Transient attenuation of visual evoked potentials during focal status epilepticus in a patient with occipital lobe epilepsy.
Seizures originating in the occipital areas are relatively uncommon. They are usually characterized by visual hallucinations and illusions or other symptoms related to the eyes and vision. In a 54-year-old woman with occipital lobe epilepsy, complex visual hallucinations, illusions, and migraine-like headache constitute the major clinical manifestations. During focal status epilepticus, ictal electroencephalography revealed rhythmic focal spikes in the right occipital region, rapidly propagating to the right parietal and contralateral occipital areas. Ictal brain single-photon emission computed topography revealed hyperperfusion of the right occipital region. Using a full-field pattern-shift visual evoked potential (VEP) study, we found that the P100 responses on both sides were markedly attenuated in amplitude during occipital focal status epilepticus, whereas the latencies of the VEPs were normal. The amplitude and morphology of P100 responses on both sides, however, returned to the normal range 7 days after cessation of the seizures. In addition to clinical seizure semiology, scalp EEG, SPECT and neuroimaging studies, VEP studies may be used as a supplementary examination tool to provide further information in the patients with occipital lobe seizures or epilepsies.


Use of suppressor mutants to probe the function of estrogen receptor-p160 coactivator interactions.
Estrogen-dependent recruitment of coactivators by estrogen receptor alpha (ERalpha) represents a crucial step in the transcriptional activation of target genes. However, studies of the function of individual coactivators has been hindered by the presence of endogenous coactivators, many of which are potentially recruited in the presence of agonist via a common mechanism. To circumvent this problem, we have generated second-site suppressor mutations in the nuclear receptor interaction domain of p160 coactivators which rescue their binding to a transcriptionally defective ERalpha that is refractory to wild-type coactivators. Analysis of these altered-specificity receptor-coactivator combinations, in the absence of interference from endogenous coregulators, indicated that estrogen-dependent transcription from reporter genes is critically dependent on direct recruitment of a p160 coactivator in mammalian cells and that the three p160 family members serve functionally redundant roles. Furthermore, our results suggest that such a change-of-specificity mutation may act as a transposable protein-protein interaction module which provides a novel tool with which to dissect the functional roles of other nuclear receptor coregulators at the cellular level.


Mixed Nanocomposite Fertilizers Influencing Endophytic Symbiosis and Nutritional and Antioxidant Properties of Oryza sativa as a Sustainable Alternative for Commercial Fertilizers.
This study investigated the comparative effects of mixed nanocomposite (MNC) fertilizers as an alternative to commercial fertilizers (CFs) on endophytic symbiosis and nutritional properties of rice grains. We synthesized MNC fertilizers with different concentrations and characterized them by using scanning electron microscopy and Fourier transform infrared spectroscopy. The CF was applied as per the method followed by local farmers; however, for MNC fertilizers both foliar and soil applications were done. Comparative analysis of growth and development, rice-endophyte symbiosis, and nutritional properties of rice grains was conducted. The panicles per hill, length of panicles, grain per panicles, 1000-grain weight, and dry matter of rice plants treated with MNC fertilizers were found to be not statistically (p > 0.05) different compared to those of CF. However, growth parameters were significantly (p < 0.05) higher in MNC fertilizer-treated crops than in CF-treated crops. Several predominant endophytes such as Penicillium spp., Aspergillus fumigatus, Rhizopus spp., and Fusarium spp. that could have significant effects on the enhancement of growth and nutritional properties of rice grains were identified in rice plants treated with MNC fertilizers at different concentrations. Contrarily, stem-associated Cercospora spp. was found in the CF-treated field and fission yeast was observed in the blank-treated field. In addition, the contents of proteins, fibers, carbohydrates, energy-yielding components, vitamin A, and minerals were significantly increased in rice plants treated with MNC fertilizers. Thus, we would like to conclude that MNC fertilizers could be one of the most potential alternatives to CFs for achieving better rice-endophyte symbiosis as well as nutritional improvements in rice grains for sustainable production.


Design and development of anti-hepatitis B virus agents.
Hepatitis B virus (HBV) infected hepatitis is the common infectious disease. In the World Conservative Estimate Plan, the number of persons chronically infected with HBV is more than 300 million. Current regimen of treatment is far from satisfactory, as it is associated with certain side effects and viral resistance capacity. Therefore, a serious attention has recently been paid to the design and development of new potent anti-HBV agents. A variety of drugs have been synthesized and screened for their anti-HBV effects. These include nucleosides, natural compounds, quinolines, benzodiazepines, indoles, etc. Many of them are in wide trend in current treatment regimen. In this review, we have presented the recent development on the design and development of all categories HBV inhibitors studied.


Effects of an upper-limb exercise program for improving muscular strength and range of movement on respiratory function of stroke patients.
[Purpose] This study aims to investigate the effects of upper-limb exercises on the respiratory functions of stroke patients. [Subjects and Methods] This study was performed with 25 stroke patients. The subjects were divided into the control group (n=12) which did not perform upper arm training and the experimental group (n=13) which conducted upper arm training. Forced vital capacity and forced expiratory volume in the first second, both of which are used in this study, are well-known indicators of respiratory capabilities. Peak cough flow is used to indicate cough capability. [Results] Concerning changes in forced vital capacity, forced expiratory volume in the first second and the peak cough flow of each group after the exercise, while the control group did not show significant differences, the experimental group showed statistically significant increases. [Conclusion] The results of the study indicate that exercise programs that increase the mobility of upper limbs and increase muscular strength have the effect of normalizing vertebral alignment for stroke patients, and thus can provide effective interventions for improving respiratory function.


Ban on Filipino maids going abroad, 20 January 1988.
On 20 January 1988, the President of the Philippines prohibited Filipino maids from going abroad to work. Later in 1988, the ban was lifted for some countries after the institution of safeguards in agreements with those countries. Among these countries is Saudi Arabia. See Philippine Labor, Vol. 14, No. 10, 1988.


Overexpression of clusterin in ovarian cancer is correlated with impaired survival.
Clusterin has been found to be overexpressed in several human malignancies and also be expressed in ovarian carcinoma tissues. However, to date, no study has investigated the prognostic significance of clusterin expression in ovarian carcinoma. Therefore, we examined the relationship between clusterin overexpression and clinicopathological features to determine its prognostic relevance. Eighty-six patients diagnosed with primary ovarian cancer between 1993 and 2004 were selected and recorded follow-up data and clinicopathological data. The expression of clusterin was detected on the sections of tissue microarray by immunohistochemistry and was evaluated the association with patient's clinical features and prognosis. Overexpression of clusterin protein in ovarian cancer was observed in 46.5% of the patients and was found more often in disease that was in the advanced stage (P = 0.0001). The expression levels of clusterin was associated with International Federation of Gynecology and Obstetrics stage (P = 0.0001) and histologic type (P = 0.002). However, no significant association was observed between clusterin expression and patient age or tumor Silverberg grade (P > 0.05). In addition, the average survival time of the patients with clusterin overexpression was significantly shorter than that with normal expression of clusterin. Clusterin expression was associated with survival of patients with primary ovarian cancer (relative risk for overall survival 1.69; 95% confidence interval, 1.52 to 1.95 (P = 0.033)). Our data show that clusterin is not only a biomarker associated with ovarian cancer, but it also appears to be a prognostic factor associated with adverse outcome.


Pooled analysis of the prognostic and predictive effects of KRAS mutation status and KRAS mutation subtype in early-stage resected non-small-cell lung cancer in four trials of adjuvant chemotherapy.
We undertook this analysis of KRAS mutation in four trials of adjuvant chemotherapy (ACT) versus observation (OBS) to clarify the prognostic/predictive roles of KRAS in non-small-cell lung cancer (NSCLC). KRAS mutation was determined in blinded fashion. Exploratory analyses were performed to characterize relationships between mutation status and subtype and survival outcomes using a multivariable Cox model. Among 1,543 patients (763 OBS, 780 ACT), 300 had KRAS mutations (codon 12, n = 275; codon 13, n = 24; codon 14, n = 1). In OBS patients, there was no prognostic difference for overall survival for codon-12 (mutation v wild type [WT] hazard ratio [HR] = 1.04; 95% CI, 0.77 to 1.40) or codon-13 (HR = 1.01; 95% CI, 0.47 to 2.17) mutations. No significant benefit from ACT was observed for WT-KRAS (ACT v OBS HR = 0.89; 95% CI, 0.76 to 1.04; P = .15) or codon-12 mutations (HR = 0.95; 95% CI, 0.67 to 1.35; P = .77); with codon-13 mutations, ACT was deleterious (HR = 5.78; 95% CI, 2.06 to 16.2; P < .001; interaction P = .002). There was no prognostic effect for specific codon-12 amino acid substitution. The effect of ACT was variable among patients with codon-12 mutations: G12A or G12R (HR = 0.66; P = .48), G12C or G12V (HR = 0.94; P = .77) and G12D or G12S (HR = 1.39; P = .48; comparison of four HRs, including WT, interaction P = .76). OBS patients with KRAS-mutated tumors were more likely to develop second primary cancers (HR = 2.76, 95% CI, 1.34 to 5.70; P = .005) but not ACT patients (HR = 0.66; 95% CI, 0.25 to 1.75; P = .40; interaction, P = .02). KRAS mutation status is not significantly prognostic. The potential interaction in patients with codon-13 mutations requires validation. At this time, KRAS status cannot be recommended to select patients with NSCLC for ACT.


The influence of empty-nest living on the health of the older people living in the rural areas of Lishui, China: A cross-sectional study.
The empty-nest older people are becoming a significant social phenomenon in the rural of China. Most studies on the health of the empty-nest older people contain these older people who have no children or dead children. The emotional experience of the older people with and without children is quite different, our study only chose the empty-nest older people who had children in the rural of Lishui, China. The purpose of this study is to explore the differences of the health conditions between empty-nest and non-empty-nest older people living in the rural areas of China, including items of chronic metabolic diseases, fall injury, and mental health. Our research found that empty-nest older people had higher incidence of fall injury (17.00% vs 6.31%, P = .006) and suffer more severe depression (P = .015) than the non-empty-nest older people. The adjusted odds ratio of fall injury and depression for empty-nest older people compared with the non-empty-nest older people were 2.76 (95% CI, 1.17-6.48) and 2.25 (95% CI, 1.36-3.67), respectively. Our results suggest that empty-nest older people are more likely to suffer from depression and fall injury than non-empty-nest older people living in the rural of China.


