Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120

BACKGROUND: Cellulose acetate phthalate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was shown to inhibit infection by the human immunodeficiency virus type 1 (HIV-1) and several herpesviruses. CAP formulations inactivated HIV-1, herpesvirus types 1 (HSV-1) and 2 (HSV-2) and the major nonviral sexually transmitted disease (STD) pathogens and were effective in animal models for vaginal infection by HSV-2 and simian immunodeficiency virus. METHODS: Enzyme-linked immunoassays and flow cytometry were used to demonstrate CAP binding to HIV-1 and to define the binding site on the virus envelope. RESULTS: 1) CAP binds to HIV-1 virus particles and to the envelope glycoprotein gp120; 2) this leads to blockade of the gp120 V3 loop and other gp120 sites resulting in diminished reactivity with HIV-1 coreceptors CXCR4 and CCR5; 3) CAP binding to HIV-1 virions impairs their infectivity; 4) these findings apply to both HIV-1 IIIB, an X4 virus, and HIV-1 BaL, an R5 virus. CONCLUSIONS: These results provide support for consideration of CAP as a topical microbicide of choice for prevention of STDs, including HIV-1 infection

Nitrogen uptake and internal recycling in Zostera marina exposed to oyster farming: eelgrass potential as a natural biofilter

Oyster farming in estuaries and coastal lagoons frequently overlaps with the distribution of seagrass meadows, yet there are few studies on how this aquaculture practice affects seagrass physiology. We compared in situ nitrogen uptake and the productivity of Zostera marina shoots growing near off-bottom longlines and at a site not affected by oyster farming in San Quintin Bay, a coastal lagoon in Baja California, Mexico. We used benthic chambers to measure leaf NH4 (+) uptake capacities by pulse labeling with (NH4)-N-15 (+) and plant photosynthesis and respiration. The internal N-15 resorption/recycling was measured in shoots 2 weeks after incubations. The natural isotopic composition of eelgrass tissues and vegetative descriptors were also examined. Plants growing at the oyster farming site showed a higher leaf NH4 (+) uptake rate (33.1 mmol NH4 (+) m(-2) day(-1)) relative to those not exposed to oyster cultures (25.6 mmol NH4 (+) m(-2) day(-1)). We calculated that an eelgrass meadow of 15-16 ha (which represents only about 3-4 % of the subtidal eelgrass meadow cover in the western arm of the lagoon) can potentially incorporate the total amount of NH4 (+) excreted by oysters (similar to 5.2 x 10(6) mmol NH4 (+) day(-1)). This highlights the potential of eelgrass to act as a natural biofilter for the NH4 (+) produced by oyster farming. Shoots exposed to oysters were more efficient in re-utilizing the internal N-15 into the growth of new leaf tissues or to translocate it to belowground tissues. Photosynthetic rates were greater in shoots exposed to oysters, which is consistent with higher NH4 (+) uptake and less negative delta C-13 values. Vegetative production (shoot size, leaf growth) was also higher in these shoots. Aboveground/belowground biomass ratio was lower in eelgrass beds not directly influenced by oyster farms, likely related to the higher investment in belowground biomass to incorporate sedimentary nutrients

Adaptation of Deeplab V3+ for Damage Detection on Port Infrastructure Imagery

Regular inspection and maintenance of infrastructure facilities are crucial to ensure their functionality and safety for users. However, current inspection methods are labor-intensive and can vary depending on the inspector. To improve this process, modern sensor systems and machine learning algorithms can be deployed to detect defects based on rapidly acquired data, resulting in lower downtime. A quality-controlled processing chain allows to provide hence informed uncertainty assessments to inspection operators. In this study, we present several Deeplab V3+ models optimized to predict corroded segments of the quay wall at JadeWeserPort, Germany, which is a dataset from the 3D HydroMapper research project. Our models achieve generally high accuracy in detecting this damage type. Therefore, we examine the use of a Region Growing-based weakly supervised approach to efficiently extend our model to other common types in the future. This approach achieves about 90 % of the results compared to corresponding fully supervised networks, of which a ResNet-50 variant peaks at 55.6 % Intersection-over-Union regarding the test set's corrosion class

Collaborative navigation simulation tool using kalman filter with implicit constraints

Collaborative Positioning (CP) is a networked positioning technique in which different multi-sensor systems (nodes) enhance the accuracy and precision of these navigation solutions by performing measurements or by sharing information (links) between each other. The wide spectrum of available sensors that are used in these complex scenarios bring the necessity to analyze the sensibility of the system to different configurations in order to find optimal solutions. In this paper, we discuss the implementation and evaluation of a simulation tool that allows us to study these questions. The simulation tool is successfully implemented as a plane based localization problem, in which the sensor measurements are fused in a Collaborative Extended Kalman Filter (C-EKF) algorithm with implicit constraints. Using a real urban scenario with three vehicles equipped with various positioning sensors, the impact of the sensor configuration is investigated and discussed by intensive Monte Carlo simulations. The results show the influence of the laser scanner measurements on the accuracy and precision of the estimation, and the increased performance of the collaborative navigation techniques with respect to the single vehicle method. © Authors 2019

