Search

Invasive weeds cause significant crop yield and economic losses in agriculture. The highest indirect impact may be attributed to the role of invasive weeds as virus reservoirs within commercial growing areas. The new tobamovirus tomato brown rugose fruit virus (ToBRFV), first identified in the Middle East, overcame the Tm-22 resistance allele of cultivated tomato varieties and caused severe damage to crops. In this study, we determined the role of invasive weed species as potential hosts of ToBRFV and a mild strain of pepino mosaic virus (PepMV-IL). Of newly tested weed species, only the invasive species Solanum elaeagnifolium and S. rostratum, sap inoculated with ToBRFV, were susceptible to ToBRFV infection. S. rostratum was also susceptible to PepMV-IL infection. No phenotype was observed on ToBRFV-infected S. elaeagnifolium grown in the wild or following ToBRFV sap inoculation. S. rostratum plants inoculated with ToBRFV contained a high ToBRFV titer compared to ToBRFV-infected S. elaeagnifolium plants. Mixed infection with ToBRFV and PepMV-IL of S. rostratum plants, as well as S. nigrum plants (a known host of ToBRFV and PepMV), displayed synergism between the two viruses, manifested by increasing PepMV-IL levels. Additionally, when inoculated with either ToBRFV or PepMV-IL, disease symptoms were apparent in S. rostratum plants and the symptoms were exacerbated upon mixed infections with both viruses. In a bioassay, ToBRFV-inoculated S. elaeagnifolium, S. rostratum and S. nigrum plants infected tomato plants harboring the Tm-22 resistant allele with ToBRFV. The distribution and abundance of these Solanaceae species increase the risks of virus transmission between species.

Neurofibromatosis Type 2 is an inherited disease characterized by Schwann cell tumors of cranial and peripheral nerves. The NF2 gene encodes Merlin, a member of the ERM family consisting of an N-terminal FERM domain, a central α-helical region, and a C-terminal domain. Changes in the intermolecular FERM-CTD interaction allow Merlin to transition between an open, FERM accessible conformation and a closed, FERM-inaccessible conformation, modulating Merlin activity. Merlin has been shown to dimerize, but the regulation and function Merlin dimerization is not clear. We used a nanobody based binding assay to show that Merlin dimerizes via a FERM-FERM interaction, orientated with each C-terminus close to each other. Patient derived and structural mutants show that dimerization controls interactions with specific binding partners, including HIPPO pathway components, and correlates with tumor suppressor activity. Gel filtration experiments showed that dimerization occurs after a PIP2 mediated transition from closed to open conformation monomers. This process requires the first 18 amino acids of the FERM domain and is inhibited by phosphorylation at serine 518. The discovery that active, open conformation Merlin is a dimer represents a new paradigm for Merlin function with implications for the development of therapies designed to compensate for Merlin loss.

COVID-19 outbreak associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) raised health concerns across the globe and has been considered highly transmissible between people. In attempts for finding therapeutic treatment for the new disease, this work has focused on examining the polymerase inhibitors against the SARS-CoV-2 nsp12 and co-factors nsp8 and nsp7. Several polymerase inhibitors were examined against PDB ID: 6M71 using computational analysis evaluating the ligand’s binding affinity to replicating groove to the active site. The findings of this analysis showed Cytarabine of -5.65 Kcal/mol with the highest binding probability (70%) to replicating groove of 6M71. The complex stability was then examined over 19 ns molecular dynamics simulation suggesting that Cytarabine might be possible potent inhibitor for the SARS-CoV-2 RNA Dependent RNA Polymerase.

The aim of this study was to evaluate the content of periradicular surgery-related YouTube videos available for patients’ education. YouTube search was made for videos related to periradicular surgery using specific terms. After exclusions, 42 videos were selected, viewed and assessed by two independent observers. The videos were assessed in terms of duration, days since upload, country of upload, number of views, likes and dislikes, authorship source, viewing rate and interaction index. To grade the content of videos about periradicular surgery, a usefulness score was created with 10 elements based mainly on the American Association of Endodontists guidelines. Each element was given a score of 0 or 1. SPSS software (SPSS Inc, Chicago, IL, USA) was used to analyze data at a 95% confidence level. An inter-evaluator reliability analysis for the scoring system was performed using the Kappa statistic. The videos received an average of 35103.9 views (range: 9–652378) with an average duration of 338.71 seconds (range: 42–2081), respectively. Most videos were provided by individuals (57%). Half of the videos were posted by authors from the United States. The inter-evaluator reliability for usefulness scoring was 94.5%. No video covered the 10 scoring elements completely, presenting very low usefulness scores (mean: 3.2; range: 1–7). The most discussed elements were supporting media (100%) and steps of the procedure (90.5%) followed by indications and contraindications (45.2%) and symptoms (31%). None of the included videos discussed the procedure’s cost or prognosis. In terms of usefulness score, no significant difference was detected between different sources of upload (chi-square test, P > 0.05). Information on periradicular surgery in YouTube videos is not comprehensive and patients should not rely on YouTube as the only source of information. Dental professionals should enrich the content of YouTube with good quality videos by providing full and evidence-based information that will positively affect patients’ attitudes and satisfaction.

