Impact of automobile exhaust on biochemical and genomorphic characteristics of Mimusops elengi L. growing along roadsides of Lahore city, Pakistan.

Automobile exhaust releases different types of pollutants that are at great risk to the air quality of the environment and incidental distress to the nature of roadside plants. Mimusops elengi L. is an evergreen medicinal tree cultivated along the roadside of Lahore City. This research aimed to investigate physiological, morphological and genomorphic characteristics of M. elengi under the influence of air pollution from vehicles. Healthy and mature leaves were collected from trees on Canal Bank and Mall roads of Lahore as the experimental sites and control sites were 20 km away from the experimental site. Different physiochemical, morphological, air pollution tolerance index (APTI) and molecular analysis for the detection of DNA damage were performed through comet assay. The results demonstrated the mean accumulated Cd, Pb, Cu and Ni heavy metal contents on the leaves were higher than the control plants (1.27, 3.22, 1.32 and 1.46 µg mg-1). APTI of trees was 9.04. Trees in these roads significantly (p < 0.01) had a lower leaf area, petiole length and leaf dry matter content in comparison to control site. Increased comet tail showed that DNA damage was higher for roadside trees than trees in the control area. For tolerance of air pollution, it necessary to check the APTI value for the M. elengi at the polluted road side of Lahore city. For long-term screening, the source and type of pollutants and consistent monitoring of various responses given by the trees should be known.

Improving primary prophylaxis of variceal bleeding by adapting therapy to the clinical stage of cirrhosis. A competing-risk meta-analysis of individual participant data.

BACKGROUND & AIMS: Non-selective ß-blockers (NSBBs) and endoscopic variceal-ligation (EVL) have similar efficacy preventing first variceal bleeding. Compensated and decompensated cirrhosis are markedly different stages, which may impact treatment outcomes. We aimed to assess the efficacy of NSBBs vs EVL on survival in patients with high-risk varices without previous bleeding, stratifying risk according to compensated/decompensated stage of cirrhosis. METHODS: By systematic review, we identified RCTs comparing NSBBs vs EVL, in monotherapy or combined, for primary bleeding prevention. We performed a competing-risk, time-to-event meta-analysis, using individual patient data (IPD) obtained from principal investigators of RCTs. Analyses were stratified according to previous decompensation of cirrhosis. RESULTS: Of 25 RCTs eligible, 14 failed to provide IPD and 11 were included, comprising 1400 patients (656 compensated, 744 decompensated), treated with NSBBs (N = 625), EVL (N = 546) or NSBB+EVL (N = 229). Baseline characteristics were similar between groups. Overall, mortality risk was similar with EVL vs. NSBBs (subdistribution hazard-ratio (sHR) = 1.05, 95% CI = 0.75-1.49) and with EVL + NSBBs vs either monotherapy, with low heterogeneity (I2 = 28.7%). In compensated patients, mortality risk was higher with EVL vs NSBBs (sHR = 1.76, 95% CI = 1.11-2.77) and not significantly lower with NSBBs+EVL vs NSBBs, without heterogeneity (I2 = 0%). In decompensated patients, mortality risk was similar with EVL vs. NSBBs and with NSBBs+EVL vs. either monotherapy. CONCLUSIONS: In patients with compensated cirrhosis and high-risk varices on primary prophylaxis, NSBBs significantly improved survival vs EVL, with no additional benefit noted adding EVL to NSBBs. In decompensated patients, survival was similar with both therapies. The study suggests that NSBBs are preferable when advising preventive therapy in compensated patients.

Corrigendum: Effects of chlorantraniliprole on the life history traits of fall armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae).

[This corrects the article DOI: 10.3389/fphys.2023.1155455.].

Resistance monitoring and mechanism in the fall armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae) for chlorantraniliprole from Sichuan Province, China.