Defining the management role of the department medical director.
Through analysis of medical and administrative director positions it is possible to identify an organizational structure for medical departments that enhances departmental operations. Possible roles and tasks that describe managerial responsibilities are considered, and a review of the literature identifies options for how these roles or tasks can be shared between medical and nonmedical managers at the departmental level. These options are refined based on interviews with department-level managers at a case study hospital. Three models are then explored: unity of command, shared accountability, and split accountability. The unity of command model is recommended. In this model, the medical director assumes total authority and accountability for departmental operations through some sort of "enfranchisement." A more formal planning process and a review of job descriptions are also recommended.


Composite endpoints in trials of type-2 diabetes.
Composite endpoints (CEPs) are being used more frequently as outcomes for trials of drugs in type-2 diabetes. We reviewed the literature to determine how CEPs have been used to date in trials of drugs for type-2 diabetes. A systematic search was undertaken on Medline, Embase and Cochrane databases and Clinicaltrials.gov for randomized controlled trials of currently marketed agents including SGLT-2 inhibitors (dapagliflozin), GLP-1 agonists (exenatide, liraglutide) and DPP-4 inhibitors (linagliptin, saxagliptin, sitagliptin and vildagliptin). CEPs used were identified as well as numbers and percentages of patients achieving each. Thirty-six studies were identified that reported results on ≥1 CEP; 15 different CEPs were reported (7 with 2 components, 8 with 3 components). All CEPs addressed goals recommended by the American Diabetes Association (ADA). All included HbA1c<7%; other endpoints measured weight, blood pressure and hypoglycaemic events. Results were obtained for CEPs from 6 months to 2 years. Rates of achieving CEPs decreased with increasing numbers of components and outcomes assessed. CEPs are becoming used as indicators of clinical outcomes in type-2 diabetes trials, but are still not common. More research is required to identify optimal CEPs. Standardization of outcomes and their reporting is needed.


Standard Assays for the Study of Autophagy in the Ex Vivo Retina.
Autophagy is a catabolic pathway that mediates the degradation and recycling of intracellular components, and is a key player in a variety of physiological processes in cells and tissues. Recent studies of autophagy in the eye suggest that this pathway is fundamental for the preservation of retinal homeostasis. Given its accessible location outside the brain, the retina is an ideal organ in which to study the central nervous system and a wide range of neuronal processes, from development to neurodegeneration. Here we review several methods used to assess autophagy in the retina in both physiological and pathological conditions.


Management of uncorrected exstrophy of the bladder in women.
A 28-year-old Hispanic woman presented with uncorrected exstrophy of the bladder and accompanying defects of the external genitalia. These defects were corrected in a single operation. The objectives of the operation and the rationale for choosing the specific methods used are discussed in detail.


Gas chromatography/mass spectrometric study of non-commercial C-4-substituted 1,4-dihydropyridines and their oxidized derivatives.
A gas chromatography/mass spectrometry (GC/MS) method for the qualitative and quantitative determination of the calcium-channel antagonists C-4-substituted 1,4-dihydropyridines, and their corresponding N-ethyl derivatives, is presented. Also, the electrochemical oxidation and the reactivity of the compounds with alkyl radicals derived from 2,2'-azobis-(2-amidinopropane) were monitored by GC/MS. Mass spectral fragmentation patterns for the C-4-substituted 1,4-dihydropy-ridine parent drugs were significantly different from those of their oxidation products, generated either by electrochemical oxidation or by reaction with alkyl radicals. However, for N-ethyl-1,4-dihydropyridine compounds it was not possible to detect the final products (pyridinium salts) using these experimental conditions.


Expression of TRIM28 correlates with proliferation and Bortezomib-induced apoptosis in B-cell non-Hodgkin lymphoma.
Tripartite motif containing 28 (TRIM28) as a transcriptional co-repressor has been reported playing a role in regulating DNA damage response (DDR), cell differentiation, immune response, and tumorigenesis. The present study was performed to explore the biological function and clinical significance of TRIM28 in B-cell non-Hodgkin lymphoma (B-NHL). Results of the study displayed that high expression of TRIM28 was positively associated with the poorer survival of B-NHL patients as an independent prognostic factor. In addition, TRIM28 could promote the B-NHL cells proliferation through modulating cell cycle progression. The change of cyclinA, P21, and PCNA expression after TRIM28 expression modified further illustrated the mechanism in which TRIM28 participated in cell proliferation progression. Moreover, inhibition TRIM28 expression in B-NHL cells enhanced the sensibility to Bortezomib by regulating p53-mediated apoptosis pathway. Taken together, the present study showed that TRIM28 functions as a tumor promoter in B-NHL and may be a novel target for drug resistance to Bortezomib.


Increased epoxyeicosatrienoic acids and reduced soluble epoxide hydrolase expression in the preeclamptic placenta.
Epoxyeicosatrienoic acids (EETs) derived from cytochrome P450 (CYP)-dependent metabolism of arachidonic acid are increased in the plasma of women with preeclampsia as compared with normal pregnancy and are significantly higher in fetal than in maternal plasma and erythrocytes. We hypothesized that differences in EET synthesis or metabolism in the feto-placental unit contributed to the observed differences in circulating EETs. To evaluate EETs, formation as well as the expression of relevant CYP isoforms and the metabolizing enzyme, soluble epoxide hydrolase (sEH), biopsies of placenta were collected from 19 normal pregnancy and 10 preeclampsia at the time of cesarean section delivery. EETs were extracted from tissue homogenates and analyzed by liquid chromatography coupled with tandem mass spectrometry. Both cis-EETs and trans-EETs were detected in the placenta. Concentration of total EETs was higher in the placenta from preeclampsia compared with normal pregnancy (2.37 ± 1.42 ng/mg vs. 1.20 ± 0.72 ng/mg, mean ± SD, P < 0.01), especially the 5,6-, 8,9- and 11,12-EETs, measured in a subgroup of tissue samples (normal pregnancy = 10, preeclampsia = 5). By immunohistochemistry, sEH, CYP2J2, CYP4A11 were present in placental villi with different pattern distribution, whereas CYP2C8 was not detectable. Neither were CYP2J2, CYP4A11, and CYP2C8 detected in the umbilical cord. Western blot analysis of placenta homogenates showed reduced expression of sEH in preeclampsia as compared with normal pregnancy. Increased EETs in the placenta and umbilical cord are associated with the presence of CYP2J2, whereas reduced expression of sEH in preeclampsia may be the key factor of increased EETs in the placenta.


[Accessibility for water molecules and relative stability of the A- and B-forms of DNA].
Accessible surface areas of DNA molecules (A- and B-forms) for different probe particle radii were calculated for poly(dA).poly(dT) and poly[d(A-T)].poly[d(A-T)] sequences. The problem of different forms stability is discussed in connection with accessible surface area characteristics as well as coulombic interaction between base pairs. The coulombic interaction was shown to play an important role in sequence dependent stability of the DNA molecule.


C-alkylation of N-acetoxy-N-2-acetylaminofluorene: effects on its reaction with DNA in vitro.
In vitro reactions of DNA with N-acetoxy-N-2-acetylaminofluorene (N-AcO-AAF), N-acetoxy-7-ethyl-N-2-acetylaminofluorene (N-AcO-EtAAF), N-acetoxy-7-n-butyl-N-2-acetylaminofluorene (N-AcO-But-AAF) are compared. C-alkylation of N-AcO-AAF affects the reactivity of the metabolite towards DNA. The electronic effect and the size of alkyl group seem to determine the reactivity of the metabolite. Although the adducts are about the same for the three metabolites, the proportion of guanine-C-8 adducts diminishes with an increase in the size of the alkyl group.


Online faculty development in low- and middle-income countries for health professions educators: a rapid realist review.
Health professions educators require support to develop teaching and learning, research, educational leadership, and administrative skills to strengthen their higher education role through faculty development initiatives. Where administration has pursued face-to-face and online faculty development initiatives, results have positively influenced health professions educators. There is limited evidence demonstrating how online faculty development works for health professions educators in low- and middle-income countries who engage in online health professions education (HPE) faculty development. A Conjecture Map for online HPE faculty development courses identified candidate theories for a rapid realist review. The Conjecture Map and candidate theories, Community of Inquiry and the Conversational Framework guided the development of search terms and analysis for this review. Three searches using EbscoHost databases yielded 1030 abstracts. A primary and secondary research team participated in a multi-reviewer blinded process in assessing abstracts, selecting full-text articles, and data extraction. The primary research team analysed eight articles for this rapid realist review to answer the research question: How do online HPE faculty development courses work, or not work, in low- and middle-income countries? Data were analysed and mapped to the initial Conjecture Map and the research question. The research references US-based organisations forming partnerships with low- and middle-income countries, and who provide funding for online HPE faculty development initiatives. These initiatives design courses that facilitate learning through engagement from which participants report beneficial outcomes of professional and career development. The review does not clarify if the reported outcomes are generalisable for facilitators from low-and middle-income countries. The findings of this review demonstrate the role of a community of practice as the dominant mechanism through which the outcomes are achieved, based on a design that incorporates six triggering events. The design aligns the triggering events with the three categories of the Community of Inquiry-a theory for designing online learning environments. Health professions educators in low- and middle-income countries can develop professional and interpersonal skills through a well-designed, specifically constructed online community that prioritises active discussion.


The coronary anomaly: right coronary artery originates from the mid left anterior descending artery.
The most common coronary anomaly is the left circumflex artery (LCX) arising from the proximal right coronary artery (RCA). This variant is benign. The anomalous RCA often originates from the left sinus or from the proximal of the left main coronary artery. This case report presents a single coronary artery that is the RCA originating from the mid left anterior descending artery. The case is rare. We discuss how to make a accurate diagnosis and how to administer appropriate treatment.


In Situ Crumpling of Gold Nanosheets into Spherical Three-Dimensional Architecture: Probing the Aggregation-Induced Enhancement in Photothermal Properties.
Assembling two-dimensional noble metal nanocrystals into a three-dimensional mesoporous structure is of great value to solve the re-stacking issue for the practical application, which still remains a challenging technique. Herein, we report the one-pot fabrication of gold (Au) nanostructures with a crumpled paper ball-like morphology (Au NCPBs). The success of current work relies on the use of glutathione to crumple the branched Au nanosheets formed during the early stage, into spherical three-dimensional architecture, where the nanosheets are assembled with a mesoporous structure without intimate contact. When working as the agent toward photothermal conversion, the Au NCPBs exhibit enhanced photothermal conversion efficiency (η = 19.9%), as compared to that of flat and wrinkled Au nanosheets. Such an enhancement should be owing to the aggregation-induced effect, where the shortened inter-sheet distance contributes to an increased coupling between the plasmon oscillations/fields of the interacting Au nanosheets. The present study offers a feasible strategy to create spherical architecture of crumpled Au nanosheets and validates their structural advantage in photothermal applications, which could be potentially extended to other metals or alloys.


