Mother-Grandmother and Mother-Father Coparenting Across Time among Mexican-Origin Adolescent Mothers and Their Families.
The current study examined mothers' reports of coparenting relationship dynamics (i.e., conflict, communication) within and between mother-father and mother-grandmother subsystems from 10 months post-partum to 5 years post-partum among 178 Mexican-origin teen mothers (M age = 16.78 years; SD = 1.00). Specifically, within subsystems, more frequent mother-father coparenting conflict was associated with less frequent mother-father coparenting communication from 10 months to 5 years post-partum, and more frequent mother-father coparenting communication was associated with less frequent mother-father conflict from 3 to 4 years post-partum. Further, more frequent mother-grandmother coparenting communication was associated with less frequent mother-grandmother conflict from 10 months to 2 years post-partum. Regarding relations across subsystems, more frequent mother-father coparenting conflict was associated with more frequent mother-grandmother conflict from 10 to 24 months post-partum, as well as from 3 to 4 years post-partum. Findings have implications for future interventions focused on coparenting relationships within the context of adolescent parenthood.


Light-induced formation of the 410 nm intermediate from reconstituted bacteriorhodopsin.
Light-induced formation of the 410 nm intermediate was investigated with reconstituted bacteriorhodopsin. Only bacteriorhodopsin with all-trans retinal formed the 410 nm intermediate in response to light excitation. In equilibrium in the dark, both native and reconstituted bacteriorhodopsin contained about equal amounts of the all-trans and 13-cis forms over a wide range of temperature.


Micellar Effects on Photoinduced Electron Transfer in Aqueous Solutions Revisited: Dramatic Enhancement of Cage Escape Yields in Surfactant Ru(II) Diimine Complex/[Ru(NH3)6](2+) Systems.
The effect of cationic micelle incorporation on light induced electron transfer, charge separation and back electron transfer between an aqueous electron donor, [Ru(NH3)6](2+), and a series of Ru(II) diimine complex chromophores/acceptors, is presented. The chromophores have the general formula [(bpy)2Ru(LL)](2+) (LL = bpy; 4-R-4'-methyl-2,2'-bpy, R = pentyl (MC5), terdecyl (MC13), heptadecyl (MC17); 4,4'-di(heptadecyl)-2,2'-bpy (DC17)). Of the five chromophores, the MC13, MC17, and DC17 complexes associate with the added micelle forming surfactant, cetyltrimethylammonium bromide (CTAB). Quenching of the luminescence of the bpy and MC5 complexes by [Ru(NH3)6](2+) is unaffected by addition of surfactant, while rate constants for quenching of the MC13 and MC17 complexes are decreased. Cage escape yields following photoinduced electron transfer to generate [(bpy)2Ru(LL)](+) and [Ru(NH3)6](3+) are approximately 0.1 for all the water-soluble chromophores (excluding DC17) in the absence of added CTAB. In the presence of surfactant, the cage escape yields dramatically increase for the MC13 (0.4) and MC17 (0.6) complexes, while remaining unchanged for [Ru(bpy)3](2+) and the MC5 complex. Back electron transfer of the solvent separated ions is also strongly influenced by the presence of surfactant. For the MC13 and MC17 complexes, back electron transfer rate constants decrease by factors of 270 and 190, respectively. The MC5 complex exhibits two component back electron transfer, with the fast component having a rate constant close to that in the absence of surfactant and a slow component nearly 200 times smaller. Results are interpreted in terms of the partitioning of the 2+ and 1+ forms of the chromophores between aqueous and micellar phases. The extended lifetimes of the radical ions may prove useful in coupling the strong reductants formed to kinetically facile catalysts for reduction of water to hydrogen.


Effects of PPARγ Ligands on Leukemia.
Peroxisome proliferator-activated receptors (PPARs) and retinoic acid receptors (RARs), members of the nuclear receptor superfamily, are transcription factors that regulate a variety of important cellular functions. PPARs form heterodimers retinoid X receptor (RXR), an obligate heterodimeric partner for other nuclear receptors. Several novel links between retinoid metabolism and PPAR responses have been identified, and activation of PPAR/RXR expression has been shown to increase response to retinoids. PPARγ has emerged as a key regulator of cell growth and survival, whose activity is modulated by a number of synthetic and natural ligands. While clinical trials in cancer patients with thiazolidinediones (TZD) have been disappointing, novel structurally different PPARγ ligands, including triterpenoids, have entered clinical arena as therapeutic agents for epithelial and hematopoietic malignancies. Here we shall review the antitumor advances of PPARγ, alone and in combination with RARα ligands in control of cell proliferation, differentiation, and apoptosis and their potential therapeutic applications in hematological malignancies.


[A new protocol for use and storage of tooth-brushing material for school children].
The aim of this study was to evaluate the storage and distribution of toothbrushing material for school children. Twenty individuals responsible for the collective oral hygiene of school children from Bauru - SP and São José dos Campos - SP participated in the first stage of the study, answering 2 questionnaires about five different kits for use by school children. The statistical analysis was performed using Wilcoxon (p<0,05). In the second stage, the amount of toothpaste or liquid cleanser applied to the toothbrush by 178 school children aged 4 to 8 years from 2 cities from the state of São Paulo (Bauru e Bariri) was weighed using a portable balance. The statistical analysis was obtained by using Pearson's correlation coefficient and analysis of covariance (p <0,05). Kit 5 obtained levels of satisfaction and high satisfaction when compared with the others kits (1 - 4). The school children from Bauru (0.41g) used smaller amounts of toothpaste than the school children from Bariri (0.48g). The average of the amount of liquid cleanser applied by the sample was 0.15g. The "drop technique" (liquid cleanser) was considered practical for dispensing a small, standardized quantity of the product. Kit 5 was considered a good alternative for establishing a collective oral health protocol in the Brazilian health system.


A successful cross-training experience of reference service at UCLA.
This paper describes a successful cross-training and reference librarian exchange experience involving two librarians at UCLA, one based at the Louise M. Darling Biomedical Library and the other based at the College Library, which primarily serves undergraduates. The experience has increased the reference skills and expertise of both librarians by introducing them to new sets of reference tools and databases, and has broadened their network of colleagues within the UCLA Library system. The participating libraries have also benefited from the exchange, and the program is expanding to include other UCLA libraries.


Is molecular oxygen, O(2), the reactive radical behind oxidations of (aut)oxidable agents to which the bases of DNA belong?
The transfer of charges to reducible oxygen plays a basic role in the supply of energy to living organisms. These electron transfer (ET) reactions may be performed by selenium (Se) enzymes and autoxidable agents. Among the molecules which have satisfactory structures for this purpose are (hypo)xanthine, dopamine (DA), serotonin, arginine, creatine, thyroid hormones T(2)/T(3)/T(4) and the bases of DNA. Single-strand DNA breaks may be initiated by these reactions to yield the bases for the transfer of charges. But a high rate of DNA single-strand breaks may be caused by destructive oxidations. If the activity of the O(2) protective enzymes (Se enzymes such as gluthatione peroxidase (Gpx), superoxide dismutase (SOD) and catalase) is limited, the oxygen species H(2)O(2), O(2)(-) and OH generate free O(2). I believe that randomized oxidations are performed by the radical O(2) (two unshared orbitals) when it is not enzyme protected. Among the substances exposed to oxidation are the autoxidable agents. Are the bases of DNA and RNA to be included in these, taking part in ET reactions?


The short-latency respiratory response to sudden withdrawal of hypercapnia and hypoxia in man.
Five healthy young male subjects were maintained in a state of mild asphyxia (PA, CO2 approximately 45 torr, 6.0 kPa, PA, O2 approximately 50 torr, 6.6 kPa), i.e. with moderately strong drives from both arterial and intracranial chemoreceptors VT, TT and TI were recorded and V and TE derived breath by breath. The arterial chemoreceptor component was briefly and abruptly reduced, perhaps silenced, by two separate procedures, each repeated twenty-four times on each subject: B, removal of hypercapnia (two breaths hypoxia with PI, CO2 = 0 through a separate inspiratory line) and C, removal of asphyxia (two breaths O2). In control tests, A, the maintenance mixture was replaced by an identical mixture, using an identical manipulation. For each subject means of B and C were compared with means of A and with each other. Quick reflex changes (first three breaths) in V, VT and TE in tests B were not appreciably different from those in tests C in any subject; changes in TI were minimal in all. Thus removal of only the hypercapnic component of the arterial chemoreflex drive appears to be as efficient as the removal of both components simultaneously.


A Phenotypic and Genotypic Evaluation of Developmental Toxicity of Polyhexamethylene Guanidine Phosphate Using Zebrafish Embryo/Larvae.
Polyhexamethylene guanidine-phosphate (PHMG-P), a guanidine-based cationic antimicrobial polymer, is an effective antimicrobial biocide, potent even at low concentrations. Due to its resilient bactericidal properties, it has been used extensively in consumer products. It was safely used until its use in humidifiers led to a catastrophic event in South Korea. Epidemiological studies have linked the use of PHMG-P as a humidifier disinfectant to pulmonary fibrosis. However, little is known about its harmful impacts other than pulmonary fibrosis. Thus, we applied a zebrafish embryo/larvae model to evaluate developmental and cardiotoxic effects and transcriptome changes using RNA-sequencing. Zebrafish embryos were exposed to 0.1, 0.2, 0.3, 0.4, 0.5, 1, and 2 mg/L of PHMG-P from 3 h to 96 h post fertilization. 2 mg/L of PHMG-P resulted in total mortality and an LC50 value at 96 h was determined at 1.18 mg/L. Significant developmental changes were not observed but the heart rate of zebrafish larvae was significantly altered. In transcriptome analysis, immune and inflammatory responses were significantly affected similarly to those in epidemiological studies. Our qPCR analysis (Itgb1b, TNC, Arg1, Arg2, IL-1β, Serpine-1, and Ptgs2b) also confirmed this following a 96 h exposure to 0.4 mg/L of PHMG-P. Based on our results, PHMG-P might induce lethal and cardiotoxic effects in zebrafish, and crucial transcriptome changes were linked to immune and inflammatory response.


