Search

Summary Background/Aims Methods Results Conclusions Patients with hepatocellular cancer (HCC) are vulnerable to psychological distress given a new cancer diagnosis superimposed on pre‐existing chronic liver disease. We aimed to characterise the psychiatric burden in HCC, risk factors for incident diagnosis and treatment patterns over time.Using IQVIA PharMetrics® Plus for Academics—a nationally representative claims database of the commercially insured US population—we identified psychiatric diagnoses and treatment among patients with newly diagnosed HCC. Multivariable logistic regression modelling identified factors associated with psychiatric diagnosis and treatment.Of 11,609 patients with HCC, 2166 (18.6%) had a psychiatric diagnosis after cancer diagnosis with depression (58.3%) and anxiety (53.0%) being most common. Women (aOR 1.33, 95% CI [1.19–1.49]), pre‐existing psychiatric diagnoses (aOR 9.12 [8.08–10.3]) and HCC treatment type (transplant: aOR 2.15 [1.66–2.77]; locoregional therapies: aOR 1.74 [1.52–1.99]; hospice: aOR 2.43 [1.79–3.29]) were significantly associated with psychiatric diagnosis. Female sex, ascites, higher comorbidity and treatment type were associated with incident psychiatric diagnosis. Pharmacotherapy was used in 1392 (64.3%) patients with a psychiatric diagnosis, with antidepressants (46.2%) and anxiolytics (32.8%) being most common. Psychiatric diagnoses increased from 14.8% in 2006–2009 to 21.1% in 2018–2021 (p < 0.001). In almost 20% of patients with pre‐existing psychiatric conditions, therapy was discontinued after HCC diagnosis.Nearly 2 of 10 patients with HCC were diagnosed with a psychiatric condition after cancer diagnosis with unique sociodemographic and clinical risk factors identified. This highlights a risk for increased psychological burden in need of early evaluation and treatment among patients with newly diagnosed HCC. [ABSTRACT FROM AUTHOR]

Objective: To establish effective methods of obesity prevention among young adults, we analyzed the relationship between obesity-related food intake and metabolic factors in Japanese university students. Methods: We performed a cross-sectional analysis of nutrient intake information and metabolic parameters among 1,206 Gifu University students categorized by body mass index. Results: The overweight/obesity rate was significantly higher in males. Additionally, among males, the intake of protein, potassium, magnesium, phosphorus, iron, zinc, all lipids/fats, and all metabolic parameters including blood sugar, hemoglobin A1c, uric acid, alanine aminotransferase, aspartate aminotransferase, low-density lipoprotein, high-density lipoprotein, triglycerides, and blood pressure significantly differed between the obese and non-obese groups. However, the same comparison among females revealed no significant differences in nutrient intake and significant differences in only half of the parameters. Among males, energy intake from protein and fat was significantly higher in the obese group, while the percentage of total energy intake from carbohydrates and fat was lower and higher, respectively, among females in the obese group. Conclusions: Overeating of protein and fat in males and unbalanced nutrition in females are sex-specific characteristics of Japanese university students with obesity, and metabolic abnormalities in students with obesity are more remarkable in males than in females. [ABSTRACT FROM AUTHOR]

The past few decades have seen a rise in research on vertebrate cilia and ciliopathy, with interesting collaborations between basic and clinical scientists. This work includes studies on ciliary architecture, composition, evolution, and organelle generation and its biological role. The human body has cells that harbour any of the following four types of cilia: 9+0 motile, 9+0 immotile, 9+2 motile, and 9+2 immotile. Depending on the type, cilia play an important role in cell/fluid movement, mating, sensory perception, and development. Defects in cilia are associated with a wide range of human diseases afflicting the brain, heart, kidneys, respiratory tract, and reproductive system. These are commonly known as ciliopathies and affect millions of people worldwide. Due to their complex genetic etiology, diagnosis and therapy have remained elusive. Although model organisms like Chlamydomonas reinhardtii have been a useful source for ciliary research, reports of a fascinating and rewarding translation of this research into mammalian systems, especially humans, are seen. The current review peeks into one of the complex features of this organelle, namely its birth, the common denominators across the formation of both 9+0 and 9+2 ciliary types, the molecules involved in ciliogenesis, and the steps that go towards regulating their assembly and disassembly. [ABSTRACT FROM AUTHOR]

This work is toward the study of theory of IF-automata based on residuated lattices (ILF-automaton) and to use ILF-topological concepts for study of algebraic concepts therein. We introduce the notion of ILF-subsystems and strong ILF-subsystems of an ILF-automaton and show that these are precisely the ILF-closed sets with respect to the ILF-topologies introduced on state-set of an ILF-automaton. Finally, we study the characterization of separated ILF-subsystem for an ILF-automaton. [ABSTRACT FROM AUTHOR]

Peer-reviewed conferences, the main publication venues in CS, rely critically on matching highly qualified reviewers for each paper. Because of the growing scale of these conferences, the tight timelines on which they operate, and a recent surge in explicitly dishonest behavior, there is now no alternative to performing this matching in an automated way. This paper introduces Large Conference Matching (LCM) , a novel reviewer–paper matching approach that was recently deployed in the 35th AAAI Conference on Artificial Intelligence (AAAI 2021), and has since been adopted (wholly or partially) by other conferences including ICML 2022, AAAI 2022-2024, and IJCAI 2022-2024. LCM has three main elements: (1) collecting and processing input data to identify problematic matches and generate reviewer–paper scores; (2) formulating and solving an optimization problem to find good reviewer–paper matchings; and (3) a two-phase reviewing process that shifts reviewing resources away from papers likely to be rejected and towards papers closer to the decision boundary. This paper also describes an evaluation of these innovations based on an extensive post-hoc analysis on real data—including a comparison with the matching algorithm used in AAAI's previous (2020) iteration—and supplements this with additional numerical experimentation.2 [ABSTRACT FROM AUTHOR]

This study aimed to investigate the solar flat plate collector (FPC) thermal performance using a hybrid nanofluid made of Cu-MWCNTs-water. The study involved varying the FPC flow rates, inclination angle, and radiation intensity. The ANN and mathematical model has been developed on the basis of experimental data to predict instantaneous efficiency. The concentration, flow rate, angle of inclination, and intensity were input to the network, and instantaneous efficiency was output from the network. The neurons having minimal mean square error (MSE) and coefficient of determination (R2) were selected. An enhancement of 32.25 % was observed using Cu-MWCNTs hybrid nanofluid in instantaneous efficiency. The R2 ranges are 0.8857–0.9533 and 0.94938–0.9989, respectively, showing the proposed correlation and neural network accuracy. The present study is useful in making highly optimised predictions of the instantaneous efficiency in FPC using a hybrid nanofluid for heat transfer, fluid heating, space heating, etc. • Experimental performance of solar FPC is analysed using hybrid nanofluid. • XRD, FESEM, EDAX, and FTIR are used for Characterization of nanoparticles. • Performance of FPC is predicted using the developed MLP ANN model. • A unique mathematical correlation is predicted using experimental data. • Statistical analysis is used to evaluate the performance of the present model. [ABSTRACT FROM AUTHOR]