Research issues for nursing and midwifery contributions in emergencies.
This special report was prepared as a white paper for the First World Health Organization (WHO) Consultation on Nursing and Midwifery Contributions in Emergencies held in Geneva on 22-24 November 2006. Pertinent issues related to research of nurses and midwives were identified based on prior international conferences. Using this information, gaps between the current and proposed state of preparedness research activities were identified. Global perspective recommendations were made for consideration by the WHO and other nursing organizations. Finally, possible discussion questions were posed that were used during the consultation, but could also be used in other international nursing conferences.


Does Complexity Equal Anything?
We present a new infinite class of gravitational observables in asymptotically anti-de Sitter space living on codimension-one slices of the geometry, the most famous of which is the volume of the maximal slice. We show that these observables display universal features for the thermofield-double state: they grow linearly in time at late times and reproduce the switchback effect in shock wave geometries. We argue that any member of this class of observables is an equally viable candidate as the extremal volume for a gravitational dual of complexity.


Electro-extractive fermentation for efficient biohydrogen production.
Electrodialysis, an electrochemical membrane technique, was found to prolong and enhance the production of biohydrogen and purified organic acids via the anaerobic fermentation of glucose by Escherichia coli. Through the design of a model electrodialysis medium using cationic buffer, pH was precisely controlled electrokinetically, i.e. by the regulated extraction of acidic products with coulombic efficiencies of organic acid recovery in the range 50-70% maintained over continuous 30-day experiments. Contrary to previous reports, E. coli produced H(2) after aerobic growth in minimal medium without inducers and with a mixture of organic acids dominated by butyrate. The selective separation of organic acids from fermentation provides a potential nitrogen-free carbon source for further biohydrogen production in a parallel photofermentation. A parallel study incorporated this fermentation system into an integrated biohydrogen refinery (IBR) for the conversion of organic waste to hydrogen and energy.


Generic placement of the Neotropical species of " Phragmatobia" (Erebidae, Arctiinae), with a remarkable matrivorous species from the Peruvian Andes.
Phragmatobia Stephens is briefly reviewed and a diagnosis is provided. The South American species currently placed in Phragmatobia Stephens are revised to two new genera, Andesobia Schmidt and De Freina, gen. n., and Patagobia Schmidt and De Freina, gen. n. (subtribe Spilosomina). Both Andesobia and Patagobia exhibit adaptations to high altitude habitats, including micropterous females in Andesobia (Patagobia females are unknown) and diurnal flight of males. The adults, immature stages, and mating behaviour of Andesobia jelskii (Oberthür, 1881) are described. Males of Andesobia jelskii enter the female cocoon to mate, and the micropterous, flightless females remain in the cocoon following oviposition where newly hatched larvae feed initially on the female's body.Four species are included in Andesobia, Andesobia jelskiicomb. n. (= Paracles imitatrix Rothschild, 1922, syn. n.), Andesobia flavata (Hampson, 1901), comb. n., Andesobia boliviana (Gaede, 1923), comb. n. (=Turuptiana flavescens Rothschild, 1933, syn. n.), and Andesobia sanguinea (Hampson, 1907), comb. n.Patagobia includes only Patagobia thursbyi (Rothschild, 1910), comb. n., and Patagobia thursbyi pluto Toulgoët is relegated to its synonymy. Patagobia shows affinities to Phaos Walker, 1855 of Australia, Metacrias Meyrick, 1886 of New Zealand, and Pseudophragmatobia Krüger, 2009 of South Africa, suggesting a common ancestry of circumantarctic origin. Phragmatobia karsholti Toulgoët, 1991 is transferred to Venedictoffia Toulgoët, comb. n., an unrelated genus that is removed from subtribe Arctiina and provisionally placed in the Phaegopterina. Phragmatobia oberthueri Rothschild, 1910, described from Tibet, is a synonym of Lachana alpherakii (Grum-Grzhimailo, 1891) [Erebidae: Lymantriinae], syn. n., comb. n.


Morphology and Thermal Properties of Calcium Alginate/Reduced Graphene Oxide Composites.
Calcium alginate (CaAlg) is a kind of biodegradable and eco-friendly functional material, and CaAlg/reduced graphene oxide (rGO) composites are expected to be applied as new textile, heat-generating, and flame-retardant materials. In this paper, the CaAlg/rGO composites were prepared by a sol-gel method and their morphological and thermal properties were studied. The results showed that the introduction of rGO can efficiently improve the thermal stability of CaAlg. Further study showed that rGO increased the carbon formation rate by 4.1%, indicating that the thermal stability was improved by the promotion of carbon formation. Moreover, the weight loss rate of the composites was faster at 180⁻200 °C than that of CaAlg, after which the rate was less comparatively, suggesting the better thermal stability of the composite. This maybe because the high heat transfer efficiency of rGO allowed the material to reach the temperature of the thermal decomposition of the glycan molecule chain within a short time, and then promoted carbon formation. The thermal cracking mechanism of the composites is proposed based on the experimental data.


Physical activity monitoring: a responsive and meaningful patient-centered outcome for surgery, chemotherapy, or radiotherapy?
In surgical and clinical oncology, there is a growing need for patient-centered outcomes that are responsive, meaningful, and fit for purpose. The aim of this study was to validate physical activity (PA) monitoring as a responsive outcome measure at different stages of disease and treatment, by verifying correlations between PA, performance score, and quality of life (QoL). Daily life PA of 162 cancer patients, monitored by a device that records time sitting/lying, time standing, time walking, number of steps taken, and walking cadence, was compared with 20 healthy volunteers. In a subgroup of patients, functional status and QoL were assessed using the World Health Organization/Eastern Cooperative Oncology Group and the Karnofsky Performance Status scores and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) questionnaire. The PA of patients with resectable gastrointestinal cancer did not differ significantly from controls. In contrast, patients with advanced cancer took 45% fewer steps and spent an extra 2.8 hours/day lying/sitting (P=0.001). Patients undergoing neoadjuvant chemotherapy and surgery (5-6 weeks after operation) experienced a similar reduction in PA. There were significant correlations between PA and the physical and role domains as well as fatigue subscale of the EORTC QLQ-C30 scale. Objective PA scores correlate significantly with disease stage, functional status, and QoL of patients with cancer. Therefore, activity monitoring can make meaningful objective estimates of patient function in response to cancer and its treatment and may provide surrogate outcomes of QoL.


Serum antibodies against peripheral nervous system antigens in leprosy.
Since antibodies against peripheral nervous system (PNS) antigens may play a pathogenetic role in the mechanism of nerve damage in leprosy, sera from leprosy patients and contacts were investigated for anti-PNS antibodies by ELISA and immunoblot. In ELISA, elevated anti-PNS antibody levels were detected in 4 of 98 (4.1%) leprosy patients (4 of 52, 7.7%, lepromatous leprosy patients), in 1 of 28 (3.6%) contacts, and in 1 of 18 (5.6%) normal controls. There was no correlation between anti-PNS antibody levels and the bacterial index or neuropathy in leprosy. Immunoblot with a sample of six leprosy and five control sera showed that the antigenic binding pattern (mainly within the 100-200-kDa region) was very similar in patients and controls. Staining intensity, however, appeared to be higher with the leprosy sera than with the control sera. IgM and IgG were found to contribute to the staining pattern: IgM in the 150-200-kDa range, IgG with multiple bands between 25 kDa and 200 kDa. Thus, the presence and levels of serum anti-PNS antibodies in leprosy appear to be unrelated to parameters of disease activity, neuropathy in particular, and do not seem to be critically involved in the pathogenesis of nerve damage.


The effect of insulin and FFA on myocardial glucose uptake.
In addition to direct stimulation of glucose uptake and metabolism in cardiac myocytes, insulin inhibits lipolysis and, thereby, reduces serum free fatty acid (FFA) concentrations. This, in turn, has been suggested to enhance myocardial glucose utilization. To study the mechanism of insulin action on myocardial glucose uptake (MGU) in vivo, five patients with stable coronary artery disease were studied with positron emission tomography (PET) and [18F]FDG. All patients underwent two PET studies after a 12-h fast, once during low serum FFA but high insulin concentrations (during insulin clamp), and once during low serum FFA and low insulin concentrations (in the fasting state after two oral doses of 250 mg of an antilipolytic drug, acipimox). The MGU in the normal myocardium was measured using dynamic PET imaging. Plasma glucose concentrations were comparable during the insulin clamp and after administration of acipimox (5.0 +/- 0.4 v 5.2 +/- 0.3 mmol/l, n.s.). Serum insulin concentrations were high during clamp but remained in low fasting concentrations after acipimox (74 +/- 9 mU/l v 6 +/- 5 mU/l, P = 0.0001). Serum FFA concentrations were similar during both approaches (230 +/- 110 v 200 +/- 40 mumol/l, respectively, n.s.). No difference in cardiac work load was detected between the approaches. The calculated MGU values in normal myocardium were similar during both approaches (57 +/- 23 mumol/min/100 g v 61 +/- 14 mumol/min/100 g, respectively, n.s.). The MGU values correlated inversely to serum FFA concentration (r = -0.87, P = 0.001) and directly to myocardial work load (r = 0.73, P = 0.016) but not to serum insulin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)


Omega-3 Polyunsaturated Fatty Acids EPA and DHA as an Adjunct to Non-Surgical Treatment of Periodontitis: A Randomized Clinical Trial.
Periodontitis is a chronic multifactorial inflammatory disease that leads to the loss of supportive tissues around the teeth with gradual deterioration of masticatory function and esthetics, resulting eventually in the decrease of the life quality. Host immune response triggered by bacterial biofilm is responsible for the chronic periodontal inflammation and ongoing tissue loss. Omega-3 polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory properties, thus may be used for the treatment of chronic inflammatory diseases. In this study, we aimed to evaluate the effect of dietary supplementation with omega-3 PUFA in the patients with stage III and IV periodontitis. Thirty otherwise healthy patients were treated with scaling and root planning (SRP). In the test group (n = 16), patients were additionally supplemented with 2.6 g of EPA and 1.8 g of DHA. In the control group (n = 14), patients received only SRP. Periodontal examination was performed at baseline and three months following initial therapy. Salivary samples were taken twice at baseline and at the end of the experiment. We found that there was a statistically significant reduction in the bleeding on probing (BOP) and improvement of clinical attachment loss (CAL) at three months in the test group compared to the control group. Moreover, a statistically significant higher percentage of closed pockets (probing depth ≤ 4 mm without BOP) was achieved in the test group vs. control group after three months of treatment. Accordingly, the levels of pro-inflammatory cytokines/chemokines interleukin (IL)-8 and IL-17 were markedly lower, while the level of anti-inflammatory IL-10 was significantly higher in the salivary samples of the patients supplemented with omega-3 PUFA at three months in comparison to the patients treated with SRP alone. Our findings demonstrate that dietary intervention with high-dose of omega-3 PUFA during non-surgical therapy may have potential benefits in the management of periodontitis.