Qualitative and Quantitative Analysis of the Immune Synapse in the Human System Using Imaging Flow Cytometry.
The immune synapse is the area of communication between T cells and antigen-presenting cells (APCs). T cells polarize surface receptors and proteins towards the immune synapse to assure a stable binding and signal exchange. Classical confocal, TIRF, or super-resolution microscopy have been used to study the immune synapse. Since these methods require manual image acquisition and time-consuming quantification, the imaging of rare events is challenging. Here, we describe a workflow that enables the morphological analysis of tens of thousands of cells. Immune synapses are induced between primary human T cells in pan-leukocyte preparations and Staphylococcus aureus enterotoxin B (SEB)-loaded Raji cells as APCs. Image acquisition is performed with imaging flow cytometry, also called In-Flow microscopy, which combines features of a flow cytometer and a fluorescence microscope. A complete gating strategy for identifying T cell/APC couples and analyzing the immune synapses is provided. As this workflow allows the analysis of immune synapses in unpurified pan-leukocyte preparations and hence requires only a small volume of blood (i.e., 1 mL), it can be applied to samples from patients. Importantly, several samples can be prepared, measured, and analyzed in parallel.


Mdr2 (Abcb4)-/- mice spontaneously develop severe biliary fibrosis via massive dysregulation of pro- and antifibrogenic genes.
Mdr2 (Abcb4)-/- mice develop hepatic lesions resembling primary sclerosing cholangitis. Our aim was to characterize the evolution of fibrosis in Mdr2-/- mice. Mdr2-/-mice and their wild-type littermates were sacrificed at 2, 4 and 8 weeks after birth. Hepatic collagen was determined biochemically. Fibrosis related transcript levels were quantified from livers by real-time RT-PCR, and MMP activities determined by substrate assays. Liver histology was assessed by connective tissue staining and immunohistochemistry for alpha-smooth muscle actin (alpha-SMA). Mdr2-/- mice demonstrated a time-dependent increase of relative and total hepatic collagen (fivefold at 8 weeks, compared to wildtype controls), and maximal alpha-SMA immunoreactivity at 4 weeks. Compared to wildtype controls profibrogenic mRNA levels for procollagen alpha1(I), TGFbeta1, TGFbeta2, MMP-2 and -13, TIMP-1, PDGFbeta receptor, and PAI-1 were upregulated up to 27-fold. Most transcripts peaked at 4 weeks, but procollagen alpha1(I) mRNA increased steadily, TIMP-1 mRNA was constantly elevated (20-fold), MMP-13 mRNA was suppressed and interstitial collagenase and gelatinase activities were downregulated. Mdr2-/- mice spontaneously progress to severe biliary fibrosis. This is due to a characteristic temporal pattern of upregulated profibrogenic and downregulated fibrolytic genes and activities. These mice are an attractive model to test potential antifibrotics for the treatment of (biliary) liver fibrosis.


Time to invest in developing community mental health services.
To report on the evaluation of publicly funded community mental health services in two New South Wales health districts. Qualitative and quantitative data from 28 publicly funded adult community mental health teams in two NSW health districts were gathered using structured interviews, benchmarking surveys, focus groups and online questionnaires. The community mental health services studied lacked a coherent strategic and recovery oriented framework or model of care for service delivery. There was evidence of poor role definition at the team level, resulting in duplication and inefficiency. There were inadequate staffing levels for stated objectives, a lack of training and continuing education in evidence based intervention, poor consumer and family participation in service design, and no development and monitoring of meaningful outcome measures. This review and benchmarking study highlights the need for mental health policy implementation to be further supported with: development of a service delivery framework outlining essential components of a specialist community mental health system; operational guidance to enable effective team specialisation in accordance with research; investment in practitioner training to support the development of evidence based practice; and processes to ensure effective consumer and carer participation in developing recovery oriented services.


High-performance capillary electrophoresis to determine intact keratan sulfate and hyaluronic acid in animal origin chondroitin sulfate samples and food supplements.
Chondroitin sulfate is extracted from animal cartilaginous tissues and is commercialized as active principle against osteoarthritis. Its biological activity depends on its purity grade and could be altered by the presence of other glycosaminoglycans like keratan sulfate that could be contemporarily extracted from animal tissues or like hyaluronic acid that, instead, is added on purpose in food supplements. Although numerous methods are reported in literature for quality control analyses of chondroitin sulfate, few of them are able to detect other glycosaminoglycans. In this paper, for the first time, a new high-performance CE method was set up to quantify the chondroitin sulfate, the eventual keratan sulfate, and hyaluronic acid as intact chains: five chondroitin sulfate standards and 13 animal origin samples or food supplements from six different suppliers were analyzed. The new method was able to determine keratan sulfate similarly to a previously reported high-performance anion-exchange chromatography method, but in addition it showed the advantage to determine also the hyaluronic acid as never reported before.


In vitro blood distribution and plasma protein binding of the tyrosine kinase inhibitor imatinib and its active metabolite, CGP74588, in rat, mouse, dog, monkey, healthy humans and patients with acute lymphatic leukaemia.
To determine blood binding parameters of imatinib and its metabolite CGP74588 in humans and non-human species. The blood distribution and protein binding of imatinib and CGP74588 were determined in vitro using (14)C labelled compounds. The mean fraction of imatinib in plasma (f(p)) was 45% in dog, 50% in mouse, 65% in rat, 70% in healthy humans and up to 92% in acute lymphatic leukaemia (AML) patients. Similarly, f(p) for CGP74588 was low in dog and monkey (30%), higher in rat, mouse and humans (70%) and highest in some AML patients (90%). The unbound fraction of imatinib and CGP74588 in plasma was lower in rat, mouse, healthy humans and AML patients (2.3-6.5% at concentrations < or = 5000 ng ml(-1)) compared to monkey and dog (7.6-19%). Both compounds displayed high binding to human alpha(1)-acid glycoprotein. AML patients had a reduced haematocrit and showed greatest variability in their blood binding parameters. Imatinib and CGP74588 displayed very similar blood binding parameters within all species/groups investigated. The five species clustered into two distinct groups with rat, mouse and humans being clearly different from dog and monkey. For both compounds, higher protein binding was associated with a decreased partitioning into blood cells.


Investigating compensation and recovery of fathead minnow (Pimephales promelas) exposed to 17alpha-ethynylestradiol with metabolite profiling.
1H NMR spectroscopy was used to profile metabolite changes in the livers of fathead minnows (Pimephales promelas) exposed to the synthetic estrogen 17alpha-ethynylestradiol (EE2) via a continuous flow water exposure. Fish were exposed to either 10 or 100 ng EE2/L for 8 days, followed by an 8 day depuration phase. Livers were collected after days 1, 4, and 8 of the exposure, and at the end of the depuration phase. Analysis of polar extracts of the liver revealed a greater impact of EE2 on males than females, with metabolite profiles of the former assuming similarities with those of the females (i.e., feminization) early in the exposure. Biochemical effects observed in the males included changes in metabolites relating to energetics (e.g., glycogen, glucose, and lactate) and liver toxicity (creatine and bile acids). In addition, amino acids associated with vitellogenin (VTG) synthesis increased in livers of EE2-exposed males, a finding consistent with increased plasma concentrations of the lipoprotein in the fish. Using partial least-squares discriminant analysis (PLS-DA), the response trajectories of the males at both exposure concentrations were compared. This revealed an apparent ability of the fish to compensate for the presence of EE2 later in the exposure, and to partially recover from its effects after the chemical was removed.


Microbiota in obesity: interactions with enteroendocrine, immune and central nervous systems.
Western diets, with high consumption of simple sugars and saturated fats, contribute to the rise in the prevalence of obesity. It now seems clear that high-fat diets cause obesity, at least in part, by modifying the composition and function of the microorganisms that colonize in the gastrointestinal tract, the microbiota. The exact pathways by which intestinal microbiota contribute to obesity remain largely unknown. High-fat diet-induced alterations in intestinal microbiota have been suggested to increase energy extraction, intestinal permeability and systemic inflammation while decreasing the capability to generate obesity-suppressing short-chain fatty acids. Moreover, by increasing systemic inflammation, microglial activation and affecting vagal nerve activity, 'obese microbiota' indirectly influence hypothalamic gene expression and promote overeating. Because the potential of intestinal microbiota to induce obesity has been recognized, multiple ways to modify its composition and function are being investigated to provide novel preventive and therapeutic strategies against diet-induced obesity.


Modifications of fatty acids profile, lipid peroxidation and antioxidant capacity in raw and cooked rabbit burgers added with ginger.
Effects of ginger powder were evaluated on fatty acid (FA) profile, lipid peroxidation (TBARS) and antioxidant capacity (ABTS, DPPH and FRAP) of rabbit burgers. Burgers were manufactured as control samples (only meat) and two additions of ginger powder (1% and 2%) and stored raw at 4°C for 7days. At day 1, 4 and 7 of storage burgers were analysed both as raw and cooked. Ginger powder affected all the tested parameters; both PUFAω3 and PUFAω6 were incremented in raw and cooked samples leading to decreased atherogenicity and thrombogenicity indexes and increased hypo/hypercholesterolemic index and peroxidability index. Lipid peroxidation values of raw and cooked burgers added with ginger were lower than control burgers, at the same time, ABTS, DPPH and FRAP values were incremented by the addition of ginger powder. The results obtained demonstrate the antioxidant capacity of ginger powder as rabbit meat products additive and highlight the capacity of this spice to maintain its characteristics after burgers' cooking.


Characterization and intracellular localization of the Rok1 protein involved in yeast cell division.
The ROK1 gene is essential for the cell cycle progression in Saccharomyces cerevisiae. ROK1 has been predicted to encode an ATP-dependent RNA helicase of the DEAD-box family. We have analyzed the ROK1 gene expression both at the protein and RNA levels. Polyclonal antibodies were raised against trpE::rok1 hybrid proteins and were affinity purified by using lacZ::rok1 hybrid proteins. Western blot experiments using anti-Rok1 antibodies revealed a single protein band of 64 kDa which is an expected size from the Rok1 amino acid sequence. Indirect immuno-fluorescence showed that the Rok1 protein is localized predominantly to the cytoplasm of the vegetatively growing cells. We have detected immunocross-reactive homologs of Rok1p in Candida albicans and Drosophila melanogaster.


