplasmin (α2AP) is associated with inflammatory response and fibrosis progression. We investigated the role of α2AP on fibrosis progression in DN using a streptozotocin-induced DN mouse model. α2AP deficiency attenuated EndoMT and fibrosis progression in DN model mice. We also showed that the high glucose condition/AGEs induced α2AP production in fibroblasts (FBs), and the reduction of receptor for AGEs (RAGE) by siRNA attenuated the AGEs-induced α2AP production in FBs. Furthermore, the bloackade of α2AP by the neutralizing antibody attenuated the high glucose condition-induced pro-fibrotic changes in FBs. On the other hand, the hyperglycemic condition/AGEs induced EndoMT in vascular endothelial cells (ECs), the FBs/ECs co-culture promoted the high glucose condition-induced EndoMT compared to ECs mono-culture. Furthermore, α2AP promoted the AGEs-induced EndoMT, and the blockade of α2AP attenuated the FBs/ECs co-culture-promoted EndoMT under the high glucose condition. The high glucose conditions induced α2AP production, and α2AP is associated with EndoMT and fibrosis progression in DN. These findings provide a basis for clinical strategies to improve DN.


The lack of a relationship between atopic dermatitis and nonmelanoma skin cancers.
Very little has been published on whether a relationship exists between atopic dermatitis (AD) and skin cancer. The goal of this study was to investigate whether individuals with AD are more likely than other patients with dermatologic conditions to develop nonmelanoma skin cancer. This was a case-control, mailed-survey study. Of those contacted, 69.8% (3207 of 4591) filled out the survey. Of the control patients, 18.4% (254) had a history of AD as defined by the United Kingdom Working Party diagnosis criteria and composed 13.7% (210) of the cases. The unadjusted odds ratio of AD to nonmelanoma skin cancer was 0.70 (95% confidence interval 0.57-0.85). After fully adjusting for age, sex, ethnicity, and topical steroid use the odds ratio was 0.78 (0.61, 0.98). Using different definitions of AD had little effect on this result. It does not appear that patients with a history of AD are more likely to develop nonmelanoma skin cancers than other patients with dermatologic conditions.


Definitive radiotherapy for hilar and/or mediastinal lymph node metastases after stereotactic body radiotherapy or surgery for stage I non-small cell lung cancer: 5-year results.
The optimal treatment for hilar or mediastinal lymph node (LN) recurrence developing after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer remains unclear. This study evaluated 5-year results of radiotherapy in such patients in comparison with those for postoperative LN metastases. Between 2004 and 2013, 27 patients with hilar and/or mediastinal LN metastases without local recurrence and distant metastasis after SBRT (n = 14) or surgery (n = 13) were treated with definitive conventional radiotherapy. The median total dose for treating metastatic LN was 60 Gy for the post-SBRT group and 66 Gy for the post-surgery group. The median follow-up for the 5 surviving patients was 62 months. The overall survival, cause-specific survival, progression-free survival, and local control rates at 5 years after mediastinal irradiation were 14%, 45%, 21%, and 58%, respectively, for the 14 patients in the post-SBRT group. These rates were 36%, 45%, 39%, and 92%, respectively for the post-surgery group (p = 0.066, 0.64, 0.38, and 0.41, respectively). Four patients in the post-SBRT group survived 3 or more years (range 36-92 months) after mediastinal irradiation. A proportion of patients in both groups achieved long-term survival by conventional radiotherapy.


Constructing a CdS QDs/silica gel composite with high photosensitivity and prolonged recyclable operability for enhanced visible-light-driven NADH regeneration.
Visible-light-driven nicotinamide adenine dinucleotide (NADH) regeneration is one of the most effective measures, and cadmium sulfide (CdS) materials are typically used as low-cost photocatalysts. The CdS photocatalysts, however, still suffer from low regeneration efficiency and poor cycle stability. In this work, the CdS quantum dots (QDs) less than 10 nm embedded onto silica gel (CdS QDs/Silica gel) were constructed for visible-light-driven NADH regeneration by a successive ionic layer adsorption reaction and ball milling method. Results demonstrate that the photosensitivity of the CdS QDs/Silica gel composite was 31 times higher than that of the bulk CdS. Moreover, the conduction band (CB) edge of the CdS QDs/Silica gel composite is -1.34 eV, which is more negative 0.5 eV than that of the bulk CdS. The obtained CdS QDs/Silica gel composites showed the highest NADH regeneration yields of 68.8% under visible-light (LED, 420 nm) illumination and can be reused for over 40 cycles. Finally, the bioactivity of NADH toward enzyme catalysis is further confirmed by the hydrogenation of benzaldehyde to benzyl alcohol catalyzed with an alcohol dehydrogenase as enzyme catalysis.


Palladium-Catalyzed Synthesis of 2-Aryl-2H-Benzotriazoles from Azoarenes and TMSN3.
Substrate-directed ortho C-H amination of azoarenes using TMSN3 as the source of nitrogen leading to the synthesis of 2-aryl-2H-benzotriazoles has been accomplished with the help of Pd/TBHP combinations. An intermolecular o-azidation (C-N bond formation) followed by an intramolecular N-N bond formation via nucleophilic attack of one of the azo nitrogen onto the o-azide nitrogen leads to cyclization with the expulsion of N2.


DHCR24 reverses Alzheimer's disease-related pathology and cognitive impairment via increasing hippocampal cholesterol levels in 5xFAD mice.
Accumulating evidences reveal that cellular cholesterol deficiency could trigger the onset of Alzheimer's disease (AD). As a key regulator, 24-dehydrocholesterol reductase (DHCR24) controls cellular cholesterol homeostasis, which was found to be downregulated in AD vulnerable regions and involved in AD-related pathological activities. However, DHCR24 as a potential therapeutic target for AD remains to be identified. In present study, we demonstrated the role of DHCR24 in AD by employing delivery of adeno-associated virus carrying DHCR24 gene into the hippocampus of 5xFAD mice. Here, we found that 5xFAD mice had lower levels of cholesterol and DHCR24 expression, and the cholesterol loss was alleviated by DHCR24 overexpression. Surprisingly, the cognitive impairment of 5xFAD mice was significantly reversed after DHCR24-based gene therapy. Moreover, we revealed that DHCR24 knock-in successfully prevented or reversed AD-related pathology in 5xFAD mice, including amyloid-β deposition, synaptic injuries, autophagy, reactive astrocytosis, microglial phagocytosis and apoptosis. In conclusion, our results firstly demonstrated that the potential value of DHCR24-mediated regulation of cellular cholesterol level as a promising treatment for AD.


