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Purpose: To compare the nanoleakage between bulkfill and incremental-fill resin composites in class II slot preparations for primary and permanent teeth restored by the snowplow technique. Materials and Methods: Class II slots were prepared in 32 M (16 exfoliated/extracted primary and 16 permanent molars). Optibond All-InOne self-etching adhesive was applied and cured. A flowable composite, Premise, was then injected into the gingival seat without curing using the snowplow technique. Cavities were restored using Sonicfill/bulkfill or microhybrid Herculite composites. Energy dispersive X-ray spectrometry was used to assess nanoleakage as silver deposition percentages along the axial and cervical walls. Multivariate analysis of variance was used to assess the effect of tooth type (primary and permanent teeth) and placement technique (bulkfill and incremental techniques) on nanoleakage at the axial and cervical walls. Results: Bulkfill restorations had significantly greater nanoleakage than incremental restorations at the cervical walls in primary and permanent molars (mean = 1.21 vs 0.49 in primary molars and 0.76 vs 0.24 in permanent molars). Equivalent results were observed at the axial walls of the restorations (mean = 0.66 vs 0.14 in primary molars and 0.28 vs 0.08 in permanent molars, with a P value of

The present investigation is designed to evaluate the ameliorative efficacy of spirulina and its active constituent, C-phycocyanin, on hepatorenal injury induced by titanium dioxide nanoparticles (TiO2 NPs). Forty-eight male albino rats were randomly divided into six groups: control group, Spirulina treated group, C-phycocyanin treated group, TiO2 NPs treated group, TiO2 NPs+ Spirulina treated group and TiO2 NPs+ C-phycocyanin treated group. The estimation of hepatic and renal function markers and oxidative status as well as histopathologic alterations in hepatic and renal tissues were analyzed. Spirulina and C- phycocyanin treatments caused significant improvement in all hematological indices such as RBCs, Hb, HCT, and total and differential WBCs relative to the untreated TiO2 NPs group. Also, spirulina and C-phycocyanin treatments significantly alleviated hepatic enzymes and bilirubin concentrations. Oral administration of spirulina and C- phycocyanin decreased total cholesterol and triglycerides content significantly. Both Spirulina and C- phycocyanin attenuated creatinine, urea, and uric acid significantly. Furthermore, the present study revealed that spirulina and C- phycocyanin significantly increased hepatorenal antioxidants content and retard malondialdehyde (MDA) formation. Histopathological examinations displayed that both spirulina and C- phycocyanin treatments repaired mostly the abnormal architecture of hepatic and renal tissues induced by TiO2 NPs. In conclusion, the modulatory role of spirulina and C-phycocyanin may be due to their strong antioxidative effects and other active constituents of spirulina.

The present study aimed at verifying the usefulness of dietary 2.5% bee-pollen (BP) or propolis (PROP) to overcome the genotoxic and endocrine disruptive effects of malathion polluted water in Oreochromis niloticus (O. niloticus). The acute toxicity test was conducted in O. niloticus in various concentrations (0–8 ppm); mortality rate was assessed daily for 96 h. The 96 h-LC50 was 5 ppm and therefore 1/5 of the median lethal concentration (1 ppm) was used for chronic toxicity assessment. In experiment (1), fish (n = 8/group) were kept on a diet (BP/PROP or without additive (control)) and exposed daily to malathion in water at concentration of 5 ppm for 96 h “acute toxicity experiment”. Protective efficiency against the malathion was verified through chromosomal aberrations (CA), micronucleus (MN) and DNA-fragmentation assessment. Survival rate in control, BP and PROP groups was 37.5%, 50.0% and 100.0%, respectively. Fish in BP and PROP groups showed a significant (P

The analysis undertaken in this paper applies a multimarket model to simulate two policy measures based on the assumption that the government of Sudan would pursue two policies on the Gezira scheme the biggest irrigated scheme in Africa in attempts to achieve food self-sufficiency from wheat (major food crop), or to improve the foreign exchange earnings from cotton (major cash crop) through expanding their portions of cultivated land. The paper investigates the implications of each scenario on crops output, food self-sufficiency indicators and tenants’ welfare. Findings show that, the food security scenario raises self-sufficiency from wheat by 40% and reduces it for sorghum by 4%. However, it reduces the welfare level as the earnings from exports and revenues from tariffs decline. The foreign earning scenario on the other hand, improves the overall foreign earnings and enhances farmers’ welfare. Nonetheless, the study suggests that none of the two policies would achieve both objectives alone, hence it is recommended that, both policies are to be considered in a policy package that considers as well other related components.