3-Chloro-6-[2-(cyclo-pentyl-idene)hydrazin-1-yl]pyridazine.
The asymmetric unit of the title compound, C(9)H(11)ClN(4), contains two virtually planar mol-ecules that differ in conformation about the bond connecting the hydrazine and pyridazine units. The 3-chloro-6-hydrazinylpyridazine and cyclo-pentane groups are oriented at dihedral angles of 4.5 (3) and 8.8 (4)° in the two mol-ecules. In the crystal, the mol-ecules form a one dimensional polymeric structure extending along the a axis via N-H⋯N hydrogen bonds. The crystal stucired was an inversion twin [ratio of the twin domains = 0.73 (9):0.27 (9)].


Spinal cord injury/dysfunction and medication management: a qualitative study exploring the experiences of community-dwelling adults in Ontario, Canada.
To explore the attitudes, beliefs and experiences pertaining to the management of prescribed and unprescribed medications among community-dwelling adults with spinal cord injury/dysfunction (SCI/D) in Ontario, Canada. In-depth semi-structured interviews were conducted by telephone. Each interview was audio-recorded, transcribed verbatim and analyzed using inductive thematic analysis. Of the 19 participants, 11 were male and 8 were female, with an age range from 36 to 76 years; 14 participants had traumatic SCI and 5 had non-traumatic spinal cord dysfunction. All but three participants were taking five or more medications, including prescription medications, over-the-counter medications and natural health products. The three main themes identified were: disruptive nature of medications, fear of negative outcomes and self-management: playing a critical role. Medication management is a complex, multifaceted and non-linear process. Persons with SCI/D described experiences with medication-taking that are not well understood by current medication management frameworks. Thus, it is essential to broaden our lens and situate persons with SCI/D medication-taking experiences within self-management frameworks to allow for a more comprehensive and reflective understanding of their experiences. Based on the findings from this study, recommendations for future research, practice and policy have been suggested.IMPLICATIONS FOR REHABILITATIONPersons with spinal cord injury/dysfunction identified numerous challenges and concerns with medication use post-injury.Educational medication management programs should be implemented post-discharge to improve the state of knowledge around medications (indication, side effects, strategies for taking medications) and how to optimize medication management.In order to optimize experiences and outcomes, there is a need for explicit and ongoing discussions around medication management between persons with spinal cord injury/dysfunction and their healthcare providers.


Bacteriophage typing and antibiotic sensitivity pattern of Staphylococcus aureus from clinical specimen in and around Solapur (South Maharashtra).
Two hundred and eighty nine strains of Staphylococcus aureus isolated from pus and wound swabs (149), blood (36), urine (28), sputum (14), stool (12), throat swab (9) and CSF (4) were subjected for bacteriophage typing and antibiotic susceptibility pattern. 113 (39.11%) strains were typable. Among the typable strains, 16 (5.53%) belonged to phage group I, 33 (11.41%) strains belonged to phages group II, 38 (13.14%) belonged to phage group III, 26 (8.99%) strains belonged to the phages which have not been allocated to any group (Miscellaneous group) 176 (60.89%) strains were untypable. Only one (0.34%) strain was sensitive to all the drugs tested. Almost all the isolates were resistant to Ampicillin and Tobramycin (99.3% each). 286 (98.96%) strains were found to be resistant to Penicillin and Erythromycin followed by Kanamycin 272 (94.11%) and Gentamicin 263 (91.3%). 113 (39.1%) strains were Methicillin resistant Staphylococcus aureus (MRSA). All MRSA strains were resistant to all drugs tested except vancomycin. Resistance to most of the commonly used antimicrobial agents indicates a need to replace these drugs with other agents and maintenance of surveillance to detect changing patterns of resistance.


Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukrainian population.
Metagenomic studies confirm that obesity is associated with a composition of gut microbiota. There are some controversies, however, about the composition of gut microbial communities in obese individuals in different populations. To examine the association between body mass index and microbiota composition in Ukrainian population, fecal concentrations of Bacteroidetes, Firmicutes, Actinobacteria and Firmicutes/Bacteroidetes (F/B) ratio were analyzed in 61 adult individuals. The relative abundance of Actinobacteria was small (5-7%) and comparable in different BMI categories. The content of Firmicutes was gradually increased while the content of Bacteroidetes was decreased with increasing body mass index (BMI). The F/B ratio also raised with increasing BMI. In an unadjusted logistic regression model, F/B ratio was significantly associated with BMI (OR = 1.23, 95% CI 1,09-1,38). This association continued to be significant after adjusting for confounders such as age, sex, tobacco smoking and physical activity (OR = 1.33, 95% CI 1,11-1,60). The obtained data indicate that obese persons in Ukraine adult population have a significantly higher level of Firmicutes and lower level of Bacteroidetes compared to normal-weight and lean adults.


Pilots' mental workload prediction based on timeline analysis.
The aircraft cockpit is a highly intensive human-computer interaction system, and its design directly affects flight safety. To optimize the display interface design in complex flight tasks, the present study aimed to propose a dynamic conceptual framework and a timeline task analysis method for the quantization of the dynamic time effect of mental workload and the influencing factors of task types in the mental workload prediction model. The multi-factor mental workload prediction model based on attention resource allocation was integrated to establish the dynamic prediction model of mental workload. The ergonomics simulation experiment was carried out by recording the data on the performance of embedded subtasks, National Aeronautics and Space Administration-Task Load Index (NASA-TLX) subjective evaluation, and eye tracking. The results indicated that the prediction model had a good prediction accuracy and effectiveness under different simulated interfaces and complex tasks, and the real-time monitoring of pilots' mental workload state was realized. In conclusion, the prediction model and the experimental method could be applied to avoid the overload of the pilot throughout the flight phase by optimizing the display interface and adjusting the flight task.


Spin liquid and infinitesimal-disorder-driven cluster spin glass in the kagome lattice.
The interplay between geometric frustration (GF) and bond disorder is studied in the Ising kagome lattice within a cluster approach. The model considers antiferromagnetic short-range couplings and long-range intercluster disordered interactions. The replica formalism is used to obtain an effective single cluster model from where the thermodynamics is analyzed by exact diagonalization. We found that the presence of GF can introduce cluster freezing at very low levels of disorder. The system exhibits an entropy plateau followed by a large entropy drop close to the freezing temperature. In this scenario, a spin-liquid (SL) behavior prevents conventional long-range order, but an infinitesimal disorder picks out uncompensated cluster states from the multi-degenerate SL regime, potentializing the intercluster-disordered coupling and bringing the cluster spin-glass state. To summarize, our results suggest that the SL state combined with low levels of disorder can activate small clusters, providing hypersensitivity to the freezing process in geometrically frustrated materials and playing a key role in the glassy stabilization. We propose that this physical mechanism could be present in several geometrically frustrated materials. In particular, we discuss our results in connection with the recent experimental investigations of the Ising kagome compound Co3Mg(OH)6Cl2.


Prolonged Capecitabine Chemotherapy Following Capecitabine and Oxaliplatin (CAPOX) Regimen Chemotherapy Failed to Improve Survival of Stage III Colorectal Cancer After Radical Resection.
BACKGROUND Colorectal cancer (CRC) is considered to be a worldwide health problem because of its increasing incidence and prevalence. Surgery offers an opportunity for cure, but the postoperative recurrence rate is still high despite the advancement of chemotherapy. This study aimed to assess the efficacy and safety of prolonged capecitabine chemotherapy following CAPOX chemotherapy for stage III CRC after radical surgery. MATERIAL AND METHODS This study included 212 patients with stage III CRC undergoing open radical surgery from July 2010 to June 2015. Among those patients, 104 patients received prolonged capecitabine chemotherapy (prolonged group) following 8 cycles of CAPOX regimen chemotherapy, while the other 108 patients (control group) received no prolonged chemotherapy. The prolonged chemotherapy consisted of capecitabine (1000 mg/m² per day for 2 weeks) and was repeated every 3 weeks for 8 cycles at most. Long-term survival and toxicities were retrospectively compared. RESULTS Patient characteristics did not differ between the 2 groups. For all patients, no significant difference was found in the 3-year disease-free survival (DFS) (P=0.7775) or 3-year overall survival (OS) rates between the 2 groups (P=0.5787). The prolonged group had significantly higher frequency of hand-foot syndrome (P=0.0267) and paresthesia (P=0.0164). In further subgroup analyses, no benefit for 3-year DFS or 3-year OS of prolonged capecitabine chemotherapy was found in colon cancer or rectal cancer. CONCLUSIONS Prolonged capecitabine chemotherapy following CAPOX regimen chemotherapy failed to improve the survival of patients with stage III CRC after radical surgery.


Cationic Polyarginine Conjugated Mesoporous Bioactive Glass Nanoparticles with Polyglycerol Coating for Efficient DNA Delivery.
Mesoporous bioactive glass (MBG) is a type of material with high biological activity and excellent biocompatibility. Because of its high specific surface area and adjustable surface morphology, MBG is usable for loading and delivering molecules. In our previous report, MBG particles were used as gene vectors and showed good transfection rate. In this paper, MBG, prepared through a sacrificial liquid template method in sol–gel process, was covered with polyglycerol (PG) and the resulting MBG-PG was further functionalized with octaarginine (Arg8. More specifically, MBG-PG-Arg8 particles were synthesized by PG functionalization of MBG through ring-opening polymerization of glycidol on the MBG surface, followed by multistep organic transformations (–OH→ –OTs (tosylate)→ –N3 in the PG layer and click conjugation of the Arg8 terminated with propargyl glycine. MBG-PG-Arg8 was successfully taken up by cells more efficiently due to the cellpenetrating property of Arg8, and thus showed higher plasmid DNA loading and cell transfection efficiency than MBG modified with amino groups. This novel arginine-functionalized MBG may be a good candidate as a vector for gene delivery with higher efficiency.


Relationship of triglyceride accumulation to insulin clearance and hormonal responsiveness in bovine hepatocytes.
The accumulation of triglycerides in the liver has been associated with reduced hepatic function; however, direct evidence that fat accumulation causes decreased liver function is lacking. Hepatocyte monolayers isolated from ruminating calves with an initial low triglyceride concentration were either loaded or not loaded with triglycerides by incubation with 1.5 or 0 mM exogenous nonesterified fatty acids from 12 to 48 h after plating. Basal rates of synthesis of albumin and protein were not affected by triglycerides in the cell. Inclusion of insulin and glucagon from 12 to 72 h after plating increased rates of albumin and protein synthesis. Hepatocytes loaded with triglycerides were less sensitive to the hormonal stimulation of albumin and protein synthesis than were normal hepatocytes. Insulin clearance rates were also lower in hepatocytes loaded with triglycerides than in normal hepatocytes. Decreased insulin clearance and hormonal control of protein synthesis could contribute to the etiology of metabolic disorders that are associated with periparturient fatty liver in dairy cows.