Urethral distension as a novel method to simulate sphincter insufficiency in the porcine animal model.
To describe a novel animal model of intrinsic sphincter deficiency. The study was carried out on 10 female pigs. Injury to the urethral sphincter was induced by distension of the urethra. This was obtained by using the balloon of an 18-F Dufour catheter for 5 min followed by its retraction through the urethra without draining the balloon. The urethral pressure profile was evaluated before injury, immediately postinjury and at day 28 postinjury in the experimental group (n = 5), and on day 1 and day 28 in the control uninjured group (n = 5). The maximal urethral closure pressure, the functional urethral length and the area under curve of the urethral pressure profile were measured. The mean maximal urethral closure pressure at the beginning of the experiment was 32 cmH(2) O, and the mean functional urethral length was 4.88 cm. The assessment at day 28 showed a reduction of the maximal urethral closure pressure (50% of the control, P > 0.05), the functional urethral length (52.5% of the control, P < 0.05) and the area under curve (52% of the control, P < 0.05) in injured pigs. Histologically, a fibrosis of the sphincter was detected without rupture of the muscle layer in all the samples. The proposed porcine model can be used to obtain intrinsic sphincter deficiency-like urodynamic findings without rupturing the sphincter. This methodology can be applied to investigate therapies for intrinsic sphincter deficiency.


Scleral Cross-Linking Using Glyceraldehyde for the Prevention of Axial Elongation in the Rabbit: Blocked Axial Elongation and Altered Scleral Microstructure.
This study aims to assess the efficacy of the scleral collagen cross-linking method using glyceraldehyde solution for prevention of lens-induced axial elongation in New Zealand rabbits and investigate the biochemical and microstructural changes that occur. The right eyes of New Zealand rabbits aged seven weeks were randomly divided into three groups: the cross-linking group (n = 6), non-crosslinking group (n = 5), and untreated control group (n = 5). Eyes in cross-linking and non-crosslinking groups were treated with a -8.00 Diopter spherical lens over the course of two weeks. The cross-linking effects were achieved by a sub-Tenon's injection of 0.15 ml 0.5 M glyceraldehyde to eyes in the CL group. Ocular parameters were measured on the 1st, 7th, and 14th days. Biomechanical testing, light and electronic microscopy were used. Following the cross-linking treatment, eyes in the cross-linking group had a shorter axial length compared to those in the non-crosslinking group (p = 0.006). Collagen fibrils larger than 240 nm were observed in the scleral stroma of cross-linking group, which were absent in the scleral stroma of the non-crosslinking and untreated control group. The mean ultimate stress and Young's modulus was significantly greater in the cross-linking group compared to those in the non-crosslinking and untreated control group (p < 0.05). No histological damage observed in the retina or choroid. This study demonstrates that lens-induced axial elongation in rabbits can be effectively blocked by cross-linking using glyceraldehyde, with anatomical and mechanical modification and no deleterious effects.


[Unidirectional Hybridization of Kaluga Acipenser dauricus Georgi, 1775 and Amur Sturgeon Acipenser schrenckii Brandt, 1869, Inferred from the Mitochondrial DNA Genotyping of Their Natural Hybrids].
In 2009 through 2011, among 730 individuals of kaluga and Amur sturgeon collected in the lower reaches of the Amur River and the Amursky Liman, 17 morphologically intermediate individuals (hybrids) with the body length of 56 to 202 cm (median, 81 cm) were identified, including 11 individuals (4.6%) found in 2009, three individuals (1.6%) found in 2010, and three individuals (1.1%), in 2011. In 16 hybrids 819 bp of the mtDNA control regions were sequences and 11 haplotypes were identified. Since all these haplotypes were from the mtDNA lineages of kaluga, it was concluded that hybridization occurred in one direction, kaluga (♀) x Amur sturgeon (♂). This asymmetry could be caused by the large difference in sizes of these species. Since the earlier examined morphologically typical Amur sturgeons showed the absence of alien haplotypes (Shedko, et al., 2015), the absence of the mtDNA introgression is claimed. This can be caused by low viability or sterility of the backcross females (kaluga (♀) x Amur sturgeon (♂)) x Amur sturgeon (♂). The samples of hybrids and typical kaluga individuals demonstrated no differences in the frequency spectra of the mtDNA haplotypes. However, haplotype and nucleotide diversity in the first sample was somewhat higher than in the second one (0.950 versus 0.927 and 0.0054 versus 0.0044, respectively). The data obtained will be useful for population monitoring of kaluga and Amur sturgeon, Amur River endemics, which are classified as critically endangered by the IUCN Red List of Threatened Species.


Operant self-control procedure in modifying Type A behavior.
A multiple-baseline across subjects design was used to evaluate the effects of operant self-control procedure on altering speed/impatient behaviors of the Type A behavior pattern (TABP). The operant-self-control procedure consisted of self-monitoring, self-evaluation, and self-reinforcement. The results demonstrated empirically significant decreases in S/I behaviors of the TABP following transfer to the self-reinforcement condition. Significant reductions in the Jenkins Activity Survey and physical symptoms scores additionally evidenced the effects of the operant self-control procedure. The possibility of pathogenic factors of the TABP varying with culture, and the advantages of the operant self-control procedure are discussed.


Targeting IFN activity to both B cells and plasmacytoid dendritic cells induces a robust tolerogenic response and protection against EAE.
Type I Interferon (IFN) was the very first drug approved for the treatment of Multiple Sclerosis (MS), and is still frequently used as a first line therapy. However, systemic IFN also causes considerable side effects, affecting therapy adherence and dose escalation. In addition, the mechanism of action of IFN in MS is multifactorial and still not completely understood. Using AcTaferons (Activity-on-Target IFNs, AFNs), optimized IFN-based immunocytokines that allow cell-specific targeting, we have previously demonstrated that specific targeting of IFN activity to dendritic cells (DCs) can protect against experimental autoimmune encephalitis (EAE), inducing in vivo tolerogenic protective effects, evidenced by increased indoleamine-2,3-dioxygenase (IDO) and transforming growth factor β (TGFβ) release by plasmacytoid (p) DCs and improved immunosuppressive capacity of regulatory T and B cells. We here report that targeting type I IFN activity specifically towards B cells also provides strong protection against EAE, and that targeting pDCs using SiglecH-AFN can significantly add to this protective effect. The superior protection achieved by simultaneous targeting of both B lymphocytes and pDCs correlated with improved IL-10 responses in B cells and conventional cDCs, and with a previously unseen very robust IDO response in several cells, including all B and T lymphocytes, cDC1 and cDC2.