Background: It is proven that children have significantly milder COVID-19 disease compared to adults. Various immunological characteristics influence this age-related difference in protection against COVID-19. Pediatric COVID-19 in Jordan is extremely under reported. Objectives: The primary goal of this work is to identify the anti_S and anti_N antibody responses in a random group of children in Jordan and compare it to that of naturally infected-unvaccinated adults. Methods: 151 unvaccinated children, 4 days to 18 years old, were screened for anti_S and anti_N antibodies. History of COVID-19 infection or exposure to infection and symptom severity were reported by parents on a special questionnaire. Results: 78.9 % and 65.3 % of participants were seropositive for anti_S IgG and anti_N Abs, respectively. There was a remarkable association between age and anti_S IgG and anti_N IgG antibody titers, as children aged 12 years or older had increased anti_S IgG titers (mean = 19.3 BAU/mL) compared to younger groups (means of 10.15, 9.24, 7.91 BAU/mL for age groups 6–12, 1–6, less than 1 year, respectively). Gender did not show a statistically important role in anti_S and anti_N IgG seropositivity rates or titers. Children displayed significantly elevated anti_S titers (mean = 13.23 BAU/mL) compared to naturally infected adults (mean = 9.72 BAU/mL), in contrast, adults’ anti_N titers (mean = 39.64 U/mL) were significantly higher compared to those of children (mean = 10.77 U/mL). Conclusions: The current work provides evidence of distinctly robust and persistent humoral immunity displayed by high anti_S and anti_N IgG in children, even >12 months post-infection. Age was the only factor that had a significant statistical impact on anti_S and anti_N Ab levels among the pediatric group in this study. Children exhibited significantly higher anti_S titers than naturally infected adults. In contrast, adults’ anti_N titers were significantly higher. Such information can assist direct pediatric SARS-CoV-2 immunization programs, with implications for creating age-targeted strategies for diagnostic and population protection measures.

Preeclampsia is a syndrome with multiple etiologies. The diagnosis can be made without proteinuria in the presence of dysfunction of at least 1 organ associated with hypertension. The common pathophysiological pathway includes endothelial cell activation, intravascular inflammation, and syncytiotrophoblast stress. There is evidence to support, among others, immunologic causes of preeclampsia. Unlike defense immunology, reproductive immunology is not based on immunologic recognition systems of self/non-self and missing-self but on immunotolerance and maternal–fetal cellular interactions. The main mechanisms of immune escape from fetal to maternal immunity at the maternal–fetal interface are a reduction in the expression of major histocompatibility complex molecules by trophoblast cells, the presence of complement regulators, increased production of indoleamine 2,3-dioxygenase, activation of regulatory T cells, and an increase in immune checkpoints. These immune protections are more similar to the immune responses observed in tumor biology than in allograft biology. The role of immune and nonimmune decidual cells is critical for the regulation of trophoblast invasion and vascular remodeling of the uterine spiral arteries. Regulatory T cells have been found to play an important role in suppressing the effectiveness of other T cells and contributing to local immunotolerance. Decidual natural killer cells have a cytokine profile that is favored by the presence of HLA-G and HLA-E and contributes to vascular remodeling. Studies on the evolution of mammals show that HLA-E, HLA-G, and HLA-C1/C2, which are expressed by trophoblasts and their cognate receptors on decidual natural killer cells, are necessary for the development of a hemochorial placenta with vascular remodeling. The activation or inhibition of decidual natural killer cells depends on the different possible combinations between killer cell immunoglobulin-like receptors, expressed by uterine natural killer cells, and the HLA-C1/C2 antigens, expressed by trophoblasts. Polarization of decidual macrophages in phenotype 2 and decidualization of stromal cells are also essential for high-quality vascular remodeling. Knowledge of the various immunologic mechanisms required for adequate vascular remodeling and their dysfunction in case of preeclampsia opens new avenues of research to identify novel biological markers or therapeutic targets to predict or prevent the onset of preeclampsia.