Sida is one of the most diverse genera, with about 200 species distributed in tropical and subtropical regions of the world. Among 18 species distributed in India, Sida acuta , Sida cordifolia , Sida rhombifolia , and Sida cordata are used in traditional medicines along with its possible adulterant Abutilon indicum for several therapeutic uses. The non-availability of marker-based validated methods for the identification and classification of these species leads to adulteration. Indoloquinoline and quinazoline are the major bioactive alkaloids distributed in Sida spp. First time, a simple, economical and high throughput method was developed and validated for the simultaneous determination of 20-hydroxyecdysone (1), vasicine (2), vasicinone (3), cryptolepine (4), quindolinone (5), and cryptolepinone (6) using HPTLC-UV densitometry. The method was validated to meet globally accepted ICH guidelines. The method was sensitive with LOD and LOQ ranging from 0.38–0.63 and 1.57–2.12 µg/band. The samples were spiked at 3 different concentrations, the recovery values were 93.49–98.88%. In addition, the greenness index of the HPTLC method was estimated using four different greenness assessment techniques. Targeted HPTLC analysis indicated the distribution of specialized metabolites in Sida spp. and A. indicum. However, the occurrence of cryptolepine in A. indicum was not reported in the literature, so this was further confirmed by liquid chromatographic studies of the samples from different locations. The chromatographic data was statistically evaluated by principal component analysis (PCA) and hierarchical clustering (HCA). HPTLC-based targeted metabolite quantitation explains the adulteration/substitution in Sida raw material and derived herbal preparations. [Display omitted] • Validated HPTLC-UV method for quantification of Six markers in four Sida spps. and A. indicum. • Four greenness assessment tools ensured the greenness of the method. • Markers were identified to discriminate different Sida spp. • Liquid chromatographic studies also confirmed the presence of cryptolepine in A. indicum. [ABSTRACT FROM AUTHOR]

This study examines how physical activity affects critical health outcomes among older people in India, focusing on functional limitations and depressive symptoms. The sample consists of 4,214 individuals aged 60 or above. The study uses binary logistic regression and Wooldridge residual analysis. The results indicate that 49.5 percent and 42.3 percent of the sample have functional limitations and depressive symptoms respectively. The study finds that physical activity is negatively related to functional limitations and positively related to depression. Furthermore, physical activity influences depressive symptoms both directly and indirectly. Additionally, functional limitations escalate the likelihood of depressive symptoms among older people. Older males with functional limitations are more prone to depressive symptoms than older females. Conversely, older females without functional limitations are more likely to have depressive symptoms than older males. Therefore, the study advocates such interventions which address multiple levels and aspects, such as how people think and feel about physical activity, and what their surroundings are like in order to help people who face challenges of being physically active. [ABSTRACT FROM AUTHOR]

The retirement decision can significantly affect an individual's well‐being for many years. There are many reasons and issues for retirement decision for a government official. Financial and health concerns are a major part of the retirement decision but there are other issues that bring about the retirement decision that are unrelated to an individual's financial and health status. In Nepal, majority of government workers have compulsory retirement due to age concern. To study the profile of the retired employees and their perception toward retirement. A descriptive cross‐sectional research methodology was used in this study. About 85% (out of 105) of the retired employees attending Pension Management Office were male, which was due to the absence of female inclusiveness in employment before 2006. There were several reasons for retirement. The most common reason for being retired was the compulsory retirement, which was followed by the reasons of poor health and family problems, each counting about 14.2%. Most of the retired employees, that is, 48.5% (51) rated the retirement program as fair and about 42% (44) rated it as poor. Preserving the skilled and productive manpower in civil service is equally important as the nation has greater effort in building them up in terms of career and capacity. [ABSTRACT FROM AUTHOR]

Purpose: To compare brachytherapy to external beam radiation therapy (EBRT) with respect to overall survival (OS) and disease-specific survival (DSS) among NSCLC patients undergoing limited surgical resection. Methods: All cases of T1-4 N0 M0 NSCLC undergoing limited resection and either brachytherapy or EBRT diagnosed between 2004 and 2014 were extracted from the Surveillance, Epidemiology, and End Results database. Chi-square test and Fisher's exact analysis were used to analyze categorical variables while Student's t-test was used to analyze continuous variables. Univariate analysis to assess for differences in survival with respect to covariates was performed with the log-rank test. Multivariable analysis was performed with Cox proportional hazards regression models among the entire cohort and after sub-stratification by T stage. Results: Among 543 patients, 471 underwent EBRT and 72 underwent brachytherapy. Brachytherapy demonstrated improved OS and DSS on univariate analysis as compared to EBRT (p < 0.05). Cox regression also demonstrated improved OS and DSS with brachytherapy (HR 0.604; 95% CI [0.380; 0.961] and HR 0.524; 95% CI [0.303; 0.908], respectively). Sub-cohort analysis demonstrated significant improvement in survival only among patients with T1 disease with similar survival between brachytherapy and EBRT among higher stage disease. Conclusions: Patients undergoing brachytherapy for T1-T4, N0, M0 NSCLC demonstrated at least similar survival as compared to those undergoing EBRT among patients undergoing limited resection. Improved survival was demonstrated among patients with T1 disease. [ABSTRACT FROM AUTHOR]

A retrospective analysis of the Surveillance, Epidemiology, and End Results database was performed to evaluate the effect of radiotherapy (RT) on overall survival and disease-specific survival. Patients undergoing RT had improved overall survival and disease-specific survival on multivariate Cox regression and after propensity score matching as compared with patients who did not receive RT. Introduction: The aim of this study was to perform a Surveillance, Epidemiology, and End Results (SEER) analysis on the effect of radiotherapy (RT) on survival among patients with prostate ductal adenocarcinoma (DA), a rare variant of prostate cancer. Patients and Methods: Cases of T1 to 4 N0 M0 prostate DA diagnosed between 2004 and 2013 were extracted from SEER. The association between categorical variables and radiation therapy was assessed for statistical significance using the x² test or Fisher exact test. Difference in continuous variables across the RT groups was assessed for statistical significance using the 2-sample t test or non-parametric test. The distribution of overall survival (OS) and disease-specific survival (DSS) between the RT groups was assessed using the Kaplan-Meier method and the log rank test and after propensity matching. The association between hazards of death (HR) and covariates was examined using Cox proportional hazards model. A 2-sided P-value of .05 was used to determine statistical significance. Results: A total of 205 patients met inclusion criteria. On univariate analysis, RT was associated with significant improvement in OS and DSS. On multivariate Cox regression, RT significantly decreased risk of death for both OS and DSS (HR, 0.516; 95% confidence interval [CI], 0.273-0.978 and HR, 0.232; 95% CI, 0.082-0.658, respectively). After propensity score matching, RT demonstrated a persistent improvement in both OS and DSS. Conclusions: RT decreased risk of death for both OS and DSS in patients with node-negative, nonmetastatic prostate DA on multivariable analysis. RT was also associated with improved OS and DSS after propensity matching. [ABSTRACT FROM AUTHOR]