The fall armyworm, Spodoptera frugiperda (Noctuidae: Lepidoptera), is a wide-reaching notorious insect pest of important cereal crops, which has developed resistance to multiple classes of insecticides. It invaded the Sichuan Province of China in 2019. In this study, we performed resistance monitoring of insecticides for 11 field-collected populations from Sichuan, and all the populations were susceptible to emamectin benzoate and chlorpyrifos. The variations in resistance level to indoxacarb (resistance ratio (RR), 9.23-45.53-fold), spinetoram (RR, 4.32-18.05-fold), and chlorantraniliprole (RR, 2.02-10.39-fold) were observed among these populations. To investigate the resistance mechanism of chlorantraniliprole, synergism tests were performed and showed that piperonyl butoxide had a slight synergistic effect on chlorantraniliprole for the QJ-20 population (1.43-fold) in moderate resistance (RR, 10.39-fold) compared with the treatment group without synergist. Furthermore, the expression scanning for resistance-related genes showed that five P450 genes (CYP6AE43, CYP321A8, CYP305A1, CYP49A1, and CYP306A1) and the ryanodine receptor gene (Ryr, chlorantraniliprole target) were overexpressed in the QJ-20 population. These results indicated that the fall armyworm in Sichuan has exhibited diverse susceptibilities to several classes of insecticides, and the overexpression of Ryr and several P450 genes may contribute to the development of resistance in S. frugiperda to chlorantraniliprole.

Effects of chlorantraniliprole on the life history traits of fall armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae).

Introduction: Spodoptera frugiperda is an important nomadic agricultural pest with a diverse host range and resistance against several insecticides. The current study investigated the life history traits of two strains of the field-collected population against chlorantraniliprole using an age-stage two-sex life table. Method: For this, we established the chlorantraniliprole-susceptible (Crp-SUS G12), and chlorantraniliprole-reduced susceptible (Crp-RES G12) strains derived from the sixth generation of the QJ-20 population having a resistance ratio (RR) of 10.39-fold, compared with the reported susceptible population. Results: The results showed that the chlorantraniliprole-reduced susceptible strain attained a 4.0-fold RR, while the chlorantraniliprole-susceptible strain attained an RR of 0.85-fold, having overlapped fiducial limits (FLs) with the referred susceptible baseline. Meanwhile, the present study revealed that the development time of the susceptible strain was significantly longer than that of the reduced susceptible strain. Similarly, the mean longevity, adult pre-oviposition period (APOP), and total pre-oviposition period (TPOP) of the female chlorantraniliprole-susceptible strain were considerably longer than those of the female chlorantraniliprole-reduced susceptible strain. Contrarily, the population parameters, including the intrinsic rate of increase (r), finite rate of increase (λ), and net reproductive rate (R), of the chlorantraniliprole-susceptible strain were considerably lower than those of the chlorantraniliprole-reduced susceptible strain, while the mean generation time (T) of the chlorantraniliprole-susceptible strain was substantially longer than the chlorantraniliprole-reduced susceptible strain. The age-stage characteristic survival rate (s xj ) and age-stage characteristic life expectancy (e xj ) of the chlorantraniliprole-susceptible strain were longer than those of the chlorantraniliprole-reduced susceptible strain, but the age-stage-specific reproductive value (v xj ) of the chlorantraniliprole-susceptible strain was shorter than that of the chlorantraniliprole-reduced susceptible strain. Moreover, the contents of vitellogenin (Vg) and VgR in the chlorantraniliprole-reduced susceptible strain were higher than those in the chlorantraniliprole-susceptible strain. Discussion: These findings showed that reducing susceptibility to chlorantraniliprole promoted population growth in S. frugiperda. Therefore, this study could provide conceptual support for the integrated pest management (IPM) approach to control S. frugiperda in the field.

Eco-friendly deacetylated chitosan base siRNA biological-nanopesticide loading cyromazine for efficiently controlling Spodoptera frugiperda.