Summary: The development of anti-infectives against a large range of AB-like toxin-producing bacteria includes the identification of compounds disrupting toxin transport through both the endolysosomal and retrograde pathways. Here, we performed a high-throughput screening of compounds blocking Rac1 proteasomal degradation triggered by the Cytotoxic Necrotizing Factor-1 (CNF1) toxin, which was followed by orthogonal screens against two toxins that hijack the endolysosomal (diphtheria toxin) or retrograde (Shiga-like toxin 1) pathways to intoxicate cells. This led to the identification of the molecule C910 that induces the enlargement of EEA1-positive early endosomes associated with sorting defects of CNF1 and Shiga toxins to their trafficking pathways. C910 protects cells against eight bacterial AB toxins and the CNF1-mediated pathogenic Escherichia coli invasion. Interestingly, C910 reduces influenza A H1N1 and SARS-CoV-2 viral infection in vitro. Moreover, parenteral administration of C910 to mice resulted in its accumulation in lung tissues and a reduction in lethal influenza infection.

Failure of the abdominal wall to close and the persistence of the herniated bowel beyond week 12 gestation is known as an omphalocele. This condition occurs in 1 in 4000 live births and can be associated with several chromosomal anomalies and anatomical malformations. Meckel's diverticulum can be found within an omphalocele in up to 28% of cases, however the presence of a perforated Meckel's diverticulum adherent within an omphalocele has seldom been reported. Herein we present a case of a newborn male transferred to our institution with a perforated Meckel's diverticulum adherent within an omphalocele.

Objectives: Colorectal cancer (CRC) is a serious gastrointestinal disease. Cancer cells can survive in a microenvironment that includes distinct immune cells, various immune checkpoints including HLA-G, and different immune effectors such as interleukin-6 (IL-6), TNF-alpha (TNF-α), and interferon-gamma (IFN-γ). Thus, the objective of this study was to investigate HLA-G involvement in CRC as a prognostic factor in the Tunisian population, both in its soluble form (sHLA-G) and in its form linked to extracellular vesicles (HLA-GEV). Additionally, we examined its association to the secretion of cytokines. Methods: Fifty Tunisian patients, diagnosed with CRC, matched with ninety-eight healthy blood donors (HD) were enrolled in this study. Levels of sHLA-G, HLA-GEV, IL-6, TNF-α, and IFN-γ were dosed in plasma samples using specific ELISA. For the functional assay, we assessed sHLA-G effects on the production of cytokines by stimulated T lymphocytes. We measured the concentration of IL-6, TNF-α, and IFN-γ produced by activated T lymphocytes pre-stimulated by plasma sHLA-G and HLA-GEV. Results: Our case-control analysis showed high concentration of both sHLA-G (8.8 [0–63] ng/ml vs. 2.1 [0–63] ng/ml, p

Summary: Background: We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods: Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings: Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation: This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenges. Funding: The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity, National Institute for Health Research Moorfields Biomedical Research Centre, Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The Seva Foundation, British Council for the Prevention of Blindness, and Christian Blind Mission. Translations: For the French, Spanish, Chinese, Portuguese, Arabic and Persian translations of the abstract see Supplementary Materials section.

Prostate cancer is the second most frequent among men. Bones and lymph nodes are the most common sites of metastases in advanced prostate cancer. Oral cavity metastases are rare. We report a case of 65-year-old man with a prostate adenocarcinoma revealed by gingival metastasis. We analyze through this observation the clinical, morphological and therapeutic characteristics of this neoplasia.

