An important role for syndecan-1 in herpes simplex virus type-1 induced cell-to-cell fusion and virus spread

Herpes simplex virus type-1 (HSV-1) is a common human pathogen that relies heavily on cell-to-cell spread for establishing a lifelong latent infection. Molecular aspects of HSV-1 entry into host cells have been well studied; however, the molecular details of the spread of the virus from cell-to-cell remain poorly understood. In the past, the role of heparan sulfate proteoglycans (HSPG) during HSV-1 infection has focused solely on the role of HS chains as an attachment receptor for the virus, while the core protein has been assumed to perform a passive role of only carrying the HS chains. Likewise, very little is known about the involvement of any specific HSPGs in HSV-1 lifecycle. Here we demonstrate that a HSPG, syndecan-1, plays an important role in HSV-1 induced membrane fusion and cell-to-cell spread. Interestingly, the functions of syndecan-1 in fusion and spread are independent of the presence of HS on the core protein. Using a mutant CHO-K1 cell line that lacks all glycosaminoglycans (GAGs) on its surface (CHO-745) we demonstrate that the core protein of syndecan-1 possesses the ability to modulate membrane fusion and viral spread. Altogether, we identify a new role for syndecan-1 in HSV-1 pathogenesis and demonstrate HS-independent functions of its core protein in viral spread.     

Monolithic Endocrown Vs. Hybrid Intraradicular Post/Core/Crown Restorations for Endodontically Treated Teeth; Cross-sectional Study

The gold standard for restoring Endodontically Treated Teeth (ETT) with successful clinical longevity requires having minimal invasive preparations and maximal tissue conservation. Many dentists still consider hybrid post/core/crown to be the first choice for restoring ETT. Endocrown is a viable alternative treatment modality to hybrid post/core/crown. This study aims to assess the proper judgment of dentists working in Riyadh, Saudi Arabia on the use of monolithic endocrown versus hybrid post/core/crown for restoring ETT. The IRB of Princess Nourah Bint Abdulrahman University (PNU) Institutional Review Board reviewed this study. The questionnaire was validated and electronically distributed. The participants were pre-informed that their responses are completely anonymous and used for professional purposes only. The questionnaire surveyed dentists working in Riyadh, Saudi Arabia, about their preference for different ETT restorative modalities at various clinical scenarios. Data were analyzed using One-way ANOVA and t-test. All P-values of < 0.05 were considered statistically significant. A total of 275 responses were collected; 61.45% were females and 38.55% males. 56% of them were general practitioners, while 16% were consultants. Prefabricated post/core was the most preferred technique among the participants (18.55%), followed by endocrown (12.36%), and lastly, cast post/core (8.73%). The amount of remaining tooth structure was the most influential in the treatment selection (30.18%), followed by the presence or absence of 1–2 mm ferrule (17.82%). Interocclusal space (12.36%) was the least influential factor. Endocrown recorded 63.27% as the most preferred line of treatment in case of insufficient inter-occlusal space. 40.36% preferred endocrown for patients with occlusal risk factors. The amount of the remaining tooth structure and the tooth position significantly affect the treatment options of the participants. Endocrown was the most preferred treatment modality for restoring ETT for patients with occlusal consideration.     

A 3-O-sulfated heparan sulfate binding peptide preferentially targets herpes simplex virus 2-infected cells

Herpes simplex virus 2 (HSV-2) is the primary cause of genital herpes, which is one of the most common sexually transmitted viral infections worldwide and a major cofactor for human immunodeficiency virus infection. The lack of an effective vaccine or treatment and the emergence of drug-resistant strains highlight the need for developing new antivirals for HSV-2. Here, we demonstrate that a low-molecular-weight peptide isolated against 3-O-sulfated heparan sulfate (3-OS HS) can efficiently block HSV-2 infection. Treatment with the peptide inhibited viral entry and cell-to-cell spread both in vitro and in vivo using a mouse model of genital HSV-2 infection. Quite interestingly, the peptide showed a preferential binding to HSV-2-infected cells, with more than 200% increased binding compared to uninfected cells. Our additional results show that heparan sulfate expression is upregulated by 25% upon HSV-2 infection, which is a significant new finding that could be exploited for designing new diagnostic tests and treatment strategies against HSV-2-infected cells. In addition, our results also raise the possibility that 3-OS HS modifications within HS may be upregulated even more to accommodate for a significantly higher increase in the peptide binding to the infected cells.     