Spodoptera frugiperda is a serious threat to various crops, such as corn and rice, and results in severe economic losses. Herein, a chitin synthase sfCHS highly expressed in the epidermis of S. frugiperda was screened, and when interfered by an sfCHS-siRNA nanocomplex, most individuals could not ecdysis (mortality rate 53.3 %) or pupate (abnormal pupation 80.6 %). Based on the results of structure-based virtual screening, cyromazine (CYR, binding free energy -57.285 kcal/mol) could inhibit ecdysis (LC50, 19.599 µg/g). CYR-CS/siRNA nanoparticles encapsulating CYR and SfCHS-siRNA with chitosan (CS) were successfully prepared, as confirmed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and 74.9 mg/g CYR was characterized in the core of CYR-CS/siRNA by high-performance liquid chromatography and Fourier transform infrared spectroscopy. Small amounts of prepared CYR-CS/siRNA containing only 1.5 µg/g CYR could better inhibit chitin synthesis in the cuticle and peritrophic membrane (mortality rate 84.4 %). Therefore, chitosan/siRNA nanoparticle-loaded pesticides were useful for pesticide reduction and comprehensive control of S. frugiperda.

Status of Fungicide Resistance and Physiological Characterization of Tebuconazole Resistance in Rhizocotonia solani in Sichuan Province, China.

The resistance prevalence of chemical fungicides has caused increasingly serious agro-ecological environmental problems. However, there are few previous reports about resistance to succinate dehydrogenase (SDHI) or sterol demethylation inhibitor (DMI) in Rhizoctonia solani, one of the main agro-diseases. In this study, the fungicide resistance of 122 R. solani isolates in Sichuan Province was monitored by the mycelial growth rate method. Results showed that all isolates were susceptible to hexaconazole and most isolates were susceptible to thifluzamide, except for the field isolate MSRS-2-7 due to a moderate resistance to thifluzamide (16.43-fold resistance ratio, RR), compared to the sensitivity baseline of thifluzamide (0.042 µg/mL EC50 values). On the contrary, many isolates showed moderate or high resistance to tebuconazole (10.59- to 60.78-fold RR), reaching EC50 values of 0.54~3.10 µg/mL, especially for a highly resistant isolate LZHJ-1-8 displaying moderate resistance to epoxiconazole (35.40-fold RR due to a 3.54 µg/mL EC50 value). The fitness determination found that the tebuconazole-resistant isolates showed higher fitness cost with these characteristics, including a lower growth rate, higher relative electric conductivity, an increased ability to tolerate tebuconazole, and high osmotic pressure. Four new mutations of cytochrome P450 sterol 14α-demethylase (CYP51), namely, S94A, N406S, H793R, and L750P, which is the target for DMI fungicides, was found in the tebuconazole-resistant isolates. Furthermore, the lowest binding energy with tebuconazole was also found in the LZHJ-1-8 isolate possessing all the mutations through analyses with Discovery Studio software. Therefore, these new mutation sites of CYP51 may be linked to the resistance against tebuconazole, and its application for controlling R. solani should be restricted in some areas.

Carvedilol reduces the risk of decompensation and mortality in patients with compensated cirrhosis in a competing-risk meta-analysis.