One of the best ways to design new biocidal agents is synthesizing hybrid molecules by combining two or more bioactive moieties in a single molecular scaffold. So, new series of quinolines bearing a thiazole moiety were synthesized using thiosemicarbazones 2a-f. Cyclization of 2a-f with ethyl chloroacetate, ethyl 2-chloropropanoate or chloroacetone afforded the corresponding thiazoles 3-5. The antimicrobial activity of the new quinoline derivatives was evaluated. The most of tested compounds revealed potent both of the antibacterial and antifungal activities. Fourfold potency of amphotericin B for the inhibition the growth of the A. fumigatus was displayed by ccompound 5e. The latter compound displayed twofold potency of gentamycin for inhibition the growth of N. gonorrhoeae. Moreover, this compound showed equipotent potency of references drugs for inhibition of the growth of S. flexneri, S. pyogenes, P. vulgaris, A. clavatus, G. candidum and P. marneffei. So, quinolines bearing a thiazole moiety can be suggested as interesting scaffolds for the development both of the novel antibacterial and antifungal agents. Some new derivatives were studied as peptide deformylase enzyme inhibitors. Thiazolidin-4-one derivative 3d and 2,3-dihydrothiazole derivative 5c had shown good PDF inhibition activity, which had been supported by the docking results with highest binding affinity and lowest docking energy score. These results suggested that the most potent compounds might be possible agents as novel bacterial PDF inhibitor., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Two novel series of 6-(4-benzamido-/4-phthalimido)-3-cyanopyridine derivatives were designed and synthesized as inhibitors of PIM-1 kinase. Based on cytotoxicity results via MTT assay against prostate carcinoma PC3, human hepatocellular carcinoma HepG2 and breast adenocarcinoma MCF-7 cell lines, the most potent cytotoxic cyanopyridine hits, 6, 7, 8, 12 and 13 were 1.5-3.3 times more inhibitor of cell proliferation than the reference standard, 5-FU. Selectivity profile of the latter compounds on normal human cells (WI-38), was executed, indicating that they are highly selective (IC 50  > 145 μM) in their cytotoxic effect. The promising compounds were further evaluated as PIM-1 kinase inhibitors. These compounds elicited remarkable inhibition of PIM-1 kinase (76.43-53.33%). Extensive studies on apoptosis were conducted for these compounds; they enhanced caspase-3 and boosted the Bax/Bcl-2 ratio 27-folds in comparison to the control. Molecular docking study of the most potent compound, 13 in PIM-1 kinase active site was consistent with the in vitro activity. Finally, prediction of chemo-informatic properties released compound 13 as the most promising ligand., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In this study, anti-proliferative effects of twenty-seven indeno[1,2-b]quinoxalin-11-one derivatives were investigated in three human cancer cell lines, namely: the colon cancer cell line HCT-116, the liver cancer cell line HepG-2, and the breast cancer cell line MCF-7. Among them, 5, 6, 13, 14a, b and 15d-f derivatives displayed excellent anti-proliferative activities against the three tested cell lines compared to the reference standard Imatinib. Therefore, they were selected for further studies. First, to ensure the safety of our hits, investigation of the IC 50 values on normal human cells (WI-38) was executed indicating that, they are highly selective (IC 50  > 107 μM) in their cytotoxic effect. Second, the induction of apoptosis by these active compounds was achieved by down-regulation of Bcl-2 and up-regulation of BAX and caspase-3. Further investigations have shown that 14b and 15f, the most potent derivatives, induced cell cycle arrest at G2/M phase. Moreover, in silico evaluation of ADME properties indicated that all the potent compounds are orally bioavailable with no permeation to the blood brain barrier., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Mercury (Hg) is an environmental pollutant that threatens aquatic life. Many environmental factors, including water temperature, are reported to influence the toxicity of dissolved chemicals in the aquatic ecosystem. Therefore, we investigated the impact of thermal stress on Hg-induced subchronic toxicity in Nile tilapia (Oreochromis niloticus). Fish were randomly allocated into five groups. Group I served as the control and kept at 25 °C. Groups II, III, IV, and V were reared at 25, 28, 31, and 34 °C, respectively, and co-exposed to HgCl 2 (1/10 LC 50 ) for 42 days. Blood and tissue samples were collected after 21 and 42 days. All HgCl 2 -exposed groups exhibited significant elevations in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine, along with decreases in the serum total protein and albumin. In addition, marked reductions in antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSPx), were observed. Remarkable increases in Hg tissue concentrations were detected along with increases in heat shock protein (HSP) 70 mRNA expression. Interestingly, the patterns data that were recorded were more coincident with the water temperature than the period of exposure. In conclusion, water temperature and exposure period are two crucial factors modulating HgCl 2 -induced toxicity and bioaccumulation in Nile tilapia. Our findings provide new insights concerning the impact of thermal stress as an environmental factor on Hg toxicity and bioaccumulation in Nile tilapia and, in turn, on fish and fish consumer health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