Clot Permeability,Agonist Transport,and Platelet Binding Kinetics in Arterial Thrombosis

The formation of wall-adherent platelet aggregates is a critical process in arterial thrombosis. A growing aggregate experiences frictional drag forces exerted on it by fluid moving over or through the aggregate. The magnitude of these forces is strongly influenced by the permeability of the developing aggregate; the permeability depends on the aggregate’s porosity. Aggregation is mediated by formation of ensembles of molecular bonds; each bond involves a plasma protein bridging the gap between specific receptors on the surfaces of two different platelets. The ability of the bonds existing at any time to sustain the drag forces on the aggregate determines whether it remains intact or sheds individual platelets or larger fragments (emboli). We investigate platelet aggregation in coronary-sized arteries using both computational simulations and in vitro experiments. The computational model tracks the formation and breaking of bonds between platelets and treats the thrombus as an evolving porous, viscoelastic material, which moves differently from the background fluid. This relative motion generates drag forces which the fluid and thrombus exert on one another. These forces are computed from a permeability-porosity relation parameterized from experimental measurements. Basing this relation on measurements from occlusive thrombi formed in our flow chamber experiments, along with other physiological parameter values, the model produced stable dense thrombi on a similar timescale to the experiments. When we parameterized the permeability-porosity relation using lower permeabilities reported by others, bond formation was insufficient to balance drag forces on an early thrombus and keep it intact. Under high shear flow, soluble agonist released by platelets was limited to the thrombus and a boundary layer downstream, thus restricting thrombus growth into the vessel lumen. Adding to the model binding and activation of unactivated platelets through von Willebrand-factor-mediated processes allowed greater growth and made agonist-induced activation more effective.     

The impact of lockdown strategies on the basic reproductive number of coronavirus (COVID-19) cases in Saudi Arabia

Background & ObjectivesIn late December 2019, an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS COV-2) occurred in the city of Wuhan, the capital of the Hubei province in the central part of the People’s Republic of China (Ren et al., 2020). In Saudi Arabia, the first case of COVID-19 was reported in March 2, 2020. In March 8, 2020, the Saudi authorities adopted the lockdown strategy to contain the disease. The aim of this study was to determine the effectiveness of the various phases of the lockdown strategy in Saudi Arabia and its impact on the basic reproductive number (R0) of the COVID-19 outbreak.Material and MethodsThe timeline of the COVID-19 outbreak in Saudi Arabia was divided into three-time intervals. Google Mobility Community Reports (2020) was used to estimate the changes in community mobility during the various phases of the lockdown. The basic reproductive number (R0) of the COVID-19 outbreak was calculated daily using the Susceptible, Infected and Recovered (SIR) model based on the Saudi Ministry of Health (MOH) daily reports. This is a standard system to determine the spread of the virus on the basis of infection rate, quarantine rate as well as confirmation rate. The mean values of the calculated R0 during each interval were compared using one-way ANOVA test.ResultsThere was no statistically significant difference between the mean values of the different phases of the lockdown (P > 0.05). Moreover, mean R0 value of the second interval was 0.09 higher than the initial interval with free community mobility. Furthermore, the mean R0 values of the third interval with the full lockdown was 0.28 higher than the initial interval.ConclusionEarly implementation of lockdown strategy combined with other social distancing strategies help in containing infectious outbreaks in their early phases. Continuous assessment of such strategies’ effectiveness provides decision makers with precious information needed to justify their application when considering their economic impact.     

Decline of Supportive Attitudes among Husbands toward Female Genital Mutilation and Its Association to Those Practices in Yemen

Objectives

To elucidate the attitudes of women and their husband’s towards female genital mutilation (FGM) and their associations with the continuation of FGM upon their daughters.

Methods

Subjects were 10,345 (in 1997) and 11,252 (in 2003) ever married women aged 15 to 49 years from the Yemen Demographic Health Surveys. Performances of FGM on the most-recently-born daughters were investigated. Attitudes of women and their husbands were assessed by their opinions on the continuation of FGM. The association between the attitudes of women and their husbands and performance of FGM on the most-recently-born daughters were investigated after adjusting for age and education of the women.

Findings

The percentage among the most-recently-born daughters who received FGM of women who had undergone FGM declined from 61.9% in 1997 to 56.5% in 2003 (p<0.001). The percentages of women who had undergone FGM and who supported the continuation of FGM and of husbands who also supported its continuation decreased from 78.2% and 60.1% in 1997 to 70.9% and 49.5% in 2003, respectively (both p<0.001). When the women or the husbands did not agree with FGM, it was less likely to be performed on their daughter than when the women or the husbands agreed in 1997 (odds ratio=0.11, 95% confidence interval 0.07-0.16 and odds ratio=0.07, 95% confidence interval 0.04-0.12, respectively) and in 2003 (odds ratio=0.12, 95% confidence interval 0.09-0.16 and odds ratio=0.11, 95% confidence interval 0.07-0.16, respectively).

