Rhizophora mucronata Lam., a halophyte from Mauritius Island, inhibits the entry of Zika virus in human cells (A549)- an in vitro and in silico analysis.

The recent appearance of Zika virus (ZIKV) in Brazil should serve as a wake-up call to international authorities, as it poses a threat to global public health. In the present study, we investigated whether a mangrove plant, Rhizophora mucronata Lam. (R. mucronata) collected in Mauritius, possesses anti-ZIKV activity at the non-cytotoxic doses. ZIKVMC-MR766NIID (ZIKVGFP) was used for assessing anti ZIKV activity. In silico docking (Autodock 4) and molecular simulation were performed on collected data. Using a recombinant ZIKV expressing reporter green fluorescent protein(GFP) protein, we discovered that fruit and root methanolic, decocted fruit and root extracts were effective inhibitors of ZIKV infection in human epithelial A549 cells at negligible cytotoxicity. The mechanisms by which such extracts prevented ZIKV infection are linked to the inability of the virus to attach to the host cell surface. The outcomes of this study were supported by the docking calculations in which some of the dominant compounds have shown high binding affinity against ZIKV. The scientific data gathered in this study might pave the way for the future development of possible R. mucronata inhibitors to combat ZIKV.fCommunicated by Ramaswamy H. Sarma.

Antiviral Effect of Stenocline ericoides DC. and Stenocline inuloides DC., Two Flavonoid-Rich Endemic Plants from Madagascar, against Dengue and Zika Viruses.

Dengue and Zika viruses are identified as the most medically important arthropod-borne viral pathogens. Over the past 20 years, the global dengue incidence has dramatically increased with epidemics of severe dengue where the case fatality rate can reach up to 20% in untreated patients. The association between Zika virus infection and severe congenital anomalies was first reported in 2015. Today no specific antiviral therapies are available for dengue and Zika virus infections, accentuating the need of adapted antiviral strategies based on medicinal plant drug discovery. Plants are a potential source of antiviral phytocompounds which act primarily by blocking virus entry in the host-cell. In the present study, we evaluated whether crude extracts from Stenocline ericoides DC. and Stenocline inuloides DC., two endemic plants from Madagascar, may have antiviral effects against dengue and Zika viruses. We showed that S. ericoides has virucidal action whereas S. inuloides inhibits the early steps of virus infection with a non-cytotoxic effect in human cells. The administration of S. ericoides and S. inuloides extracts in zebrafish had no effect on the behavior of animals at the active doses against dengue and Zika viruses, suggesting the absence of adverse effects at these doses. LC-HRMS2 and molecular networking analyses revealed the richness of these two plants in polyphenols and flavonoid with the presence of clusters of phytocompounds specific to each Stenocline species. Consequently, S. ericoides and S. inuloides represent potential sources for natural and safe antiviral phytocompounds against flaviviruses of medical concern.

In Vitro Bioactivities of Extracts from Tomato Pomace.

BACKGROUND: Tomato pomace (TP) is a coproduct generated by the extraction of tomato pulp, and is a potential source of bioactive molecules. In this study, we isolated several fractions from TP and evaluated their biological properties. MATERIALS AND METHODS: TP was treated by maceration at room temperature with green solvents (ethanol, ethyl acetate, ethanol:water and ethanol:ethyl acetate) or supercritical CO2 (SC-CO2). The extracts were analyzed by HPLC-DAD to determine their composition, and their antioxidant activity was assessed. The potential therapeutic effects of the isolated fractions were assessed in vitro. RESULTS: We identified 30 molecules on chromatography profiles, which revealed an abundance in phenolic acids, carotenoids, flavonoids and tannins, with differences in selectivity according to the solvent and pretreatment used. The highest radical scavenging activities were measured at 64-72% inhibition, corresponding to the ethanol or ethanol:water extracts with the highest polyphenol or flavonoid contents. Carotenoid content was increased by chemical pretreatment, to attain levels of 161 mg ß-carotene/g ethyl acetate extract. This level of carotenoids seemed to have anti-inflammatory effects, with an IC50 of 9.3 µg/mL. In terms of anti-diabetic effects, the activities of α-glucosidase and α-amylase were best inhibited by extraction in an ethanol-to-water mixture (50:50). Cytotoxicity in a tumor cell line were highest for SC-CO2 extracts (64.5% inhibition) and for ethanol extracts obtained after the enzymatic pretreatment of TP (37% inhibition). Some extracts also had dose-dependent activity against Zika virus. CONCLUSIONS: New fractions obtained from TP with ecocompatible solvents in mild conditions are rich in bioactive molecules. A comparison of the chromatographic profiles of the extracts led to the identification of several key molecules with therapeutic properties. The chemical pretreatment of TP is justified as a mean of increasing the carotenoid content of ethyl acetate fractions, whereas enzymatic pretreatment can increase the antioxidant activity of ethyl acetate fractions and increase the cytotoxicity of ethanol fractions. The SC-CO2 fraction contained a smaller number of metabolites detectable on HPLC, but it had high levels of cytotoxicity and antioxidant activity. Finally, the fractions obtained appeared to be suitable for use to target one or several of the biological activities studied.