Acute and chronic effects of anti-endothelin-1 antibody on blood pressure in spontaneously hypertensive rats.
To evaluate the significance of endogenous endothelin (ET) in the maintenance of blood pressure in hypertensive and normotensive conditions, we examined the acute and chronic effects of anti-ET-1 antibody in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. Immunoglobulin (Ig) solution purified from anti-ET-1 rabbit serum was injected intravenously in conscious rats aged 12-14 weeks (SHR: n = 7, WKY: n = 7). In the control group (SHR: n = 5, WKY: n = 4), Ig prepared from nonimmune rabbit serum was administered. One week after the first injections of Ig, second intravenous injections were given. After the intravenous injections of ET-1 antibody, there were no significant changes in directly measured blood pressure (BP) for up to 60 min in both strains. On the first, third, and seventh days after the first administration of ET-1 antibody, as well as on the first, third, and seventh days after the second injection, there were no appreciable differences in BP between SHR treated with anti-ET-1 antibody and SHR with control Ig. No significant changes in BP were observed throughout the observation period in WKY groups. Plasma levels of immunoreactive ET-1 were similar in SHR and WKY. This study suggests that circulating ET may not play a significant role in the maintenance of hypertension in SHRs or in the regulation of blood pressure in WKY rats.


On a probability distribution to study the open birth interval and its application.
"A probability distribution for describing the variation in the length of open birth interval regardless of parity has been derived assuming that fecundability varies from female to female and the births are of two types, one which results [in] infant death and the other [which does] not. To get the estimates of the parameters, expressions for the first two moments have been derived. The model has been applied to the data taken from the survey 'Rural Development and Population Growth--A Sample Survey 1978,' conducted under the auspices of the Demographic Research Centre, Banaras Hindu University [India]."


Enrichment of activated sludge in a sequencing batch reactor for polyhydroxyalkanoate production.
The paper describes the start up of a process for the production of polyhydroxyalkanoates (PHAs) from activated sludge. The excess sludge from a wastewater treatment plant was inoculated in a lab-scale sequencing batch reactor (SBR) to be enriched under aerobic conditions through intermittent feeding with a mixture of organic acids. Enriching of activated sludge was monitored through the measurement of polymer concentrations either in the mixed liquor or in the microbial biomass. The bacterial population dynamics during the SBR start up was followed through denaturing gradient gel electrophoresis and the main species present at the steady state were identified. All the measured parameters significantly changed in the SBR during first two weeks after the inoculum was seeded into the reactor, they then stabilized. At the steady state, the SBR produced 2.6 gVSSl(-1) d(-1), with a PHA content of 11% (on a COD basis). The enriched microbial biomass was then transferred into a batch reactor where the bacterial polymer content was increased through a new feeding. In the final batch stage, maximum storage rate and maximum polymer content in the biomass were 405 mgCOD gCOD(-1) h(-1) and 44% (on a COD basis), respectively. The PHA storage from the enriched microbial biomass was about 20 times faster and the PHA content was about 4 times higher than that of the inoculated activated sludge. Observations by fluorescence microscopy showed that the majority of microorganisms in the enriched biomass could be stored. Among the numerically most representative genera in the enriched biomass, Thauera, Candidatus Meganema perideroedes, and Flavobacterium were identified.


Prognostic significance of sites of extrathoracic metastasis in patients with non-small cell lung cancer.
Metastatic non-small cell lung cancer (NSCLC) continues to have a poor prognosis despite recent advances in both targeted radiotherapy methodologies such as stereotactic body radiotherapy (SBRT) and immunotherapies. The impact of location of metastatic disease in patients with NSCLC has not been investigated; we aimed to investigate this using the Surveillance, Epidemiology, and End Results (SEER) database. We included 39,910 patients from the SEER database treated for M1b NSCLC from 2010-2013. We identified patients with metastatic disease in the brain, lung, liver, and bone. We used Kaplan-Meier analyses and Cox proportional hazards models to assess the impact of varying sites of metastatic disease on overall survival (OS). Patients with disease coded as in the brain without other disease in the lung, liver, or bone had improved OS relative to all other comers with M1b disease (HR =0.84, 95% CI, 0.84-0.90, P<0.001). Likewise, patients with disease coded as in the bone without other disease in the lung, liver, or brain had improved OS relative to all other comers with M1b disease (HR =0.89, 95% CI, 0.86-0.92, P<0.001). This hypothesis-generating analysis suggests that patients with limited metastatic NSCLC to the bone or brain may particularly benefit from aggressive upfront therapies.


Stable NaCl Tolerance of Tobacco Cells Is Associated with Enhanced Accumulation of Osmotin.
Osmotin is a major protein which accumulates in tobacco cells (Nicotiana tabacum L. var Wisconsin 38) adapted to low water potentials. Quantitation of osmotin levels by immunoblots indicated that cells adapted to 428 millimolar NaCl contained 4 to 30 times the level of osmotin found in unadapted cells, depending on the stage of growth. Unadapted cells accumulated low levels of osmotin with apparent isoelectric points, (pl) of 7.8 and >8.2. Upon transfer of NaCl-adapted cells to medium without NaCl and subsequent growth for many cell generations, the amount of osmotin declined gradually to a level intermediate between that found in adapted and unadapted cells. NaCl-adapted cells grown in the absence of NaCl accumulated both pl forms; however, the form accumulated by cells adapted to NaCl (pl > 8.2) was most abundant. Adapted cells grown in the absence of NaCl exhibited absolute growth rates and NaCl tolerance levels which were intermediate to those of NaCl-adapted and unadapted cells. The association between osmotin accumulation and stable NaCl tolerance indicates that cells with a stable genetic change affecting the accumulation of osmotin are selected during prolonged exposure to high levels of NaCl. This stable alteration in gene expression probably affects salt tolerance.


SAR Exploration of Tight-Binding Inhibitors of Influenza Virus PA Endonuclease.
Significant efforts have been reported on the development of influenza antivirals including inhibitors of the RNA-dependent RNA polymerase PA N-terminal (PAN) endonuclease. Based on recently identified, highly active metal-binding pharmacophores (MBPs) for PAN endonuclease inhibition, a fragment-based drug development campaign was pursued. Guided by coordination chemistry and structure-based drug design, MBP scaffolds were elaborated to improve activity and selectivity. Structure-activity relationships were established and used to generate inhibitors of influenza endonuclease with tight-binding affinities. The activity of these inhibitors was analyzed using a fluorescence-quenching-based nuclease activity assay, and binding was validated using differential scanning fluorometry. Lead compounds were found to be highly selective for PAN endonuclease against several related dinuclear and mononuclear metalloenzymes. Combining principles of bioinorganic and medicinal chemistry in this study has resulted in some of the most active in vitro influenza PAN endonuclease inhibitors with high ligand efficiencies.


Gene expression profile prospectively predicts peritoneal relapse after curative surgery of gastric cancer.
Peritoneal relapse is the most common pattern of tumor progression in advanced gastric cancer. Clinicopathological findings are sometimes inadequate for predicting peritoneal relapse. The aim of this study was to identify patients at high risk of peritoneal relapse in a prospective study based on molecular prediction. RNA samples from 141 primary gastric cancer tissues after curative surgery were profiled using oligonucleotide microarrays covering 30,000 human probes. Firstly, we constructed a molecular prediction system and validated its robustness and prognostic validity by 500 times multiple validation by repeated random sampling in a retrospective set of 56 (38 relapse-free and 18 peritoneal-relapse) patients. Secondly, we applied this prediction to 85 patients of the prospective set to assess predictive accuracy and prognostic validity. In the retrospective phase, repeated random validation yielded approximately 68% predictive accuracy and a 22-gene expression profile associated with peritoneal relapse was identified. The prediction system identified patients with poor prognosis. In the prospective phase, the molecular prediction yielded 76.9% overall accuracy. Kaplan-Meier analysis of peritoneal-relapse-free survival showed a significant difference between the "good signature group" and "poor signature group" (log-rank p = 0.0017). Multivariate analysis by Cox regression hazards model identified the molecular prediction as the only independent prognostic factor for peritoneal relapse. Gene expression profile inherent to primary gastric cancer tissues can be useful in prospective prediction of peritoneal relapse after curative surgery, potentially allowing individualized postoperative management to improve the prognosis of patients with advanced gastric cancer.


IFN regulatory factor 3 contributes to the host response during Pseudomonas aeruginosa lung infection in mice.
Pseudomonas aeruginosa is a major opportunistic pathogen. However, host defense mechanisms involved in P. aeruginosa lung infection remain incompletely defined. The transcription factor IFN regulatory factor 3 (IRF3) is primarily associated with host defense against viral infections, and a role of IRF3 in P. aeruginosa infection has not been reported previously. In this study, we showed that IRF3 deficiency led to impaired clearance of P. aeruginosa from the lungs of infected mice. P. aeruginosa infection induced IRF3 translocation to the nucleus, activation of IFN-stimulated response elements (ISRE), and production of IFN-beta, suggesting that P. aeruginosa activates the IRF3-ISRE-IFN pathway. In vitro, macrophages from IRF3-deficient mice showed complete inhibition of CCL5 (RANTES) and CXCL10 (IP-10) production, partial inhibition of TNF, but no effect on CXCL2 (MIP-2) or CXCL1 (keratinocyte-derived chemokine) in response to P. aeruginosa stimulation. In vivo, IRF3-deficient mice showed complete inhibition of CCL5 production and partial or no effects on production of other cytokines and chemokines in the bronchoalveolar lavage fluids and lung tissues. Profiling of immune cells in the airways revealed that neutrophil and macrophage recruitment into the airspace was reduced, whereas B cell, T cell, NK cell, and NKT cell infiltration was unaffected in IRF3-deficient mice following P. aeruginosa lung infection. These data suggest that IRF3 regulates a distinct profile of cytokines and chemokines and selectively modulates neutrophil and macrophage recruitment during P. aeruginosa infection. Thus, IRF3 is an integral component in the host defense against P. aeruginosa lung infection.