Tuberculosis, HIV, and viral hepatitis diagnostics in eastern Europe and central Asia: high time for integrated and people-centred services.
Globally, high rates (and in the WHO European region an increasing prevalence) of co-infection with tuberculosis and HIV and HIV and hepatitis C virus exist. In eastern European and central Asian countries, the tuberculosis, HIV, and viral hepatitis programmes, including diagnostic services, are separate vertical structures. In this Personal View, we consider underlying reasons for the poor integration for these diseases, particularly in the WHO European region, and how to address this with an initial focus on diagnostic services. In part, this low integration has reflected different diagnostic development histories, global funding sources, and sample types used for diagnosis (eg, typically sputum for tuberculosis and blood for HIV and hepatitis C). Cooperation between services improved as patients with tuberculosis needed routine testing for HIV and vice versa, but financial, infection control, and logistical barriers remain. Multidisease diagnostic platforms exist, but to be used optimally, appropriate staff training and sensible understanding of different laboratory and infection control risks needs rapid implementation. Technically these ideas are all feasible. Poor coordination between these vertical systems remains unhelpful. There is a need to increase political and operational integration of diagnostic and treatment services and bring them closer to patients.


UVB-activated psoralen reduces luminal narrowing after balloon dilation because of inhibition of constrictive remodeling.
In this study we have explored the potential of PUVB (8-MOP + UVB) therapy for the reduction of luminal narrowing after arterial injury. In 15 rabbits, balloon dilation of iliac arteries was performed. In 20 arteries, dilation was combined with the delivery of pulsed ultraviolet light B (UVB) irradiation with 10 arteries being previously subjected to sensitizer infusion. Changes in vessel diameter, proliferation and extracellular matrix protein content at 6 weeks were evaluated by means of angiography and histomorphometry-immunohistochemistry. We found that PUVB, applied at the time of dilation, induced reduction in late loss (LL) at 6 weeks (percutaneous transluminal angioplasty vs UVB vs PUVB: 0.64 +/- 0.15 mm vs 0.61 +/- 0.05 mm vs 0.29 +/- 0.05 mm; p = 0.018). The same holds true for constrictive remodeling (0.53 +/- 0.15 mm vs 0.45 +/- 0.06 mm vs 0.15 +/- 0.05 mm; p = 0.016). In the irradiation groups, LL was independent of acute gain (AG), as opposed to the control. Collagen content increased significantly after PUVB in media and adventitia, without increased cellular proliferation in all vessel layers. Thus, PUVB at the time of dilation reduced luminal narrowing at follow-up without effecting proliferation. This effect was independent of AG and was associated with increased collagen content in media and adventitia.


Attitudes toward physician-assisted suicide and death anxiety among Kuwaiti students.
In a sample of 116 Kuwaiti students, the approval of physician-assisted suicide was not correlated with age, sex, or scores on death anxiety and fears of death and dying of self and others.


Intrahepatic stones: the Taiwan experience.
From 1970 to 1979, 95 patients with intrahepatic stones were seen. Since 1974, however, the annual rate of cases has been only half that of the previous decades. Patients with this disease are young; onset of symptoms in over a third of the patients occurred before 20 years of age and in 14 patients before 15 years. Average length of time between onset of symptoms and definitive diagnosis was 8.3 years. Southeast Asian stones are multiple, soft, muddy, pigmented, and located in the primary and secondary biliary radicles (particularly in the left hepatic lobe). Transhepatic cholangiography is the best diagnostic maneuver. Many procedures have been tried but no one procedure is entirely satisfactory. Previously unoperated patients (44) had cholecystectomy and exploration of the common bile duct. Patients whose stones recurred after exploration needed reoperation after an average of 2.5 years; patients whose stones recurred after cholecystectomy were seen an average of 5.7 years later, and 11 of 18 were treated medically. The mortality rate was surprisingly low.


Nonlinkage between C6 and chromosome 6 markers.
C6 typing was performed in a family material by two different techniques: serum or plasma samples were subjected either to high-voltage agarose gel electrophoresis or to isoelectric focusing in polyacrylamide gel slabs. Proteins with C6 activity were then visualized by a specific, hemolytic assay. In 81 unrelated adults within the family material the following allele frequencies were found: C6A:0.61 and C6B:0.39. Linkage studies exclude linkage between C6 and HLA region marker loci, and also between C6 and another chromosome 6 marker locus PGM3.


Safety assessment of cyclomethicone, cyclotetrasiloxane, cyclopentasiloxane, cyclohexasiloxane, and cycloheptasiloxane.
Cyclomethicone (mixture) and the specific chain length cyclic siloxanes (n = 4-7) reviewed in this safety assessment are cyclic dimethyl polysiloxane compounds. These ingredients have the skin/hair conditioning agent function in common. Minimal percutaneous absorption was associated with these ingredients and the available data do not suggest skin irritation or sensitization potential. Also, it is not likely that dermal exposure to these ingredients from cosmetics would cause significant systemic exposure. The Cosmetic Ingredient Review Expert Panel concluded that these ingredients are safe in the present practices of use and concentration.


Full-scale pore characteristics in coal and their influence on the adsorption capacity of coalbed methane.
Coalbed methane (CBM) is primarily stored and transported through the pores in the coal matrix, making it essential to study the development of different scales of pores in coal to better understand the evaluation and exploration of CBM. In this study, four coal samples of varying ranks (Ro,max = 0.68%-2.86%) were selected, and different scale pores were obtained through low-pressure CO2 and Ar adsorption (LP-CO2/ArGA) and mercury intrusion porosimetry (MIP) experiments. A full-scale pore evaluation model was established, and the impact of pores on methane adsorption and restriction was analyzed and discussed through high-pressure adsorption experiments. Our results show that (1) at high pressures (> 100 MPa), the MIP technique caused pore compression and overestimated the pore size below 30 nm by up to 47.2%; (2) to obtain a comprehensive pore evaluation, we developed an accurate model that combines LP-CO2/ArGA with NLDFT and BJH and NLDFT models to determine micropore (0.3-1.5 nm) and mesopore (1.5-30 nm) parameters. By combining this model with MIP test results, we can obtain a full-scale pore size in the range of 0.3 nm-200 μm; (3) coal rank affected the development of full-scale pore characteristics. As coal rank increased, the specific surface area (SSA) of micropores and adsorption capacity of methane first decreased, then increased. Micropores were found to be the most important storage space for CBM and control gas adsorption, with a microporous SSA and PV to total SSA and total PV ratio of 97.93% and 63.69%, respectively. (4) We also observed a significant linear relationship between the fractal dimension of micropores and the Langmuir volume (VL) based on fractal theory. As the fractal dimension increased, VL also increased (R2 = 0.8581), indicating that VL is controlled by the complexity of micropores, which is consistent with the comprehensive evaluation index (Dt) and VL (R2 = 0.8744). Based on our predicted model, VL can be estimated using the SSA of micropores and Dt. Our findings shed light on the relationship between pore morphology and CBM occurrence and have practical implications for fields such as catalytic synthesis, E-CBM, and gas purification.


