Search

Introduction: The delineation of organs-at-risk and lymph node areas is a crucial step in radiotherapy, but it is time-consuming and associated with substantial user-dependent variability in contouring. Artificial intelligence (AI) appears to be the solution to facilitate and standardize this work. The objective of this study is to compare eight available AI software programs in terms of technical aspects and accuracy for contouring organs-at-risk and lymph node areas with current international contouring recommendations., Material and Methods: From January-July 2023, we performed a blinded study of the contour scoring of the organs-at-risk and lymph node areas by eight self-contouring AI programs by 20 radiation oncologists. It was a single-center study conducted in radiation department at the Lorraine Cancer Institute. A qualitative analysis of technical characteristics of the different AI programs was also performed. Three adults (two women and one man) and three children (one girl and two boys) provided six whole-body anonymized CT scans, along with two other adult brain MRI scans. Using a scoring scale from 1 to 3 (best score), radiation oncologists blindly assessed the quality of contouring of organs-at-risk and lymph node areas of all scans and MRI data by the eight AI programs. We have chosen to define the threshold of an average score equal to or greater than 2 to characterize a high-performing AI software, meaning an AI with minimal to moderate corrections but usable in clinical routine., Results: For adults CT scans: There were two AI programs for which the overall average quality score (that is, all areas tested for OARs and lymph nodes) was higher than 2.0: Limbus (overall average score = 2.03 (0.16)) and MVision (overall average score = 2.13 (0.19)). If we only consider OARs for adults, only Limbus, Therapanacea, MVision and Radformation have an average score above 2. For children CT scan, MVision was the only program to have a average score higher than 2 with overall average score = 2.07 (0.19). If we only consider OARs for children, only Limbus and MVision have an average score above 2. For brain MRIs: TheraPanacea was the only program with an average score over 2, for both brain delineation (2.75 (0.35)) and OARs (2.09 (0.19)). The comparative analysis of the technical aspects highlights the similarities and differences between the software. There is no difference in between senior radiation oncologist and residents for OARs contouring., Conclusion: For adult CT-scan, two AI programs on the market, MVision and Limbus, delineate most OARs and lymph nodes areas that are useful in clinical routine. For children CT-scan, only one IA, MVision, program is efficient. For adult brain MRI, Therapancea,only one AI program is efficient., Trial Registration: CNIL-MR0004 Number HDH434., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by ethics and conducted in accordance with the ethical standards of the Declaration of Helsinki (as revised in 2013). This study was approved by Ethics committee named the French National Commission of Informatics and Liberty (CNIL) (CNIL-MR0004 Number HDH434). The present study has been approved by the French Health Data Institute (Health DataHub) as the number HDH301. All methods were carried out in accordance with relevant guidelines and regulations. All participants have signed informed consent to the use of their data for research purposes. Consent for publication: Not applicable. Competing interests: The authors have declared no conflicts of interest. The Lorraine Cancer Institute used MVision AI software until January 1, 2023., (© 2024. The Author(s).)

The interplay between human microbiota and various physiological systems has garnered significant attention in recent years. The gut microbiota plays a critical role in maintaining physiological homeostasis and influences various aspects of human health, particularly via the gut brain axis. Since 2017, the challenging concept of the gut-retina axis has emerged thanks to a network analysis emphasizing the potential role of the gut microbiota disruption in the development of the age-related macular degeneration and further retinal damages. Many other ocular disorders have been linked to the dysbiosis of the gut microbiota, including uveitis and glaucoma. It has been shown that age related macular degeneration can be prevented or reversed using a diet that induces changes in the gut microbiota. The potential link between the gut microbiota as well as others types of microbiota such as the ocular surface microbiota and the development/progression of age related as well as inherited retinal degenerations and other degenerative eye diseases, has recently been broadened. Therefore, the pathogenesis of several eye diseases has recently been associated with a larger perception called the gut eye axis. This mini-review examines the potential mechanisms underlying the gut eye axis and suggests implications for the management of eye diseases. By understanding the modulation of the gut microbiota and its impact on eye disease, this mini-review provides insight into potential therapeutic interventions and avenues for future research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kammoun, Rekik, Dlensi, Aloulou, Smaoui, Sellami, Trigui, Gargouri, Chaari, Sellami, Elatoui, Khemakhem, Hadrich, Neji, Abdelmoula and Bouayed Abdelmoula.)