• Food choice motives and attitude-social influence-self efficacy framework were used. • Four consumer segments were identified. • Attitude, self-efficacy, and environmental concern are crucial to reduce food waste. • Multiple factors influence food waste among which food familiarity is central. Understanding consumers' food waste behaviour has become increasingly crucial, given its adverse impacts on sustainability. Therefore, this study segmented consumers based on their food choice motives and investigated key factors influencing food waste reduction behaviour in university canteens employing attitude, social influence, and self-efficacy (ASE) framework extended with environmental concern, situational, and sociodemographic and lifestyle factors. An online survey was conducted in Denmark among university canteen users (n = 438). Hierarchical cluster analysis identified four segments, (1) Familiarity sensitive consumers – 34.9 % of participants, (2) Unconcerned consumers – 19.9 %, (3) Food for health and mood consumers – 19.2 %, and (4) Unfamiliar consumers – 26 %. Partial least squares structural equation modelling analysis shows that attitude, self-efficacy, and environmental concern significantly influenced behavioural intention, eventually influencing food waste reduction behaviour. Social influence and situational factors did not influence behavioural intention. Sensory appeal, price, health–mood, and familiarity significantly influenced behavioural attitude, whereas familiarity and weight control significantly influenced behaviour. Sociodemographic and lifestyle factors indirectly influence behavioural intention by their effects on attitudes, self-efficacy, and environmental concerns. Education, income, dietary patterns, and body mass index directly impacted food waste reduction behaviour. We suggest that improving consumers' attitudes and environmental concern while enhancing their self-efficacy might positively influence food waste reduction behaviour. Besides psychosocial factors, intervention should also consider focusing on consumers' food choice motives and sociodemographic and lifestyle factors to effectively influence food waste reduction behaviour in university canteen or similar settings. [ABSTRACT FROM AUTHOR]

To map the cellular topography of the rare 3-O-sulfated structural motif of heparan sulfate (HS), we constructed quantum dot-based probes for antithrombin and FGF2, which reveal widely different distribution of the targeted HS motifs. The technology helps show that old and young aortic endothelia display widely different levels of the antithrombin-binding 3-O-sulfated HS motif. [ABSTRACT FROM AUTHOR]

Background: Cerebrospinal fluid from amyotrophic lateral sclerosis patients (ALS-CSF) induces neurodegenerative changes in motor neurons and gliosis in sporadic ALS models. Search for identification of toxic factor(s) in CSF revealed an enhancement in the level and enzyme activity of chitotriosidase (CHIT-1). Here, we have investigated its upregulation in a large cohort of samples and more importantly its role in ALS pathogenesis in a rat model.Methods: CHIT-1 level in CSF samples from ALS (n = 158), non-ALS (n = 12) and normal (n = 48) subjects were measured using ELISA. Enzyme activity was also assessed (ALS, n = 56; non-ALS, n = 10 and normal-CSF, n = 45). Recombinant CHIT-1 was intrathecally injected into Wistar rat neonates. Lumbar spinal cord sections were stained for Iba1, glial fibrillary acidic protein and choline acetyl transferase to identify microglia, astrocytes and motor neurons respectively after 48 h of injection. Levels of tumour necrosis factor-α and interleukin-6 were measured by ELISA.Findings: CHIT-1 level in ALS-CSF samples was increased by 20-fold and it can distinguish ALS patients with a sensitivity of 87% and specificity of 83.3% at a cut off level of 1405.43 pg/ml. Enzyme activity of CHIT-1 was also 15-fold higher in ALS-CSF and has a sensitivity of 80.4% and specificity of 80% at cut off value of 0.1077989 μmol/μl/min. Combining CHIT-1 level and activity together gave a positive predictive value of 97.78% and negative predictive value of 100%. Administration of CHIT-1 increased microglial numbers and astrogliosis in the ventral horn with a concomitant increase in the levels of pro-inflammatory cytokines. Amoeboid-shaped microglial and astroglial cells were also present around the central canal. CHIT-1 administration also resulted in the reduction of motor neurons.Conclusions: CHIT-1, an early diagnostic biomarker of sporadic ALS, activates glia priming them to attain a toxic phenotype resulting in neuroinflammation leading to motor neuronal death. [ABSTRACT FROM AUTHOR]

PURPOSE: Detection of bacteria‐specific metabolism via positron emission tomography (PET) is an emerging strategy to image human pathogens, with dramatic implications for clinical practice. In silico and in vitro screening tools have recently been applied to this problem, with several monosaccharides including l‐arabinose showing rapid accumulation in Escherichia coli and other organisms. Our goal for this study was to evaluate several synthetically viable arabinofuranose‐derived 18F analogs for their incorporation into pathogenic bacteria. PROCEDURES: We synthesized four radiolabeled arabinofuranose‐derived sugars: 2‐deoxy‐2‐[18F]fluoro‐arabinofuranoses (d‐2‐18F‐AF and l‐2‐18F‐AF) and 5‐deoxy‐5‐[18F]fluoro‐arabinofuranoses (d‐5‐18F‐AF and l‐5‐18F‐AF). The arabinofuranoses were synthesized from 18F‐ via triflated, peracetylated precursors analogous to the most common radiosynthesis of 2‐deoxy‐2‐[18F]fluoro‐d‐glucose ([18F]FDG). These radiotracers were screened for their uptake into E. coli and Staphylococcus aureus. Subsequently, the sensitivity of d‐2‐18F‐AF and l‐2‐18F‐AF to key human pathogens was investigated in vitro. RESULTS: All 18F radiotracer targets were synthesized in high radiochemical purity. In the screening study, d‐2‐18F‐AF and l‐2‐18F‐AF showed greater accumulation in E. coli than in S. aureus. When evaluated in a panel of pathologic microorganisms, both d‐2‐18F‐AF and l‐2‐18F‐AF demonstrated sensitivity to most gram‐positive and gram‐negative bacteria. CONCLUSIONS: Arabinofuranose‐derived 18F PET radiotracers can be synthesized with high radiochemical purity. Our study showed absence of bacterial accumulation for 5‐substitued analogs, a finding that may have mechanistic implications for related tracers. Both d‐2‐18F‐AF and l‐2‐18F‐AF showed sensitivity to most gram‐negative and gram‐positive organisms. Future in vivo studies will evaluate the diagnostic accuracy of these radiotracers in animal models of infection. [ABSTRACT FROM AUTHOR]

Poly(ADP-ribose) polymerase (PARP) inhibitors represent one of the successful novel approaches to targeted cancer treatment. Indeed, the US Food and Drug Administration (FDA) has recently approved PARP inhibitors for the treatment of breast and ovarian cancers. Despite the proven efficacy of these agents, certain challenges remain with their use. Among the most important are primary and secondary resistance. Here, we review the mechanism of action of PARP inhibitors and their ability to exploit certain inherent deficiencies among malignant cells to improve cell killing, with a focus on deficiencies in homologous recombination among cells with BRCA1 and BRCA2 mutations. Moreover, we discuss the different mechanisms of resistance including development of secondary resistance and strategies to overcome them. Finally, we discuss the limitations of novel therapeutic interventions and possible future studies to exploit biochemical pathways in order to improve therapeutic efficacy of PARP inhibitors. [ABSTRACT FROM AUTHOR]

The synergistic effectiveness of chitosan with zinc oxide nanomicelles (CZNPs) on broad spectrum of multidrug resistance (MDR) was previously evidenced in our labs, requiring elucidation of the therapeutic index (TI) for safe in vivo use. This in vitro assessment estimated the effective dose (ED 50) of micellar CZNPs for eradication of the MDR Enterococcus faecium 1449 model and the corresponding cytotoxic dose (LD 50) against rat small intestinal epithelial cells as functions of TI. In order to visually determine the mechanistic effects of micellar CZNPs on bacterial biofilm size reduction, LIVE/DEAD viability assay was used in conjunction with advanced fluorescence imaging and 3D confocal microscopy. Biofilm quantification was performed through the measure of the fluorescence intensity, using the Biotek Synergy Neo2 for calculating the ED 50. To generate the LD 50 , the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay was implemented. Quantification results revealed, at the same concentration (200 µg/mL), micellar CZNPs had average biofilm reduction of approximately 50.22% at 24 h (ED 50 = 199.13 µg/mL, LD 50 = 240.20 µg/mL, TI = 1.2062), compared to chitosan (15.66%) and ZnO (13.94%) alone. Conclusively, the ED 50 of micellar CZNPs on MDR bacterial biofilms (199.13 µg/mL) as a function of TI reveals a promising nanotherapeutic agent in comparison to either Chitosan or ZnO alone. [ABSTRACT FROM AUTHOR]