Evaluation of the Happiness Through Goal-Setting Training.
This paper describes the evaluation of the Happiness through Goal-Setting Training, a multiple intervention approach which helps participants to reflect on, and modify their reasons for goal pursuit. The training is theoretically grounded in the goal-striving reasons framework. This framework captures four important reasons for goal pursuit and has received a substantial amount of empirical support for its predictive power in relation to positive psychological functioning. The four goal-striving reasons are the pursuit of goals out of pleasure, altruism, fear of self-esteem loss or necessity. The evaluation of the training, employing a before-and-after study design, is based on two data sets comprising data from a face-to-face delivery of the training (N = 41) and an online delivery of the training (N = 40). Overall, the findings from both studies, using paired sample t-tests, show that the Happiness through Goal-Setting Training significantly improves the quality of people's reasons for goal pursuit as well as their positive psychological functioning measured through life satisfaction, positive affect, negative affect and work-engagement. Thus, the Happiness through Goal-Setting Training complements the existing suite of well-being interventions by providing a happiness training that focusses specifically on improving people's reasons for goal-pursuit.


Inhibition of TEA-induced LTP by aluminum.
Brief application of tetraethylammonium (TEA) to hippocampal slices causes long-term potentiation (TEA LTP) at synapses of CA1 pyramidal neurons characterized by a long-lasting increase of field excitatory postsynaptic potential (fEPSP) slope and population spike (PS) amplitude. Since this kind of potentiation requires the activation of voltage-dependent calcium channels, we examined the effect of the inorganic calcium channel blocker aluminum, which has been shown to impair tetanus-induced LTP (eLTP). We found that Al inhibited in a concentration-dependent manner both fEPSP slope and PS amplitude potentiation by TEA; 0.68 microgram/ml A1 attenuated TEA LTP, while a complete block of long-lasting potentiation was obtained for 2.7 micrograms/ml Al. Occlusion experiments revealed that both concentrations of Al allowed the induction of eLTP 60 min after TEA/Al exposure. However, longer application (15 min) of 2.7 micrograms/ml Al before the induction of TEA LTP prevented the subsequent induction of eLTP although no significant differences concerning the action on TEA LTP were observed. This indicates a general loss of neuronal plasticity which might be due to progressive neuronal cell damage. Since the effective concentration range of Al is directly comparable to the action of Al on eLTP, our data provide evidence for shared mechanisms of both potentiations. Although based on different induction mechanisms, Ca2+ is assumed to be a general intracellular trigger for both forms of LTP and thus it can be hypothesized that the neurotoxic action of Al is due to interference with Ca(2+)-dependent processes by inhibition of calcium conductances.


[Surgery for hyperthyroidism. Results and current trends].
From 1974 to 1990, the same surgeon operated 96 cases of hyperthyroidism: 72 cases of Basedow's disease, and 24 basedoid goiters. The preliminary preparation with antithyroid agents, sedation, Lugol and beta-blockers is particularly important, as is rehydration, high-dose sedation and beta-blockers, if required, during the postoperative period. There are few complications: 1 hematoma, 1 permanent unilateral laryngeal paralysis, 1 permanent hypocalcemia, 5 transient psychical and/or cardiac disorders, 1 malignant exophthalmia. There was no thyrotoxic crisis. Long-term follow-up allows nothing 4 recurrences as well as hypothyroidism in 46% of all cases. The size of the thyroid remains left in place is closely related to hypothyroidism. One case of vesiculo-papillary carcinoma is noted among the 24 cases of basedoid goiters (4.5%), which justifies total thyroidectomy in such cases. There also was one papillary carcinoma among the 72 patients with Basedow's disease (1.3%).


Moving to nucleic acid-based detection of genital Chlamydia trachomatis.
Laboratory diagnosis of the bacterium Chlamydia trachomatis has gone through a complete phase of evolution since it was first identified as a significant cause of sexually transmitted infection. As a fragile, obligatory intracellular organism, it was initially only grown in eggs. Subsequently, diagnosis relied on culture in continuous cell lines. To address the limitations of culture, immunological methods were developed and direct antigen detection using enzyme immunoassay and immunofluorescence flourished. With the advent of molecular technologies, nucleic acid-based amplification techniques became the methods of choice, offering improved standard of care for diagnosis and opening up the possibility of screening using noninvasive, patient-acceptable specimens. In this article, the various currently available molecular methods are examined, some of the existing problems discussed and a view on what we think might happen in the next 5 years to the technology and requirement in diagnosis and screening is given.


The influence of exon 7 Phe389Leu polymorphism on P120 catenin interactions with E-cadherin and three-dimensional model rebuilt.
The significance of endothelial P120 catenin (P120ctn) activity has been recognized for many years, however it was only recently that the complicated regulation of this constitutively expressed enzyme in endothelial cells was identified. A critical component of the P120ctn regulatory cycle in endothelial cells is its intracellular localization to caveolae. The caveolar coordination of P120ctn, more specifically its interaction with E-cadherin plays a major role in normal endothelial P120ctn activity and vascular bioavailability of nitric oxide. We have recently shown that the presence of P120ctn exon 7 Phe389Leu polymorphism caused diminished shear which was dependent catenin activation, was less extensively associated with caveolae, and had a decreased degree of interaction with E-cadherin. Here, we carried out preliminary investigations to identify possible mechanisms of the genotype-dependent endothelial cell responses we observed in our previous investigations. Through this approach we tested the hypothesis that computer simulations could provide insights regarding the contribution of this single nucleotide polymorphism to regulation of the P120ctn isoform. We observed that in the Phe/Leu and Leu/Leu mutant genotypes, the amount of P120ctn associated with E-cadherin was significantly lower. Additionally, we have shown, using a theoretical computational model, that mutation of an amino acid at position 389 might affect the protein-protein interactions and localization of the P120ctn protein. These alterations might also affect the protein function and explain the enhanced disease risk associated with the presence of Phe389Leu polymorphism in the P120ctn protein.


Management of laryngotracheal stenosis on the basis of site and severity.
Seventy-five cases of laryngotracheal stenosis treated between 1981 and 1991 were reviewed to determine the effectiveness of surgical treatment on the basis of site and severity of stenosis. Decannulation and absence of exertional dyspnea were the criteria of successful management. The treatment methods used were endoscopic laser incision and dilatation, expansion laryngotracheoplasty, and segmental resection. Endoscopic procedures were effective in treating thin (< 1 cm) stenoses in the subglottis and trachea. Laryngotracheoplasty was most effective in treating thick stenoses of the glottis and subglottis. Tracheal stenoses were most effectively treated by segmental resections. The probability for decannulation decreased with longer narrower stenoses and with increasing clinical stage.


Nanoarchitectonics of Cartilage-Targeting Hydrogel Microspheres with Reactive Oxygen Species Responsiveness for the Repair of Osteoarthritis.
Clinically, intra-articular administration can hardly achieve the truly targeted therapy, and the drugs are usually insufficient to show local and long-term therapeutic effects because of their rapid clearance. Herein, inspired by the phenomenon that bees track the scent of flowers to collect nectar, we developed cartilage-targeting hydrogel microspheres with reactive oxygen species (ROS)-responsive ability via combining the microfluidic method and photopolymerization processes to integrate cartilage-targeting peptides and ROS-responsive nanoparticles in the hydrogel matrix. The hydrogel microspheres with cartilage-targeting properties promoted better retention in the joint cavity and enhanced cellular uptake of the nanoparticles. Moreover, the ROS-responsive nanoparticles could react with osteoarthritis (OA)-induced intracellular ROS, resulting in the depolymerization of nanoparticles, which could not only eliminate excess ROS and reduce inflammation but also promote the release of dexamethasone (Dex) and kartogenin (KGN) in situ, realizing effective OA therapy. It was demonstrated that this hydrogel microsphere showed favorable ROS-responsive ability and enhanced chondrogenic differentiation as well as the downregulation of pro-inflammatory factors in vitro. Additionally, the hydrogel microspheres, similar to bees, could target and effectively repair cartilage in the OA model. Thus, the injectable hydrogel microspheres exerted an excellent potential to repair OA and may also provide an effective avenue for inflammatory bowel disease therapy.


Endocrine Regulation of Maturation and Sex Change in Groupers.
Groupers are widely distributed in tropical and subtropical areas worldwide, are key species to coastal ecosystems, and valuable fishery targets. To facilitate artificial seed production technology for grouper aquaculture, the mechanisms of reproduction and gonad development are being elucidated for these important species. In addition, since groupers are sexually dimorphic fish with female-first maturity (protogynous hermaphrodite fish), research is being conducted to clarify the ecological mechanism of sex change and their reproductive physiology, focusing on the endocrine system. In recent years, research on groupers has also been conducted to understand changes in the coastal environment caused by ocean warming and man-made chemicals. However, due to difficulties associated with conducting research using wild populations for breeding experiments, knowledge of the physiology and ecology of these fish is lacking, especially their reproductive physiology. In this review, we present information on the reproductive physiology and endocrinology of groupers obtained to date, together with the characteristics of their life history.


Oximated ruthenium tris-bipyridyl complex: synthesis and luminescent response specifically for ClO(-) in water containing multiple ions.
Hypochlorite has been widely and essentially used as the disinfecting agent of water in our daily life. Rapidly, specifically, quantitatively and simply monitoring ClO(-) in water remains to be investigated and is of importance. For this purpose a novel complex bis(2,2'-bipyridine)(4'-methyl-2,2'-bipyridyl-4-carbaldehyde oxime)ruthenium chloride (Ru-C[double bond, length as m-dash]N-OH) was prepared. In water, reaction of complex Ru-C[double bond, length as m-dash]N-OH and ClO(-) results in bis(2,2'-bipyridine)(4'-methyl-2,2'-bipyridyl-4-carboxylic acid)ruthenium (Ru-CO2H) and thereby offers an efficient luminescence response. This was ascertained to be a specific oxidation reaction of complex Ru-C[double bond, length as m-dash]N-OH with ClO(-), and can be used for quantitatively monitoring aqueous ClO(-). The product of the oxidation reaction of complex Ru-C[double bond, length as m-dash]N-OH and ClO(-) was isolated and assigned to Ru-CO2H. The luminescent emission spectra of complex Ru-C[double bond, length as m-dash]N-OH in the presence of ClO(-) demonstrated that the coexistence of F(-), Cl(-), Br(-), I(-), HCO3(-), HSO4(-), H2PO4(-), S2O3(2-), SO3(2-), CO3(2-), PO4(3-), HPO4(2-), NO3(-), AcO(-), Li(+), Na(+), K(+), Ca(2+), Mg(2+), Zn(2+), Co(2+), Fe(3+), Ni(2+), Pb(2+), Hg(2+), Mn(2+) and Cu(2+) did not interfere in the quantitative change of the intensity of the luminescent emission.