Late corticosteroid withdrawal can be safely performed for kidney recipients with stable graft function under pathological confirmation.
Corticosteroid withdrawal (CSWD) protocols to minimize the risk of cardiovascular events after kidney transplantation have been reported. However, most of them were within one year post-transplant, and the pathological survey after CSWD was poorly done. We conducted the present retrospective study to elucidate the usefulness and safety of late-steroid withdrawal more than one year after transplantation in kidney recipients with pathological evaluation. Twenty kidney recipients with stable graft function more than one year post-transplant, and whose corticosteroid (CS) was withdrawn were enrolled in this study. The change in their clinical parameters of graft function (sCr and uP/Cr), metabolic profiles, and histological graft status (Banff 97 scoring system) were studied pre- and post-CSWD, and compared with a control cohort taking continuous CS. The dose of CS was tapered gradually and has been maintained with the minimal dose of CS (1.25-5 mg of prednisone) by three months after transplant. CS was furthermore reduced thereafter, if graft function had been stable more than one year and a patient wanted CS to be withdrawn, then a graft biopsy was undertaken. CSWD was accomplished between 16 and 195 (median 41.5) months post-transplant, if there was no significant histological graft damage or on-going acute rejection. A repeat biopsy was carried out two to 21 months after CSWD. In contrast, the observation point of the control cohort was 24 to 49 (median 36.5) months after transplant, and the second biopsy was done five to 30 months after the initial biopsy. The control cohort took 2.5 to 5 (median 2.5) mg of prednisone daily. There were no significant alterations of graft function between pre- and post-CSWD (sCr: 1.14 +/- 0.1 and 1.17 +/- 0.1 mg/dL, respectively, p = 0.3299, uP/Cr: 0.12 +/- 0.01 and 0.21 +/- 0.06, respectively, p = 0.0574). The hypertension rate between both groups was not different between double biopsy points. In addition the rates of glucose intolerance and hyperlipidemia were comparable between two points in both cohorts. There was no significant change in the acute/active lesion scoring (2 t1 and 3 i1 were only positive factors before CSWD and they all returned to t0 and i0 after CSWD). Moreover, chronic/sclerosing allograft nephropathy scorings were minimal and similar between pre- and post-CSWD compared with the control. CSWD for more than one year is safe for patients whose graft functions are stable with pathological confirmation; however, a longer follow-up study is warranted.


The cytoplasmic tails of infectious bronchitis virus E and M proteins mediate their interaction.
Virus-like particle (VLP) formation by the coronavirus E and M proteins suggests that interactions between these proteins play a critical role in coronavirus assembly. We studied interactions between the infectious bronchitis virus (IBV) E and M proteins using in vivo crosslinking and VLP assembly assays. We show that IBV E and M can be crosslinked to each other in IBV-infected and transfected cells, indicating that they interact. The cytoplasmic tails of both proteins are important for this interaction. We also examined the ability of the mutant and chimeric E and M proteins to form VLPs. IBV M proteins that are missing portions of their cytoplasmic tails or transmembrane regions were not able to support VLP formation, regardless of their ability to be crosslinked to IBV E. Interactions between the E and M proteins and the membrane bilayer are likely to play an important role in VLP formation and virus budding.


Anticancer clinical efficiency and stochastic mechanisms of belinostat.
Cancer progression is strongly affected by epigenetic events in addition to genetic modifications. One of the key elements in the epigenetic control of gene expression is histone modification through acetylation, which is regulated by the synergy between histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs are thought to offer considerable potential for the development of anticancer medications, particularly when used in conjunction with other anticancer medications and/or radiotherapy. Belinostat (Beleodaq, PXD101) is a pan-HDAC unsaturated hydroxamate inhibitor with a sulfonamide group that has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of refractory or relapsed peripheral T-cell lymphoma (PTCL) and solid malignancies or and other hematological tissues. This drug modifies histones and epigenetic pathways. Because HDAC and HAT imbalance can lead to downregulation of regulatory genes, resulting in tumorigenesis. Inhibition of HDACs by belinostat indirectly promotes anti-cancer therapeutic effect by provoking acetylated histone accumulation, re-establishing normal gene expressions in cancer cells and stimulating other routes such as the immune response, p27 signaling cascades, caspase 3 activation, nuclear protein poly (ADP-ribose) polymerase-1 (PARP-1) degradation, cyclin A (G2/M phase), cyclin E1 (G1/S phase) and other events. In addition, belinostat has already been discovered to increase p21WAF1 in a number of cell lines (melanoma, prostate, breast, lung, colon, and ovary). This cyclin-dependent kinase inhibitor actually has a role in processes that cause cell cycle arrest and apoptosis. Belinostat's clinical effectiveness, comprising Phase I and II studies within the areas of solid and hematological cancers, has been evidenced through several investigative trials that have supported its potential to be a valuable anti-cancer drug. The purpose of this research was to provide insight on the specific molecular processes through which belinostat inhibits HDAC. The ability to investigate new therapeutic options employing targeted therapy and acquire a deeper understanding of cancer cell abnormalities may result from a better understanding of these particular routes.