Background The COVID-19 pandemic has sparked a surge in the use of virtual communication tools for delivering clinical services for many non-urgent medical needs allowing telehealth or telemedicine, to become an almost inevitable part of the patient care. However, most of patients with vascular disease may require face-to-face interaction and are at risk of worse outcomes if not managed in timely manner. Objective We aimed to describe the utilization of telemedicine services in the outpatient vascular surgery clinics in a tertiary hospital. Methods A retrospective analysis of data on all vascular outpatient encounters during 2019 and 2020 was conducted and compared to reflect the pattern of practice prior to and during the COVID-19 pandemic. Results The study showed that 61% of the total patient encounters in 2020 were reported through teleconsultation. Females were the majority of patients who sought the virtual vascular care. Consultations for the new cases decreased from 29% to 26% whereas, the follow-up cases increased from 71% to 74% in 2020 (p = 0.001). The number of procedures performed in the vascular outpatient clinics decreased by 46% in 2020 when compared to 2019. This decrease in procedures was more evident in the duration from February 2020 to April 2020 in which the procedures decreased by 97%. The proportion of procedures represented 22.6% of the total encounters in 2019 and 10.5% of the encounters during 2020, (p = 0.001). Conclusions Teleconsultation, along with supporting practice guidelines, can be used to maximize the efficiency of care in vascular surgery patients during the pandemic and beyond. Adoption of the ‘hybrid care’ which combines both virtual and in-person services as an ongoing practice requires evidence obtained through audits and studies on patients and healthcare providers levels. It is essential to establish a clear practice that ensures patient’s needs.

We experimentally investigate an intervention that ought to motivate innovative behavior by changing risk perceptions. Participants run a virtual lemonade stand and face a trade-off between exploiting a known strategy and exploring untested approaches. Innovation through testing new approaches comes along with a risk of failure because participants are compensated based on the profits generated by their virtual business. We test whether we can draw attention away from this risk by implementing a salience mechanism, which ought to focus participants on the input rather than the outcome of the innovative process. However, we find that this intervention is not effective in motivating innovative behavior—rather, it jeopardizes innovation. We discuss potential behavioral channels and encourage further research of risk salience as a tool to foster innovation. Our pre-registered study highlights the importance of evaluating interventions before implementation, as even carefully designed interventions may turn out to be ineffective or even backfire.

Objective To evaluate the educational value of YouTube as a learning tool for dental students regarding endodontic access cavity preparation. Methods and findings YouTube search was made for videos related to endodontic access cavity preparation using specific terms. After exclusions, 41 videos were chosen and assessed for tooth type, video length, days since upload, country of origin, number of views and likes, source of authorship, and viewing rate. To grade the content of videos, a usefulness score with seven elements was developed. Each element was given a score of 0 or 1. Statistical tests were run by using Kruskal-Wallis and Mann-Whitney tests (SPSS Inc, Chicago, IL, USA) at a 5% significance level. The videos received a mean of 181198.5 views with a mean duration of 686.1 seconds. The mean number of “likes” was 1047.8. Almost half of the videos covered content related to molar teeth. Most videos were provided by health care professionals with almost 50% uploaded from India. The mean usefulness score was 4.29 (range: 1–7) and the most discussed elements were description, instruments used, access cavity demonstration, and evaluation criteria. About a quarter of the videos were classified as good, while 46.3% as moderate and 29.3% as poor. Among the content usefulness categories, no difference was found in the video demographics (p>0.05) except “days since upload” (p = 0.018) in which good quality videos were found to have the highest median. Moreover, although insignificant, good videos were found to have the longest duration and lowest number of views, likes, and viewing rate. The mean usefulness score of videos released during the COVID-19 pandemic was lower than that for pre-pandemic videos (p = 0.042), and videos uploaded by academic institutions had a higher mean usefulness score than videos uploaded by health care professionals (p Conclusions Information on endodontic access cavity preparation is not comprehensive in most of the reviewed YouTube videos and could be of low educational value.