Highlights • Craniopharyngioma, a neurological disorder with high recurrence in children. • Primary cultures from rat brain hypothalamus were exposed to different concentration of Craniopharyngioma cyst fluids to scrutinize the health and viability of neurons and glial cells. • A gradual and significant loss of cell viability was observed in vitro with increasing concentration of CCF. • CCF induced increased expression of Caspase-3 expression in both neurons and glial cells in vitro. Abstract Craniopharyngiomas (CPs) are rare, epithelial tumors of the central nervous system (CNS) that could lead to manifestation of multiple post-operative symptoms, ranging from hormonal imbalance to obesity, diabetes, visual, neurological and neurocognitive impairments. CP is more frequent in children, and has been reported in middle aged adults as well. In fact, arterial laceration and/or brain stroke which may occur following the removal of some CPs is mainly due to calcification of that CPs along with strong attachments to the blood vessels. The dense oily fluid content of CPs is reported to cause brain tissue damage, demyelination and axonal loss in the hypothalamus; however, its exact effect on different cell types of CNS is still unexplored. In this study, we have collected CP cyst fluid (CCF) from mostly young patients during surgical removal and exposed it 9–10 days in vitro to the primary cultures derived from rat brain hypothalamus for 48 h. A gradual decline in cell viability was noted with increasing concentration of CCF. Moreover, a distinct degenerative morphological transformation was observed in neurons and glial cells, including appearance of blebbing and overall reduction of the cell volume. Further, enhanced expression of Caspase-3 in neurons and glial cells exposed to CCF by immunofluorescence imaging, supported by Western blot experiment suggest CCF induced apoptosis of hypothalamic cells in culture. In this study, we have demonstrated the deleterious effects of the cyst fluid on various cell types within the tumors originating region of the brain and its surroundings for the first time. Taken together, this finding could be beneficial towards identifying the region specific toxic effects of the cyst fluid and its underlying mechanism. [ABSTRACT FROM AUTHOR]

Objectives: To forecast lifetime outcomes and cost of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis (CF) with homozygous phe508del mutation from the US payer perspective.Methods: A lifetime Markov model was developed from a US payer perspective. The model included five health states: 1) mild lung disease (percent predicted forced expiratory volume in 1 second [FEV1] >70%), 2) moderate lung disease (40% ≤ FEV1 ≤ 70%), 3) severe lung disease (FEV1 < 40%), 4) lung transplantation, and 5) death. All inputs were derived from published literature. We estimated lumacaftor/ivacaftor's improvement in outcomes compared with a non-CF referent population as well as CF-specific mortality estimates.Results: Lumacaftor/ivacaftor was associated with additional 2.91 life-years (95% credible interval 2.55-3.56) and additional 2.42 quality-adjusted life-years (QALYs) (95% credible interval 2.10-2.98). Lumacaftor/ivacaftor was associated with improvements in survival and QALYs equivalent to 27.6% and 20.7%, respectively, for the survival and QALY gaps between CF usual care and their non-CF peers. The incremental lifetime cost was $2,632,249.Conclusions: Lumacaftor/ivacaftor increased life-years and QALYs in CF patients with the homozygous phe508del mutation and moved morbidity and mortality closer to that of their non-CF peers but it came with higher cost. [ABSTRACT FROM AUTHOR]

Periodically fully developed two-dimensional (2D) flow in a furrowed wavy channel is investigated numerically at various Reynolds numbers (100–2123). For the laminar and transitional flow regime, the study is done for six geometrically different channels; corresponding to various nondimensional amplitude (0.05, 0.075, and 0.1) and wavelength (0.5 and 1). Critical Reynolds number—for the onset of periodic flow—decreases with increasing amplitude and wavelength. A flow regime map—demarcating steady and unsteady flow regime—is proposed. It is shown that the size of the vortex in streamlines and waviness in isotherms increase with increasing Reynolds number, amplitude and wavelength. The performance of wavy as compared to straight channel is studied with the help of ratio of Nusselt number, friction factor and area-goodness factor, and thermal-performance factor. With increasing Reynolds number, all these parameters remain almost constant in the steady regime and increase almost linearly in the unsteady regime. For the largest Reynolds number (close to 2000) studied here, the increase in the Nusselt number ratio—within the periodic flow regime—is 11.21% and 133% for the amplitude equal to 0.075 and 0.1, respectively, at a wavelength of 0.5; at a wavelength of 1.0, the increase is 101%, 134%, and 181% for the amplitude of 0.05, 0.075, and 0.1, respectively. [ABSTRACT FROM PUBLISHER]

The aim of this study was to know the prevalence of Staphylococcus aureus in bovine milk samples and to evaluate the occurrence of methicillin-resistant Staphylococcus aureus (MRSA) among S. aureus isolates. A total of 150 bovine milk samples were analysed which showed the prevalence of S. aureus in 56.67% of samples. The mecA gene detection by PCR among S. aureus revealed the distribution of MRSA in 29.33% of bovine milk samples. Antibiotic sensitivity pattern reveals that 86.36 and 95.45 percent MRSA isolates were resistant to penicillin and ampicillin respectively, whereas 80.49 and 87.80 percent non-MRSA isolates were found to be resistant to penicillin and ampicillin antibiotics respectively. [ABSTRACT FROM AUTHOR]

The Na+-dependent glutamate transporter GLT-1 (EAAT2) shows selective expression in astrocytes, and neurons induce the expression of GLT-1 in astrocytes. In an unpublished analysis of GLT-1 promoter reporter mice, we identified an evolutionarily conserved domain of 467 nucleotides ~ 8 kb upstream of the GLT-1 translation start site that is required for astrocytic expression. Using in silico approaches, we identified Pax6 as a transcription factor that could contribute to the control of GLT-1 expression by binding within this region. We demonstrated the expression of Pax6 protein in astrocytes in vivo. Lentiviral transduction of astrocytes with exogenous Pax6 increased the expression of enhanced green fluorescent protein ( eGFP) in astrocytes prepared from transgenic mice that use a bacterial artificial chromosome containing a large genomic region surrounding the GLT-1 gene to control expression of eGFP. It also increased GLT-1 protein and GLT-1-mediated uptake, whereas there was no effect on the levels of the other astroglial glutamate transporter, glutamate aspartate transporter (GLAST). Transduction of astrocytes with an sh RNA directed against Pax6 reduced neuron-dependent induction of GLT-1 or eGFP. Finally, we confirmed Pax6 interaction with the predicted DNA-binding site in electrophoretic mobility assays and chromatin immunoprecipitation (Ch IP). Together, these studies show that Pax6 contributes to the regulation of GLT-1 through an interaction with these distal elements and identify a novel role of Pax6 in astrocyte biology. [ABSTRACT FROM AUTHOR]