Compact spectrum splitter for laterally arrayed multi-junction concentrator photovoltaic modules.
A spectrum splitter based on micro-prism arrays is demonstrated for laterally arrayed multi-junction concentrator photovoltaic modules. The conjugate micro-optics design delivers high-transmission, efficient spectrum splitting with minimum aberration, a low profile, and low-cost fabrication, thus allowing large-scale production of micro-concentrator photovoltaic modules. A dispersive optic prototype based on a four-prism design is fabricated and characterized through outdoor measurements showing excellent agreement with our design model.


New insights into fish swimming: a proteomic and isotopic approach in gilthead sea bream.
Moderate exercise enhances fish growth, although underlying physiological mechanisms are not fully known. Here we performed a proteomic and metabolic study in white (WM) and red (RM) muscle of gilthead sea bream juveniles swimming at 1.5 body lengths per second. Continuous swimming for four weeks enhanced fish growth without increasing food intake. Exercise affected muscle energy stores by decreasing lipid and glycogen contents in WM and RM, respectively. Protein synthesis capacity (RNA/protein), energy use (estimated by lipid-δ(13)C and glycogen-δ(13)C), and enzymatic aerobic capacity increased in WM, while protein turnover (expressed by δ(15)N-fractionation) did not change. RM showed no changes in any of these parameters. 2D-PAGE analysis showed that almost 15% of sarcoplasmic protein spots from WM and RM differed in response to exercise, most being over-expressed in WM and under-expressed in RM. Protein identification by MALDI-TOF/TOF-MS and LC-MS/MS revealed exercise-induced enhancement of several pathways in WM (carbohydrate catabolism, protein synthesis, muscle contraction, and detoxification) and under-expression of others in RM (energy production, muscle contraction, and homeostatic processes). The mechanism underpinning the phenotypic response to exercise sheds light on the adaptive processes of fish muscles, being the sustained-moderate swimming induced in gilthead sea bream achieved mainly by WM, thus reducing the work load of RM and improving swimming performance and food conversion efficiency.


Indices of physiological strain for firefighters of the Australian Defence Forces.
High levels of exertion and physiological strain are the leading cause of fireground injuries. The Physiological Strain Index (PSI) provides a rating of strain based on body core temperature and heart rate; however, it may underestimate the strain of workers in protective clothing as skin temperature may be elevated. This study aimed to examine the relationship between the PSI and an Adaptive Physiological Strain Index (aPSI) that incorporates skin temperature, among firefighters wearing protective clothing. Nine male firefighters of the Australian Defence Force volunteered to participate. Participants conducted scenario-based activities while wearing turnout gear and breathing apparatus. Working in teams of four, participants would respond to a situation around and within a small building with several rooms that could be filled with smoke, however, no live fire was present. Heart rate, gastrointestinal temperature, and skin temperature were monitored throughout work and rehabilitation. Physiological strain was estimated via the PSI and aPSI. Absolute peak PSI and aPSI ratings were significantly different during work (PSI: 7.3 ± 1.6; aPSI 8.2 ± 2.0; p < 0.001). The aPSI produced higher ratings of physiological strain, >0.5 above PSI, progressively from a moderate level of strain (>6). The aPSI may provide a more accurate indication of a level of "maximal strain" for encapsulated workers than the original PSI, coincident with the occupational limits for body core temperature of 38.0 °C for general occupational groups, or 38.5 °C for selected and acclimatised personnel.


First Comprehensive Characterization of Phayre's Leaf-Monkey (Trachypithecus phayrei) Karyotype.
The chromosomal homologies of human (Homo sapiens-HSA) and Trachypithecus phayrei (TPH-Phayre's leaf-monkey, family Cercopithecidae) have previously been studied by using classical chromosome staining/banding and fluorescence in situ hybridization (FISH) from the 1970s to 1990s. In this study, we carried out molecular cytogenetics applying human multicolor banding (MCB), locus-specific, and human heterochromatin-specific probes to establish the first detailed chromosomal map of TPH, which was not available until now. Accordingly, it was possible to precisely determine evolutionary-conserved breakpoints (ECBs) and the orientation of evolutionary-conserved segments compared to HSA. It could be shown that five chromosomes remained completely unchanged between these two species, and 16 chromosomes underwent only intrachromosomal changes. In addition, 50 ECBs that failed to be resolved in previous reports were exactly identified and characterized in this study. It could also be shown that 43.5% of TPH centromere positions were conserved and 56.5% were altered compared to HSA. Interestingly, 82% ECBs in TPH corresponded to human fragile sites. Overall, this study is an essential contribution to future studies and reviews on chromosomal evolution in Cercopithecidae.


Oxidative Stress and Vascular Damage in Hypertension: Role of Angiotensin II.
Reactive oxygen species are oxygen derivates and play an active role in vascular biology. These compounds are generated within the vascular wall, at the level of endothelial and vascular smooth muscle cells, as well as by adventitial fibroblasts. In healthy conditions, ROS are produced in a controlled manner at low concentrations and function as signaling molecules regulating vascular contraction-relaxation and cell growth. Physiologically, the rate of ROS generation is counterbalanced by the rate of elimination. In hypertension, an enhanced ROS generation occurs, which is not counterbalanced by the endogenous antioxidant mechanisms, leading to a state of oxidative stress. In the present paper, major angiotensin II-induced vascular ROS generation within the vasculature, and relative sources, will be discussed. Recent development of signalling pathways whereby angiotensin II-driven vascular ROS induce and accelerate functional and structural vascular injury will be also considered.


Strengthening primary health care in China: governance and policy challenges.
Primary care is often the weakest link in health systems despite its acknowledged central importance in promoting population's health at economical cost. A key reason for the lacunae is that both scholars and practitioners working on the subject typically underestimate the enormity of the task and the range of complementary measures required to build an effective primary care system. The objective of the paper is to highlight theoretical gaps and practical limitations to strengthening primary care. The challenges and difficulties are illustrated through a case study of China where primary care continues to struggle despite the government's strong political, financial and policy support in recent years. In this paper, we review the development of primary health care in China and how it is governed, provided, and financed, highlighting the gaps and misalignments that undermine its performance. We argue that governance deficiencies coupled with flawed financing and payments arrangements are major impediments to improving performance. China's experience offers valuable lessons for other governments seeking to strengthen primary health care.


Serious crisis in the practice of international health by the World Health Organization: the Commission on Social Determinants of Health.
The Commission on Social Determinants of Health (CSDH) is the latest effort by the World Health Organization to improve health and narrow health inequalities through action on social determinants. The CSDH does not note that much work has already been done in this direction, does not make a sufficient attempt to analyze why earlier efforts failed to yield the desired results, and does not seem to have devised approaches to ensure that it will be more successful this time. The CSDH intends to complement the work of the earlier WHO Commission on Macroeconomics and Health, which has not had the desired impact, and it is unclear how the CSDH can complement work that suffers from such serious infirmities. Inadequacies of both commissions reflect a crisis in the practice of international health at the WHO, stemming from a combination of unsatisfactory administrative practices and lack of technical competence to provide insights into the problems afflicting the most needy countries. Often the WHO has ended up distorting the rudimentary health systems of the poor countries, by pressuring them into accepting health policies, plans, and programs that lack sound scientific bases. The WHO no longer seems to take into account historical and political factors when it sets out to improve the health situation in low-income countries--which is supposed to be the focus of the CSDH. An alternative approach is suggested.


Detection of lymph node micrometastases by gene promoter hypermethylation in samples obtained by endosonography- guided fine-needle aspiration biopsy.
Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become a fundamental procedure for gastrointestinal and lung cancer staging. However, there is growing evidence that micrometastases are present in lymph nodes, which cannot be detected with standard pathological methods. The aim of this study was to evaluate whether hypermethylation gene promoter analysis was feasible on samples obtained by EUS-FNA from lymph nodes, as well as to establish the usefulness of this strategy for the detection of micrometastases in patients with gastrointestinal and non-small cell lung cancer. Suspicious lymph nodes based on EUS findings from consecutive patients with esophageal, gastric, rectal, and non-small cell lung cancer were sampled by EUS-FNA. Hypermethylation analysis of the MGMT, p16(INK4a), and p14(ARF) gene promoter CpG islands were performed by methylation-specific PCR. Effectiveness of conventional cytology, methylation analysis, and their combination were established with respect to the definitive diagnosis. Twenty-seven patients were included, thus representing a total of 42 lymph nodes (esophageal cancer, n = 11; rectal cancer, n = 7; gastric cancer, n = 3; and lung cancer, n = 21). According to definitive diagnosis, 21 (50%) corresponded to metastatic lymph nodes. Sensitivity, specificity, and overall accuracy of conventional cytology were 76%, 100%, and 88%, respectively, whereas the corresponding values for the methylation analysis were 81%, 67%, and 74%, respectively. Combination of both techniques increased sensitivity (90%) but decreased specificity (67%) with respect to conventional cytology. In conclusion, it is feasible to detect occult neoplastic cells in EUS-FNA samples by hypermethylation gene promoter analysis. Moreover, addition of methylation analysis to conventional cytology may increase its sensitivity at the expenses of a decrease in its specificity.