BACKGROUND & AIMS: Whether non-selective ß-blockers can prevent decompensation of cirrhosis warrants clarification. Carvedilol might be particularly effective since its intrinsic vasodilatory activity may ameliorate hepatic vascular resistance, a major mechanism of portal hypertension in early cirrhosis. We assessed whether carvedilol may prevent decompensation and improve survival in patients with compensated cirrhosis and clinically significant portal hypertension (CSPH). METHODS: By systematic review we identified randomized-controlled trials (RCTs) comparing carvedilol vs. control therapy (no-active treatment or endoscopic variceal ligation [EVL]) in patients with cirrhosis and CSPH without previous bleeding. We performed a competing-risk time-to-event meta-analysis using individual patient data (IPD) obtained from principal investigators of RCTs. Only compensated patients were included. Primary outcomes were prevention of decompensation (liver transplantation and death were competing events) and death (liver transplantation was a competing event). Models were adjusted using propensity scores for baseline covariates with the inverse probability of treatment weighting (IPTW) approach. RESULTS: Among 125 full-text studies evaluated, 4 RCTs were eligible. The 4 provided IPD and were included, comprising 352 patients with compensated cirrhosis, 181 treated with carvedilol and 171 controls (79 received EVL and 92 placebo). Baseline characteristics were similar between groups. Standardized differences were <10% by IPTW. The risk of developing decompensation of cirrhosis was lower with carvedilol than in controls (subdistribution hazard ratio [SHR] 0.506; 95% CI 0.289-0.887; p = 0.017; I2 = 0.0%, Q-statistic-p = 0.880), mainly due to a reduced risk of ascites (SHR 0.491; 95% CI 0.247-0.974; p = 0.042; I2 = 0.0%, Q-statistic-p = 0.384). The risk of death was also lower with carvedilol (SHR 0.417; 95% CI 0.194-0.896; p = 0.025; I2 = 0.0%, Q-statistic-p = 0.989). CONCLUSIONS: Long-term carvedilol therapy reduced decompensation of cirrhosis and significantly improved survival in compensated patients with CSPH. This suggests that screening patients with compensated cirrhosis for CSPH to enable the prompt initiation of carvedilol could improve outcomes. PROSPERO REGISTRATION NUMBER: CRD42019144786. LAY SUMMARY: The transition from compensated cirrhosis to decompensated cirrhosis is associated with markedly reduced life expectancy. Therefore, preventing decompensation in patients with compensated cirrhosis would be associated with greatly improved patient outcomes. There has been controversy regarding the use of non-selective ß-blockers (portal pressure-lowering medications) in patients with cirrhosis and elevated portal blood pressure (portal hypertension). Herein, using a competing-risk meta-analysis to optimize sample size and properly investigate cirrhosis as a multistate disease and outcomes as time-dependent events, we show that carvedilol (a non-selective ß-blocker) is associated with a reduced risk of decompensating events and improved survival in patients with cirrhosis and portal hypertension.

Maf regulates the overexpression of CYP307A1, which is involved in the fitness advantage of bistrifluron-resistant Spodoptera litura (Fab.) (Noctuidae: Lepidoptera).

Spodoptera litura is a widely distributed multifeeding pest, that has developed high resistance to many chemical insecticides. In the present study, a bistrifluron-resistant (Bis-SEL) strain showing 113.8-fold resistance ratio relative to a bistrifluron-susceptible (Bis-UNSEL) strain was obtained and showed a fitness advantage (resurgence). First, we found that the observed resurgence might have resulted from Maf transcription factor overexpression in the Bis-SEL strain, which would influence the synthesis of ecdysone and chitin. Additionally, a co-expression relationship between Maf and CYP307A1 was verified by weighted correlation network analysis (WGCNA) and qRT-PCR, and the expression of CYP307A1, a key gene in ecdysone synthesis, was significantly downregulated by Maf interference. The assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and a yeast one-hybrid showed that Maf could bind to the cncc:maf-s element in the CYP307A1 promoter region. The synthesis of ecdysone, which stimulated chitin synthesis, was also decreased significantly following Maf and CYP307A1 interference. Therefore, the upregulation of Maf expression leaded to the upregulation CYP307A1 expression, which led to an increase in the synthesis of ecdysone, resulting in resurgence accompanied by resistance to bistrifluron.

The fitness advantages of bistrifluron resistance related to chitin synthase A in Spodoptera litura (Fab.) (Noctuidae: Lepidoptera).