High Glucose Induces in HK2 Kidney Cells an IFN-Dependent ZIKV Antiviral Status Fueled by Viperin.

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that rapidly became a major medical concern worldwide. We have recently reported that a high glucose level decreases the rate of Zika virus (ZIKV) replication with an impact on human kidney HK-2 cell survival. However, the mechanisms by which cells cultured in a high glucose medium inhibit ZIKV growth remain unclear. Viperin belongs to interferon-stimulated genes (ISG) and its expression is highly up-regulated upon viral infection, leading to antiviral activity against a variety of viruses, including flaviviruses. As such, viperin has been shown to be a major actor involved in the innate immune response against Zika virus (ZIKV). Our present study aims to further characterize the involvement of viperin in ZIKV growth inhibition under high glucose concentration (HK-2HGC). We show for the first time that endogenous viperin is over-expressed in HK-2 cells cultured under high glucose concentration (HK-2HGC), which is associated with ZIKV growth inhibition. Viperin knockdown in HK-2HGC rescues ZIKV growth. In addition, our results emphasize that up-regulated viperin in HK-2HGC leads to ZIKV growth inhibition through the stimulation of IFN-ß production. In summary, our work provides new insights into the ZIKV growth inhibition mechanism observed in HK-2 cells cultured in a high glucose environment.

Cranberry Pomace Extract Exerts Antiviral Activity against Zika and Dengue Virus at Safe Doses for Adult Zebrafish.

Mosquito-borne dengue virus (DENV) and zika virus (ZIKV) infections constitute a global health emergency. Antivirals directly targeting the virus infectious cycle are still needed to prevent dengue hemorrhagic fever and congenital zika syndrome. In the present study, we demonstrated that Cranberry Pomace (CP) extract, a polyphenol-rich agrifood byproduct recovered following cranberry juice extraction, blocks DENV and ZIKV infection in human Huh7.5 and A549 cell lines, respectively, in non-cytotoxic concentrations. Our virological assays identified CP extract as a potential inhibitor of virus entry into the host-cell by acting directly on viral particles, thus preventing their attachment to the cell surface. At effective antiviral doses, CP extract proved safe and tolerable in a zebrafish model. In conclusion, polyphenol-rich agrifood byproducts such as berry extracts are a promising source of safe and naturally derived nutraceutical antivirals that target medically important pathogens.

A Novel Simplified Workflow for Guided Endodontic Surgery in Mandibular Molars With a Thick Buccal Bone Plate: A Case Report.