Thy-1 and T-cell receptor antigen expression in mycosis fungoides and benign inflammatory dermatoses.
We have studied human Thy-1 and T-cell receptor (TCR) antigen expression in mycosis fungoides and benign inflammatory dermatoses. The study included 24 biopsy specimens from 21 patients with mycosis fungoides (nine patch stage from eight patients, 13 plaque stage from 11 patients, and two tumor stage from two patients), six specimens from five patients with premycotic parapsoriasis (pre-mycosis fungoides), three specimens from three patients with lichen planus, 11 specimens from 11 patients with lupus erythematosus, 13 specimens from 13 patients with dermatitis, six specimens from six patients with drug eruptions, nine normal skin specimens from nine subjects, and three specimens from three patients with small plaque (benign) parapsoriasis. Immunoperoxidase studies using the avidin-biotin complex technique on serial frozen sections were performed. Primary antibodies were anti-human Thy-1, anti-alpha heterodimer of the TCR, anti-beta heterodimer of the TCR, and anti-delta heterodimer of the TCR. An extensive dendritic network of Thy-1+ cells was seen in all cases of mycosis fungoides. Epidermotropic cells were Thy-1 negative, and Thy-1 was expressed perivascularly in normal individuals and patients as previously reported. Epidermal gamma/delta cells were seen only in mycosis fungoides, where up to 60% of the epidermal lymphocytes expressed this TCR. The increased numbers of Thy-1 and gamma/delta T cells in mycosis fungoides were statistically significant when compared with normal skin or benign inflammatory dermatoses. The role of these dendritic dermal Thy-1+ cells and epidermal gamma/delta T cells in mycosis fungoides is unclear. The significant numbers of these potentially immunomodulating cells that were seen suggest that they are involved in the pathogenesis of mycosis fungoides.


Response to Combination Cholinergic/Noradrenergic Treatments in a Patient With Alzheimer's Disease.
A patient with probable Alzheimer's disease participated in four studies involving cholinergic and combination cholinergic/noradrenergic treatment regimens. This patient demonstrated clinically significant improvement only with the combination of physostigmine and clonidine. The implications of these findings are discussed with regard to strategies for neurotransmitter augmentation therapy for Alzheimer's disease.


Activation, travel distance, and environmental change influence food carrying in rats with hippocampal, medial thalamic and septal lesions: implications for studies on hoarding and theories of hippocampal function.
Rats transport food from exposed areas to covered areas where they eat it or leave it. Although there is evidence that limbic structures play a role in food transport, their role is controversial. Here it was found that although many rats with large hippocampal, septal/diagonal band of Broca or dorsomedial thalamic lesions did not carry food but ate it where they found it, a few presentations of an auditory stimulus could restore food carrying. Once restored, most features of food carrying in hippocampal rats were normal in relation to food presentation schedules, deprivation levels, ambient illumination, circadian cycles, food size, and eating times. Nevertheless, food carrying impairments re-emerged when the testing environment was changed. Hippocampal rats were also excessively responsive to increases in travel distance and stopped carrying food at distances over which control rats would still carry large food pellets. Auditory stimulation did not restore food carrying over long travel distances. The findings that sensory stimulation, environmental change, and travel distance influence food carrying probabilities in rats with limbic system lesions is discussed in relation to research on limbic control of food hoarding and theories of limbic system function.


Prototyping a Hybrid Cooperative and Tele-robotic Surgical System for Retinal Microsurgery.
This paper presents the design of a tele-robotic microsurgical platform designed for development of cooperative and tele-operative control schemes, sensor based smart instruments, user interfaces and new surgical techniques with eye surgery as the driving application. The system is built using the distributed component-based cisst libraries and the Surgical Assistant Workstation framework. It includes a cooperatively controlled EyeRobot2, a da Vinci Master manipulator, and a remote stereo visualization system. We use constrained optimization based virtual fixture control to provide Virtual Remote-Center-of-Motion (vRCM) and haptic feedback. Such system can be used in a hybrid setup, combining local cooperative control with remote tele-operation, where an experienced surgeon can provide hand-over-hand tutoring to a novice user. In another scheme, the system can provide haptic feedback based on virtual fixtures constructed from real-time force and proximity sensor information.


Effects of cereal and protein source on performance, apparent ileal protein digestibility and intestinal characteristics in weaner piglets.
Rye and rapeseed meal (RSM) are alternatives to wheat and soybean meal (SBM) in pig nutrition. The inclusion of rye and RSM instead of wheat and SBM may increase dietary fibre content in the feed, which may affect digestive physiology and intestinal function. However, research on the combined feeding of rye and RSM in piglets is still scarce. The aim of this study was to investigate the effects of rye and RSM containing feed on growth performance, protein and amino acid digestibility, physical characteristics of the digesta and the intestinal morphology in weaner piglets. A total of 88 piglets aged 28 d were randomly allotted to four different feeding groups at weaning: wheat/SBM, wheat/RSM, rye/SBM, rye/RSM. Cereals were included at 48%, SBM at 25% and RSM at 30%. Body weight gain and feed intake were recorded weekly. After 33 d, piglets were euthanised for assessment of digesta and intestinal morphology. Rye did not affect performance, whilst RSM resulted in reduced weight gain (p = 0.024) and feed intake (p = 0.037). Apparent ileal digestibility of crude protein and amino acids was decreased by rye and RSM (p < 0.05). Rye caused an acidification (p = 0.045) and increased viscosity (p = 0.013) of small intestinal digesta, a lower dry matter content of jejunal and colonic digesta (p < 0.05) and an increased relative weight of the colon tissue (p < 0.001). In conclusion, performance was not reduced when rye was used as an alternative to wheat in diets for weaner piglets. The inclusion of RSM instead of SBM to piglets' diet lowered animal performance under our conditions. Further investigations are warranted to characterise the quality of rapeseed meal and the optimum inclusion level in the diet for young pigs.


The solution structure and dynamics of the DNA-binding domain of HMG-D from Drosophila melanogaster.
The HMG-box is a conserved DNA-binding motif that has been identified in many high mobility group (HMG) proteins. HMG-D is a non-histone chromosomal protein from Drosophila melanogaster that is closely related to the mammalian HMG-box proteins HMG-1 and HMG-2. Previous structures determined for an HMG-box domain from rat and hamster exhibit the same global topology, but differ significantly in detail. It has been suggested that these differences may arise from hinge motions which allow the protein to adapt to the shape of its target DNA. We present the solution structure of HMG-D determined by NMR spectroscopy to an overall precision of 0.85 A root mean squared deviation (rmsd) for the backbone atoms. The protein consists of an extended amino-terminal region and three alpha-helices that fold into a characteristic 'L' shape. The central core region of the molecule is highly stable and maintains an angle of approximately 80 degrees between the axes of helices 2 and 3. The backbone dynamics determined from 15N NMR relaxation measurements show a high correlation with the mean residue rmsd determined from the calculated structures. The structure determined for the HMG-box motif from HMG-D is essentially identical to the structure determined for the B-domain of mammalian HMG-1. Since these proteins have significantly different sequences our results indicate that the global fold and the mode of interaction with DNA are also likely to be conserved in all eukaryotes.


A Straightforward Route to Potent Phenolic Chain-Breaking Antioxidants by Acid-Promoted Transposition of 1,4-Benzo[b]oxathiines to Dihydrobenzo[b]thiophenes.
The transformation of simple phenols with limited antioxidant activity into potent chain-breaking antioxidants was achieved by a three-step protocol, consisting of the conversion of phenols into 1,4-benzo[b]oxathiines followed by an unprecedented acid-promoted transposition to o-hydroxydihydrobenzo[b]thiophenes, or dihydrobenzo[de]thiochromenes, starting from phenols or naphthols, respectively. These derivatives, bearing a benzo-fused heterocycle with a sulfide sulfur ortho to the phenolic OH, have a rate constant of reaction with alkylperoxyl radicals (kinh ) comparable to that of α-tocopherol. A solid rationale for the transposition mechanism as well as for the structure-antioxidant activity relationship is presented.


A new tool for testing and training ophthalmoscopic skills.
The direct fundoscopic examination is an important clinical skill, yet the examination is difficult to teach and competency is difficult to assess. Currently there is no defined proficiency assessment for this physical examination, and the objective of this study was to assess the feasibility of a simulation model for evaluating the fundoscopic skills of residents. Emergency medicine and ophthalmology residents participated in simulation sessions using a commercially available eye simulator that was modified with customized slides. The slides were designed with the goal of having a quantifiable measure of visualization in addition to a more traditional descriptive outcome. To assess feasibility, participants' ease of use, time to perform the examination, and user satisfaction were assessed. The simulation could be completed in a timely fashion (mean time per slide, 61-95 seconds), and there were no significant differences in performance between emergency medicine and ophthalmology residents in completion of this task. Residents expressed an interest in fundoscopy through simulation but found this model technically challenging. This simulation model has potential as a means of training and testing fundoscopy. A concern was low user satisfaction, and further refinement of the model is needed.


Physical and monetary ecosystem service accounts for Europe: A case study for in-stream nitrogen retention.
In this paper we present a case study of integrated ecosystem and economic accounting based on the System of Environmental Economic Accounting - Experimental Ecosystem Accounts (SEEA-EEA). We develop accounts, in physical and monetary terms, for the water purification ecosystem service in Europe over a 20-year time period (1985-2005). The estimation of nitrogen retention is based on the GREEN biophysical model, within which we impose a sustainability threshold to obtain the physical indicators of capacity - the ability of an ecosystem to sustainably supply ecosystem services. Key messages of our paper pertain the notion of capacity, operationalized in accounting terms with reference to individual ecosystem services rather than to the ecosystem as a whole, and intended as the stock that provides the sustainable flow of the service. The study clarifies the difference between sustainable flow and actual flow of the service, which should be calculated jointly so as to enable an assessment of the sustainability of current use of ecosystem services. Finally, by distinguishing the notion of 'process' (referred to the ecosystem) from that of 'capacity' (pertaining specific services) and proposing a methodology to calculate capacity and flow, we suggest an implementable way to operationalize the SEEA-EEA accounts.


Lynch-like syndrome with germline WRN mutation in Bulgarian patient with synchronous endometrial and ovarian cancer.
Synchronous endometrial and ovarian cancer (SEOC) accounts for 50-70% of all synchronous gynecology cancers in women. Approximately 14% of SEOC cases are caused by Lynch syndrome (LS). The widespread introduction of "universal screening" at LS (all cases with CRC and all EC cases diagnosed before age 60 should be tested for MMR deficiency) has led to an increasing number of suspected LS cases- MMR-deficient tumors without germline mutation in the MMR genes. These cases are attributed to the so-called Lynch-like syndrome (LLS). We present a case of LLS with a detected germline, likely pathogenic variant in the WRN gene. The proband was a woman diagnosed with SEOC at the age of 51 years. Histology of both tumors (endometrium and ovary) was endometroid and showed loss of MLH1 and PMS protein expression. Genetic testing by next generation sequencing (NGS) detected a germline mutation (in the heterozygous state) in the WRN gene - c.4109del, p.(Asn1370ThrfsTer23) in the proband. The presented case contributes to the etiology of LLS and confirms the need for specific genetic testing, together with genetic counseling, in hereditary cancer syndromes. The use of combined information from clinicians, pathologists, genetic counselors, and data from NGS testing for cancer predisposition, clinical surveillance, and follow-up management in women with gynecology cancers, especially SEOC, could be improved.