Lead (Pb) is one of the most common heavy metals with toxicological effects on many tissues in humans as well as animals. In order to counteract the toxic effects of this metal, the administration of synthetic or natural antioxidants is thus required. The aim of this study was to examine the beneficial effect of the aqueous extract of Ononis natrix (AEON) against lead acetate-induced damage from a behavioral, biochemical, and histological point of view. Forty-eight male mice were divided into four equal groups: Ctr (control); Pb (lead acetate 1g/l); Pb + On 100 mg/kg (lead acetate 1 g/l + AEON 100 mg/kg); Pb + On 500 mg/kg (lead acetate 1 g/l + AEON 500 mg/kg). AEON was administered orally from day 21 after the start of lead exposure up to the end of the experiment. The results revealed that lead induced behavioral disorders, increased serum levels of liver markers (AST, ALT, and bilirubin), as well as kidney markers (urea and creatinine). At the same time, levels of thiobarbituric acid reactive substances (TBARS) and glutathione peroxidase (GPx) increased significantly. Moreover, Pb caused structural changes in the liver and kidneys of Pb-exposed mice. However, AEON administration significantly improved all lead-induced brain, liver, and kidney dysfunctions. Our results suggest that AEON could be a source of molecules with therapeutic potential against brain, liver, and kidney abnormalities caused by lead exposure., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background. Catheter-related bloodstream infection (CRBSI) is defined as the presence of bacteremia originating from a venous catheter and is one of the most common and costly complications, often followed by death and septicemia. Objectives. To evaluate the effectiveness of specific interventions on CRBSI reduction rates and other outcomes. Materials and Methods. The review has been performed by consulting scientific evidence through the PUBMED/MEDLINE database using MeSh terms and Boolean operators. Studies related to the formulated hypothesis have been selected and included. Results. The results showed that thanks to a series of interventions it was possible to decrease the risk of CRBSI and lowered the risk of catheter removal, hospitalization rate and morbidity rate. Discussion and Conclusions. Proper catheter care and follow-up procedures are the first steps in preventing infection. Audit and education of dialysis unit personnel is essential., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

Aberrant mechanotransduction and compromised epithelial barrier function are associated with numerous human pathologies including inflammatory skin disorders. However, the cytoskeletal mechanisms regulating inflammatory responses in the epidermis are not well understood. Here we addressed this question by inducing a psoriatic phenotype in human keratinocytes and reconstructed human epidermis using a cytokine stimulation model. We show that the inflammation upregulates the Rho-myosin II pathway and destabilizes adherens junctions (AJs) promoting YAP nuclear entry. The integrity of cell-cell adhesion but not the myosin II contractility per se is the determinative factor for the YAP regulation in epidermal keratinocytes. The inflammation-induced disruption of AJs, increased paracellular permeability, and YAP nuclear translocation are regulated by ROCK2, independently from myosin II activation. Using a specific inhibitor KD025, we show that ROCK2 executes its effects via cytoskeletal and transcription-dependent mechanisms to shape the inflammatory response in the epidermis., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Introduction: Both exercise and pre-meal metformin could lower postprandial glucose and lipid profiles., Aims: To explore whether pre-meal metformin administration is superior to metformin administration with the meal in reducing postprandial lipid and glucose metabolism, and whether its combination with exercise confer superior benefits in metabolic syndrome patients., Materials and Methods: In a randomized crossover design, 15 metabolic syndrome patients were assigned to 6 sequences including 3 experimental conditions: metformin administration with a test meal (met-meal), metformin administration 30 min prior to a test meal (pre-meal-met) with or without an exercise bout designed to expend 700 Kcal at 60% VO 2 peak performed the evening just before pre-meal-met condition. Only 13 participants (3 males, 10 females; age: 46 ± 9.86, HbA1c: 6.23 ± 0.36) were included in the final analysis., Results: Postprandial triglyceridemia was unaffected by any condition (all P > .05). However, both pre-meal-met (-7.1%, P = .009) and pre-meal-metx (-8.2%, P = .013) significantly reduced total cholesterol AUC with no significant differences between the two latter condition ( P = .616). Similarly, LDL-cholesterol levels were significantly lower during both pre-meal-met (-10.1%, P = .013) and pre-meal-metx (-10.7%, P = .021) compared to met-meal with no difference between latter conditions ( P = .822). Plasma glucose AUC was significantly reduced by pre-meal-metx compared to both pre-meal-met (-7.5%, P = .045) and met-meal (-8%, P = .03). Insulin AUC was significantly lower during pre-meal-metx compared to met-meal (-36.4%, P = .044)., Conclusions: Metformin administration 30 minutes prior to meal seems to exert favorable effects on postprandial TC and LDL-Cholesterol levels compared to its administration with meal. Addition of one exercise bout only improved postprandial glycemia and insulinemia., Trial Registry: Pan African clinical trial registry, Identifier PACTR202203690920424.