BACKGROUND: Spodoptera litura is one of the major agricultural pests in China, and it has developed serious resistance to many traditional chemical insecticides. In the present study, the bistrifluron-resistant (Bis-SEL) strain accompanied by a higher oviposition, 113.8-fold RR compared to the bistrifluron-susceptible (Bis-UNSEL) strain, was obtained by bidirectional screening. A comparison of their gonad coefficiency and genes related to oviposition or resistance was used to elucidate the resurgence mechanism. RESULTS: The ovarian index, oviposition, and potential egg production in the Bis-SEL strain of female adults were significantly higher than those in the Bis-UNSEL strain, and the length of ovariole in the Bis-SEL strain was also significantly elongated. The protein contents of vitellogenin (Vg) and vitellogenin receptor (VgR) in the Bis-UNSEL strain were lower than those in the Bis-SEL strain, consistent with their gene expressions levels, and there was a significantly positive linear correlation between Vg and VgR protein contents, further confirming that resistant strains have high reproductive fitness. Moreover, the chitin synthase A in the Bis-SEL strain was clearly up-regulated, and a mutation (H866Y) near the QRRRW in the catalytic domain caused a rise in the hydrogen bond between UDP-GlcNAc and chitin synthase, and its chitin content was higher than that in the Bis-UNSEL strain. Nevertheless, the sensitivity of the Bis-SEL strain to bistrifluron was significantly recovered when it was knocked down though RNA interference. CONCLUSION: The fitness advantages of bistrifluron resistance may be related to the up-regulation and mution of chitin synthase A. © 2021 Society of Chemical Industry.

Status of insecticide resistance and biochemical characterization of chlorpyrifos resistance in Sogatella furcifera (Hemiptera:Delphacidae) in Sichuan Province, China.

The white-backed planthopper, Sogatella furcifera (Horváth) (Hemiptera, Delphacidae), is an energetic rice insect pest in rice production or rice-growing areas. Due to excessive use of the chemical insecticide, S. furcifera has produced the high resistance to some frequently used insecticides. In this paper, the resistance levels of S. furcifera from the eight different areas of Sichuan Province against the five chemicals were monitored by using the rice seedling dipping during 2017-2018 to understand the resistance levels. The results showed that most of all populations have developed low or moderate level of resistance for chlorpyrifos (3.4 to 44.3-fold) and thiamethoxam (3.9- to 15.5-fold), the populations in the LS (1.7 to 5.4- fold)and WS (1.6 to 5.0- fold) regions were still sensitive or low resistance levels compared with other local populations. Almost all populations displayed the susceptible to imidacloprid (0.9- to 5.0-fold), buprofezin (0.9- to 4.3-fold) or low levels of resistance to pymetrozine (1.5- to 6.8-fold). The synergism experiment indicated that P450 enzymes may be important contributed to the metabolic detoxification of chlorpyrifos. The cross-resistance bioassay showed that there was no cross-resistance between chlorpyrifos and triflumezopyrim, but for sulfoxaflor, in the XY17 population. The relative expression level of twelve insecticide resistant-related P450 genes were analyzed by using qRT-PCR and found that CYP4C77, CYP418A1, CYP418A2, CYP408A3 and CYP6ER4 were significantly more expressed in the 3rd-instar nymph of the XY17 and XY18 field populations. To determine the main resistant-related P450 gene for chlorpyrifos, the relative expression level of five P450 genes were detected by using qRT-PCR from the G2 and G4 generation of XY17 under the pressure with LC50 of chlorpyrifos. The results showed that CYP6ER4 was significantly up-regulated expression in XY17 G2 and G4 generations population over 700-fold (P < 0.01). The full length and proteins tertiary structure were also cloned and predicted. Meanwhile, the function of CYP6ER4 was analyzed by RNA interference and the results indicated that the relative expression of CYP6ER4 in the XY17 (G4) population after injected dsRNA was lower than that in the dsGFP injected group. Moreover, the mortality rates of the S. furcifera treated with the LC50 concentration of chlorpyrifos after dsRNA microinjection was significantly higher than that of the dsGFP injected group 72 h after treatment (P < 0.01). Therefore, the overexpression of CYP6ER4 may be one of the primary factors in the development of chlorpyrifos resistance in S. furcifera.

Sublethal Effects of Triflumezopyrim on Biological Traits and Detoxification Enzyme Activities in the Small Brown Planthopper Laodelphax striatellus (Hemiptera: Delphacidae).