Simultaneous analysis of polychlorinated biphenyls and polychlorinated naphthalenes by isotope dilution comprehensive two-dimensional gas chromatography high-resolution time-of-flight mass spectrometry.
Polychlorinated biphenyls (PCBs) and polychlorinated naphthalenes (PCNs) are listed as persistent organic pollutants (POPs) under the Stockholm Convention. Because they have similar physical and chemical properties, they are coeluted and are usually analyzed separately by different gas chromatography high-resolution mass spectrometry (GC-HRMS) methods. In this study, a novel method was developed for simultaneous analysis of six indicator PCBs, 12 dioxin-like PCBs, and 16 PCNs using isotope dilution comprehensive two-dimensional gas chromatography with high-resolution time-of-flight mass spectrometry (GC × GC-HRTOF-MS). The method parameters, including the type of GC column, oven temperature program, and modulation period, were systematically optimized. Complete separation of all target analytes and the matrix was achieved with a DB-XLB column in the first dimension and a BPX-70 column in the second dimension. The isotope dilution method was used for quantification of the PCBs and PCNs by GC × GC-HRTOF-MS. The method showed good linearity from 5 to 500 pg μL(-1) for all the target compounds. The instrumental limit of detection ranged from 0.03 to 0.3 pg μL(-1) for the 18 PCB congeners and from 0.09 to 0.6 pg μL(-1) for the 16 PCN congeners. Repeatability for triplicate injections was always lower than 20%. The method was successfully applied to the determination of 18 PCBs present at 0.9-2054 pg g(-1) and 16 PCNs present at 0.2-15.7 pg g(-1) in three species of fish. The GC × GC-HRTOF-MS results agreed with those obtained by GC-HRMS. The GC × GC-HRTOF-MS method proved to be a sensitive and accurate technique for simultaneous analysis of the selected PCBs and PCNs. With the excellent chromatographic separation offered by GC × GC and accurate mass measurements offered by HRTOF-MS, this method allowed identification of non-target contaminants in the fish samples, including organochlorine pesticides and polycyclic aromatic hydrocarbons.


Quantitative proteomics for cancer biomarker discovery.
The mass spectrometry (MS)-based quantitative proteomics is powerful to discover disease biomarkers that can provide diagnostic, prognostic and therapeutic targets, and it also can address important problems in clinical and translational medical research. The current status of MS-based quantification strategy and technical advances of several main quantitative assays (two-dimensional (2-D) gel-based methods, stable isotope labeling with amino acids in cell culture (SILAC), isotope-coded affinity tag (ICAT), the isobaric tags for relative and absolute quantification (iTRAQ), ¹⁸O labeling, absolute quantitation and label-free quantitation) have been summarized and reviewed. At present, except 2-D gel-based methods, several stable isotope labeling quantitative techniques, including SILAC, ICAT and iTRAQ, etc, have been widely applied in identification of differential expression of proteins, post-translational modifications and protein-protein interactions in order to look for novel candidate cancer biomarkers from different physiological states of cells, body fluids or tissue samples. Also, the advantages and challenges of different quantitative proteomic approaches are discussed in identification and validation of candidate targets.


Treatment and Imaging Modalities of Giant Coronary Aneurysms Resulting from Kawasaki Disease and Presenting as Acute Inferior Wall Myocardial Infarction.
Giant coronary aneurysms are late sequelae of Kawasaki disease (KD). We describe a 53-year-old patient who presented with acute myocardial infarction and proximal aneurysms of all three coronary arteries. Coronary angiography demonstrated the aneurysms, but CT angiography allowed accurate assessment of the real dimensions of the aneurysms and making the decision on the preferred method of revascularization. The patient underwent coronary bypass surgery and is asymptomatic at follow-up.


Changes in the structure and functional properties of soybean isolate protein: Effects of different modification methods.
Soybean protein isolate (SPI) is an important plant protein in food processing; however, its spherical structure prevents the exposure of its hydrophobic residues and affects its functional properties. In this study, we elucidate the effects of deamidation, phosphorylation, and glycosylation on the structure (Fourier-transform infrared spectroscopy, circular dichroism, fluorescence, and scanning electron microscopy) and functional properties (solubility, emulsifying activity index (EAI), and emulsifying stability index (ESI)) of SPI. The zeta potentials of the deamidated, phosphorylated, and glycosylated (DSPI, PSPI, and MSPI, respectively) samples decreased significantly (p < 0.05) relative to those of SPI. The functional properties of the modified SPI samples were improved, with MSPI-2 showing the best solubility (86.73 ± 0.34%), EAI (118.89 ± 0.73 m2/g), and ESI (273.33 ± 0.59 min). Moreover, the effects of the three modifications on the SPI functional properties increase in the order MSPI > PSPI > DSPI. These results provide a theoretical understanding the relationship between the modifications and SPI structure.


Cardio-ankle vascular index (CAVI) measured by a new device: protocol for a validation study.
Cardio-ankle vascular index (CAVI) is a new marker of arterial stiffness (AS) that can assess vascular wall stiffness in the aorta, femoral artery and tibial artery. CAVI is less affected by blood pressure at the time of measurement than the gold standard method (carotid-femoral pulse wave velocity (PWV)). Our group has developed a device called VOPITB (Velocidad Onda de Pulso Índice Tobillo Brazo) that uses the oscillometric method and easily and accurately measures the PWV in the arms and legs separately, allowing new AS indices to be studied. This article describes the research protocol to determine CAVI using VOPITB and to validate the device against a reference device (VaSera VS-1500) and assess its clinical utility. A cross-sectional, descriptive and observational study will be conducted. In all, 120 subjects (a minimum of 40% of subjects from any one gender) will be evaluated. CAVI will be determined from the measurement by VOPITB and VaSera VS-1500. For each subject, the average of the three readings taken with each device will be calculated. The Bland-Altman plot will be used to determine whether any bias exists in the data-that is, a tendency of the size of the difference to vary with the mean. The participants will be divided roughly equally between the following age bands: <30, 30-60 and >60 years. The study has been approved by the ethics committee of the Hospital San Pedro de Alcántara, Cáceres, Spain. The participants will be required to sign an informed consent form before inclusion in the study, in accordance with the Declaration of Helsinki and WHO standards for observational studies. The dissemination plan of the research study results will be through presentations in relevant national and international conferences and scientific publications in peer-reviewed journals. NCT04303546.


[Multicolor fluorescence in situ hybridization (mFISH].
Various techniques are now available for wide genome screening of alterations in copy number, structure and expression of genes and DNA sequences. Molecular cytogenetics has special techniques of comparative genomic hybridization (CGH), spectral karyotyping (SKY) and multicolor FISH (mFISH). We present principles of these methods, their use in molecular cytogenetic examinations of patients. We quote our experience with mFISH for analyses of complex chromosomal rearrangements in neoplastic cells and identification of inborn supernumerary marker chromosome. Further, we also review the first experiences with multicolor high resolution banding of chromosome (mBAND). This method was used for analysis of bone marrow cells of patient with myelodysplastic syndrome and deletion of chromosome No. 5. With mBAND exact breakpoints were localized. Multicolor fluorescence methods mFISH and mBAND becones the new tools for more precise analyses of inborn and acquired numerical and structural chromosomal rearrangements.


Angiogenesis during exercise and training.
In this review the factors involved in angiogenesis are discussed in their various roles in initiating angiogenesis and inducing changes in the extracellular matrix to facilitate sprouting angiogenesis which is a major part of the angiogenesis seen in exercise and exercise training. A key role in angiogenesis is played by vascular endothelial growth factor (VEGF). The regulation of blood vessel growth to match the needs of the tissue depends on the control of VEGF production through changes in the stability of its mRNA and in its rate of transcription. The detailed studies describing its characteristics and its upregulation in acute exercise are presented along with a brief overview of the changes in the extracellular matrix that facilitate sprouting angiogenesis that occurs in response to exercise and training. Although the mechanisms involved in the growth and remodeling of arterioles and larger vessels are less detailed some recent studies have provided new insights. These are presented here to show a relationship between capillary development and arteriolar growth or remodeling in exercise training that raises questions to be addressed in future studies.


The role of the CoREST/REST repressor complex in herpes simplex virus 1 productive infection and in latency.
REST is a key component of the HDAC1 or 2, CoREST, LSD1, REST (HCLR) repressor complex. The primary function of the HCLR complex is to silence neuronal genes in non-neuronal cells. HCLR plays a role in regulating the expression of viral genes in productive infections as a donor of LDS1 for expression of α genes and as a repressor of genes expressed later in infection. In sensory neurons the HCLR complex is involved in the silencing of viral genome in the course of establishment of latency. The thesis of this article is that (a) sensory neurons evolved a mechanism to respond to the presence and suppress the transmission of infectious agents from the periphery to the CNS and (b) HSV evolved subservience to the HCLR with at least two objectives: to maintain a level of replication consistent with maximal person-to-person spread and to enable it to take advantage of neuronal innate immune responses to survive and be available for reactivation shielded from adaptive immune responses of the host.


Immigrants and the professions.
"The extent to which migrants holding professional qualifications have been able to put these qualifications to productive use in Australia has long been a contentious issue. This article provides some answers which we hope will allow the debate on the extent and causes of migrant professional progress in Australia to proceed on a firmer foundation." The authors find that "migrants have made a major contribution to Australia's professionally-qualified workforce. Those arriving pre-1980s and early 1980s have largely been able to convert their qualifications into professional level employment. However, later arriving migrants have been far less successful."


Genomic sequencing and analysis of Sucra jujuba nucleopolyhedrovirus.
The complete nucleotide sequence of Sucra jujuba nucleopolyhedrovirus (SujuNPV) was determined by 454 pyrosequencing. The SujuNPV genome was 135,952 bp in length with an A+T content of 61.34%. It contained 131 putative open reading frames (ORFs) covering 87.9% of the genome. Among these ORFs, 37 were conserved in all baculovirus genomes that have been completely sequenced, 24 were conserved in lepidopteran baculoviruses, 65 were found in other baculoviruses, and 5 were unique to the SujuNPV genome. Seven homologous regions (hrs) were identified in the SujuNPV genome. SujuNPV contained several genes that were duplicated or copied multiple times: two copies of helicase, DNA binding protein gene (dbp), p26 and cg30, three copies of the inhibitor of the apoptosis gene (iap), and four copies of the baculovirus repeated ORF (bro). Phylogenetic analysis suggested that SujuNPV belongs to a subclade of group II alphabaculovirus, which differs from other baculoviruses in that all nine members of this subclade contain a second copy of dbp.