Nocturnal agitation: From sleep state dissociation to sleep-related dissociative state.
Nocturnal agitation refers to a broad spectrum of symptoms from simple movements to aggressive behaviors with partial or complete loss of awareness. An accurate identification of its etiology is critical for appropriate therapeutic intervention. In children and young adults, distinguishing between non-rapid eye movement (NREM) sleep parasomnias and psychogenic non-parasomniac manifestations, a condition known as sleep-related dissociative disorder (SRDD), can be challenging. This review aims to summarize current clinical, neurophysiological, and epidemiological knowledge on NREM parasomnia and SRDD, and to present the pathophysiological hypotheses underlying these nocturnal manifestations. Sleepwalking, sleep terror and confusional arousals are the three main presentations of NREM parasomnias and share common clinical characteristics. Parasomniac episodes generally occur 30minutes to three hours after sleep-onset, they are usually short, lasting no more than few minutes and involve non-stereotyped, clumsy behaviors with frequent amnesia. The prevalence of NREM parasomnia decreases from 15-30% in children to 2-4% in adults. Parasomniac episodes are incomplete awakening from the deepest NREM sleep and are characterized by a dissociated brain activity, with a wake-like activation in motor and limbic structures and a preserved sleep in the fronto-parietal regions. SRDD is a less known condition characterized by dramatic, often very long episodes with frequent aggressive and potentially dangerous behaviors. SRDD episodes frequently occur in quiet wakefulness before falling asleep. These dissociative manifestations are frequently observed in the context of psychological trauma. The pathophysiology of SRDD is poorly understood but could involve transient changes in brain connectivity due to labile sleep-wake boundaries in predisposed individuals. We hypothesize that SRDD and NREM parasomnia are forms of sleep-related dissociative states favored by a sleep-wake state dissociation during sleep-onset and awakening process, respectively.


Cavity architecture based modulation of ligand binding tunnels in plant START domains.
The Steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain represents an evolutionarily conserved superfamily of lipid transfer proteins widely distributed across the tree of life. Despite significant expansion in plants, knowledge about this domain remains inadequate in plants. In this work, we explore the role of cavity architectural modulations in START protein evolution and functional diversity. We use deep-learning approaches to generate plant START domain models, followed by surface accessibility studies and a comprehensive structural investigation of the rice START family. We validate 28 rice START domain models, delineate binding cavities, measure pocket volumes, and compare these with mammalian counterparts to understand evolution of binding preferences. Overall, plant START domains retain the ancestral α/β helix-grip signature, but we find subtle variation in cavity architectures, resulting in significantly smaller ligand-binding tunnels in the plant kingdom. We identify cavity lining residues (CLRs) responsible for reduction in ancestral tunnel space, and these appear to be class specific, and unique to plants, providing a mechanism for the observed shift in domain function. For instance, mammalian cavity lining residues A135, G181 and A192 have evolved to larger CLRs across the plant kingdom, contributing to smaller sizes, minimal STARTs being the largest, while members of type-IV HD-Zip family show almost complete obliteration of lipid binding cavities, consistent with their present-day DNA binding functions. In summary, this work quantifies plant START structural & functional divergence, bridging current knowledge gaps.


Effect of educational interventions on health in childhood: A meta-analysis of randomized controlled trials.
The purpose of this study was to summarize the evidences from randomized controlled trials (RCTs) investigating the effects of educational interventions in overweight/obesity childhood by using meta-analytic approach. PubMed, Embase, and the Cochrane Library databases were searched from the inception to April 2018. Weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) were used to measure the effects of educational interventions during childhood in the random-effects models. Thirty RCTs reporting data on 35,296 children were included in the meta-analysis. The summary WMD indicated that children received educational interventions had lower levels of body mass index (BMI) (WMD: -0.15; 95% CI: -0.24 to -0.05; P = .003), BMI z-score (WMD: -0.03; 95% CI: -0.05 to -0.02; P < .001), waist circumference (WMD: -0.97; 95% CI: -1.95 to -0.00; P = 0.050), triceps skinfold (WMD: -1.39; 95% CI: -2.41 to -0.37; P = .008), systolic blood pressure (WMD: -1.13; 95% CI: -2.20 to -0.07; P = .037), total cholesterol (WMD: -4.04; 95% CI: -7.18 to -0.90; P = .012), and triglyceride (WMD: -2.62; 95% CI: -4.33 to -0.90; P = .003). However, educational interventions were not associated with the levels of waist-to-hip ratio, diastolic blood pressure, high-density lipoprotein, and low-density lipoprotein. The study findings elucidate the positive effects of educational interventions on BMI, BMI z-score, waist circumference, triceps skinfold, systolic blood pressure, total cholesterol, and triglyceride.


Enhanced recovery of low concentration protein and peptide solutions on ultra-low binding microplates.
SiO2 Medical Products (SIO) developed PureWARE™ Ultra-Low Binding (ULB) plasma-treated microplates with the combined benefits of enhanced protein recovery and reduced extractables. This study demonstrates enhanced protein recoveries, but at ten-times lower protein concentration, or 0.1 nM, compared with a prior study. In addition, no significant effect on enhanced protein recovery of plasma-treated microplates was observed in a long-term stability study carried out for 26 months under ambient storage conditions. Furthermore, recovery of three different peptide solutions, in the concentration range of 1.5-12 nM, was also shown to be enhanced on plasma-treated microplates relative to standard polypropylene microplates.


An urgent need to include risk-benefit analysis in clinical trials investigating conjugated linoleic acid supplements in cancer patients.
Malnutrition and weight loss are common in patients with cancer, both factors could potentially affect the response and tolerance to treatment, decreased quality of life, and thus associate them with poor survival. Conjugated linoleic acid (CLA) is shown to have beneficial health effects in healthy and disease situations including chemoprotective properties in various experimental cancer models. However, the anticarcinogenic property of CLA in animal and tissue culture models could not be confirmed in the Netherlands Cohort Study on Diet and Cancer and a prospective cohort of Swedish women. Cancer patients are already at increased risk of anorexia and there are evidences that CLA suppresses appetite even in healthy individuals. Risk/benefit analysis of CLA supplementation has never been reported before and it is not clear whether any beneficial anti-tumor effect of CLA prevails over its anti-appetite and/or weight lowering side effect in these patients. I suggest that clinical trials investigating CLA supplements in cancer patients, measure appropriate variables such as food intake, weight, and appetite change to yield preliminary data for future trials. I also suggest that data from previous trials that have administered CLA supplements to cancer patients be re-analyzed retrospectively to attempt to find out any effect from routine nutritional measures such as weight, serum albumin and such as those.