Numerical study is done at various Reynolds numbers (100–2000), for periodically fully developed flow and heat transfer in five geometrically different wavy channels. Time signal analysis is done to distinguish various unsteady flow regimes and a flow regime map is proposed; demarcating steady, two types of periodic as well as quasi-periodic, and chaotic flow regimes. Temporal variation of flow structure and Nusselt number as well as friction factor are presented – in the various unsteady regimes – and discussed for a unified cause-and-effect study. Effect of different flow regimes on the thermal-hydraulic performance of wavy as compared to plane channel is presented. Effect of Prandtl numbers (0.01–100) is also studied. [ABSTRACT FROM AUTHOR]

Down syndrome is the most common chromosomal disorder in humans as well as the most common cause of inherited intellectual disability. A spectrum of physical and functional disability is associated with the syndrome as well as a predisposition to developing particular malignancies, including testicular cancers. These tumours ordinarily have a high cure rate even in widely disseminated disease. However, individuals with Down syndrome may have learning difficulties, behavioural problems, and multiple systemic complications that have the potential to make standard treatment more risky and necessitates individualized approach in order to avoid unacceptable harm. There is also suggestion that tumours may have a different natural history. Further, people with learning disabilities have often experienced poorer healthcare than the general population. In order to address these inequalities, legislation, professional bodies, and charities provide guidance; however, ultimately, consideration of the person in the context of their own psychosocial issues, comorbidities, and possible treatment strategies is vital in delivering optimal care. We aim to present a review of our own experience of delivering individualized care to this group of patients in order to close the existing health inequality gap. [ABSTRACT FROM AUTHOR]

Down syndrome is the most common chromosomal disorder in humans as well as the most common cause of inherited intellectual disability. A spectrum of physical and functional disability is associated with the syndrome as well as a predisposition to developing particular malignancies, including testicular cancers. These tumours ordinarily have a high cure rate even in widely disseminated disease. However, individuals with Down syndrome may have learning difficulties, behavioural problems, and multiple systemic complications that have the potential to make standard treatment more risky and necessitates individualized approach in order to avoid unacceptable harm. There is also suggestion that tumours may have a different natural history. Further, people with learning disabilities have often experienced poorer healthcare than the general population. In order to address these inequalities, legislation, professional bodies, and charities provide guidance; however, ultimately, consideration of the person in the context of their own psychosocial issues, comorbidities, and possible treatment strategies is vital in delivering optimal care. We aim to present a review of our own experience of delivering individualized care to this group of patients in order to close the existing health inequality gap. [ABSTRACT FROM AUTHOR]

More than half of Danes buy organic food products every week; however, this has not been reflected in the retail sale of organic fish and shellfish. Therefore, this paper aims to perform consumer segmentation through the food-related lifestyle (FRL) instrument and determine the factors influencing intention to buy organic fish among Danish consumers applying the theory of planned behaviour (TPB). Survey data were collected using a validated questionnaire from 237 Danish convenient consumers. The structural equation model (SEM) was used to analyze the relationships between the TPB constructs. Consumer segmentation was based on the FRL instrument (incl. The shopping scripts, higher-order product attributes, and meal preparation scripts) as a basis for consumer segmentation. Factor analysis with hierarchical clustering yielded four consumer segments: the "Careless" (31.6% of the respondents), the "Rational" (17.3%), the "Cooks" (31.6%), and the "Eco-moderate" (19.4%). Consumers from the Careless segment had the highest percentage of respondents buying organic fish (39.1%), followed by those from the Cooks (33.1%). However, consumers from the Cooks segment purchase organic fish regularly, followed by the Careless segment (27.3% and 11.5%, respectively). The results from SEM indicated that past experience, perceived barriers such as difficulty to judge the quality, and availability of organic fish were significant predictors of the intention to buy organic fish. However, attitudes, subjective norms, and perceived price were not significant predictors of the intention to buy organic fish. The intention to buy organic fish showed a strong positive correlation with the reported consumption frequency of organic fish. Hence, focusing on perceived barriers, past experience with buying organic, and promoting availability among consumers is likely to trigger a behavioural intention of buying organic fish, thereby potentially increasing the purchasing frequency of organic fish. • We performed consumer segmentation and quantify the effect of factors influencing intention to buy organic fish. • Food related lifestyle instrument and the theory of planned behaviour were utilized. • Four consumer segments were identified. • Past experience, availability and perceived barriers are the most important factors driving intention to buy organic fish. [ABSTRACT FROM AUTHOR]

Heparin has been extensively used as an anticoagulant for the last eight decades. Recently, the administration of a contaminated batch of heparin caused 149 deaths in several countries including USA, Germany, and Japan. The contaminant responsible for the adverse effects was identified as oversulfated chondroitin sulfate (OSCS). Here, we report a rapid, ultrasensitive method of detecting OSCS in heparin using a nanometal surface energy transfer (NSET) based gold-heparin-dye nanosensor. The sensor is an excellent substrate for heparitinase enzyme, as evidenced by ∼70% recovery of fluorescence from the dye upon heparitinase treatment. However, the presence of OSCS results in diminished fluorescence recovery from the nanosensor upon heparitinase treatment, as the enzyme is inhibited by the contaminant. The newly designed nanosensor can detect as low as 1 × 10-9 % (w/w) OSCS making it the most sensitive tool to date for the detection of trace amounts of OSCS in pharmaceutical heparins. [ABSTRACT FROM AUTHOR]

Abstract: Background: Active surveillance (AS) aims to allow men with favourable-risk, localised prostate cancer to avoid unnecessary treatment. Objective: To describe the clinical outcomes of a prospective study of AS. Design, setting, and participants: A single-centre, prospective cohort study. Eligibility criteria included histologically proven prostate adenocarcinoma, age 50–80 yr, stage T1/T2, prostate-specific antigen level (PSA) <15 ng/ml, Gleason score (GS) ≤3+3 (GS ≤3+4 if aged >65 yr), and percent positive biopsy cores (PPC) ≤50%. Intervention: Patients were assessed by serum PSA level, and digital rectal examination at 3-mo intervals in year 1, 4-mo intervals in year 2, and at 6-mo intervals thereafter. Transrectal ultrasound-guided prostate biopsy was performed after 18–24 mo and every 2 yr thereafter. Treatment was recommended for PSA velocity (PSAV) >1 ng/ml per year or adverse histology, defined as GS ≥4+3 or PPC >50%. Outcome measurements and statistical analysis: Outcomes described, using Kaplan-Meier methods, were rate of adverse histology on repeat biopsy, freedom from treatment, biochemical control after deferred treatment, and overall survival. Analyses using Cox regression were performed to determine predictors of deferred treatment and adverse histology. Results and limitations: The study enrolled 471 eligible patients from 2002 to 2011. Median age was 66 yr and median initial PSA value was 6.4 ng/ml. Eighty-eight percent of patients had T1 disease and 93% had GS ≤3+3. At median follow-up of 5.7 yr, the 5-yr rate of adverse histology and treatment-free probability was 22% (95% confidence interval [CI], 16–29%) and 70% (95% CI, 65–75%), respectively. There were two deaths from prostate cancer. Predictors of time to adverse histology were GS 7, PSAV >1 ng/ml per year, low ratio of free PSA to total PSA, and PPC >25%. Longer follow-up is needed to confirm the safety of this strategy. Conclusions: This study demonstrates satisfactory medium-term outcomes for AS in selected men with localised prostate cancer. [Copyright &y& Elsevier]