One of the challenges in apical surgery in mandibular molars is the thick buccal cortical bone plate, which might lead to access errors, damage to neighboring teeth, and injury to healthy tissue. Surgical guide templates with 3-dimensional (3D) impressions have been suggested for use in such cases, allowing greater precision. Usually, this technique involves a cone-beam computed tomography (CBCT) examination related to a 3D oral scanning to generate surgical templates printed from 3D imaging data. This study reports a novel workflow possibility in which apical surgery is performed with the aid of a surgical guide planned only with CBCT, excluding the need for 3D oral scanning. A 32-year-old woman presented with asymptomatic apical periodontitis and external root resorption on the mesial root of tooth #19. A surgical template was planned using only the patient's CBCT scan to provide precise access to the lesion and remove a mandibular cortical bone block. The procedure was carried out with apicoectomy, root-end preparation, and retrograde filling, and the bone block was repositioned before suture. No postoperative complications were reported. After 1 year, the patient presented asymptomatic, and a CBCT scan confirmed bone healing. The current 3D-printed guides may be planned and printed through a novel simplified workflow with a CBCT scan only, which allows its application in apical surgery for precise apex and surgical site location.

Postoperative Pulmonary Hemodynamics and Systemic Inflammatory Response in Pediatric Patients Undergoing Surgery for Congenital Heart Defects.

There is scarce information about the relationships between postoperative pulmonary hemodynamics, inflammation, and outcomes in pediatric patients with congenital cardiac communications undergoing surgery. We prospectively studied 40 patients aged 11 (8-17) months (median with interquartile range) with a preoperative mean pulmonary arterial pressure of 48 (34-54) mmHg who were considered to be at risk for postoperative pulmonary hypertension. The immediate postoperative pulmonary/systemic mean arterial pressure ratio (PAP/SAPIPO, mean of first 4 values obtained in the intensive care unit, readings at 2-hour intervals) was correlated directly with PAP/SAP registered in the surgical room just after cardiopulmonary bypass (r = 0.68, p < 0.001). For the entire cohort, circulating levels of 15 inflammatory markers changed after surgery. Compared with patients with PAP/SAPIPO ≤ 0.40 (n = 22), those above this level (n = 18) had increased pre- and postoperative serum levels of granulocyte colony-stimulating factor (p = 0.040), interleukin-1 receptor antagonist (p = 0.020), interleukin-6 (p = 0.003), and interleukin-21 (p = 0.047) (panel for 36 human cytokines) and increased mean platelet volume (p = 0.018). Using logistic regression analysis, a PAP/SAPIPO > 0.40 and a heightened immediate postoperative serum level of macrophage migration inhibitory factor (quartile analysis) were shown to be predictive of significant postoperative cardiopulmonary events (respective hazard ratios with 95% CIs, 5.07 (1.10-23.45), and 3.29 (1.38-7.88)). Thus, the early postoperative behavior of the pulmonary circulation and systemic inflammatory response are closely related and can be used to predict outcomes in this population.

Initial experience with del Nido cardioplegia solution at a Pediatric and Congenital Cardiac Surgery Program in Brazil.

OBJECTIVE: The aim of this study was to evaluate outcome measures between our standard multidose cardioplegia protocol and a del Nido cardioplegia protocol in congenital heart surgery patients. METHODS: Retrospective single-center study including 250 consecutive patients that received del Nido cardioplegia (DN group) with a mandatory reperfusion period of 30% of cross clamp time and 250 patients that received a modified St. Thomas' solution (ST group). Groups were matched by age, weight, gender, and Risk Adjustment for Congenital Heart Surgery (RACHS-1) scores. Preoperative hematocrit and oxygen saturation were also recorded. Outcomes analyzed were the vasoactive inotropic score (VIS), lactate, ventilation time, ventricular dysfunction with low cardiac output syndrome (LCOS), intensive care unit (ICU) length of stay (LOS), hospital LOS, bypass and aortic cross-clamp times, and in-hospital mortality. RESULTS: Both groups were comparable demographically. Statistically significant differences (p ⩽ 0.05) were noted for cardiac dysfunction with LCOS, hematocrit at end of surgery (p = 0.0038), VIS on ICU admission and at end of surgery (p = 0.0111), and ICU LOS (p = 0.00118) with patients in the DN group having more desirable values for those parameters. Other outcome measures did not reach statistical significance. CONCLUSION: In our congenital cardiac surgery population, del Nido cardioplegia strategy was associated with less ventricular dysfunction with LCOS, a lower VIS and decreased ICU LOS compared with patients that received our standard myocardial protection using a modified St. Thomas' solution. Despite the limitation of this study, including its retrospective nature and cohort size, these data supported our transition to incorporate del Nido cardioplegia solution with a mandatory reperfusion period as the preferred myocardial protection method in our program.