Quinpirole and 8-OH-DPAT induce compulsive checking behavior in male rats by acting on different functional parts of an OCD neurocircuit

This study investigated whether the serotonin 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) can induce compulsive checking in a large open field, as does the dopamine D2/D3 receptor agonist quinpirole. To induce compulsive checking, male rats were exposed to eight injections of either 8-OH-DPAT (1 mg/kg), quinpirole (0.2 mg/kg), or saline. Subsequently, to assess cross-sensitization, rats received an acute challenge of 8-OH-DPAT or quinpirole. The results showed that treatment with 8-OH-DPAT induces compulsive checking and may have a stronger effect on this behavior compared with quinpirole. However, there was no cross-sensitization between 8-OH-DPAT and quinpirole on measures of compulsive checking and locomotion. Moreover, the spatial distribution of locomotor paths in 8-OH-DPAT animals was more confined and invariant than in quinpirole rats; their rate of locomotor sensitization was also faster than that in quinpirole animals. Thus, although 8-OH-DPAT and quinpirole can induce compulsive checking in a large open field, the results suggest that they do so differently. It is suggested that 8-OH-DPAT and quinpirole probably produce compulsive behavior by acting on different parts of a security motivation circuit underlying obsessive-compulsive disorder. Quinpirole may induce compulsive checking behavior by directly driving dopaminergic activity mediating the motivational drive to check. Conversely, 8-OH-DPAT may perpetuate the activated motivational state by inhibiting the serotonergic-negative feedback signals that normally deactivate the obsessive-compulsive disorder circuit

Hepatotoxic and hematotoxic effects of sage oil-loaded ifosfamide nanoemulsion in Ehrlich ascites carcinomabearing mice

Purpose: To investigate the hepatotoxic and hematotoxic effects of sage oil-loaded ifosfamide (IFO) nanoemulsion (NE) in Ehrlich ascites carcinoma (EAC)-bearing mice. Methods: Ifosfamide (IFO) was loaded into a NE containing sage oil, and its hepatotoxic and hematotoxic effects were assessed in EAC-bearing mice. Female Swiss albino mice (n = 50) weighing 25 - 30 g (mean weight = 27.5 ± 2.50 g) were randomly assigned to five groups of ten mice each. With the exception of group 1, the mice were inoculated intraperitoneally (i.p.) with 2.5 × 106 EAC/mouse for 48 h. Group I served as negative control, C (-); group II served as positive control, C (+); while groups III - V were treated i.p. with 60 mg/kg IFO in 0.3mL water (free-IFO); 0.3 mL NE (SAGE-NANO), and 60 mg/kg IFO in 0.3 mL SAGE-NANO (SAGE-IFO), respectively. The treatments were administered for three days. Results: Treatment with 60 mg/kg bwt IFO (free-IFO) significantly elevated the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT, p < 0.05). However, subsequent treatment with SAGE-IFO significantly reduced the activity of these liver enzymes (p < 0.05). The concentration of reduced glutathione (GSH) as well as the activities of catalase and glutathione reductase (GR) significantly increased, while malondialdehyde (MDA) level decreased significantly in SAGE-IFO group, when compared with free-IFO group (p < 0.05). Treatment with SAGE-IFO significantly restored white blood cell (WBC) count and platelet levels which were altered by free-IFO (p < 0.05). Conclusion: The results obtained in this study suggest that loading IFO in sage oil-NE greatly reduces its hepatotoxicity and hematotoxicity

Protective role of nanoemulsion containing roman chamomile oil against mitomycin C-induced toxicity in Ehrlich ascites carcinoma bearing mice

Mitomycin-C (MC), an anticancer agent, induces oxidative stress in normal tissues causing severe toxicity. The present study aimed to evaluate whether the side effects of MC may be diminished by the incorporation of MC into nanoemulsion containing Roman chamomile oil (RCM-NE). Fifty mice were equally divided into five groups. The first and second groups were the control and the untreated Ehrlich ascites carcinoma bearing mice (EAC), respectively, while the other three groups were EAC-bearing mice treated once intraperitoneally with a dose of 200 µL of RCM-NE, 1 mg/kg−1 MC/200 µL normal saline, and 1 mg/kg−1 MC/200 µL RCM-NE. The protective effect of the RCM-NE was examined by measuring the alterations in complete blood count, organs weight indices, and levels of serum biochemical parameters. The oxidative stress was assessed by measuring lipid peroxidation and enzyme activities of catalase, superoxide dismutase, glutathione reductase, and thioredoxin reductase-1. MC-RCM-NE has significantly reduced the toxicity of MC on the white blood cells and platelets. It improved the renal and cardiac biomarker levels and the antioxidants of the kidney, heart, and thymus. The protective effect of the RCM-NE on the blood and organs against MC toxicity was associated with the decreasing of oxidative stress and maintaining the activity of the antioxidants