• Production method information significantly increases consumer liking of wild-caught smoked salmon. • Consumers primarily paid more attention to liking of taste in the evaluation of overall liking of smoked salmon. • Consumers' belief related to food safety, animal welfare and sustainability as well as purchasing habits may influence preference and liking of smoked salmon. • Consumers liked organic smoked salmon better than wild-caught smoked salmon under blind condition. Product information is capable of steering the consumers' expectation formation process. Therefore, this paper aims to investigate whether information on production method influence consumers' preference and liking of smoked salmon. A consumer test was conducted among 92 consumers to determine liking of the smoked salmon on a 7-point hedonic scale before (blind) and after (informed) receiving information about production method (organic, conventional and wild-caught). Further, two explanatory focus group discussions (n = 5 in each group) were conducted to determine consumers' belief on production method. A linear mixed-effects model analysis indicated that the consumer overall liking of wild-caught smoked salmon significantly increased after production method information was provided, while regarding organic and conventional smoked salmon no significant difference was noted. Post hoc test indicated that organic smoked salmon was significantly more liked than wild-caught smoked salmon (mean difference ± standard error: 0.652 ± 0.19, p < 0.01) in blind condition, however, between organic and conventional smoked salmon no significant difference was noted (-0.032 ± 0.19, p = 0.983). Further, in informed condition, organic smoked salmon was significantly more liked than conventional smoked salmon (0.50 ± 0.19, p < 0.05), however, between organic and wild-caught smoked salmon no significant difference was noted (0.228 ± 0.19, p = 0.452). Relative importance analysis results suggest that liking of taste was the most important contributor (26.84%) to smoked salmon overall liking (p < 0.05, R2 = 74.17%). Focus group discussion revealed that consumer beliefs related to food safety, animal welfare and sustainability as well as purchasing habits seem to influence smoked salmon preferences. Thus, organic aquaculture sector should focus on promoting consumer beliefs by providing reliable information based on scientific evidences that helps differentiates their products with that of conventional and wild-caught smoked salmon. Future studies might investigate other fish species to better understand the role of product method information on consumer preference and liking of fish. [ABSTRACT FROM AUTHOR]

Two photochromic spirodihydroindolizine/betaine systems for tethering to peptides and proteins via a maleimide function have been prepared. The absorption spectra of the betaines are in the red region of the visible spectrum and in the near-IR spectral domain, which are suitable energies of light for future in vivo applications. The half-times of cyclization have been determined for both DHI/betaine systems. The findings are consistent with a thermal barrier of varying size between the transoid and cisoid conformers of the betaines. [ABSTRACT FROM AUTHOR]

Abstract: Markov Decision Processes (MDPs) describe a wide variety of planning scenarios ranging from military operations planning to controlling a Mars rover. However, todayʼs solution techniques scale poorly, limiting MDPsʼ practical applicability. In this work, we propose algorithms that automatically discover and exploit the hidden structure of factored MDPs. Doing so helps solve MDPs faster and with less memory than state-of-the-art techniques. Our algorithms discover two complementary state abstractions — basis functions and nogoods. A basis function is a conjunction of literals; if the conjunction holds true in a state, this guarantees the existence of at least one trajectory to the goal. Conversely, a nogood is a conjunction whose presence implies the non-existence of any such trajectory, meaning the state is a dead end. We compute basis functions by regressing goal descriptions through a determinized version of the MDP. Nogoods are constructed with a novel machine learning algorithm that uses basis functions as training data. Our state abstractions can be leveraged in several ways. We describe three diverse approaches — GOTH, a heuristic function for use in heuristic search algorithms such as RTDP; ReTrASE, an MDP solver that performs modified Bellman backups on basis functions instead of states; and SixthSense, a method to quickly detect dead-end states. In essence, our work integrates ideas from deterministic planning and basis function-based approximation, leading to methods that outperform existing approaches by a wide margin. [Copyright &y& Elsevier]

The advancement of biomedicine in a socioeconomically sustainable manner while achieving efficient patient-care is imperative to the health and well-being of society. Magnetic systems consisting of iron based nanosized components have gained prominence among researchers in a multitude of biomedical applications. This review focuses on recent trends in the areas of diagnostic imaging and drug delivery that have benefited from iron-incorporated nanosystems, especially in cancer treatment, diagnosis and wound care applications. Discussion on imaging will emphasise on developments in MRI technology and hyperthermia based diagnosis, while advanced material synthesis and targeted, triggered transport will be the focus for drug delivery. Insights onto the challenges in transforming these technologies into day-to-day applications will also be explored with perceptions onto potential for patient-centred healthcare. [ABSTRACT FROM AUTHOR]

We report a new class of derivatized 4,4'-bipyridinium ligands for use in synthesizing highly fluorescent, extremely stable, water-soluble CdSe and CdTe quantum dots (QDs) for bioconjugation. We employed an evaporation-condensation technique, also known as solvated metal atom dispersion (SMAD), followed by a digestive ripening procedure. This method has been used to synthesize both metal nanoparticles and semiconductors in the gram scale wish several stabilizing ligands in various solvents. The SMAD technique comprised evaporation condensation and stabilization of CdSe or CdTe in tetsahydrofuran. The as-prepared product was then digestively ripened in both water and dimethyl formamide, leading to narrowing of the particle size distributions. The ligands were synthesized by nucleophilic substitution (SN2) reactions using 4,4'-bipyridine as a nucleophile. Confocal microscopy images revealed the orange color of the nanocrystalline QDs with diameters of ΙS nm. The size has been confirmed by using transmission electron microscopy. As a part of our strategy, 85% of the 4,4'bipyridinium salt was synthesized as propionic arid derivative and used to both stabilize the QDs in water and label basic amino acids and different biomarkers utilizing the carboxylic acid functional group. Fifteen percent of the 4,4'-bipyridinium salt was synthesized as N-propyl maleimide and used as a second ligand to label any protein containing the amino acid cysteine by means of a 1,4-Michael addition. [ABSTRACT FROM AUTHOR]

The glutamate transporter-1 [GLT-1 (excitatory amino acid transporter 2)] subtype of glutamate transporter ensures crisp excitatory signaling and limits excitotoxicity in the CNS. Astrocytic expression of GLT-1 is regulated during development, by neuronal activity, and in neurodegenerative diseases. Although neurons activate astrocytic expression of GLT-1, the mechanisms involved have not been identified. In the present study, astrocytes from transgenic mice that express enhanced green fluorescent protein (eGFP) under the control of a bacterial artificial chromosome (BAC) containing a very large region of DNA surrounding the GLT-1 gene (BAC GLT-1 eGFP mice) were used to assess the role of nuclear factor-κB (NF-κB) in neuron-dependent activation of the GLT-1 promoter. We provide evidence that neurons activate NF-κB signaling in astrocytes. Transduction of astrocytes from the BAC GLT-1 eGFP mice with dominantnegative inhibitors of NF-κB signaling completely blocked neuron-dependent activation of a NF-κB reporter construct and attenuated induction of eGFP. Exogenous expression of p65 and/or p50 NF-κB subunits induced expression of eGFP or GLT-1 and increased GLT-1-mediated transport activity. Using wild-type and mutant GLT-1 promoter reporter constructs, we found that NF-κB sites at -583 or -251 relative to the transcription start site were required for neuron-dependent reporter activation. Electrophoretic mobility shift and supershift assays reveal that p65 and p50 interact with these same sites ex vivo. Finally, chromatin immunoprecipitation showed that p65 and p50 interact with these sites in adult cortex, but not in kidney (a tissue that expresses no detectable GLT-1). Together, these studies strongly suggest that NF-κB contributes to neuron-dependent regulation of astrocytic GLT-1 transcription. [ABSTRACT FROM AUTHOR]