The small brown planthopper [Laodelphax striatellus (Fallén) (Hemiptera, Delphacidae)] is one of the most destructive insect pests of rice and has developed strong resistance to several kinds of chemical insecticides. Triflumezopyrim, a novel mesoionic insecticide developed by Corteva Agriscience (formerly DuPont Crop Protection), has efficient biological activity in controlling sucking insects, such as the planthopper. However, the effects of triflumezopyrim on the growth and reproduction of L. striatellus have not been reported. In this study, an F5 generation was obtained by conducting five rounds of insecticide screening on a sensitive L. striatellus strain (F0 generation). An age-stage life table procedure was used to evaluate the effects of a sublethal concentration (LC50) of triflumezopyrim on the biological parameters of L. striatellus. Compared with those of the F0 generation, the intrinsic rate of increase (r), the finite rate (λ), and the net reproductive rate (R 0) of the F5 generation were significantly decreased; nevertheless, the average duration of life (T) was not significantly affected. The results of detoxification enzyme activity assays indicated that the glutathione S-transferase and cytochrome P450 monooxygenase (P450) activities in the F5 generation were significantly higher than those in the F0 generation. The contents of vitellogenin (Vg) and vitellogenin receptor (VgR) were also detected, and the results indicated that the contents of Vg and VgR in the F5 generation were significantly decreased compared to those in the F0 generation. Furthermore, we detected the relative expression of ecdysone receptor (EcR), Vg, and VgR in the F0 and F5 generations and found that the relative expression levels of Vg and VgR in the F5 generation female adults were obviously lower than those in the F0 generation (P < 0.05), whereas the relative expression of EcR was slightly increased, although the difference was not significant (P > 0.05). Based on these results, a sublethal concentration (median lethal concentration, LC50) of triflumezopyrim may inhibit the generational growth and reproduction of L. striatellus. Moreover, our results may provide a reference for further studies of the suitability and resistance mechanisms of L. striatellus subjected to a sublethal dose of triflumezopyrim.

The population growth, development and metabolic enzymes of the white-backed planthopper, Sogatella furcifera (Hemiptera: Delphacidae) under the sublethal dose of triflumezopyrim.

Triflumezopyrim, a new nicotinic acetylcholine receptor (nAChR) inhibition, can effectively control piercing-sucking insect pests such as white-backed planthopper (Sogatella furcifera). At present, there has been no reports on the effects of triflumezopyrim on the population growth and development of S. furcifera. In this experiment, an age-stage two-sex life table was used to evaluate the impact of triflumezopyrim on the biological parameters of S. furcifera. The results showed that the adult preoviposition period (APOP) and total preoviposition period (TPOP) of the F1 generation were significantly higher than those of the F0 and F4 generations, on the contrary the average fecundity, intrinsic rate of increase (r) and finite rate of increase (λ) of the F4 generation were higher than those of the F0 and F1 generations. The results of synergists and enzyme activities indicated that the CarE and P450 activities in the F4 generation were significantly higher than those in the F0 generation (P < 0.05). The protein contents of vitellogenin (Vg) and vitellogenin receptor (VgR) and relative expression quality of VgR in the F4 female adults were also significantly higher than those in the F0 generation (P < 0.05). These results showed that triflumezopyrim at a low concentration could promote the growth and reproduction of S. furcifera, and that may provide a reference for the rational use of triflumezopyrim in the future.

Laplace-domain diffuse optical measurement.

Time-domain diffuse optical measurement systems determine depth-resolved absorption changes by using the time of flight distribution of the detected photons. It is well known that certain feature data, such as the Laplace transform of the temporal point spread function, is sufficient for image reconstruction and diffuse optical sensing. Conventional time-domain systems require the acquisition of full temporal profiles of diffusive photons and then numerically compute the feature dataset, for example, Laplace transformed intensities for imaging applications. We have proposed a novel method for directly obtaining the Laplace transform data. Our approach can significantly improve the data acquisition speed for time-domain diffuse optical imaging. We also demonstrated that the use of negative Laplace parameters can provide enhanced sensitivity to perturbations located in deep regions.