Context: Chondroitin 6 sulphate (C6S) is a glycosaminoglycan (GAG) whose accumulation is notable in mucopolysaccharidosis type IVA and VII. Flaxseed, Linum usitatissimum L. (Linaceae) (FS), is reported to have comparable properties to those of soybean, a source of genistein, a potential new treatment for MPSs., Objective: We assess the effect of total ethanol flaxseed extract (EFSE) in an animal model of C6S accumulation., Materials and Methods: The study was performed in adult male Wistar rats ( n  = 24) for 15 successive days. The animals were divided into four groups: (1) control injected with physiological saline buffer, (2) intoxicated rats injected intraperitoneally with C6S, (3) intoxicated with C6S and treated with EFSE, and (4) treated with EFSE. All groups were subjected to histopathological and biochemical studies. The antioxidant and phytochemical properties of EFSE were examined., Results: Dry EFSE contains total phenols (6.28 mg EAG/g), condensed tannins (2.98 mg ECAT/g) and flavonoids (0.44 mg ECAT/g) with high antioxidant potential [RPE (IC 50 = 8.37 ± 0.176), DPPH (IC 50 = 12.79 ± 0.273)]. The LD 50 is higher than 5000 mg/kg. The histopathological examination showed an accumulation of C6S in the C6S intoxicated group, which disappeared in the C6S-EFSE treated group. GAGs assays showed an increased excretion in the C6S intoxicated group and increased excretion of 14% in the C6S-EFSE group compared to the C6S group., Discussion and Conclusions: EFSE showed significant potential for chelation. Its use for the treatment of GAG accumulation could be suggested and generalized to a larger study population.

Post-COVID19 patients suffer from persistent respiratory, cardiovascular, neurological, and musculoskeletal health complaints such as dyspnea, chest pain/discomfort, and fatigue. In Tunisia, the potential benefits of a cardiorespiratory rehabilitation program (CRRP) after COVID19 remain unclear. The main aim of this study was to evaluate the impact of a CRRP on submaximal exercise capacity, evaluated through the 6-min walk test (6MWT) data in post-COVID19 Tunisian patients. This was a cross-sectional study including 14 moderate to severe COVID19 patients aged from 50 to 70 years. CRRP was performed after the end of patients' hospitalization in COVID19 units for extensive or severe extents of COVID19. Dyspnea (modified medical research council), spirometry data, handgrip strength values, 6MWT data, and 6-min walk work (i.e., 6-min walk distance x weight) were evaluated 1-week pre-CRRP, and 1-week post-CRRP. CRRP included 12 sessions [3 sessions (70 min each)/week for 4 weeks]. Exercise-training included aerobic cycle endurance, strength training, and educational sessions. Comparing pre- and post- CRRP results showed significant improvements in the means±standard deviations of dyspnea by 1.79 ± 0.80 points ( p < 0.001), forced expiratory volume in one second by 110 ± 180 ml ( p = 0.04), 6-min walk distance by 35 ± 42 m ( p = 0.01), 6-min walk work by 2,448 ± 3,925 mkg ( p = 0.048), resting heart-rate by 7 ± 9 bpm ( p = 0.02) and resting diastolic blood pressure by 6 ± 10 mmHg ( p = 0.045). In Tunisia, CRRP seems to improve the submaximal exercise capacity of post-COVID19 patients, mainly the 6-min walk distance and work., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer IL declared to the handling editor a shared affiliation with all authors besides AA at the time of review., (Copyright © 2022 Toulgui, Benzarti, Rahmani, Aissa, Ghannouchi, Knaz, Sayhi, Sellami, Mahmoudi, Jemni, Gargouri, Hayouni, Ouanes, Ammar and Ben saad.)