Microglia, the primary resident immune cells of the central nervous system (CNS), exhibit dynamic behavior involving rapid process motility and cellular migration that is thought to underlie key functions of immune surveillance and tissue repair. Although age-related changes in microglial activation have been implicated in the pathogenesis of neurodegenerative diseases of aging, how dynamic behavior in microglia is influenced by aging is not fully understood. In this study, we employed live imaging of retinal microglia in situ to compare microglial morphology and behavioral dynamics in young and aged animals. We found that aged microglia in the resting state have significantly smaller and less branched dendritic arbors, and also slower process motilities, which probably compromise their ability to survey and interact with their environment continuously. We also found that dynamic microglial responses to injury were age-dependent. While young microglia responded to extracellular ATP, an injury-associated signal, by increasing their motility and becoming more ramified, aged microglia exhibited a contrary response, becoming less dynamic and ramified. In response to laser-induced focal tissue injury, aged microglia demonstrated slower acute responses with lower rates of process motility and cellular migration compared with young microglia. Interestingly, the longer term response of disaggregation from the injury site was retarded in aged microglia, indicating that senescent microglial responses, while slower to initiate, are more sustained. Together, these altered features of microglial behavior at rest and following injury reveal an age-dependent dysregulation of immune response in the CNS that may illuminate microglial contributions to age-related neuroinflammatory degeneration. [ABSTRACT FROM AUTHOR]

Abstract: This paper introduces a novel approach to the task of lexical translation between languages for which no translation dictionaries are available. We build a massive translation graph, automatically constructed from over 630 machine-readable dictionaries and Wiktionaries. In this graph each node denotes a word in some language and each edge denotes a word sense shared by and . Our current graph contains over 10,000,000 nodes and expresses more than 60,000,000 pairwise translations. The composition of multiple translation dictionaries leads to a transitive inference problem: if word A translates to word B which in turn translates to word C, what is the probability that C is a translation of A? The paper describes a series of probabilistic inference algorithms that solve this problem at varying precision and recall levels. All algorithms enable us to quantify our confidence in a translation derived from the graph, and thus trade precision for recall. We compile the results of our best inference algorithm to yield PanDictionary, a novel multilingual dictionary. PanDictionary contains more than four times as many translations as in the largest Wiktionary at precision 0.90 and over 200,000,000 pairwise translations in over 200,000 language pairs at precision 0.8. [Copyright &y& Elsevier]

Abstract: Nanotechnology has widespread application in agricultural, environmental and industrial sectors ranging from fabrication of molecular assemblies to microbial array chips. Despite the booming application of nanotechnology, there have been serious implications which are coming into light in the recent years within different environmental compartments, namely air, water and soil and its likely impact on the human health. Health and environmental effects of common metals and materials are well-known, however, when the metals and materials take the form of nanoparticles – consequential hazards based on shape and size are yet to be explored. The nanoparticles released from different nanomaterials used in our household and industrial commodities find their way through waste disposal routes into the wastewater treatment facilities and end up in wastewater sludge. Further escape of these nanoparticles into the effluent will contaminate the aquatic and soil environment. Hence, an understanding of the presence, behavior and impact of these nanoparticles in wastewater and wastewater sludge is necessary and timely. Despite the lack of sufficient literature, the present review attempts to link various compartmentalization aspects of the nanoparticles, their physical properties and toxicity in wastewater and wastewater sludge through simile drawn from other environmental streams. [Copyright &y& Elsevier]

Abstract: Bacillus thuringiensis var. kurstaki (Btk) predominantly used as a microbial insecticide was tested for concomitant degradation of dimethyl phthalate (DMP). Different concentrations of DMP, 100, 200, 500, 1000 and 2000mg/l were initially spiked in tryptic soya broth medium. A control of tryptic soya broth without DMP was also included. The experiments were carried out for 48h at 30°C and 250rpm and growth, enzyme and biocontrol assay was evaluated. DMP concentration until 500mg/l did not affect Btk cell growth, however, for DMP concentration of 1000–2000mg/l, there was a 10 and 100 times decrease in cell and spore concentration, respectively. The enzyme concentration reduced by a factor of 1.5, 2, and 2.3 times for protease, esterase and amylase, respectively, at 1000 and 2000mg/l suggesting toxicity of DMP at higher concentrations. Interestingly, the entomotoxicity (insect toxicity, taken as measure of biocontrol) was higher at 1000 and 5000mg/l with 12 and 13 billion spruce budworm units/l, as tested against spruce budworm larvae. After 48h of incubation, DMP concentration decreased to 1–3mg/l at initial concentrations ranging from 100 to 500mg/l, and the removal was relatively lower with 89 and 87% at 1000 and 2000mg/l of DMP, respectively. These results suggest that Btk produces panoply of enzyme systems which can assist in degradation of DMP. [Copyright &y& Elsevier]

Summary  (1) Our earlier studies indicate a downsteam regulatory role of the β-adrenergic receptor (β-AR) system in thyroid hormone induced differentiation and maturation of astrocytes. In the present study we have investigated the contributions of the subtypes of β-AR in the above phenomenon. (2) Primary astrocyte cultures were grown under thyroid hormone deficient as well as under euthyroid conditions. [125I]Pindolol ([125I]PIN) binding studies showed a gradual increase in the specific binding to β2-AR when observed at 5, 10, 15, and 20 days under both cultural conditions. Thyroid hormone caused an increase in binding of [125I]PIN to β2-AR compared to thyroid hormone deficient controls at all ages of astrocyte culture. (3) Saturation studies using [125I]PIN in astrocyte membranes prepared from 20-day-old cultures showed a significant increase in the affinity of the receptors (K D) in the thyroid hormone treated cells without any change in receptor number (B max). (4) β2-AR mRNA levels were measured by real-time PCR during ontogenic development as well as during exposure of 10-day-old hypothyroid cultures to normal levels of thyroid hormone for 2, 6, 12, and 24 h. None of the conditions caused any significant change in the β2-adrenergic receptor mRNA levels when compared with corresponding hypothyroid controls. (5) Over expression of β2-AR cDNA in hypothyroid astrocytes caused morphological transformation in spite of the absence of thyroid hormone in the medium. (6) Taken together, results suggest thyroid hormone causes a selective increase in [125I]PIN binding to β2-AR due to increase in receptor affinity, which may lead to maturation of astrocytes. [ABSTRACT FROM AUTHOR]