Bruguiera gymnorhiza (L.) Lam. at the Forefront of Pharma to Confront Zika Virus and Microbial Infections-An In Vitro and In Silico Perspective.

The recent emergence of Zika virus (ZIKV) in Brazil and the increasing resistance developed by pathogenic bacteria to nearly all existing antibiotics should be taken as a wakeup call for the international authority as this represents a risk for global public health. The lack of antiviral drugs and effective antibiotics on the market triggers the need to search for safe therapeutics from medicinal plants to fight viral and microbial infections. In the present study, we investigated whether a mangrove plant, Bruguiera gymnorhiza (L.) Lam. (B. gymnorhiza) collected in Mauritius, possesses antimicrobial and antibiotic potentiating abilities and exerts anti-ZIKV activity at non-cytotoxic doses. Microorganisms Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 70603, methicillin-resistant Staphylococcus aureus ATCC 43300 (MRSA), Salmonella enteritidis ATCC 13076, Sarcina lutea ATCC 9341, Proteus mirabilis ATCC 25933, Bacillus cereus ATCC 11778 and Candida albicans ATCC 26555 were used to evaluate the antimicrobial properties. Ciprofloxacin, chloramphenicol and streptomycin antibiotics were used for assessing antibiotic potentiating activity. ZIKVMC-MR766NIID (ZIKVGFP) was used for assessing anti-ZIKV activity. In silico docking (Autodock 4) and ADME (SwissADME) analyses were performed on collected data. Antimicrobial results revealed that Bruguiera twig ethyl acetate (BTE) was the most potent extract inhibiting the growth of all nine microbes tested, with minimum inhibitory concentrations ranging from 0.19-0.39 mg/mL. BTE showed partial synergy effects against MRSA and Pseudomonas aeruginosa when applied in combination with streptomycin and ciprofloxacin, respectively. By using a recombinant ZIKV-expressing reporter GFP protein, we identified both Bruguiera root aqueous and Bruguiera fruit aqueous extracts as potent inhibitors of ZIKV infection in human epithelial A549 cells. The mechanisms by which such extracts prevented ZIKV infection are linked to the inability of the virus to bind to the host cell surface. In silico docking showed that ZIKV E protein, which is involved in cell receptor binding, could be a target for cryptochlorogenic acid, a chemical compound identified in B. gymnorhiza. From ADME results, cryptochlorogenic acid is predicted to be not orally bioavailable because it is too polar. Scientific data collected in this present work can open a new avenue for the development of potential inhibitors from B. gymnorhiza to fight ZIKV and microbial infections in the future.

Numerical modeling of a hybrid hollow-core fiber for enhanced mid-infrared guidance.

We propose a novel design of hollow-core fiber for enhanced light guidance in the mid-infrared. The structure combines an arrangement of non-touching antiresonant elements in the air core with a multilayer glass/polymer structure in the fiber's cladding. Through numerical modeling, we demonstrate that the combination of antiresonant/inhibited-coupling and photonic bandgap guidance mechanisms can decrease the optical loss of a tubular antiresonant fiber by more than one order of magnitude. More specifically, our simulations demonstrate losses of the HE11 mode in the few dB/km level, which can be tuned through mid-infrared wavelengths (5 µm-10.6 µm) by carefully optimizing the structural parameters of both structures. We also show that the hybrid hollow-core fiber design is more robust to bend-induced loss than an equivalent tubular antiresonant fiber or a Bragg/OmniGuide fiber. As a result, if successfully fabricated, the hybrid hollow-core fiber will offer low-loss, high beam-quality, effectively single-mode operation, and low bending losses, potentially solving many of the problems that affect all known mid-infrared fiber types.

Zika Virus Growth in Human Kidney Cells Is Restricted by an Elevated Glucose Level.