Background: Pregnancy affects a woman's susceptibility to and severity of certain infectious diseases. Central neuraxial block for analgesia during labor is superior to nonneuraxial methods in efficacy, safety, and maternal satisfaction. Although Coronavirus disease (COVID-19) can be vertically transmitted from mother to fetus, little is known about the effects of COVID-19 on pregnant women or about anesthesia management and the risk of adverse effects related to neuraxial techniques in women with untreated COVID-19 during gestation., Aim: This investigation assesses the effects of neuraxial analgesia during labor of COVID-19-positive parturients on their hemodynamic stability., Results: The study was conducted on 64 patients and involved 32 parturients positive for SARS-CoV-2 by polymerase chain reaction (PCR) and a similar number of control "negative" patients. The affected group had an uneventful course during gestation. Seven were positive for ground-glass opacities on chest X-rays, and none underwent computed tomography (CT) scans. Two neonates were PCR-positive for SARS-CoV-2, and all 32 neonates were released from the hospital. No clinical differences were observed between the neonates in the COVID-19 and control groups. Although parturients in both groups were hemodynamically stable, hemodynamic stability was subnormal in the COVID-19 group regarding blood pressure, oxygen saturation, heart rate, and body temperature. None of the women in either group required a vasopressor or oxygen supplementation during delivery. No other clinical differences were observed between the COVID-19 and control groups., Conclusion: This is the first case-controlled study testing the anesthetic implications of neuraxial labor analgesia in pregnant, COVID-19-positive women. Although management of neuraxial labor analgesia did not differ in pregnant women positive and negative for COVID-19, their hemodynamic characteristics differed significantly. Therefore, care is required to prevent adverse outcomes in pregnant women positive for COVID-19., (© 2022 Abdalla, Nahid, Valappil, Gudavalli, Sellami, Korichi, Ahmad, Cespedes, Gopalakrishnan, licensee HBKU Press.)

Heavy metal pollution is a challenging concern that threatens the soil environment and human health worldwide. The purpose of this work is to assess the heavy metals (Cr, Cu, Zn, and Pb) pollution in the urban and peri-urban soils in and around Setif city, eastern Algeria. The work combines chemical analysis of thirty-six soil samples, statistical valuation and interpretation of chemical data and pollution indices (geoaccumulation index, pollution index, and integrated pollution index) with thematic mapping. The average concentrations (in mg/kg) of Cd, Cr, Cu, Pb, and Zn were found < 0.02, 43.35, 43.75, 331.20, and 78.26 mg/kg, respectively. Compared with the French regulatory limits (AFNOR U44-041), Cd, Cr, and Cu still non-hazardous at Setif city scale; however, Zn and Pb concentrations are two to three times higher than the background values referred to the Chinese [Formula: see text] standard (GB15618-1995). The pollution indices indicate that Pb and Zn represent the highest threats among the studied pollutants and polluted wide areas of anthropogenic activities located respectively in the oldest district of the city, near the industrial zone and near uncontrolled landfill of domestic and industrial waste. Cu, Pb, and Zn originate seemly from vehicle emission, particles of brakes and tires, and industrial emissions. However, Cr distribution is uncorrelatable with anthropogenic sources. The Cr with an average concentration less than the background value derives seemly from animal feces and organic fertilizers. The integrated pollution index shows that the accumulation of heavy metals in the soils of Setif city from anthropogenic sources reached alarming levels that can disperse into the environment and threaten the human health. The urbanization and industrial development of Setif city are expected to grow and a subsequent heavy metal pollution will be rising prior issue. Corrective measures should be endeavored by the local authorities to mitigate the current environmental situation and a sustainable development plan for the city should be anticipated to guarantee optimal future environmental conditions., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Radiotherapy (RT) for head and neck cancer is now guided by cone-beam computed tomography (CBCT). We aim to identify a CBCT radiomic signature predictive of progression to RT., Material and Methods: A cohort of 93 patients was split into training ( n  = 60) and testing ( n  = 33) sets. A total of 88 features were extracted from the gross tumor volume (GTV) on each CBCT. Receiver operating characteristic (ROC) curves were used to determine the power of each feature at each week of treatment to predict progression to radio(chemo)therapy. Only features with AUC > 0.65 at each week were pre-selected. Absolute differences were calculated between features from each weekly CBCT and baseline CBCT1 images. The smallest detectable change ( C  = 1.96 × SD, SD being the standard deviation of differences between feature values calculated on CBCT1 and CBCTn) with its confidence interval (95% confidence interval [CI]) was determined for each feature. The features for which the change was larger than C for at least 5% of patients were then selected. A radiomics-based model was built at the time-point that showed the highest AUC and compared with models relying on clinical variables., Results: Seven features had an AUC > 0.65 at each week, and six exhibited a change larger than the predefined CI 95%. After exclusion of inter-correlated features, only one parameter remains, Coarseness. Among clinical variable, only hemoglobin value was significant. AUC for predicting the treatment response were 0.78 ( p  = .006), 0.85 ( p  < .001), and 0.99 ( p  < .001) for clinical, CBCT4-radiomics (Coarseness) and clinical + radiomics based models respectively. The mean AUC of this last model on a 5-fold cross-validation was 0.80 (±0.09). On the testing cohort, the best prediction was given by the combined model (balanced accuracy [BAcc] 0.67 , p  < .001)., Conclusions: We described a feature selection methodology for delta-radiomics that is able to select reproducible features which are informative due to their change during treatment. A selected delta radiomics feature may improve clinical-based prediction models.