Do pure squamous cell carcinomas and urothelial carcinomas have similar prognosis after radical cystectomy?
The purpose of this study was to evaluate the surgical treatment results of urothelial carcinoma (UC) and pure squamous cell carcinoma of the bladder (SCC). The records of 460 patients who have undergone radical cystectomy in our department between the years 1991 and 2011 were analyzed retrospectively, and 364 patients with UC and 60 patients with pure SCC were evaluated. Average ages of the patients with UC and SCC were 61.12 ± 8.9 and 59.38 ± 8.6 years, respectively (p = 0.902). UC group had 29 female patients, whereas SCC group had 9 female patients (p = 0.077). The mean follow-up periods were 26.09 ± 24.75 months for UC group and 22.23 ± 31.01 months for SCC group (p = 0.805). The incidence of organ-confined, extravesical, lymph node-positive diseases in UC and SCC cases was 48.9 and 32.2, 29.3 and 32.2 %, 21.8 and 35.6 %, respectively (p = 0.028). Five-year disease-specific survival (DSS) rates were 57.5 % in UC and 39.1 % in SCC group (p = 0.011). Five-year DSS rates were 81.2 % in UC and 75.0 % in SCC group in organ-confined disease (p = 0.534) and 28.2 % in UC and 40.9 % in SCC group in extravesical disease (p = 0.845). In lymph node-positive patients, DSS time was 20.9 ± 2.85 months in UC and 12.8 ± 2.07 months in SCC patients (p = 0.182). In multivariate analysis, pT stage (HR: 2.221; 95 % CI: 1.695-2.911) and lymph node involvement (HR: 2.863; 95 % CI: 1.819-4.509) were independently associated with DSS (p < 0.001), but histological subtype (HR: 1.423; 95 % CI: 0.798-2.538) was not a statistically significant factor (p = 0.232). Although pure SCC cases are diagnosed at advanced stages of the disease, UC and pure SCC cases have similar prognosis by stages. Lymph node involvement and stages are the most important prognostic factors after radical cystectomy.


Enhanced Recovery in Spine Surgery and Perioperative Pain Management.
Enhanced recovery after surgery is an interdisciplinary, multimodal approach to improve postoperative outcomes by applying multiple evidenced-based interventions. It has been adapted at multiple institutions for patients undergoing spine surgery to combat the rising rate of opioid consumption. Various preoperative, intraoperative, and postoperative pharmacologic and nonpharmacologic interventions have been introduced to augment patient care with the goal to decrease hospital length of stay and improve postoperative outcomes. Future studies will focus on health care-related quality of life outcomes to evaluate the effectiveness of enhanced recovery after surgery across various benchmarks.


Role of ascorbic acid in the modulation of inhibition of platelet aggregation by polymorphonuclear leukocytes.
We investigated the modulatory effect of ascorbate on the inhibition of platelet aggregation response by polymorphonuclear leukocytes (PMNs) and characterized the mechanism of the inhibitory response. PMNs have been reported to play a significant role in vascular homeostasis by releasing various factors including short-lived reactive oxygen species (ROS) and nitric oxide (NO). NO prevents the activation of circulating platelets and plays a significant role in hemostasis. In addition, PMNs also have the capacity to store very high concentrations of ascorbate. The physiological implications of storing such high concentrations of an antioxidant by a cell-releasing free radicals is unknown, viz. a viz. hemostatic regulation. ADP-induced aggregation in human, monkey and rat platelet-rich plasma (PRP) was monitored in the presence of PMNs treated with varying concentrations of ascorbate/dehydroascorbate. NO generation from rat and human PMNs treated with ascorbate was monitored on a FACS Calibur flow cytometer and intraplatelet cyclic guanosine 3',5'-monophosphate (cGMP) levels was also measured. PMNs induced a cell number and time-dependent inhibition of ADP-induced aggregation. The PMNs dependent inhibition was enhanced significantly at 30 min by ascorbate (300 microM). Ascorbate seemed to exert its effects through its oxidized product, dehydroascorbate, as the effects was prevented in the presence of D-glucose (10 mM). Dehydroascorbate elicited significant potentiation of the PMNs induced inhibitory responses and these effects were mediated by the release of NO and subsequent activation of platelet guanylyl cyclase. Flow cytometry experiments with human and rat PMNs confirmed the release of NO and the elevated platelet cGMP levels confirmed NO-mediated activation of guanylyl cyclase. Ascorbate in circulation seems to prevent the activation of platelets by enhancing the release of antiaggregatory NO, from neighbouring or cohabitant PMNs. The ascorbate effect is mediated through its conversion to dehydroascorbate, subsequently, gets taken up by the cell and converted back to ascorbate. Intracellular ascorbate potentiates the release of NO from the PMNs and subsequently activates guanylyl cyclase in the platelets.


Acid-assisted ultrasonic preparation of nitrogen-doped MXene quantum dots for the efficient fluorescence "off-on-off" detection of Zn(II) in water and oxalic acid in vegetables.
A novel fluorescence "off-on-off" probe was presented to detect Zn(II) and oxalic acid (OA) based on nitrogen-doped MXene quantum dots (N-MQDs), which were synthesized by an ultrasound approach at room temperature with nitric acid and ethylenediamine. These N-MQDs displayed small size (<10 nm), water dispersibility, and good photoluminescence. Furthermore, the N-MQDs showed an selective response towards Zn(II) through fluorescence enhancement, with a limit of detection (LOD) calculated as 0.127 μM in the linear range of 0-20 μM. Then, the fluorescence of N-MQDs/Zn(II) system could be selectively quenched after adding OA, with an effective response in the range from 0 to 20 μM (LOD: 0.883 μM). The fluorescence "turn-on" and "turn-off" properties of N-MQDs were resulted from the intramolecular charge transfer (ICT) of Zn(II) and the coordination between OA and Zn(II), respectively. This sensing platform was successfully applied for Zn(II) and OA detection in actual environmental and vegetable samples.


Primary malignant melanoma of the male urethra.
Primary malignant melanoma of the male urethra is a rare disease, with only 24 cases previously reported in the literature, including 1 black patient. We describe 2 additional patients with primary malignant melanoma of the urethra, one of whom was a black man. The literature is reviewed briefly and treatment recommendations are discussed.


Immunogenicity of fatty acid anilides in rabbits and the pathogenesis of the Spanish toxic oil syndrome.
Fatty acid anilides, the major xenobiotic found in the cooking oils responsible for the Spanish toxic oil syndrome, are immunogenic for rabbits as ascertained by a skin test reaction, the characterization of specific antibodies against anilides and the immunofluorescent detection of 'anilide dependent antigens' in tissue slices from treated animals.