Background Gaza has been under land, sea, and aerial closure for 13 years, during which time Palestinian patients from Gaza have been required to obtain Israeli-issued permits to access health facilities in the West Bank (including east Jerusalem), as well as in Israel and Jordan. Specific groups, like cancer patients, have a high need for permits due to lack of services in Gaza. The approval rate for patient permits to exit Gaza dropped from 94% in 2012 to 54% in 2017. We aimed to assess the impact of access restrictions due to permit denials/delays on all-cause mortality for cancer patients from Gaza referred for chemotherapy and/or radiotherapy. Methods This study matched 17,072 permit applications for 3,816 cancer patients referred for chemotherapy and/or radiotherapy from 1 January 2008 to 31 December 2017 with referrals data for the same period and mortality data from 1 January 2008 to 30 June 2018. We carried out separate analyses by period of first application (2008–14; 2015–17), in light of varying access to Egypt during these times. Primary analysis compared survival of patients according to their first referral decision (approved versus denied/delayed) using Kaplan-Meier method and Cox regression. Findings Mortality in patients unsuccessful in permit applications from 2015–17 was significantly higher than mortality among successful patients, with a hazard ratio of 1·45 (95% CI: 1·19–1·78, p Interpretation Limitations to patient access due to unsuccessful applications for permits to exit the Gaza Strip had a significant impact on mortality for cancer patients applying for chemotherapy and/or radiotherapy in the period 2015–17. The substantially higher number of annual unsuccessful permit applications from 2015, combined with severely limited alternatives to access chemotherapy and radiotherapy during these years, may be important factors to explain the difference in the impact of permits delays/denials between the two study periods.

BackgroundPharmacists have crucial role in providing drug information and medication counseling to patients. This survey aimed to benchmark the current knowledge of the pharmacists concerning food-drug interactions (FDIs) in Jordan.MethodsA cross-sectional study was conducted in Amman, the capital and largest city of Jordan, using a validated questionnaire. It was distributed to pharmacists working in community and hospital pharmacies using a convenience sampling technique. Descriptive and inferential statistics were performed in this study.ResultsA total of 340 questionnaires distributed, 300 (88%) pharmacists responded. Over 50% of pharmacists claimed that they have sufficient knowledge regarding FDI. Virtually, the overall median (interquartile range) knowledge score was 18 (15-21), approximately 60%. The highest knowledge scores were for alcohol-drug interactions section (66.6%) followed by both common food-drug interactions and the timing of drug intake to food consumption sections with a score of (58.3%) for each, reflecting a suboptimal knowledge of FDIs among the pharmacists.ConclusionPharmacists had unsatisfactory knowledge about common FDIs, with no significant difference between hospital and community pharmacists. Therefore, more attention and efforts should be played to improve awareness about potential food-drug interactions.

Breast cancer is one of the commonest cancers among Algerian females. Compared to Western populations, the median age of diagnosis of breast cancer is much lower in Algeria. The objective of this study is to explore the expression of several miRNAs reported to be deregulated in breast cancer. The miRNAs miR-21, miR-125b, miR-100, miR-425-5p, miR-200c, miR-183 and miR-182 were studied on tumor and normal adjacent Algerian breast tissues using quantitative reverse transcription real time PCR, and the results were analyzed according to clinical characteristics. Compared to the normal adjacent tissues, miR-21, miR-183, miR-182, miR-425-5p and miR-200c were found to be upregulated while miR-100 and miR-125b were insignificantly deregulated. A positive correlation was noted among miR-183, miR-182 and miR-200c and among miR-425-5p, miR-183, miR-200c and miR-21. Further global miRNA microarray profiling studies can aid in finding ethnic specific miRNA biomarkers in the Algerian breast cancer population.

For the first time, ten frequentist estimation methods are considered on stress-strength reliability R = P(Y < X) when X and Y are two independent Weibull distributions with the same shape parameter. The start point to estimate the parameter R is the maximum likelihood method. Other than the maximum likelihood method, a nine frequentist estimation methods are used to estimate R, namely: least square, weighted least square, percentile, maximum product of spacing, minimum spacing absolute distance, minimum spacing absolute-log distance, method of Cramér-von Mises, Anderson-Darling and Right-tail Anderson-Darling. We also consider two parametric bootstrap confidence intervals of R. We compare the efficiency of the different proposed estimators by conducting an extensive Mont Carlo simulation study. The performance and the finite sample properties of the different estimators are compared in terms of relative biases and relative mean squared errors. The Mont Carlo simulation study revels that the percentile and maximum product of spacing methods are highly competitive with the other methods for small and large sample sizes. To show the applicability and the importance of the proposed estimators, we analyze one real data set.