One of the many methods of treating cancer is to terminate the uncontrolled growth of cancer cells. So, aiming the apoptotic pathway is an exciting approach to finding new anticancer agents. A novel series of cyanopyridines was designed and synthesized for antiproliferative evaluation. 2-Amino-6-(4-(benzyloxy)phenyl)-4-(4-(dimethylamino)phenyl) nicotinonitrile 10f was the most potent inhibitor against the growth of PC-3, and HepG-2 cancer cell lines with IC 50 values of 2.04 uM (selectivity index, SI = 78.63, 43, respectively). Also, 10f was safe against the growth of normal human diploid lung fibroblasts cell line (WI-38) with an IC 50 value of 160.04 uM. Its analogs, 10b, 10d, 10g, and 11b, were also active against the growth of PC-3, and HepG-2 while against MCF-7 cell line, they displayed good cytotoxic activity compared to the reference standard 5-FU. Remarkably, mechanistic studies indicated that compounds 10b, 10d, 10f, 10g, and 11b stimulated the level of active caspase 3 and boosted the BAX/BCL2 ratio 20-95 folds in comparison to the control. Our results have also indicated that 10b, 10d, 10f, 10g, and 11b exhibited a very potent inhibitory activity against PIM-1 kinase enzyme, where the IC 50 values unraveled very potent molecules in the micromolar range (0.47-1.27 μM). Further investigations have shown that 10f, the most potent PIM-1 kinase inhibitor, induced a cell cycle arrest at the G2/M phase. Moreover, in silico evaluation of ADME properties indicated that all the cyanopyridine compounds are orally bioavailable with no permeation to the blood brain barrier., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Drug-induced hepatotoxicity is an extremely widespread condition and is responsible for a variety of pathological effects on the liver. It was reported that hepatotoxicity induced by angiotensin converting enzyme inhibitors (ACEIs) is cholestasis mediated hepatitis. Bradykinin-potentiating factor (BPF) is one of the natural ACEIs. Although prolonged treatment with ACEIs provides protection against liver injury, the effect of short-term treatment with ACEIs has not been fully elucidated before. Thereby, the present study sought to determine if transient ACE inhibition may exacerbate the hepatotoxicity caused by bile duct ligation (BDL) in rats., Methods: Twenty one Wistar rats were divided into 3 groups: Sham-operated group, bile duct ligated (BDL) rats, and BDL rats treated for short-term with BPF (1 μg/kg body weight) day after day for one week and biochemical parameters were measured. Also, we assessed expression level of ACE1 and detection of hepatotoxicity in the liver tissues of different groups., Results: There was a significant increase in liver enzymes, bilirubin levels, and oxidative stress in the BDL group after treatment with BPF as compared to BDL group. We found overexpression of ACE1 gene in BDL group compared to BPF and Sham-operated control group. Histopathological examination of liver treated with BPF showed severe degeneration hepatic architecture and hepatocytes as compared to BDL group. Collagen deposition increased after BPF treatment as compared to BDL groups., Conclusion: The present investigation suggests and recommends that short- term ACE inhibition pathway potentiates liver fibrosis during cholestasis disease., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: This study aimed at tracking the prevalence of body image disorder in a population of Tunisian women followed for breast cancer and the factors associated with it., Patients End Methods: The cross-sectional study was conducted at Salah-Azaiez Institute in Tunis, over a period of four months. One hundred outpatients followed for confirmed breast cancer were recruited. The questionnaire targeted the women's sexuality and their couple relationships, along with their socio-demographic, clinical, and therapeutic characteristics. The scales used were BIS, HADS, and FSFI., Results: The prevalence of body image disorder according to BIS was 45% with an average of 11.5±11.2 among the interrogated patients, 24.7% of which reported an alteration in their couple relationships and 47% in their sexual relations. In univariate analysis, body image disorder was associated with family support, change in couple relationship, depression and anxiety. Body image disorder and sexual dysfunction were interrelated: each of them fostered the prevalence of the other. Multivariate analysis showed that occupational activity was an independent predictor and the absence of anxiety an independent protective factor. Body image disorder was an independent predictive factor of depression and anxiety., Discussion: The quality of couple relation and sexuality, along with the impact of the patient's surrounding are decisive for the protection or alteration of her body image., (Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)