Stem cells of the melanocyte lineage.
Melanocytes are pigment-producing cells responsible for coloration of skin and hair. Studies using mouse models have allowed identification of putative melanocyte stem cells within the hair follicle and understanding of hair graying caused by abnormal melanocyte stem cell maintenance. The malignant transformation of melanocytes results in melanoma, the sixth most common cancer in the United States. Recent studies have offered compelling evidence for the existence of cancer stem cells in numerous tumor types, including melanoma. In this review we provide an overview of some of the current findings on follicular melanocyte stem cells, the genetic pathways involved in their regulation and maintenance, and discuss recent studies that support the existence of cancer stem cells in melanoma.


Preoperative steroid in abdominal wall reconstruction: protocol for a randomised trial.
Preoperative administration of high-dose glucocorticoid leads to improved recovery and decreased length of stay after abdominal surgery. Even so, studies on administration of glucocorticoids for patients undergoing abdominal wall reconstruction (AWR) for giant ventral hernia repair are lacking, perhaps due to a fear of impaired wound healing. We hypothesised that patients undergoing AWR would benefit from preoperative glucocorticoids and aimed at examining this in a randomised controlled trial. A total of 40 patients scheduled to undergo AWR for ventral hernias with a fascial defect exceeding 10 cm will be randomised for intravenous administration of either 125 mg methylprednisolone or saline at the induction of anaesthesia. The primary endpoint is pain at rest on the first post-operative day. Patients will be followed until 30 days post-operatively, and secondary outcomes include subjective measures, wound complications and analysis of blood and wound fluids. This is the first trial on the effect of preoperative glucocorticoid administration in patients undergoing AWR. Due to long post-operative stays and a high rate of post-operative complications, this patient group can potentially benefit much from any post-operative optimisation. Furthermore, insight into any impact of glucocorticoids on wound healing in hernia patients may provide important information. none. This study was registered with Clinicaltrials.gov (NCT02594241) and Eudra-CT (2015-004916-39).


How the VA is training the Next-Generation workforce for learning health systems.
The U.S. Department of Veterans Affairs (VA) has been a national leader in Learning Health System (LHS) implementation due to its combined mission of research, education, clinical care, and emergency preparedness. We describe the current VA LHS training ecosystem within the Veterans Health Administration's Office of Academic Affiliations (OAA), Office of Research and Development (ORD), ORD's Health Services Research and Development (HSR&D) program, and Innovation Ecosystem (IE), including lessons learned regarding their sustainment. The VA LHS training ecosystem is based on the Learning Loop and HSR&D Quality Enhancement Research Initiative (QUERI) Roadmap, which describes VA learning opportunities, underlying infrastructures, and core competencies. VA-focused LHS educational programs include data-to-knowledge initiatives in health sciences and analytics, for example, OAA/HSR&D health services and informatics research fellowships; knowledge-to-performance opportunities in implementation and quality improvement, for example, QUERI Learning Hubs and IEs' Diffusion of Excellence Initiative; and performance-to-data embedded opportunities, for example, IE's entrepreneur fellowship programs and QUERI's Advancing Diversity in Implementation Leadership. These training programs are supported by combined VA research and clinical operations investments in funding, informatics, governance, and processes. Lessons learned include ongoing alignment of research funding with operational priorities and capacity, relentless recruitment and retention of implementation, system, and information scientists especially from under-represented groups, sustainment of data infrastructures suitable for research and quality improvement, and ensuring sustainable funding opportunities for researchers to work on system-wide health care problems. There is an urgent need to expand training opportunities in LHSs, especially as health care is increasingly driven by multiple interested parties, impacted by persistent health disparities exacerbated by emerging public health threats, and rapid technology growth. With ongoing alignment of research and clinical goals, foundational support through research funding, underlying clinical operations infrastructures, and active engagement interested parties, VA's LHS training ecosystem promotes a more LHS-savvy, 21st century workforce.


β-catenin is essential for efficient in vitro premyogenic mesoderm formation but can be partially compensated by retinoic acid signalling.
Previous studies have shown that P19 cells expressing a dominant negative β-catenin mutant (β-cat/EnR) cannot undergo myogenic differentiation in the presence or absence of muscle-inducing levels of retinoic acid (RA). While RA could upregulate premyogenic mesoderm expression, including Pax3/7 and Meox1, only Pax3/7 and Gli2 could be upregulated by RA in the presence of β-cat/EnR. However, the use of a dominant negative construct that cannot be compensated by other factors is limiting due to the possibility of negative chromatin remodelling overriding compensatory mechanisms. In this study, we set out to determine if β-catenin function is essential for myogenesis with and without RA, by creating P19 cells with reduced β-catenin transcriptional activity using an shRNA approach, termed P19[shβ-cat] cells. The loss of β-catenin resulted in a reduction of skeletal myogenesis in the absence of RA as early as premyogenic mesoderm, with the loss of Pax3/7, Eya2, Six1, Meox1, Gli2, Foxc1/2, and Sox7 transcript levels. Chromatin immunoprecipitation identified an association of β-catenin with the promoter region of the Sox7 gene. Differentiation of P19[shβ-cat] cells in the presence of RA resulted in the upregulation or lack of repression of all of the precursor genes, on day 5 and/or 9, with the exception of Foxc2. However, expression of Sox7, Gli2, the myogenic regulatory factors and terminal differentiation markers remained inhibited on day 9 and overall skeletal myogenesis was reduced. Thus, β-catenin is essential for in vitro formation of premyogenic mesoderm, leading to skeletal myogenesis. RA can at least partially compensate for the loss of β-catenin in the expression of many myogenic precursor genes, but not for myoblast gene expression or overall myogenesis.


Applied anatomy of the lower cervical pedicle screw insertion.
To ascertain an accurate approach to inserting the pedicle screw into C3-C7 segments of the cervical vertebra. Anatomic morphology of lateral mass and pedicle, and their anatomic relationship with the adjacent tissue were observed on C3-C7 segments of 25 adult embalmed cadavers (50 sides). 1) The inferior edge of the base of the posterior tubercle of the transverse process and the inferior edge of the pedicle were connected with each other on 25 adult embalmed cadavers (50 sides). The transverse section which passed through the median point between the superior edge and the inferior edge of the base of the posterior tubercle of the transverse process, and the transverse section which passed through the central axis between the superior edge and the inferior edge of the pedicle, were in the same horizontal plane. The superior and inferior position of placing the pedicle screw was determined by this transverse section, which passed through the median point between the superior and the inferior edge of the base of the posterior tubercle of the transverse process. 2) There was a directed internal-downwards "triangular sulcule" between the base of the posterior tubercle of the transverse process and the anterolateral edge of the inferior articular process. The anterior wall of the triangular sulcule was the base of the posterior tubercle of the transverse process, the posterior wall was the anterolateral edge of the inferior articular process, and the bottom of the sulcule was connected with the interior edge of the pedicle. The vertical length between the top of triangle and the planes of inferior edge of the pedicle was (2.78+/-1.71) mm. The inferior edge of the cervical pedicle could be detected using a blunt probe along the "triangular sulcule" between the base of the posterior tubercle of the transverse process and the anterolateral edge of the inferior articular process in surgical operation. 3) The lateral fovea of the articular process was observed on all lateral masses (50 sides). The internal and external position of the entrance point could depend on anatomic landmarks: the lateral edge of the lateral fovea of the articular process. The horizontal length between the lateral fovea of the articular process and the entrance point was (3.14+/-1.45) mm. 4) The diameter of pedicle screw, about (2.78+/-1.71) mm, was the transverse diameter of the cancellous bone of the greatest narrow part of the cervical pedicle. The median point between the superior edge and the inferior edge of the base of the posterior tubercle of the transverse process, the lateral fovea of the articular process, and the triangular sulcule between the base of the posterior tubercle of the transverse process and the anterolateral edge of inferior articular process, are easy to be exposed and identified in surgical operation. The pedicle screw can be precisely inserted through this method.


QuantiLyse: reliable DNA amplification from single cells.
Amplification of DNA sequencesfrom single cells via PCR is increasingly used in basic research and clinical diagnostics but remains technically difficult. We have developed a cell lysis protocol that uses an optimized proteinase K solution, named QuantiLyse and permits reliable amplification from individual cells. This protocol was compared to other published methods by means of real-time PCR with molecular beacons. The results demonstrate that QuantiLyse treatment of single lymphocytes renders gene targets more availablefor amplification than other published proteinase K methods or lysis in water. QuantiLyse and an optimized alkaline lysis were equally effective in terms of target availability, although QuantiLyse offers greaterflexibility, as it does not require neutralization and can comprise a higher percentage of the final PCR volume. Maximum gene target availability is also obtained following QuantiLyse treatment of samples containing up to 10000 cells (the largest number tested). Thus, QuantiLyse maximizes the chances that targeted DNA sequences will be available for amplification during the first cycle of PCR, thereby reducing the variability among replicate reactions as well as the likelihood of amplification failure or allele drop-out. QuantiLyse will be useful in a range of investigations aimed at gene detection in small numbers of cells.


Building National Capacity for Child and Family Disaster Mental Health Research.
Disaster mental health is a burgeoning field with numerous opportunities for professional involvement in preparedness, response, and recovery efforts. Research is essential to advance professional understanding of risk and protective factors associated with disaster outcomes; to develop an evidence base for acute, intermediate, and long-term mental health approaches to address child, adult, family, and community disaster-related needs; and to inform policy and guide national and local disaster preparedness, response, and recovery programs. To address the continued need for research in this field, we created the Child & Family Disaster Research Training & Education (DRT) program, which is focused specifically on enhancing national capacity to conduct disaster mental health research related to children, a population particularly vulnerable to disaster trauma. This paper describes the structure and organization of the DRT program, reviews the training curriculum, discusses implementation and evaluation of the program, and reviews obstacles encountered in establishing the program. Finally, key lessons learned are reviewed for the purpose of guiding replication of the DRT model to address other areas of community mental health.