Mosquito-borne Zika virus (ZIKV) became a real threat to human health due to the lack of vaccine and effective antiviral treatment. The virus has recently been responsible for a global outbreak leading to millions of infected cases. ZIKV complications were highlighted in adults with Guillain-Barré syndrome and in newborns with increasing numbers of congenital disorders ranging from mild developmental delays to fatal conditions. The ability of ZIKV to establish a long-term infection in diverse organs including the kidneys has been recently documented but the consequences of such a viral infection are still debated. Our study aimed to determine whether the efficiency of ZIKV growth in kidney cells relates to glucose concentration. Human kidney HK-2 cells were infected with different ZIKV strains in presence of normal and high glucose concentrations. Virological assays showed a decrease in viral replication without modifying entry steps (viral binding, internalization, fusion) under high glucose conditions. This decrease replication was associated with a lower virus progeny and increased cell viability when compared to ZIKV-infected HK-2 cells in normal glucose concentration. In conclusion, we showed for the first time that an elevated glucose level influences ZIKV replication level with an effect on kidney cell survival.

Associating chitosan and microemulsion as a topical vehicle for the administration of herbal medicines.

A viscous solution of low molecular weight chitosan (CH) at 5% w/v (10.2 kDa, 75 % deacetylated, 1451 cP at 25 °C) was associated with a microemulsion (ME) that undergoes a phase transition after water absorption in situ (≈28 % w/w), forming a more viscous liquid crystal, which was potentially evaluated as a topical vehicle. The ME was selected from a phase diagram, selecting a composition based on Tween® 80 (52 %), myristate isopropyl (28 %), and the aqueous phase (water and polyethylene glycol 400, 60:40 w/w) (20 %), which was after replaced by CH and herbal medicines (HM). HM are alternatives to treat candidiasis, and Stryphnodendron adstringens shell extract, characterized by molecular networking, and Melaleuca alternifolia Chell essential oil (46 % of terpinen-4-ol), showed in vitro activity against Candida albicans. Associating CH in ME improved the mechanical properties of the topical formulation, as adhesiveness, which is an advantageous feature for the topical treatment of vulvovaginal candidiasis.

Zika M Oligopeptide ZAMP Confers Cell Death-Promoting Capability to a Soluble Tumor-Associated Antigen through Caspase-3/7 Activation.

Mosquito-borne Zika virus (ZIKV) is an emerging flavivirus of medical concern associated with neurological disorders. ZIKV utilizes apoptosis as a mechanism of cell killing. The structural M protein may play a role in flavivirus-induced apoptosis. The death-promoting capability of M has been restricted to an oligopeptide representing the residues M-32/40. Here, we evaluated the apoptosis inducing ability of the residues M-31/41 of ZIKV. The ZIKV M oligopeptide was associated to a soluble form of GFP (sGFP) and the resulting sGFP-M31/41 construct was assessed in Huh7 cells. Expression of sGFP-M31/41 can trigger apoptosis in Huh7 cells through caspase-3/7 activation. The translocation of sGFP-M31/41 in the endoplasmic reticulum was a prerequisite for apoptosis induction. The residues M-33/35/38 may play a critical role in the death-promoting activity of sGFP-M31/41. The effect of ZIKV M oligopeptide defined as ZAMP (for Zika Apoptosis M Peptide) on expression of a tumor-associated antigen was assayed on megakaryocyte-potentiating factor (MPF). Expression of MPF-ZAMP construct resulted in caspase-associated apoptosis activation in A549 and Huh7 cells. ZIKV has been proposed as an oncolytic virus for cancer therapy. The ability of the Zika M oligopeptide to confer death-promoting capability to MPF opens up attractive perspectives for ZAMP as an innovative anticancer agent.

Immune Reactivity of a 20-mer Peptide Representing the Zika E Glycan Loop Involves the Antigenic Determinants E-152/156/158.