We report the synthesis and preliminary characterization of IODVA1, a potent small molecule that is active in xenograft mouse models of Ras-driven lung and breast cancers. In an effort to inhibit oncogenic Ras signaling, we combined in silico screening with inhibition of proliferation and colony formation of Ras-driven cells. NSC124205 fulfilled all criteria. HPLC analysis revealed that NSC124205 was a mixture of at least three compounds, from which IODVA1 was determined to be the active component. IODVA1 decreased 2D and 3D cell proliferation, cell spreading and ruffle and lamellipodia formation through downregulation of Rac activity. IODVA1 significantly impaired xenograft tumor growth of Ras-driven cancer cells with no observable toxicity. Immuno-histochemistry analysis of tumor sections suggests that cell death occurs by increased apoptosis. Our data suggest that IODVA1 targets Rac signaling to induce death of Ras-transformed cells. Therefore, IODVA1 holds promise as an anti-tumor therapeutic agent.

IntroductionCurrent guidelines recommend maintaining vancomycin trough concentrations between 15-20 mg/L for serious methicillin resistant staphylococcus aureus (MRSA) infections. This recommendation is based on limited evidence.MethodsA retrospective study including patients with vancomycin susceptible MRSA infections (MIC< = 2 mg/L), treated with vancomycin. We compared outcomes among patients attaining high (> = 15mg/L) vs low (ResultsAmong 285 patients included, there were no significant differences between patients achieving high and low vancomycin levels in mortality (46/131, 35.1% vs 41/154, 26.6%), clinical success, microbiological success, or nephrotoxicity. Similarly, in the PS-matched cohort (n = 162), there was no significant difference in mortality between patients with high and low vancomycin levels (24/53, 45.3% vs 57/109, 52.3%, respectively), adjusted odds ratio for mortality with high levels 0.63 (95% confidence interval 0.28-1.43). In both cohorts, patients with pneumonia achieving high levels had significantly higher clinical and microbiological success (PS-matched cohort: clinical success: 16/32, 50.0% vs 5/27, 18.5%, p = 0.012; microbiological success: 19/32, 59.4% vs 7/27, 25.9%, p = 0.010), without significant differences in mortality.ConclusionsWe found no association between vancomycin levels > = 15 mg/L and clinical outcomes in patients with MRSA infections. In patients with MRSA pneumonia, vancomycin levels > = 15 mg/L were associated with higher clinical success rates. Further larger cohort studies are needed to define optimal vancomycin levels according to the site of infection.

Fusidic acid is a steroid antibiotic known since the 1960s. It is frequently used in topical preparations, i.e., ointments, for the treatment of skin and soft tissue infections caused by Staphylococcus aureus. There is an increasing number of methicillin-resistant S. aureus (MRSA) strains that harbour plasmid-borne fusB/far1 or fusC that is localised on SCC elements. In this study we examined a series of related CC30-MRSA isolates from the Arabian Gulf countries that presented with SCCmec elements and fusC, including a variant that-to the best of our knowledge-has not yet formally been described. It consisted of a class B mec complex and ccrA/B-4 genes. The fusidic acid resistance gene fusC was present, but contrary to the previously sequenced element of HDE288, it was not accompanied by tirS. This element was identified in CC30 MRSA from Kuwait, Saudi Arabia and the United Arab Emirates that usually also harbour the Panton-Valentin leukocidin (PVL) genes. It was also identified in CC8 and ST834 isolates. In addition, further CC30 MRSA strains with other SCCmec VI elements harbouring fusC were found to circulate in the Arabian Gulf region. It can be assumed that MRSA strains with SCCmec elements that include fusC have a selective advantage in both hospital and community settings warranting a review of the use of topical antibiotics and indicating the necessity of reducing over-the-counter sale of antibiotics, including fusidic acid, without prescription.