Role of cytokines and oxidative stress in the pathophysiology of acute pancreatitis: therapeutical implications.
Severe acute pancreatitis causes a high incidence of mortality due to the systemic inflammatory response syndrome leading to multiple organ failure. At present, there is no treatment against severe acute pancreatitis, other than supportive critical care. The relationship between pancreatic injury and the uncontrolled systemic response is not completely understood. Nevertheless, experimental and clinical evidences have shown that pro-inflammatory cytokines and oxidative stress are critically involved in the development of local and systemic complications associated with severe acute pancreatitis. Serum levels of pro-inflammatory cytokines, such as TNF-alpha and IL-1beta, increase during the course of acute pancreatitis and they appear to be the driving force for the initiation and propagation of the systemic response. Accordingly, pretreatment with an antibody against TNF-alpha or blockade of TNF-alpha production with pentoxifylline ameliorates experimental acute pancreatitis. In addition, serum IL-6 and IL-8 levels appear to be correlated with severity of pancreatic inflammation. The role of oxidative stress in acute pancreatitis has been evidenced indirectly by beneficial effects of antioxidants as well as directly by pancreatic glutathione depletion and increased lipid peroxidation. Furthermore, circulating xanthine oxidase released by the damaged pancreas acts as a source of systemic oxidative stress contributing to lung inflammation. In conclusion, pancreatic injury seems to trigger at least two different pathways, i.e. pro-inflammatory cytokines and oxidative stress, both involved in the systemic effects of acute pancreatitis. Elucidation of these mechanisms and their interactions is critical to develop a treatment based on the pathophysiology of acute pancreatitis.


Differential expression of the five somatostatin receptor subtypes in human benign and malignant insulinomas - predominance of receptor subtype 4.
Insulinomas constitute a subgroup of pancreatic endocrine tumors showing B cell differentiation and clinical symptoms related to inappropriate insulin secretion (WHO). Many endocrine tumors express somatostatin receptors (sstrs), which can be visualized by octreotide scintigraphy; however, about half of all insulinomas are reported to be negative. Previous immunohistochemical investigations with antibodies to sstr subtypes 1, 2, 3, and 5 have revealed differences in expression between various neuroendocrine tumors. In the present study, the immunoreactivity to all five human sstr was studied in ten benign and six malignant human insulinomas. Sstr4 was the receptor subtype most frequently expressed in both benign and malignant tumors. A difference in the immunohistochemical sstr5 expression pattern was seen between benign and malignant tumors: Three of the six malignant tumors, but none of the benign tumors, expressed sstr5. The other receptor subtypes were expressed in low numbers with no difference between benign and malignant tumors. The finding of a strong expression of sstr4 in both benign and malignant insulinomas suggests that this receptor subtype could be of importance for diagnostic and therapeutic use.


Revisiting gainsharing.
Gainsharing initiatives stalled in the past due to legal concerns, but they are enjoying a renaissance as part of broader initiatives, such as accountable care organizations and bundled payments. In the past, with so much of the focus on the legal aspects of gainsharing, the potential of gainsharing to preserve physician choice, reduce costs, and maintain or improve quality may have been underestimated. A gradual gainsharing rollout tailored to the needs of various clinical areas can boost an organization's prospects for success.


[Slaughter findings feedback systems--its use for farms of origin?].
Over a period of 22 months 13 official meat inspection authorities examined a number of 152 520 swine at an Austrian slaughterhouse for pathologic-anatomic changes (five parameters). Of those veterinarians whose reliability in the recording of findings was a given, the results were analysed by employing a mathematical model which assessed whether the activities of 25 attending veterinarians and 223 farmers actually lead to an improvement of animal health in their livestock. Mild pneumonia was registered in 14.5% of swine; no attending veterinarians had any influence whatsoever on the occurrence of this parameter. Farmers' activities improved animal health on two farms (0.9%), six farms of origin (2.69%) showed significantly lower findings than the average of all farms. Pleurisy was ascertained in 22% of all slaughter pigs. Through measures taken, four attending veterinarians (16%) caused a reduction of incidents, two works managers (0.9%) made worse, six farmers (2.69%) improved animal health of their live stock. Seven farmers (3.14%) showed significantly (p < 0.05) higher, 28 farms (12.6%) lower prevalence. Pericarditis affected 4.5% of the animals in question. On all farms of origin the condition of health remained unchanged by measures taken by veterinarians. On two farms (0.9%) the influence exercised by farmers led to a deterioration of the health of swine, six businesses (2.69%) showed higher, one (0.45%) lower prevalence than on average. 6.2% of swine showed white spots. Attending veterinarians did not influence this parameter at all. With preventive measures taken five farms (2.24%) showed less, three farms (1.35%) higher prevalence by the end of the 22 month term. Mange concerned 2.2% of all slaughter pigs. The activities of one veterinarian (4%) caused the number of incidents to double; on six farms (2.69%) a significantly higher prevalence was registered. Whatever influence exercised, the status of health of slaughter pigs remained unchanged throughout the duration of the study.


Investigation of Hole-Transporting Poly(triarylamine) on Aggregation and Charge Transport for Hysteresisless Scalable Planar Perovskite Solar Cells.
Organometallic halide perovskite solar cells (PSCs) have unique photovoltaic properties for use in next-generation solar energy harvesting systems. The highest efficiency of PSCs reached 22.1% on a laboratory scale of <0.1 cm2 device area. Thus, scaling up is the next step toward commercialization, but the difficulty in controlling the quality of large-area perovskite thin films remains a fundamental challenge. It has also been frequently reported that the J- V hysteresis is intensified in PSCs with areas larger than 1 cm2. In this study, we have fabricated a large-area perovskite layer using PbICl films, providing an intrinsic porous layer and enhancing the uniformity of the perovskite layer at areas larger than 1 cm2. Furthermore, we have investigated the polymeric properties of the prevalent hole-transporting material poly(triarylamine) (PTAA) with its photovoltaic performance. Two types of PTAAs, poly[bis(4-phenyl)(2,4-dimethylphenyl)amine] and poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine], were compared. A series of PTAAs with different molecular weights ( Mw) and polydispersity indices were studied, as the molecular weight of the PTAA is a key factor in determining the electrical properties and photovoltaic performance of the system. The fabricated PSCs with an aperture area of 1 cm2 based on a high-molecular-weight PTAA achieved a power conversion efficiency of 16.47% with negligible hysteresis and excellent reproducibility.


Prediction of cortical bone porosity in vitro by microcomputed tomography.
The high importance of intracortical porosity for mechanical strength of cortical bone has been established. The contribution of other parameters of microstructure such as osteon dimensions for strength is in discussion. The aim of this study was to evaluate the predictive value of microcomputed tomography (mCT) for porosity and other microstructural parameters of cortical bone in cortical bone biopsies. Femoral cortical bone specimens from the middiaphysis of 24 patients were harvested during the procedure of total hip replacement at the location where normally one hole (Ø 4.5 mm) for the relief of the intramedullary pressure is placed. In vitro intracortical porosity and bone mineral density (BMD) measurements by mCT were compared with structural parameters assessed in histological sections of the same specimens. A strong correlation was found between intracortical porosity measured by mCT and histological porosity (r = 0.95, P <0.0001). Porosity measured by mCT was also a strong predictor for other parameters describing dimensions of porous structures. BMD?1 was associated with osteonal area (r = -0.76, P <0.0001). We consider the measurement of porosity by mCT as a very potent procedure for assessing intracortical porosity and parameters related to porous structures of cortical bone nondestructively in vitro.


Direct binding to Rsp5 mediates ubiquitin-independent sorting of Sna3 via the multivesicular body pathway.
The sorting of most integral membrane proteins into the lumenal vesicles of multivesicular bodies (MVBs) is dependent on the attachment of ubiquitin (Ub) to their cytosolic domains. However, Ub is not required for sorting of Sna3, an MVB vesicle cargo protein in yeast. We show that Sna3 circumvents Ub-mediated recognition by interacting directly with Rsp5, an E3 Ub ligase that catalyzes monoubiquitination of MVB vesicle cargoes. The PPAY motif in the C-terminal cytosolic domain of Sna3 binds the WW domains in Rsp5, and Sna3 is polyubiquitinated as a consequence of this association. However, Ub does not appear to be required for transport of Sna3 via the MVB pathway because its sorting occurs under conditions in which its ubiquitination is impaired. Consistent with Ub-independent function of the MVB pathway, we show by electron microscopy that the formation of MVB vesicles does not require Rsp5 E3 ligase activity. However, cells expressing a catalytically disabled form of Rsp5 have a greater frequency of smaller MVB vesicles compared with the relatively broad distribution of vesicles seen in MVBs of wild-type cells, suggesting that the formation of MVB vesicles is influenced by Rsp5-mediated ubiquitination.


The efficacy and tolerability of latency-reversing agents in reactivating the HIV-1 reservoir in clinical studies: a systematic review.
Understanding the clinical potency of latency-reversing agents (LRAs) on the HIV-1 reservoir is useful to deploy future strategies. This systematic review evaluated the effects of LRAs in human intervention studies. A literature search was performed using medical databases focusing on studies with adults living with HIV-1 receiving LRAs. Eligibility criteria required participants from prospective clinical studies, a studied compound hypothesised as LRA, and reactivation or tolerability assessments. Relevant demographical data, LRA reactivation capacity, reservoir size, and adverse events were extracted. A study quality assessment with analysis of bias was performed by RoB 2 and ROBINS-I tools. The primary endpoints were HIV-1 reservoir reactivation after LRA treatment quantified by cell-associated unspliced HIV-1 RNA, and LRA tolerability defined by adverse events. Secondary outcomes were reservoir size and the effect of LRAs on analytical treatment interruption (ATI) duration. After excluding duplicates, 5182 publications were screened. In total 45 publications fulfilled eligibility criteria including 26 intervention studies and 16 randomised trials. The risk of bias was evaluated as high. Chromatin modulators were the main investigated LRA class in 24 studies. Participants were mostly males (90.1%). Where reported, HIV-1 subtype B was most frequently observed. Reactivation after LRA treatment occurred in 78% of studies and was observed with nearly all chromatin modulators. When measured, reactivation mostly occurred within 24 h after treatment initiation. Combination LRA strategies have been infrequently studied and were without synergistic reactivation. Adverse events, where reported, were mostly low grade, yet occurred frequently. Seven studies had individuals who discontinued LRAs for related adverse events. The reservoir size was assessed by HIV-1 DNA in 80% of studies. A small decrease in reservoir was observed in three studies on immune checkpoint inhibitors and the histone deacetylase inhibitors romidepsin and chidamide. No clear effect of LRAs on ATI duration was observed. This systematic review provides a summary of the reactivation of LRAs used in current clinical trials whilst highlighting the importance of pharmacovigilance. Highly heterogeneous study designs and underrepresentation of relevant patient groups are to be considered when interpreting these results. The observed reactivation did not lead to cure or a significant reduction in the size of the reservoir. Finding more effective LRAs by including well-designed studies are needed to define the required reactivation level to reduce the HIV-1 reservoir.