Multitargeting Peptide-Functionalized Star-Shaped Copolymers with Comblike Structure and a POSS-Core To Effectively Transfect Endothelial Cells.

Gene therapy meets one serious bottleneck in clinical application, namely, lack of safe and efficient gene delivery systems. In order to solve this problem, we designed a lowly cytotoxic and highly efficient gene delivery system for the transfection of endothelial cells. Octa(3-ammoniumpropyl)octasilsesquioxane octachloride reacted with 2-bromoisobutyryl bromide under alkaline condition, and sequentially initiated 2-(dimethylamino)ethyl methacrylate (DMAEMA) and poly(ethylene glycol) monomethacrylate (PEGMA) via atom transfer radical polymerization (ATRP) to prepare the eight-arm copolymer with a biocompatible polyhedral oligomericsilsesquioxane (POSS). The side chain ends of the comblike PPEGMA were double-bonded to facilitate the attachment of CAGW or CAG-TAT-NLS functional peptide, thereby enabling the star-shaped copolymers with multifunction. The peptide-functionalized star-shaped copolymers were self-assembled into nanoparticles (NPs) and used to condense pEGFP-ZNF580 (pDNA) to prepare the NPs/pDNA complexes. These complexes had low toxicity as confirmed by MTT. The results of fluorescence microscopy and flow cytometry showed that these multitargeting functionalized gene complexes could effectively transfect endothelial cells. Their transfection efficiency is higher than the positive control PEI 25 kDa group. Moreover, the Western blot test, wound healing assay, and in vitro tube formation assay also demonstrated that the transfected cells showed high migration and enhanced angiogenesis. The pDNA was effective delivered and expressed in endothelial cells by these multitargeting functionalized gene complexes, and promoted cell migration and tube formation. These star-shaped copolymers with comblike structure and a POSS core are a potential gene carrier for gene therapy.

Spread spectrum time-resolved diffuse optical measurement system for enhanced sensitivity in detecting human brain activity.

Diffuse optical spectroscopy (DOS) and imaging methods have been widely applied to noninvasive detection of brain activity. We have designed and implemented a low cost, portable, real-time one-channel time-resolved DOS system for neuroscience studies. Phantom experiments were carried out to test the performance of the system. We further conducted preliminary human experiments and demonstrated that enhanced sensitivity in detecting neural activity in the cortex could be achieved by the use of late arriving photons.

BioFed: federated query processing over life sciences linked open data.

BACKGROUND: Biomedical data, e.g. from knowledge bases and ontologies, is increasingly made available following open linked data principles, at best as RDF triple data. This is a necessary step towards unified access to biological data sets, but this still requires solutions to query multiple endpoints for their heterogeneous data to eventually retrieve all the meaningful information. Suggested solutions are based on query federation approaches, which require the submission of SPARQL queries to endpoints. Due to the size and complexity of available data, these solutions have to be optimised for efficient retrieval times and for users in life sciences research. Last but not least, over time, the reliability of data resources in terms of access and quality have to be monitored. Our solution (BioFed) federates data over 130 SPARQL endpoints in life sciences and tailors query submission according to the provenance information. BioFed has been evaluated against the state of the art solution FedX and forms an important benchmark for the life science domain. METHODS: The efficient cataloguing approach of the federated query processing system 'BioFed', the triple pattern wise source selection and the semantic source normalisation forms the core to our solution. It gathers and integrates data from newly identified public endpoints for federated access. Basic provenance information is linked to the retrieved data. Last but not least, BioFed makes use of the latest SPARQL standard (i.e., 1.1) to leverage the full benefits for query federation. The evaluation is based on 10 simple and 10 complex queries, which address data in 10 major and very popular data sources (e.g., Dugbank, Sider). RESULTS: BioFed is a solution for a single-point-of-access for a large number of SPARQL endpoints providing life science data. It facilitates efficient query generation for data access and provides basic provenance information in combination with the retrieved data. BioFed fully supports SPARQL 1.1 and gives access to the endpoint's availability based on the EndpointData graph. Our evaluation of BioFed against FedX is based on 20 heterogeneous federated SPARQL queries and shows competitive execution performance in comparison to FedX, which can be attributed to the provision of provenance information for the source selection. CONCLUSION: Developing and testing federated query engines for life sciences data is still a challenging task. According to our findings, it is advantageous to optimise the source selection. The cataloguing of SPARQL endpoints, including type and property indexing, leads to efficient querying of data resources over the Web of Data. This could even be further improved through the use of ontologies, e.g., for abstract normalisation of query terms.