Conclusion

Non-supportive attitudes of women and their husbands towards the continuation of FGM have become common and were associated with their decision not to perform FGM upon their daughters.     

A wavelet optimization approach for ECG signal classification

Wavelets have proved particularly effective for extracting discriminative features in ECG signal classification. In this paper, we show that wavelet performances in terms of classification accuracy can be pushed further by customizing them for the considered classification task. A novel approach for generating the wavelet that best represents the ECG beats in terms of discrimination capability is proposed. It makes use of the polyphase representation of the wavelet filter bank and formulates the design problem within a particle swarm optimization (PSO) framework. Experimental results conducted on the benchmark MIT/BIH arrhythmia database with the state-of-the-art support vector machine (SVM) classifier confirm the superiority in terms of classification accuracy and stability of the proposed method over standard wavelets (i.e., Daubechies and Symlet wavelets).     

Traditional knowledge of wild edible plants used in Palestine (Northern West Bank): A comparative study

Background

A comparative food ethnobotanical study was carried out in fifteen local communities distributed in five districts in the Palestinian Authority, PA (northern West Bank), six of which were located in Nablus, two in Jenin, two in Salfit, three in Qalqilia, and two in Tulkarm. These are among the areas in the PA whose rural inhabitants primarily subsisted on agriculture and therefore still preserve the traditional knowledge on wild edible plants.

Methods

Data on the use of wild edible plants were collected for one-year period, through informed consent semi-structured interviews with 190 local informants. A semi-quantitative approach was used to document use diversity, and relative importance of each species.

Results and discussion

The study recorded 100 wild edible plant species, seventy six of which were mentioned by three informants and above and were distributed across 70 genera and 26 families. The most significant species include Majorana syriaca, Foeniculum vulgare, Malvasylvestris, Salvia fruticosa, Cyclamen persicum, Micromeria fruticosa, Arum palaestinum, Trigonella foenum-graecum, Gundelia tournefortii, and Matricaria aurea. All the ten species with the highest mean cultural importance values (mCI), were cited in all five areas. Moreover, most were important in every region. A common cultural background may explain these similarities. One taxon (Majoranasyriaca) in particular was found to be among the most quoted species in almost all areas surveyed. CI values, as a measure of traditional botanical knowledge, for edible species in relatively remote and isolated areas (Qalqilia, and Salfit) were generally higher than for the same species in other areas. This can be attributed to the fact that local knowledge of wild edible plants and plant gathering are more spread in remote or isolated areas.

Conclusion

Gathering, processing and consuming wild edible plants are still practiced in all the studied Palestinian areas. About 26 % (26/100) of the recorded wild botanicals including the most quoted and with highest mCI values, are currently gathered and utilized in all the areas, demonstrating that there are ethnobotanical contact points among the various Palestinian regions. The habit of using wild edible plants is still alive in the PA, but is disappearing. Therefore, the recording, preserving, and infusing of this knowledge to future generations is pressing and fundamental.     

Cerium oxide and iron oxide nanoparticles abolish the antibacterial activity of ciprofloxacin against gram positive and gram negative biofilm bacteria

Metal oxide nanoparticles have been suggested as good candidates for the development of antibacterial agents. Cerium oxide (CeO₂) and iron oxide (Fe₂O₃) nanoparticles have been utilized in a number of biomedical applications. Here, the antibacterial activity of CeO₂ and Fe₂O₃ nanoparticles were evaluated on a panel of gram positive and gram negative bacteria in both the planktonic and biofilm cultures. Additionally, the effect of combining CeO₂ and Fe₂O₃ nanoparticles with the broad spectrum antibiotic ciprofloxacin on tested bacteria was investigated. Thus, minimum inhibitory concentrations (MICs) of CeO₂ and Fe₂O₃ nanoparticles that are required to inhibit bacterial planktonic growth and bacterial biofilm, were evaluated, and were compared to the MICs of the broad spectrum antibiotic ciprofloxacin alone or in the presence of CeO₂ and Fe₂O₃ nanoparticles. Results of this study show that both CeO₂ and Fe₂O₃ nanoparticles fail to inhibit bacterial growth and biofilm biomass for all the bacterial strains tested. Moreover, adding CeO₂ or Fe₂O₃ nanoparticles to the broad spectrum antibiotic ciprofloxacin almost abolished its antibacterial activity. Results of this study suggest that CeO₂ and Fe₂O₃ nanoparticles are not good candidates as antibacterial agents, and they could interfere with the activity of important antibiotics.