Advanced tools for digital EEG review: virtual source montages, whole-head mapping, correlation, and phase analysis.
Digital EEG allows one to combine recorded EEG channels into new montages without the need to record new data. Using spherical splines, voltages can be estimated at any point on the head. This allows one to generate various montages with the recorded or virtual electrodes at standardized locations, to interpolate bad electrodes, and to generate topographic maps over the whole head. Simulations of EEG activity originating in various brain regions are used to illustrate the effects of known generators on various montages and on whole-head maps. Some properties of spatial filters are introduced, and it is shown how they can be used to develop source montages with signals that estimate the activity in specific brain regions. The usefulness and validity of a source montage designed to focus on temporal lobe activity is illustrated with simulations and examples of temporal lobe spikes and seizures. Additional tools such as cross-correlation among channels, fast Fourier transform, and phase maps are described. These tools are useful in estimating time lags between source channels and in interpreting propagating spike and seizure activity. In combination, these tools help to analyze and to enhance activities that may be hard to detect from the background scalp EEG in traditional montages.


QRS complex duration enhancement as ventricular late potential indicator by signal-averaged ECG using time-amplitude alignments.
Ventricular late potentials (VLPs) are small-amplitude waves with a short duration that appear at the end part of the QRS complex, making a QRS complex duration larger. The signal-averaged electrocardiography (ECG) technique enhances VLPs and beats, assuming noise as the only random variable. However, ECG signals are not completely stationary and different elongations appear in both time and amplitude in each beat. This research proposes to use piecewise linear approximation to segment each beat and performs the alignment of the beats using the technique known as derivative dynamic time-warping to have beats better aligned and consequently enhance the presence of VLPs. We recorded high-resolution ECGs (HRECGs) from 50 subjects in supine position with no heart-stroke antecedents. VLPs were created synthetically and added to the HRECGs. Two cases were evaluated: (i) duration of the QRS complexes with VLPs without beats alignment, and (ii) duration of QRS complexes with VLPs using beats alignment in time and amplitude. Considering QRS duration as an indicative of VLP presence, results show that when using beats alignment in time and amplitude it is possible to reach a sensitivity of 0.96 and a specificity of 0.52, as opposed to 0.72 and 0.40, respectively, when using only averaging without beats alignment in time and amplitude.


Sustained release microspheres of diclofenac sodium using PEGylated rosin derivatives.
The PEGylated derivatives of rosin-PD-1 and PD-2 synthesized and characterized earlier (Nande et al., 2006) were investigated as potential materials for sustained release microsphere prepared by emulsion solvent evaporation method using diclofenac sodium (DCS) as model drug. All the microspheres exhibited smooth surfaces intercepted by pores; their sizes (d(90)) ranged between 11-24 microm. The entrapment efficiency (< 80%) of the microspheres increased proportionally with derivative concentration. Presence of solvent like isopropyl alcohol or dichloromethane rendered the microspheres with large sizes but with reduced drug entrapment. Microspheres with small size were obtained at an optimum viscosity of liquid paraffin; any change lead to increase in the particle size. Magnesium stearate was found to be most suitable detackifier in the present system. The drug release was directly related to the particle size--small sized microspheres released drug at a faster rate. The dissolution data complied with Higuchi equation while the mechanism of drug release was Fickian diffusion (n approximately 0.5). Controlled inhibition of edema, as tested by hind paw edema method, was observed for 10 h when the microspheres were administered intraperitoneally. The present study found the derivatives as promising materials for preparing microspheres for sustained delivery of DCS.


Molecular process in acute liver injury and regeneration induced by carbon tetrachloride.
Injection of carbon tetrachloride (CCl4) intraperitoneally into model animals induces acute liver injury mediated by reactive oxygen species (ROS) as normal metabolites in hepatocytes. In this study, the molecular process in this type of liver injury was analyzed from the aspect of liver function and regulatory factors. Down-regulation of liver-specific genes was accomplished through suppression of liver-enriched transcription factors and box A factors found in the catalase gene, and induction of NF-kappaB, AP-1 and a novel factor denoted as 'cx' in the catalase gene. Expression profiles of these genes were restored to normal levels in the late stage of injury (48 h). On the other hand, hepatocyte growth factor (HGF) and proliferating cell nuclear antigen (PCNA) were induced in the early stage (6 h) and 36 h, respectively. Interestingly, ERK2 was transiently activated at 3 h CCl4-treatment. These observations suggested that hepatotoxin by CCl4-injection concomitantly induces both processes in acute injury and liver regeneration.


Disulfide Bridged Nanoparticles of Thiolated Sodium Alginate and Eudragit RS100 for Oral Delivery of Paclitaxel: In Vitro and In Vivo Evaluation.
Most biopharmaceutics classification system (BCS) class IV drugs have limited oral bioavailability due to poor solubility and poorer permeability. This work aims to investigate the possibility of utilizing disulfide bridged nanoparticles to improve BCS IV drug solubility and oral absorption. Disulfide bridged nanoparticles were made using thiolated sodium alginate (TSA) and thiolated eudragit RS100 (TERS100). This study used paclitaxel (PTL) as a model drug to create PTL-loaded nanoparticles using the air oxidation approach. PTL-loaded nanoparticles boosted the solubility of PTL by over 11 times (∼59 μg/mL). The nanoparticles had particle sizes of 103 nm, polydispersity indices of 0.034, and zeta potentials of -21 mV, respectively. Nanoparticles demonstrated 75.34% and 89.18% entrapment and loading efficiency of PTL, respectively. The PTL release data from nanoparticles had good sustained release properties. The effective permeability of PTL from nanoparticles was 2.19-fold higher than that of pure PTL suspension. The relative bioavailability of PTL with disulfide bridged nanoparticles was 237.11%, which was much higher than that of PTL suspension, according to the pharmacokinetic data. These results show that disulfide bridged nanoparticles have a wide range of clinical applications.


Characteristic comparison of heavy metal contamination between road-deposited and roof-deposited sediments in suburban area.
Surface-deposited sediment in urban area is an essential environmental medium for assessing heavy metal contamination. A total of 10 sampling trips were conducted to collect road-deposited and roof-deposited sediments for the comparison of nickel (Ni), copper (Cu), cadmium (Cd), lead (Pb), zinc (Zn), and chromium (Cr) contamination characteristics. Results indicated that roof sediment appeared to have a finer size distribution than road sediments. Roof sediment indicated higher metal concentration and lower surface loading than road sediment. The impact of particle size on heavy metal contamination was quantified by using the developed pioneering term of finer particle effect factor; it differed according to surface types and grain size fraction. Particles in individual grain size fraction showed different contribution to the surface loading for bulk sediments. No consistent trend was found for the grain size fraction loading along with grain size for the studied heavy metals for road sediments. In contrast, an asymmetric "W" trend was observed for the roof sediments, and it had the following results: Fraction of <63 and 250-500 μm showed higher loading, while fraction of 90-125 and >850 μm indicated the smaller loading. Findings above facilitated the appropriate management practice selection for the treatment of surface-deposited sediments.


NASA--has its biological groundwork for a trip to Mars improved?
In a 1991 editorial in The FASEB Journal, Robert W. Krauss commented on a recent report of the Presidential Advisory Committee on the Future of the U.S. Space Program (Augustine report). He concluded that, although a manned mission to Mars with life sciences as the priority was endorsed by the Committee, it failed to deal realistically with one huge gap; biological sciences have never been given high priority. According to Krauss, this left a void that will cripple, perhaps fatally, any early effort to ensure long-term survival on any mission of extended duration. The gap included insufficient flight time for fundamental biological space research and insufficient funds. Krauss expressed his opinions 15 years ago. Have we better knowledge of space biology now? This question becomes more acute now that President George W. Bush recently proposed a manned return to the moon by 2015 or 2020, with the moon to become our staging post for manned missions to Mars. Will we be ready so soon? A review of the progress in the last 15 years suggests that we will not. Because of the Columbia disaster, flight opportunities for biological sciences in shuttle spacelabs and in Space Station laboratories compete with time for engineering problems and construction. Thus, research on gravity, radiation, and isolation loses out to problems deemed to be of higher priority. Radiation in deep space and graded gravity in space with on board centrifuges are areas that must be studied before we undertake prolonged space voyages. Very recent budgetary changes within National Aeronautics and Space Administration threaten to greatly reduce the fundamental space biology funds. Are we ready for a trip to Mars? Like Krauss 15 years ago, I think not for some time.


Response to the RIF-1 tumor in vitro and in C3H/Km mice to X-radiation (cell survival, regrowth delay, and tumor control), chemotherapeutic agents, and activated macrophages.
The radiation response of logarithmic growth phase and fed plateau phase RIF-1 cells in vitro was found to be characterized by D0 (slope of cell survival curve on semilog plot) values of 110 and 133 rads and extrapolation numbers of 36 and 28, respectively. The response of the tumor in vivo to X-irradiation in nonanesthetized mice showed a dependence on the tumor implantation site. In the leg muscle, the response indicated that most cells were at an intermediate level of oxygenation, whereas in the subcutaneous tissue of the flank, the response of the tumor indicated that it had a small fraction (1.5%) of hypoxic cells of maximum radioresistance. Misonidazole radiosensitized the leg-implanted tumor as measured both by cell survival and regrowth delay. The median tumor cure dose of radiation in mice was 3,990 rads (3,670--4,340), which agreed closely with that predicted from the radiation survival curve. The tumor was relatively insensitive to a single dose of 1,3-bis(2-chloroethyl)-1-nitrosourea, sensitive to a single dose of cis-platinum, and highly sensitive to a single dose of cyclophosphamide.