Mosquito-borne Zika virus (ZIKV) causes a severe congenital syndrome and neurological disorders in humans. With the aim to develop a live-attenuated ZIKV strain, we generated a chimeric viral clone ZIKALIVax with African MR766-NIID strain as backbone and the envelope E protein of epidemic Brazilian BeH810915 strain. The MR766-NIID residues E-T152/I156/Y158 were introduced into BeH810915 E protein leading to a nonglycosylated ZIKALIVax. Recently, we reported that the residues E-152/156/158 that are part of ZIKV glycan loop (GL) region might have an impact on the availability of neutralizing antibody epitopes on ZIKV surface. In the present study, we evaluated the antigenic reactivity of a synthetic 20-mer peptide representing the ZIKALIVax GL region. The GL-related peptide was effective for the detection of GL-reactive antibody in mouse anti-ZIKALIVax immune serum. We showed that the residue E-158 influences the antigenic reactivity of GL-related peptide. The ZIKALIVax peptide was effective in generating mouse antibodies with reactivity against a recombinant E domain I that encompasses the GL region. The GL peptide-reactive antibodies revealed that antigenic reactivity of E-domain I may be impacted by both residues E-152 and E-156. In conclusion, we proposed a role for the residues E-152/156/158 as key antigenic determinants of ZIKV glycan loop region.

Correction: Haddad, J.G., et al. Doratoxylon apetalum, an Indigenous Medicinal Plant from Mascarene Islands, Is a Potent Inhibitor of Zika and Dengue Virus Infection in Human Cells Int. J. Mol. Sci. 2019, 20, 2382.

The author wishes to make the following correction to this paper [...].

Papaya Fruit Pulp and Resulting Lactic Fermented Pulp Exert Antiviral Activity against Zika Virus.

There are a several emerging and re-emerging RNA viruses that are prevalent around the world for which there are no licensed vaccines or antiviral drugs. Zika virus (ZIKV) is an example of an emerging virus that has become a significant concern worldwide because of its association with severe congenital malformations and neurological disorders in adults. Several polyphenol-rich extracts from plants were used as nutraceuticals which exhibit potent in vitro antiviral effects. Here, we demonstrated that the papaya pulp extracted from Carica papaya fruit inhibits the infection of ZIKV in human cells without loss of cell viability. At the non-cytotoxic concentrations, papaya pulp extract has the ability to reduce the virus progeny production in ZIKV-infected human cells by at least 4-log, regardless of viral strains tested. Time-of-drug-addition assays revealed that papaya pulp extract interfered with the attachment of viral particles to the host cells. With a view of preserving the properties of papaya pulp over time, lactic fermentation based on the use of bacterial strains Weissella cibaria 64, Lactobacillus plantarum 75 and Leuconostoc pseudomesenteroides 56 was performed and the resulting fermented papaya pulp samples were tested on ZIKV. We found that lactic fermentation of papaya pulp causes a moderate loss of antiviral activity against ZIKV in a bacterial strain-dependent manner. Whereas IC50 of the papaya pulp extract was 0.3 mg/mL, we found that fermentation resulted in IC50 up to 4 mg/mL. We can conclude that papaya pulp possesses antiviral activity against ZIKV and the fermentation process has a moderate effect on the antiviral effect.

Zika virus subversion of chaperone GRP78/BiP expression in A549 cells during UPR activation.

Flaviviruses replicate in membranous factories associated with the endoplasmic reticulum (ER). Significant levels of flavivirus polyprotein integration contribute to ER stress and the host cell may exhibit an Unfolded Protein Response (UPR) to this protein accumulation, stimulating appropriate cellular responses such as adaptation, autophagy or cell death. These different stress responses support other antiviral strategies initiated by infected cells and can help to overcome viral infection. In epithelial A549 cells, a model currently used to study the flavivirus infection cycle and the host cell responses, all three pathways leading to UPR are activated during infection by Dengue virus (DENV), Yellow Fever virus (YFV) or West Nile virus (WNV). In the present study, we investigated the capacity of ZIKA virus (ZIKV) to induce ER stress in A549 cells. We observed that the cells respond to ZIKV infection by implementing an UPR through activation of the IRE1 and PERK pathway without activation of the ATF6 branch. By modulating the ER stress response, we found that UPR inducers significantly inhibit ZIKV replication. Interestingly, our findings provide evidence that ZIKV could manipulate the UPR to escape this host cell defence system by downregulating GRP78/BiP expression. This subversion of GRP78 expression could lead to unresolved and persistent ER stress which can be a benefit for virus growth.