Magnetic, but not non-magnetic, reduced graphene oxide in spinal cord increases nociceptive neuronal responsiveness.
The interference between external magnetic fields and neurophysiology is not new, however, the role of the neuronal magnetic field remains unclear. This study aimed at investigating a possible role of the neuronal magnetic field in nociception. Highly and poorly magnetic reduced graphene oxide (rGO) was injected intrathecally in rats. Nociceptive responsiveness was greater in rats that received highly magnetic-rGO in von Frey electronic or intraplantar capsaicin tests. Furthermore, in vitro experiments demonstrated that the number of KCl-responsive DRG-neurons was greater when treated with highly magnetic-rGO when compared with non-magnetic-rGO. Our data also suggested that the mechanism underlying the increased nociceptive responsiveness involves increased Ca2+v activity. Complementary experiments excluded the cytotoxic and inflammatory effects of the magnetic-rGO in neuronal responsiveness. These data suggest that the disturbance of the neuronal magnetic field in spinal cord increases nociceptive responsiveness, suggesting an importance of the magnetic component of the electromagnetic field in neuronal transmission.


The effect of bile salts on the formation and hydrolysis of cholesterol esters by rat liver enzymes.
To determine the effects of different bile salts on the enzymic esterification of cholesterol and the hydrolysis of cholesterol esters rat liver homogenates and rat liver microsomes were incubated with varying amounts of different bile salts. Bile salts inhibited the formation of radioactive cholesterol esters in incubations of either rat liver homogenates or rat liver microsomes containing [14C]cholesterol. Chenodeoxycholate, glycochenodeoxycholate and taurochenodeoxycholate were more potent inhibitors than their comparable cholate analogues. Bile salts stimulated the hydrolysis of cholesterol esters when incubation were carried out with the liver homogenates. The dihydroxy bile salts were again more potent in this regard than the trihydroxylated bile salts. When the effects of bile salts on cholesterol ester hydrolysis were studied in in vitro incubations of hepatic microsomes a biphasic mode of acion was observed. In the absence of Na+ or K+ bile salts stimulated the hydrolysis of cholesterol oleate. However, following the addition of either Na+ or K+ to the microsomal incubations, bile salts caused an inhibition of cholesterol ester hydrolysis. Since cholesterol esterification was also inhibited under these conditions a direct inhibitory effect (not attributable to enhanced hydrolase activity) of the bile salts on the formation of cholesterol esters by the microsomes was established. Furthermore, this inhibition takes place at the transacylation step involving the fatty acyl-CoA ester and the sterol. These results suggest that bile salts can significantly alter the cholesterol-cholesterol ester profile in the liver, and furthermore, that these effects may be influenced by small changes in the intracellular environment in the region where these reactions occur.


A survey of early-career child and adolescent psychiatrists: professional activities and perceptions.
To assess the career paths and work perceptions of early-career child and adolescent psychiatrists in the United States. Analysis of survey data of 392/797 (49.2%) of all U.S. child and adolescent psychiatrists graduating from training in 1996-1998 and on the mailing list of the American Academy of Child and Adolescent Psychiatry. Slightly more than half of those surveyed were women, and most were in their late thirties, white, married, and living in the geographic area in which they trained, with a median income for full-time workers between $121,000 and $150,000. Those with educational debt owed an average of $69,741. The sample was generally very satisfied with their work. They identified clinical work, variety, autonomy, and making a difference as the best aspects, and managed care, paperwork, and overwork as the least desirable aspects. The bulk of hours worked were in solo private practice, public sector, and group practice, with children and adolescents making up 73% of patients treated. The most common treatment modality was medication management. The present study uses a database approach to defining current practice and workforce issues among early-career child and adolescent psychiatrists. These data may facilitate objective discussion about public policies concerning workforce priorities, barriers, and facilitators to recruitment in this understaffed field.


A retrospective analysis of care in patients with dementia hospitalized at a tertiary medical center.
Hospitalization is an opportunity to address various aspects related to management of dementia, including the goals of care to avoid futile care. We studied the prevalence of these factors when patients with dementia are hospitalized. One hundred and thirty-one charts of patients with dementia admitted to a single university-based hospital were retrospectively reviewed. Data were collected and analyzed for age, gender, the severity of dementia, co-morbidities, co-existing vascular dementia, reversible causes of dementia, mental status scores, medications, consultations, procedures, complications, availability of advance directives, decision-maker, code status, and goals of care discussion. In patients with dementia, co-morbidities and vascular disease burden were frequent. When these patients were hospitalized, use of psychotropic medications, invasive procedures, and multi-specialty consultations was common. Tests of mental status, screening for reversible causes, and use of FDA-approved medications for dementia is less common. Despite the lack of advance directives, goals of care were infrequently discussed. When goals of care were discussed, proxy decision-maker preferred palliative care and long-term institutionalization on discharge. Goals of care and other aspects of management are not fully addressed in hospitalized patients with dementia.


Contrasting soil microbial responses to fertilization and tillage systems in canola rhizosphere.
Information regarding the simultaneous evaluation of tillage and fertilization on the soil biological traits in canola production is not available. Therefore, field experiments were conducted in 2007-2010 in a split plot based on randomized complete block design with three replications. Main plots consisted of conventional tillage (CT); minimum tillage (MT) and no tillage (NT). Six strategies of fertilization including (N1): farmyard manure (cattle manure); (N2): compost; (N3): chemical fertilizers; (N4): farmyard manure + compost; (N5): farmyard manure + compost + chemical fertilizers and (N6): control, were arranged in sub plots. Results showed that the addition of organic manure increased the soil microbial biomass. No tillage system increased microbial biomass compared to other tillage systems. The activities of all enzymes were generally higher in the N4 treatment. The activity of phosphatase and urease tended to be higher in the no tillage treatment compared to the CT and MT treatments.


Inhibition of redox/Fyn/c-Cbl pathway function by Cdc42 controls tumour initiation capacity and tamoxifen sensitivity in basal-like breast cancer cells.
We found that basal-like breast cancer (BLBC) cells use Cdc42 to inhibit function of the redox/Fyn/c-Cbl (RFC) pathway, which normally functions to convert small increases in oxidative status into enhanced degradation of c-Cbl target proteins. Restoration of RFC pathway function by genetic or pharmacological Cdc42 inhibition enabled harnessing of pro-oxidant effects of low µM tamoxifen (TMX) concentrations - concentrations utilized in trials on multiple tumour types - to suppress division and induce death of BLBC cells in vitro and to confer TMX sensitivity in vivo through oestrogen receptor-α-independent mechanisms. Cdc42 knockdown also inhibited generation of mammospheres in vitro and tumours in vivo, demonstrating the additional importance of this pathway in tumour initiating cell (TIC) function. These findings provide a new regulatory pathway that is subverted in cancer cells, a novel means of attacking TIC and non-TIC aspects of BLBCs, a lead molecule (ML141) that confers sensitivity to low µM TMX in vitro and in vivo and also appear to be novel in enhancing sensitivity to a non-canonical mode of action of an established therapeutic agent.