Modulation of the virus-receptor interaction by mutations in the V5 loop of feline immunodeficiency virus (FIV) following in vivo escape from neutralising antibody

<b>BACKGROUND:</b> In the acute phase of infection with feline immunodeficiency virus (FIV), the virus targets activated CD4+ T cells by utilising CD134 (OX40) as a primary attachment receptor and CXCR4 as a co-receptor. The nature of the virus-receptor interaction varies between isolates; strains such as GL8 and CPGammer recognise a "complex" determinant on CD134 formed by cysteine-rich domains (CRDs) 1 and 2 of the molecule while strains such as PPR and B2542 require a more "simple" determinant comprising CRD1 only for infection. These differences in receptor recognition manifest as variations in sensitivity to receptor antagonists. In this study, we ask whether the nature of the virus-receptor interaction evolves in vivo.<p></p> <b>RESULTS:</b> Following infection with a homogeneous viral population derived from a pathogenic molecular clone, a quasispecies emerged comprising variants with distinct sensitivities to neutralising antibody and displaying evidence of conversion from a "complex" to a "simple" interaction with CD134. Escape from neutralising antibody was mediated primarily by length and sequence polymorphisms in the V5 region of Env, and these alterations in V5 modulated the virus-receptor interaction as indicated by altered sensitivities to antagonism by both anti-CD134 antibody and soluble CD134.<p></p> <b>CONCLUSIONS:</b> The FIV-receptor interaction evolves under the selective pressure of the host humoral immune response, and the V5 loop contributes to the virus-receptor interaction. Our data are consistent with a model whereby viruses with distinct biological properties are present in early versus late infection and with a shift from a "complex" to a "simple" interaction with CD134 with time post-infection.<p></p&gt

Protective role of nanoemulsion containing roman chamomile oil against mitomycin C-induced toxicity in Ehrlich ascites carcinoma bearing mice

33-44Mitomycin-C (MC), an anticancer agent, induces oxidative stress in normal tissues causing severe toxicity. The present study aimed to evaluate whether the side effects of MC may be diminished by the incorporation of MC into nanoemulsion containing Roman chamomile oil (RCM-NE). Fifty mice were equally divided into five groups. The first and second groups were the control and the untreated Ehrlich ascites carcinoma bearing mice (EAC), respectively, while the other three groups were EAC-bearing mice treated once intraperitoneally with a dose of 200 µL of RCM-NE, 1 mg/kg−1 MC/200 µL normal saline, and 1 mg/kg−1 MC/200 µL RCM-NE. The protective effect of the RCM-NE was examined by measuring the alterations in complete blood count, organs weight indices, and levels of serum biochemical parameters. The oxidative stress was assessed by measuring lipid peroxidation and enzyme activities of catalase, superoxide dismutase, glutathione reductase, and thioredoxin reductase-1. MC-RCM-NE has significantly reduced the toxicity of MC on the white blood cells and platelets. It improved the renal and cardiac biomarker levels and the antioxidants of the kidney, heart, and thymus. The protective effect of the RCM-NE on the blood and organs against MC toxicity was associated with the decreasing of oxidative stress and maintaining the activity of the antioxidants

Outcomes of patients with thrombocytopenia evaluated at hematology subspecialty clinics

BACKGROUND: Thrombocytopenia is a frequently encountered laboratory abnormality and a common reason for hematology referrals. Workup for thrombocytopenia is not standardized and frequently does not follow an evidence-based algorithm. We conducted a systematic analysis to evaluate the laboratory testing and outcomes of patients evaluated for thrombocytopenia at hematology clinics in a tertiary referral center between 2013 and 2016. PATIENT AND METHODS: We performed a comprehensive chart review for patients evaluated for thrombocytopenia during the study period. Patients were followed for 1 year from the initial hematology evaluation and assessed for the development of a hematologic malignancy, rheumatologic, or infectious diseases among other clinical outcomes. RESULTS: We evaluated 472 patients with a median (range) age of 61 (17-94) years. The majority (63.8%) had mild thrombocytopenia. Within 1 year of follow-up, 14 patients (3.0%) were diagnosed with a hematologic malignancy. A higher likelihood of developing a hematologic malignancy was noted in patients with concurrent leukopenia (hazard ratio [HR] 9.97, 95% confidence interval [CI] 3.28-30.32, p \u3c .01) and increasing age (HR per 10-year deciles 1.52, 95% CI 1.03-2.25, p = .03). In patients with asymptomatic isolated mild thrombocytopenia, laboratory testing did not reveal any significant positive findings and patients did not receive any new major diagnosis during the follow-up period. CONCLUSION: Our findings provide basis and call for development of an evidence-based algorithmic approach for evaluation of patients with thrombocytopenia, testing, and referrals. It also supports a conservative approach mainly driven by physical exam signs, symptoms, and other laboratory findings for patients with isolated mild thrombocytopenia