Abstract  Axenic cultivation of biocontrol fungus Trichoderma viride was conducted on a synthetic medium and different wastewaters and wastewater sludges in shake flasks to search for a suitable raw material resulting in higher biocontrol activity. Soluble starch based synthetic medium, dewatered municipal sludge, cheese industry wastewater sludge, pre-treated and untreated pulp and paper industry wastewater and slaughter house wastewater (SHW) were tested for T. viride conidia and protease enzyme production. The maximum conidia production followed the order, soluble starch medium (>109 c.f.u./mL), untreated pulp and paper industry wastewater (4.9 � 107 c.f.u./mL) > cheese industry wastewater (1.88 � 107 c.f.u./mL) ≈ SHW (1.63 � 107 c.f.u./mL) > dewatered municipal sludge (3.5 � 106 c.f.u./mL) > pre-treated pulp and paper industry wastewater (1.55 � 106 c.f.u./mL). The protease activity of T. viride was particularly higher in slaughterhouse wastewater (2.14 IU/mL) and dewatered municipal sludge (1.94 IU/mL). The entomotoxicity of soluble starch based synthetic medium was lower (≈6090 SBU/μL) in contrast to other raw materials. The entomotoxicity inversely decreased with carbon to nitrogen ratio in the growth medium and the conidia concentration and protease activity also contributed to the entomotoxicity. The residual c.f.u./g formulation of T. viride conidia were up to approximately, 90% after 1 month at 4 � 1 �C and about 70% after 6 months at 25 � 1 �C. Thus, production of T. viride conidia would help in marketability of low cost biopesticide from the sludge and safe reduction of pollution load. [ABSTRACT FROM AUTHOR]

Abstract: Biomechanical model assumptions affect the interpretation of the role of the muscle or joint moments to the segmental power estimated by induced acceleration analysis (IAA). We evaluated the effect of modeling the pelvis and trunk segments as two separate segments (8 SM) versus as a single segment (7 SM) on the segmental power, support of the body, knee and hip extension acceleration produced by the joint moments during the stance phase of normal walking. Significant differences were observed in the contribution of the stance hip abductor and extensor moments to support, ipsilateral knee and hip acceleration, and ipsilateral thigh and upper body power. The primary finding was that the role of the stance hip moment in generating ipsilateral thigh and upper body power differed based on degrees of freedom in the model. Secondarily, the magnitude of contributions also differed. For example, the hip abductor and extensor moments showed greater contribution to support, hip and knee acceleration in the 8 SM. IAA and segment power analysis are sensitive to the degrees of freedom between the pelvis and trunk. There is currently no gold standard by which to evaluate the accuracy of IAA predictions. However, modeling the pelvis and trunk as separate segments is closer to the anatomical architecture of the body. An 8 SM appears to be more appropriate for estimating the role of joint moments, particularly to motion of more proximal segments during normal walking. [Copyright &y& Elsevier]

Abstract: Conidiation and lytic enzyme production by Trichoderma viride at different solids concentration of pre-treated municipal wastewater sludge was examined in a 15-L fermenter. The maximum conidia concentration (5.94×107 CFUmL−1 at 96h) was obtained at 30gL−1 suspended solids. The maximum lytic enzyme activities were achieved around 12–30h of fermentation. Bioassay against a fungal phytopathogen, Fusarium sp. showed maximum activity in the sample drawn around 96h of fermentation at 30gL−1 suspended solids concentration. Entomotoxicity against spruce budworm larvae showed maximum value ≈17290SBUμL−1 at 30gL−1 suspended solids concentration at the end of fermentation (96h). Plant bioassay showed dual action of T. viride, i.e., disease prevention and growth promotion. The rheological analyses of fermentation sludges showed the pseudoplastic behaviour. In order to maintain required dissolved oxygen concentration ≥30%, the agitation and aeration requirements significantly increased at 35gL−1 compared to 30 and 25gL−1. The oxygen uptake rate and volumetric oxygen mass transfer coefficient, k L a at 35gL−1 did not increase in comparison to 30gL−1 due to rheological complexity of the broth during fermentation. Thus, the successful fermentation operation of the biocontrol fungus T. viride is a rational indication of its potential for mass-scale production for agriculture and forest sector as a biocontrol agent. [Copyright &y& Elsevier]

Abstract: Trichoderma spp. have been widely used as antagonistic fungal agents against several pests as well as plant growth enhancers. Faster metabolic rates, anti-microbial metabolites, and physiological conformation are key factors which chiefly contribute to antagonism of these fungi. Mycoparasitism, spatial and nutrient competition, antibiosis by enzymes and secondary metabolites, and induction of plant defence system are typical biocontrol actions of these fungi. On the other hand, Trichoderma spp. have also been used in a wide range of commercial enzyme productions, namely, cellulases, hemicellulases, proteases, and β-1,3-glucanase. Information on the classification of the genus, Trichoderma, mechanisms of antagonism and role in plant growth promotion has been well documented. However, fast paced current research in this field should be carefully updated for the fool-proof commercialization of the fungi. The aim of this review is to sum up the BCA activity potential of these fungi and to shed light on commercial production processes. In this regard, this review focuses on Trichoderma spp. discussing different aspects—pest control, growth promotion, bioremediation, production processes and market values. Nevertheless, more research and review of the information regarding these biocontrol agents are needed to exploit their actual potential, which is the salient objective of this review. [Copyright &y& Elsevier]

Thyroid hormone (TH) has a profound effect on astrocyte differentiation and maturation. Astrocytes cultured under TH-deficient conditions fail to transform from flat polygonal morphology to mature, process-bearing, stellate cells. Supplementation of physiological concentrations of TH initiate gradual transformation of the cells and the process takes ≈ 48 h to complete. The signal transduction pathways associated with TH-mediated maturation of astrocytes have been investigated. TH treatment caused an initial activation of protein kinase A (PKA), with a peak activity at 2 h which fell back to basal level there after. Although there was no visible change in morphology of the cells during the observed activation of PKA, it was sufficient to drive the process of transformation to completion, suggesting the involvement of downstream regulators of PKA. PKA inhibitors as well as the MEK inhibitor PD098059 attenuated the TH-induced morphological transformation. Further studies showed that TH treatment resulted in a biphasic response on the cellular phospho-MAP kinase (p-MAPK or p-ERK) level: an initial decline in the p-ERK level followed by an induction at 18–24 h, both of which could be blocked by a PKA inhibitor. Such sustained activation of p-ERK levels by TH at this later stage coincided with initiation of morphological differentiation of the astrocytes and appeared to be critical for the transformation of astrocytes. The nitric oxide synthase (NOS) inhibitor 7-NI inhibited this induction of p-ERK activity. Moreover, the induction was accompanied by a parallel increase in phospho-CREB activity which, however, persisted at the end of the transformation of the astroglial cells. [ABSTRACT FROM AUTHOR]

Abstract: Feasibility of production of antagonistic Trichoderma sp. conidial spores using wastewater sludge as a raw material employing different suspended solids concentration (10–50g/l) was investigated in shake flasks. Maximum conidial spore count obtained for raw sludge was 1.98×104 CFU/ml, which was enhanced by sludge pre-treatments (alkaline and thermal alkaline). Conidial spore count ranging from 1.3×106 to 2.8×107 CFU/ml was observed for alkaline and thermal alkaline treated sludges. Optimal suspended solids concentration was 30g/l (107 CFU/ml) whereas, lower (&#60;20g/l) and higher (>30g/l) solids concentration were less efficient. Thermal alkaline pre-treated sludge showed diauxic growth due to multiplicity of sludge biodegradability. A simple, modified CFU filtration technique was also developed for fungal spore assessment in sludge. Bioassay of fermented sludge against spruce budworm larvae showed entomotoxicity (15036SBU/μl), on par with Bacillus thuringiensis biopesticides. This study successfully demonstrated potential of wastewater sludge as a raw material for production of value added product, aiding in sludge management and proliferation of eco-friendly and economical biocontrol agents. [Copyright &y& Elsevier]