Phase II study of paclitaxel and valspodar (PSC 833) in refractory ovarian carcinoma: a gynecologic oncology group study.
A phase II study was conducted to determine the efficacy of paclitaxel and valspodar (PSC 833) in patients with advanced epithelial ovarian cancer. Valspodar, a nonimmunosuppressive cyclosporine D analogue that reverses P-glycoprotein-mediated multidrug resistance, in combination with paclitaxel might be active in paclitaxel-resistant and refractory ovarian cancer. Patients received valspodar 5 mg/kg orally qid x 12 doses. Paclitaxel (70 mg/m(2) intravenously for 3 hours) was administered on day 2, 2 hours after the fifth or sixth dose of valspodar. This treatment was repeated every 21 days. One blood sample was collected before the sixth dose of valspodar for the first three cycles to evaluate valspodar trough concentration. Tumor tissue was obtained from patients for immunohistochemical staining of P-glycoprotein. Of 60 patients entered, 58 were assessable for response. There were five partial responses (8.6%; 90% confidence interval [CI], 3.8 to 20.0; median duration of response, 5.0 months [range, 1.9 to 10.5 months]). Median progression-free survival was 1.5 months (90% CI, 1.4 to 2.4). Grade 3 or 4 toxicities observed were neutropenia, anemia, nausea and vomiting, peripheral neuropathy, and cerebellar ataxia. The trough concentrations of valspodar were > or = 1,000 ng/mL in all but two of 40 patients in the first cycle. Immunohistochemical staining for P-glycoprotein was positive for one of two responding patients. Valspodar in combination with paclitaxel has limited activity in patients with paclitaxel-resistant ovarian carcinoma. An international randomized clinical trial of paclitaxel and carboplatin with or without valspodar as first-line therapy in advanced ovarian cancer is underway.


Post-pandemic transformations: How and why COVID-19 requires us to rethink development.
COVID-19 is proving to be the long awaited 'big one': a pandemic capable of bringing societies and economies to their knees. There is an urgent need to examine how COVID-19 - as a health and development crisis - unfolded the way it did it and to consider possibilities for post-pandemic transformations and for rethinking development more broadly. Drawing on over a decade of research on epidemics, we argue that the origins, unfolding and effects of the COVID-19 pandemic require analysis that addresses both structural political-economic conditions alongside far less ordered, 'unruly' processes reflecting complexity, uncertainty, contingency and context-specificity. This structural-unruly duality in the conditions and processes of pandemic emergence, progression and impact provides a lens to view three key challenge areas. The first is how scientific advice and evidence are used in policy, when conditions are rigidly 'locked in' to established power relations and yet so uncertain. Second is how economies function, with the COVID-19 crisis having revealed the limits of a conventional model of economic growth. The third concerns how new forms of politics can become the basis of reshaped citizen-state relations in confronting a pandemic, such as those around mutual solidarity and care. COVID-19 demonstrates that we face an uncertain future, where anticipation of and resilience to major shocks must become the core problematic of development studies and practice. Where mainstream approaches to development have been top down, rigid and orientated towards narrowly-defined economic goals, post-COVID-19 development must have a radically transformative, egalitarian and inclusive knowledge and politics at its core.


Seasonal flexibility in organ size in the Andean lizard Liolaemus moradoensis.
The understanding of animal functioning in fluctuating environments is a major goal of physiological and evolutionary ecology. In temperate terrestrial habitats, one of the most pervasive changes in environmental conditions is that associated with the seasonal change along the year. In this study, we describe the pattern of seasonal variation in the size of nine internal organs in the lizard Liolaemus moradoensis from the Andes Mountains of Central Chile. We observed that the size of digestive organs was greater during summer in comparison to other seasons. Dry masses of liver and fat bodies reached maximum values during summer and minimum during spring. We suspect that lowest spring values are related with build-up costs of energetically expensive organs (e.g., digestive, muscle mass) at the end of the hibernation period. Dry mass of the heart and lungs did not show a clear pattern of variation, suggesting that cardiac and pulmonary performance were maintained throughout the year. The dry mass of kidneys was greater during winter than during summer, a result observed in other hibernating lizards but for which there is no clear explanation. Finally, the dry mass of testes showed a maximum value during autumn and a progressive reduction toward summer, indicating that reproduction occurs during autumn. When represented in a bivariate space, acquisition (digestive), distribution (heart, lungs and kidneys), storage (liver and fat bodies), and expenditure (testes) organs generate four clusters. In general terms, observed seasonal pattern of change in organ size is in agreement with those reported for other lizard species that inhabit highly fluctuating environments.


[Laser assisted uvulopalptoplasty treatment for obstructive sleep apnea syndrome].
71 patients of obstructive sleep apnea symdrome (OSAS) were treated by Nd:YAG laser assisted uvulopalptoplasty (LAUP). According to the atonamic features of every patient, and type of operation which should be selected, the success rate of surgery would increase, and complications would be reduced. The effect rate is 97.2% by clinic, 90.0% by polysimnograph (PSG).


Synthesis and structure elucidation of potential 6-oxygenated metabolites of (22R)-6alpha,9alpha-difluoro-11beta,21-dihydroxy-1 6alpha,17alpha-propyl methylenedioxypregn-4-ene-3,20-dione, and related glucocorticosteroids.
(22R)-6alpha,9alpha-Difluoro-11beta,21-dihydroxy-16 alpha,17alpha-propylmethylenedioxypregn-4-ene-3,20-dione (rofleponide) is a synthetic glucocorticosteroid with high affinity for the rat thymus glucocorticoid receptor and a very high biotransformation rate demonstrated through incubation with a human liver S9 subcellular fraction. Because oxidation in the 6-position is an important metabolic pathway of glucocorticosteroids, the potential 6beta-hydroxy and 6-oxo metabolites of rofleponide were synthesized to be used as reference compounds. Three alternative routes were used to reach the 6-hydroxy compound: (a) a one-step procedure involving allylic oxidation of rofleponide by selenium dioxide, (b) selenium dioxide oxidation of the corresponding 1,4-diene followed by selective 1,2-hydrogenation using Wilkinson's catalyst, and (c) autoxidation of a 3-methoxypregna-3,5-diene derivative. All three routes proceeded stereospecifically. Routes (a) and (c) gave approximately the same overall yield of the 6beta-hydroxy epimer, whereas the overall yield from route (b) was much lower, primarily because of incomplete 1,2-hydrogenation. The 6-oxo compound was prepared through Pfitzner/Moffat oxidation of the 6-hydroxy compound. The stereochemistry of the 6-hydroxy substituent is discussed on the basis of 1H-NMR spectroscopy and supplementary 2D NOESY experiments.


A mutation of cauliflower mosaic virus gene I interferes with virus movement but not virus replication.
A 300-bp deletion was made in gene I of a multimeric copy of cauliflower mosaic virus (CaMV). The deleted and wild-type constructs were mobilized into Agrobacterium tumefaciens and used for the inoculation of plants and leaf discs of the host plant, turnip, by "agroinfection." Infection induced by the wild-type construct gave characteristic viral symptoms on the inoculated and systemically infected leaves of whole plants whereas no infection was detected using the deletion mutant. The possibility that the deletion in gene I affected a cis-related function (e.g., encapsidation) was tested by complementation of mutant gene I with wild-type CaMV. Double infection experiments showed that replication and spread of both viruses occurred without detectable recombination of the mutant. In contrast to the situation in plants, agroinfection (Grimsley et al., 1986, Proc. Natl. Acad. Sci. USA 83, 3282-3286) of leaf discs, detected as the accumulation of encapsidated forms of virion DNA, was recorded for both the wild-type and the deleted constructs. The reduced level of virus accumulation from the mutant was consistent with virus replication occurring only in cells involved in the primary interaction with Agrobacterium, and accordingly progeny viral DNA was only detected in cells around the edge of the tissue disc. These data provide definitive evidence that CaMV gene I encodes a movement protein and show that this function can act in trans in a virus infection.


Mortality study of two overlapping cohorts of photographic film base manufacturing employees exposed to methylene chloride.
The mortality experience of two overlapping cohorts of employees engaged in the manufacture of photographic film support was evaluated to assess the potential chronic health effects of methylene chloride exposure. In the first analysis, we examined causes of death among 1311 men initially employed between 1946 (when the solvent was first used) and 1970; in the second, we updated mortality in a 1964 to 1970 employed cohort of 1013 men. Follow-up was through 1994. The mean exposure among members of the 1946 to 1970 cohort was 39 ppm (8-hour time-weighted average) for 17 years, and the median length of follow-up from first exposure was 34 years. Members of the 1964 to 1970 cohort received an average exposure of 26 ppm for 24 years; median time from first exposure was 35 years. Compared with general population vital statistics, mortality in both cohorts was below expectation for all causes of death, ischemic heart disease, and cancer, including such sites as the lung and liver, which were target organs identified in animal toxicology studies. No statistically significant increases were observed for any cause of death. The combined results of this study and three others in the photographic film and textile fibers industries (approximately 7300 subjects) show that long-term exposure to methylene chloride does not increase the risk of death from any cause including specific diagnoses that have been associated with this widely used solvent.


Antiphospholipid antibody syndrome: an acquired cause of venous and arterial hypercoagulability.
Antiphospholipid antibody syndrome is a major acquired cause of both venous and arterial hypercoagulability. Recent advances in the understanding of antiphospholipid antibodies, their detection, clinical presentations, and management are reviewed.


Participation of patients with chronic illness in nursing care: An Iranian perspective.
The increasing number of chronically ill people has served as an impetus for the promotion of patient participation in nursing care. However, little is known about patient participation in Iran. The aim of this study was to identify the factors that are relevant to patient participation and the nature of that participation, as experienced by chronically ill patients and registered nurses in Iran. Grounded theory was used as the method. Twenty-two participants were recruited by using purposeful and theoretical sampling. The data were generated by semistructured interviews and participant observations. Constant comparison was used for the data analysis. This study indicated that participation is an interactive process between nurses, patients, and family members in the caregiving context. Participation occurred when the caring agents worked together. The core category of "convergence of the caring agents" emerged. The subcategories emerged as the levels of participation and included "adhering", "involving", "sharing", and "true participation". The factors related to the caring agents and caregiving context could be considered as predictors of the level of participation when caring for these patients.