Background Rate of cesarean section (CS), including elective CS has globally increased. Studies have found that term elective CS before 39 weeks of gestation is associated with increased risk of adverse respiratory outcomes. Objective To determine the rate of elective CS and examine the association between timing of elective term CS and adverse neonatal outcomes in a large population of Lebanese women. Methods A Multi-Center Study was conducted using data from the National Collaborative Perinatal Neonatal Network database. Simple and multivariable logistic regression models were used to examine the association between timing of term elective CS and adverse neonatal outcomes. Some of the neonatal adverse outcomes we examined included respiratory distress syndrome, admission to the NICU, and a composite of respiratory outcomes. Results A total of 28,997 low risk mothers who delivered through primary and repeat elective CS were included in the study. Uncomplicated elective planned term CS constituted 25% of all CS deliveries in Lebanon. Primary and repeat CS at 37 weeks of gestation increased the odds of most of the studied adverse neonatal outcomes. There were few associations between CS and adverse neonatal outcomes at 38 weeks of gestation. Conclusions Term primary and repeat cesarean delivery prior to 39 weeks of gestation is associated with respiratory and other adverse neonatal outcomes. Delaying birth 1–2 weeks till 39 weeks of gestation can prevent 64–77% of adverse respiratory outcomes.

The Phoenicians emerged in the Northern Levant around 1800 BCE and by the 9th century BCE had spread their culture across the Mediterranean Basin, establishing trading posts, and settlements in various European Mediterranean and North African locations. Despite their widespread influence, what is known of the Phoenicians comes from what was written about them by the Greeks and Egyptians. In this study, we investigate the extent of Phoenician integration with the Sardinian communities they settled. We present 14 new ancient mitogenome sequences from pre-Phoenician (~1800 BCE) and Phoenician (~700–400 BCE) samples from Lebanon (n = 4) and Sardinia (n = 10) and compare these with 87 new complete mitogenomes from modern Lebanese and 21 recently published pre-Phoenician ancient mitogenomes from Sardinia to investigate the population dynamics of the Phoenician (Punic) site of Monte Sirai, in southern Sardinia. Our results indicate evidence of continuity of some lineages from pre-Phoenician populations suggesting integration of indigenous Sardinians in the Monte Sirai Phoenician community. We also find evidence of the arrival of new, unique mitochondrial lineages, indicating the movement of women from sites in the Near East or North Africa to Sardinia, but also possibly from non-Mediterranean populations and the likely movement of women from Europe to Phoenician sites in Lebanon. Combined, this evidence suggests female mobility and genetic diversity in Phoenician communities, reflecting the inclusive and multicultural nature of Phoenician society.

TAP1-TAP2 heterodimeric complexes are recognized as the transporter associated with antigen processing of major histocompatibility complex class I peptides for recognition by tumor-specific cytotoxic T lymphocytes. In this study, we investigated the immunohistochemical expression of TAP1 and TAP2 in 160 patients with breast cancer and correlated their expression levels with clinicopathologic parameters. The median age of the patient cohort was 52.5 years (range, 30–86 years). Both TAP1 and TAP2 immunohistochemical expression levels correlated significantly with breast cancer characteristics (P < .001). TAP1 expression levels were low to negative in stage I breast tumors. TAP1 and TAP2 levels were significantly higher in grade 3 tumors than low-grade (grade 1 and 2) tumors. TAP1 and TAP2 expression levels were not significantly different among different levels of HER2-expressing tumors and did not vary by estrogen and progesterone receptor status or patient age. Both TAP1 and TAP2 overexpression in breast cancer might be an indicator of an aggressive breast tumor.

We estimated the effect of oligosaccharide supplementation and feed restriction on calves. The study was divided into two experimental periods of 28 days each with 20 crossbred calves that had initial body weight of 37 Kg and housed in individual pens. The animals were split in four experimental groups: animals fed 6 L milk/day (CON) in the two periods, animals fed milk restricted (3 L milk/day) in the first period and followed by CON feeding in the second period (RES), animals receiving supplementation of 5 g/day of mannanoligosaccharide (MOS) and animals receiving supplementation of 5 g/day mannan and frutoligosaccharide (MFOS). At the end of the study, all the animals were slaughtered. The average weight gain was lower in the restricted group when compared with CON and MFOS groups in the first period (P < 0.05) and there were no difference among the groups in the second period. Animals supplemented with MOS showed a significant increases in jejunal villus height and rumen papillae, which were not observed for MFOS group (P < 0.05) compared with RES and CON groups. There were no difference in ghrelin and leptin levels among treatments during periods 1 and 2 (P > 0.05). Also, the expression of ghrelin receptors in the paraventricular region of the hypothalamus did not differ among groups. We conclude that milk restriction during the first weeks of life in calves resulted in compensatory gain and did not modify the hormonal profile and expression of the ghrelin receptor in the hypothalamus. Moreover, a prebiotic supplementation changed the development of intestinal and ruminal epithelium.