The Geraniin-Rich Extract from Reunion Island Endemic Medicinal Plant Phyllanthus phillyreifolius Inhibits Zika and Dengue Virus Infection at Non-Toxic Effect Doses in Zebrafish.

The mosquito-borne viruses dengue (DENV) and Zika (ZIKV) viruses are two medically important pathogens in tropical and subtropical regions of the world. There is an urgent need of therapeutics against DENV and ZIKV, and medicinal plants are considered as a promising source of antiviral bioactive metabolites. In the present study, we evaluated the ability of Phyllanthus phillyreifolius, an endemic medicinal plant from Reunion Island, to prevent DENV and ZIKV infection in human cells. At non-cytotoxic concentration in vitro, incubation of infected A549 cells with a P. phillyreifolius extract or its major active phytochemical geraniin resulted in a dramatic reduction of virus progeny production for ZIKV as well as four serotypes of DENV. Virological assays showed that P. phillyreifolius extract-mediated virus inhibition relates to a blockade in internalization of virus particles into the host cell. Infectivity studies on ZIKV showed that both P. phillyreifolius and geraniin cause a loss of infectivity of the viral particles. Using a zebrafish model, we demonstrated that administration of P. phillyreifolius and geraniin has no effect on zebrafish locomotor activity while no morbidity nor mortality was observed up to 5 days post-inoculation. Thus, P. phillyreifolius could act as an important source of plant metabolite geraniin which is a promising antiviral compound in the fight against DENV and ZIKV.

Prognostic value of the preoperative neutrophil-lymphocyte ratio in patients undergoing the bidirectional Glenn procedure.

INTRODUCTION: The neutrophil-lymphocyte ratio (NLR) has been associated with worse outcomes in patients undergoing coronary artery bypass graft surgery. Little is known about this association in the pediatric population who require surgery for congenital heart defects, especially in patients with a single ventricle (SV). OBJECTIVE: To analyze the association of the preoperative NLR with outcomes in patients undergoing the bidirectional Glenn procedure. METHODS: This study involved a retrospective cohort analysis of 141 consecutive patients with SV undergoing the bidirectional Glenn procedure between January 2011 and December 2017 in two centers. The preoperative NLR was included in the last hemogram test before surgery. According to the NLR level, the patients were divided into group I (NLR < 1), group II (NLR between 1 and 2), and group III (NLR > 2). The primary endpoint was total hospital length of stay (LOS), and secondary endpoints were mechanical ventilation (MV) time, intensive care unit (ICU) LOS, ventricular dysfunction, complications, and middle-term mortality. RESULTS: The average follow-up duration was 48 months. There were 61, 47, and 33 patients in groups I, II, and III, respectively. Patients in group III exhibited an increased risk of prolonged total hospital LOS (P = .00). An increase in MV time (P = .03) and ICU LOS (P = .02) was also observed in this group, and these patients experienced greater mortality in 24 months following the surgery (P = .03). There was no association between the NLR and ventricular dysfunction (P = .26) and complications (P = .46). CONCLUSION: A high preoperative NLR was associated with worse outcomes in patients with SV physiology undergoing the bidirectional Glenn procedure.

Loss of genetic integrity in artificially aged seed lots of rice (Oryza sativa L.) and common bean (Phaseolus vulgaris L.).

Loss of genetic integrity can occur during the long-term conservation of seeds. We have studied these effects in seeds of rice (Oryza sativa L.) and common bean (Phaseolus vulgaris L.) exposed to accelerated aging (elevated temperature and moisture) conditions. Tests of first count, germination, and germination speed index were performed to measure physiological quality; cytogenetic tests and comet assay were used to evaluate genetic integrity. With aging, we observed a decrease in mitotic index and an increase in the frequency of chromosomal alterations in root cells of imbibed seeds, as well as increased DNA damage (comet assay) in dry and imbibed seed embryos of both species. The comet assay can be a useful technique for measuring genetic integrity in seed conservation programs.