Stretch-Induced Deformation as a Model to Study Dopaminergic Dysfunction in Traumatic Brain Injury.
Traumatic brain injury (TBI) is defined as damage to the brain that consequently disrupts normal function. Neuronal death, a hallmark of TBI, has been related to the development of neurodegenerative disorders like Parkinson's disease (PD), where loss of dopaminergic neurons and dopaminergic dysfunction are observed. To date, no in vitro model exists in which the dopaminergic damage observed in TBI is replicated. In this study, we evaluated the effects of in vitro simulated TBI on human dopaminergic neurons. To simulate TBI, neurons were subjected to 0%, 5%, 10%, 15%, 25% and 50% deformation. 24 h after injury, cell viability and apoptosis were determined by lactate dehydrogenase (LDH) release and DNA fragmentation, as well as ethidium homodimer and caspase 3/7 staining. Dopamine (DA) levels were determined by ELISA. Levels of tyrosine hydroxylase (TH) and DA transporter (DAT) were determined by western blot. Only 50% stretch increased LDH release and ethidium homodimer staining, suggesting the induction of necrosis. On the contrary, 25% and 50% stretch increased DNA fragmentation while 15%, 25% and 50% increased caspase 3/7 staining, suggesting that moderate and severe TBI promote apoptosis. Levels of intracellular DA decreased in a stretch-dependent manner with 15%, 25% and 50% stretch, which were related with a decrease in TH expression. Extracellular DA levels increased only at 50%. Levels of DAT remained unchanged regardless of treatment. These data support the use of stretch as a model to simulate TBI in vitro in human dopaminergic neurons, replicating the acute effects of TBI in the dopaminergic system.


Visual response characteristics of neurons in the second visual area of marmosets.
The physiological characteristics of the marmoset second visual area (V2) are poorly understood compared with those of the primary visual area (V1). In this study, we observed the physiological response characteristics of V2 neurons in four healthy adult marmosets using intracortical tungsten microelectrodes. We recorded 110 neurons in area V2, with receptive fields located between 8° and 15° eccentricity. Most (88.2%) of these neurons were orientation selective, with half-bandwidths typically ranging between 10° and 30°. A significant proportion of neurons (28.2%) with direction selectivity had a direction index greater than 0.5. The vast majority of V2 neurons had separable spatial frequency and temporal frequency curves and, according to this criterion, they were not speed selective. The basic functional response characteristics of neurons in area V2 resemble those found in area V1. Our findings show that area V2 together with V1 are important in primate visual processing, especially in locating objects in space and in detecting an object's direction of motion. The methods used in this study were approved by the Monash University Animal Ethics Committee, Australia (MARP 2009-2011) in 2009.


Effect of ofloxacin and netilmicin on human corneal and conjunctival cells in vitro.
The purpose of this study was to compare the cytotoxic effects of the fluoroquinolone ofloxacin with that of the aminoglycoside netilmicin. Human corneal epithelial cells (HCE-T) and human conjunctival epithelial cells (Wong-Kilbourne derivative of Chang conjunctiva) were exposed to antibiotics (0.08-5.0 mg/mL) for 4 or 24 hours. Cell proliferation and viability were assessed with the MTT assay, neutral red uptake, and bromo deoxy uridine incorporation. In both cell lines, ofloxacin inhibited cell proliferation and viability. These effects were time and dose dependent. Concentrations of ofloxacin ranging from 0.4 to 2.4 mg/mL (0.04% to 0.24%) produced a 50% inhibition of proliferation and viability. In contrast, netilmicin induced no toxic effect. The differences between ofloxacin and netilmicin were highly statistically significant (p < 0.001). This finding is particularly relevant in deciding the optimal antibiotic to be applied in clinical situations in which the epithelium is compromised.


Mathematical curves for the description of input and output variables of the daily production process in aviary housing systems for laying hens.
The objectives of this study were 1) to compute appropriate mathematical curves that describe the daily production process by the input variables daily feed consumption, water consumption, ambient temperature, and output variables hen-day egg production, egg weight, second grade eggs, floor eggs, cumulative mortality, body weight, and flock uniformity; and 2) to obtain insights into the daily variations in these variables, in order to support the poultry farmer with an aviary housing system in his daily management. Literature and research data attained from six unmolted flocks that were housed in aviary systems were used to formulate the mathematical curves. The curves were a function of the number of days in the laying period. Curves for cumulative mortality, hen-day egg production, egg weight, body weight, and percentage of floor eggs described individual flock results well (0.72 < R2adj < 1.00). The coefficients of determination for feed consumption, water consumption, flock uniformity, and percentage of second grade eggs were in general low (0.33 < R2adj < 0.54), which implies that the form of the curve differs between flocks. Egg weight, body weight, cumulative mortality, and hen-day egg production had the lowest minimum coefficients of variation (0.8 to 1.9), followed by feed consumption, water consumption, and flock uniformity (2.8 to 3.6). Ambient temperature, percentage floor eggs, and percentage of second grade eggs had the highest minimum coefficients of variation (4.8 to 9.1).


Multilocus sequence typing of sequential Candida albicans isolates from patients with persistent or recurrent fungemia.
Multilocus sequence typing (MLST) is a useful tool to explore the phylogenetics and epidemiology of Candida albicans isolates recovered from cases of invasive candidiasis. The goal of this study was to determine whether the same or different strains were responsible for persistent or recurrent fungemia through the use of MLST and ABC typing on sequential C. albicans isolates from the same patient. We applied both typing methods to 21 C. albicans strains recovered from 8 patients with persistent or recurrent candidemia. The isolates were collected during a multicenter surveillance study in four public tertiary care hospitals in Brazil. Persistent candidemia was defined as two or more blood cultures positive for C. albicans on 2 or more separate days. Recurrent candidemia was defined as an episode of candidemia occurring at least 1 month after the apparent complete resolution of an infectious episode caused by Candida species. We observed that, except for one patient, all strains from the first and second samples of the same patient showed the same MLST diploid sequence type (DST), ABC type and susceptibility profile to antifungals. Three distinct strains, well discriminated by MLST, were found in the seven samples collected sequentially over 10 days from one patient. The strains from the first four samples were indistinguishable, the fifth and sixth were also indistinguishable but different from the first four and seventh samples. Significantly, the seventh strain was the only C. albicans clade 2 isolate found in our total collection involving 61 patients, although clade 2 is commonly found worldwide. To the best of our knowledge, this is the first study describing the recovery of three distinct C. albicans strains in the same patient with a persistent blood stream infection within a short period of time.


The effects of some plasma proteins on fibrin network structure.
Pronounced differences are found between characteristics of networks developed in plasma and those developed in pure fibrinogen solution. Networks in plasma have thicker fibres, are more permeable and have lower tensile strength. In this investigation the role of some plasma proteins as determinants of network structure under physiological conditions of clotting has been examined in an attempt to account for the differences in network structure in plasma and fibrinogen solution. The effect of physiological concentrations of antithrombin III, fibronectin, albumin, alpha globulin and gamma globulin on fibrin network structure was examined using mass-length ratio (muT) from turbidity, bulk network permeability (tau) and kinetics of network development. It was found that differences in fibrin network structure developed in plasma and pure fibrinogen solution could not be accounted for by alterations induced in network properties by albumin, gamma globulin, alpha globulin, fibronectin and antithrombin III. It is concluded that the final network structure is determined by the kinetics of fibrin fibre growth and is highly responsive to the presence of plasma proteins.


Bioactive Properties of Composites Based on Silicate Glasses and Different Silver and Gold Structures.
Using an ideal biomaterial to treat injured bones can accelerate the healing process and simultaneously exhibit antibacterial properties; thus protecting the patient from bacterial infections. Therefore, the aim of this work was to synthesize composites containing silicate-based bioactive glasses and different types of noble metal structures (i.e., AgI pyramids, AgIAu composites, Au nanocages, Au nanocages with added AgI). Bioactive glass was used as an osteoconductive bone substitute and Ag was used for its antibacterial character, while Au was included to accelerate the formation of new bone. To investigate the synergistic effects in these composites, two syntheses were carried out in two ways: AgIAu composites were added in either one step or AgI pyramids and Au nanocages were added separately. All composites showed good in vitro bioactivity. Transformation of AgI in bioactive glasses into Ag nanoparticles and other silver species resulted in good antibacterial behavior. It was observed that the Ag nanoparticles remained in the Au nanocages, which was also beneficial in terms of antibacterial properties. The presence of Au nanoparticles contributed to the composites achieving high cell viability. The most outstanding result was obtained by the consecutive addition of noble metals into the bioactive glasses, resulting in both a high antibacterial effect and good cell viability.


Association of High Serum Uric Acid and Increased Arterial Stiffness is Dependent on Cardiovascular Risk Factors in Female Population.
An elevated serum uric acid (SUA) level is closely associated with increased arterial stiffness. However, whether this association is independent of conventional cardiovascular risk factors is controversial. This study aimed to investigate whether SUA is independently associated with arterial stiffness as assessed by Brachial-ankle pulse wave velocity (baPWV), and to what extent this association is dependent on cardiovascular risk factors. Increased arterial stiffness was defined as baPWV>1 400 cm/s. Cardiovascular risk factors were defined as hypertension, diabetes, dyslipidaemia, and a BMI≥24.0 kg/m2. A total of 3 342 subjects (1 334 men and 2008 women, mean age 53.79±13.18 years) were included. SUA levels exhibited a graded elevation with an increasing number of cardiovascular risk factors. In female subjects with more than two cardiovascular risk factors, compared with the first quartile of SUA, higher SUA quartiles were associated with a higher probability of increased baPWV (OR=1.500, 1.478, 1.774 for SUA Q2-Q4). In further stratified association analysis, compared with Q1, SUA quartiles showed a graded association with increased baPWV in subjects with TC≥5.2 mmol/l (OR=1.758, 1.942, 2.354 for Q2, Q3, and Q4 respectively), LDL-C≥3.3 mmol/l (OR=1.510, 2.255 for Q3 and Q4) and FBG≥7.0 mmol/l (OR=1.516, 1.748 for Q3 and Q4). In the Chinese coastal female population, the association of high SUA and increased arterial stiffness is dependent on the coexistence of at least one cardiovascular risk factor, especially hypercholesterolemia.