Diagnosis, Management And Prevention Of Hepatitis C In Pakistan 2017.

AIMS AND OBJECTIVES: Since the advent of direct acting antiviral agents, there is a revolutionary change in the management of HCV infection. Newer drugs with different mechanism of action are being introduced and are expected to be available in coming few months in Pakistan as well. The main purpose of the guideline is to review and induct the latest research in field of HCV infection in Pakistani perspective so that our healthcare professionals can apply the new recommendations in timely and judicial manner. Target groups of guidelines are general physicians treating hepatitis C, hepatologists and gastroenterologists. Other beneficiaries of these guidelines are public health institutions of Pakistan, which provide free treatment to deserving patients under National Hepatitis Prevention and Control Program and Pakistan Bait-ul- Mal Program. METHODOLOGY: These guidelines are based on the review of National consensus practice guidelines: Diagnosis, Management and Prevention of Hepatitis C Pakistan 2009. Published data in National and International Journals searched with the help of Google search and pub med, and 2015-16 guidelines of HCV by AASLD, EASL, APASL and WHO. Local studies are preferably added with references to enhance the Pakistani perspective. Evidence was also taken from published studies. Recommendations have been based upon evidence from national publications on the subject and scientific presentations at national liver meeting as well from experts' personal experience and opinion.

Carvedilol vs. esophageal variceal band ligation in the primary prophylaxis of variceal hemorrhage: a multicentre randomized controlled trial.

BACKGROUND & AIMS: Esophageal variceal bleed is a major problem in patients with cirrhosis. Endoscopic variceal ligation (EVL) has been shown to be equal to or better than propranolol in preventing first bleed. Carvedilol is a non-selective ß blocker with alpha-1 adrenergic blocker activity. Hemodynamic studies have shown carvedilol to be more effective than propranolol at reducing portal pressure. We compared efficacy of carvedilol with EVL for primary prophylaxis of esophageal variceal bleed. METHODS: Cirrhotic patients with esophageal varices were randomized to carvedilol 12.5mg daily or EVL at three university hospitals of Pakistan. End points were esophageal variceal bleeding, death or liver transplant. RESULTS: Two hundred and nine patients were evaluated. Eighty two and eighty six patients were randomized in carvedilol and EVL arms respectively. Mean age was 48 ± 12.2 years; 122 (72.7%) were males; 89.9% had viral cirrhosis; mean Child-Pugh score was 7.3 ± 1.6 and mean follow up was 13.3 ± 12.1 months (range 1-50 months). Both EVL and carvedilol groups had comparable variceal bleeding rates (8.5% vs. 6.9%), bleed related mortality (4.6% vs. 4.9%) and overall mortality (12.8% vs. 19.5%) respectively. Adverse events in carvedilol group were hypotension (n=2), requiring cessation of therapy, while transient nausea (n=18) and dyspnea (n=30) resolved spontaneously. In the EVL arm, post banding ulcer bleed (n=1) and chest pain (n=17), were termed as serious adverse events while transient dysphagia (n=58) resolved without treatment. CONCLUSIONS: Although our study is underpowered, the findings suggest that carvedilol is probably not superior to EVL in preventing first variceal bleed in patients with viral cirrhosis.