N-Acetyl-D-glucosamine decorated polymeric nanoparticles for targeted delivery of doxorubicin: Synthesis, characterization and in vitro evaluation.
A novel targeting drug delivery system containing poly(styrene-alt-maleic anhydride)58-b-polystyrene130 (P(St-alt-MA)58-b-PSt130) as a copolymer backbone, N-acetyl glucosamine (NAG) as a targeting moiety was designed and synthesized. The NAG grafted copolymer (NAG-P(St-alt-MA)58-b-PSt130) was characterized by FTIR and (1)H NMR. The NAG-P(St-alt-MA)58-b-PSt130 nanoparticles exhibited spherical shapes with an average diameter about 56.27±0.43 nm, low critical micelle concentration of 0.028 mg/mL, negative zeta potential -41.46±0.99 mV, high drug loading 25.83±1.09% and encapsulation efficiency 69.69±3.98%. In vitro cell cytotoxicity was conducted to confirm the safety of the NAG-P(St-alt-MA)58-b-PSt130 nanoparticles. Confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) results showed that the NAG targeting moiety enhanced the internalization and targeting ability of NAG-P(St-alt-MA)58-b-PSt130 nanoparticles. Anticancer activity toward MCF-7 cells and HT29 cells showed that DOX-loaded NAG-P(St-alt-MA)58-b-PSt130 nanoparticles exhibited a higher antitumor activity compared to DOX-loaded P(St-alt-MA)58-b-PSt130 nanoparticles, which could attribute to NAG receptor-mediated endocytosis. These results suggest that the biocompatible and non-toxic NAG-P(St-alt-MA)58-b-PSt130 nanoparticles may be used as an effective targeting drug delivery system for cancer therapy.


The effects of hormones on sex differences in infection: from genes to behavior.
Males of many species are more susceptible than females to infections caused by parasites, fungi, bacteria, and viruses. One proximate cause of sex differences in infection is differences in endocrine-immune interactions. Specifically, males may be more susceptible to infection than females because sex steroids, specifically androgens in males and estrogens in females, modulate several aspects of host immunity. It is, however, becoming increasingly more apparent that in addition to affecting host immunity, sex steroid hormones alter genes and behaviors that influence susceptibility and resistance to infection. Thus, males may be more susceptible to infection than females not only because androgens reduce immunocompetence, but because sex steroid hormones affect disease resistance genes and behaviors that make males more susceptible to infection. Consideration of the cumulative effects of sex steroid hormones on susceptibility to infection may serve to clarify current discrepancies in the literature and offer alternative hypotheses to the view that sex steroid hormones only alter susceptibility to infection via changes in host immune function.


Mapping the effects of motor cortex stimulation on single neurons in the dorsal column nuclei in the rat: direct responses and afferent modulation.
The major aim of this study was to define the topography of descending motor cortical influences on the dorsal column nuclei of the rat. A total of 1442 single neurons were recorded throughout the rat cuneate (Cu) or external cuneate (ECu) nuclei and classified according to their: 1) location within the nuclei, 2) receptive fields, and 3) response to standardized deep layer microstimulation in the forelimb area of the motor (MI) cortex. Excitatory neuronal responses to this MI cortical stimulation ranged in latency from 2-28 msec, with 80% of responses in the 4-12 msec range. Overall, the rostral extremity of the Cu (0.5-1.0 mm rostral to the obex), and the ECu contained the highest percentage of recorded neurons responding to the MI cortical stimulation (61%). By contrast, only 11% responded in the middle subregion of the Cu (+0.4 to -0.9 mm relative to the obex), and 28% responded in the caudal-most subregion (1.0-2.0 mm caudal to obex). A similar paradigm was used to investigate the topography of MI corticofugal modulation of afferent transmission through the Cu and ECu. The MI cortical stimulation was used as a conditioning (C) stimulus in a condition-test (C-T) paradigm in which the test (T) stimulus was standardized mechanical vibration of digit No. 4 of the contralateral forepaw. A total of 30 cells from different subregions were analyzed by measuring the averaged evoked unit responses to the T-stimuli, and plotting them as a function of C-T intervals from 0-50 msec.(ABSTRACT TRUNCATED AT 250 WORDS)


Event-related brain potentials during the monitoring of speech errors.
When we perceive speech, our goal is to extract the meaning of the verbal message which includes semantic processing. However, how deeply do we process speech in different situations? In two experiments, native Dutch participants heard spoken sentences describing simultaneously presented pictures. Sentences either correctly described the pictures or contained an anomalous final word (i.e. a semantically or phonologically incongruent word). In the first experiment, spoken sentences were task-irrelevant and both anomalous conditions elicited similar centro-parietal N400s that were larger in amplitude than the N400 for the correct condition. In the second experiment, we ensured that participants processed the same stimuli semantically. In an early time window, we found similar phonological mismatch negativities for both anomalous conditions compared to the correct condition. These negativities were followed by an N400 that was larger for semantic than phonological errors. Together, these data suggest that we process speech semantically, even if the speech is task-irrelevant. Once listeners allocate more cognitive resources to the processing of speech, we suggest that they make predictions for upcoming words, presumably by means of the production system and an internal monitoring loop, to facilitate lexical processing of the perceived speech.


Identification and molecular cloning of a gene encoding Phospholipase A2 (plaA) from Aspergillus nidulans.
The plaA gene encoding a protein that contains the cytosolic Phospholipase A(2) (cPLA(2)) motif is cloned for the first time from the filamentous fungus, Aspergillus nidulans. The translated 837 amino acid protein product of plaA comprises conserved lipase regions that are present in most mammalian cPLA(2) homologs. High expression of plaA was observed in glucose-lactose medium by Northern blot analyses. Deletion mutants of plaA grew and formed conidia similar to the wild-type strain, but showed decreased PLA(2) activity. Expression of the N-terminal truncated form of plaA in yeast cells resulted in increased Ca(2+)-dependent PLA(2) activity with (14)C-labeled phosphatidylcholine (PC) and phosphatidylethanolamine (PE) as substrates, compared with vector-transformed cells. In conclusion, we have identified and cloned a phospholipid-hydrolyzing novel cPLA(2) protein from A. nidulans for the first time.