Hepatic encephalopathy (HE) is a neurophysiological syndrome secondary to acute or chronic liver failure. Studies showed that HE patients exhibit a deficit in motor coordination, which may result from cerebellar functional impairment. The aim of this study is to assess the time-dependent alteration of locomotor behavior and the glial and neuronal alteration in rat with acute HE induced chemically. The study was carried out in male Sprague-Dawley rats with thioacetamide (TAA) induced acute liver failure at different stages 12 h, 24 h and 36 h. Hepatic and renal functions were assessed via various biochemical and histopathological examinations, while the cerebellum and the midbrain were examined using histology and immunohistochemistry for tyrosine hydroxylase (TH), cyclooxygenase-2 (COX-2) and glial fibrillary acidic protein (GFAP). We used as well, the open field test and the Rotarod test for assessing the locomotor activity and coordination. Our data showed a progressive loss of liver function and a progressive alteration in locomotor behavior and motor coordination in acute HE rats. In the cerebellum, we noted an increase in the degeneration of cerebellar Purkinje neurons parallel to increased COX-2 immunoreactivity together with astrocytic morphology and density changes. Likewise, in substantia nigra pars compacta, TH levels were reduced. We showed through the current study, a progressive deterioration in locomotor behavior in acute HE rats, as a result of Purkinje neurons death and a deficient dopaminergic neurotransmission, together with the morpho-functional astroglial modifications involving the oxidative stress and neuroinflammation., (Copyright © 2021. Published by Elsevier B.V.)

Purpose: To develop a radiomic model predicting nonresponse to induction chemotherapy in laryngeal cancers, from multicenter pretherapeutic contrast-enhanced computed tomography (CE-CT) and evaluate the benefit of feature harmonization in such a context., Methods: Patients (n = 104) eligible for laryngeal preservation chemotherapy were included in five centers. Primary tumor was manually delineated on the CE-CT images. The following radiomic features were extracted with an in-house software (MIRAS v1.1, LaTIM UMR 1101): intensity, shape, and textural features derived from Gray-Level Co-occurrence Matrix (GLCM), Neighborhood Gray Tone Difference Matrix (NGTDM), Gray-Level Run Length Matrix (GLRLM), and Gray-Level Size Zone Matrix (GLSZM). Harmonization was performed using ComBat after unsupervised hierarchical clustering, used to determine labels automatically, given the high heterogeneity of imaging characteristics across and within centers. Patients with similar feature distributions were grouped with unsupervised clustering into an optimal number of clusters (2) determined with "silhouette scoring." Statistical harmonization was then carried out with ComBat on these 2 identified clusters. The cohort was split into training/validation (n = 66) and testing (n = 32) sets. Area under the receiver operating characteristics curves (AUC) were used to evaluate the ability of radiomic features (before and after harmonization) to predict nonresponse to chemotherapy, and specificity (Sp) and sensitivity (Se) were used to quantify their performance in the testing set., Results: Without harmonization, none of the features identified as predictive in the training set remained significant in the testing set. After ComBat, one textural feature identified in the training set keeps a predictive trend in the testing set-Zone Percentage, derived from the GLSZM, was predictive of nonresponse in the training set (AUC = 0.62, Se = 70%, Sp = 64%, P = 0.04) and obtained a satisfactory performance in the testing set (Se = 80%, Sp = 67%, P = 0.03), although significance was limited by the size of the testing set. These results are consistent with previously published findings in head and neck cancers., Conclusions: Radiomic features from CE-CT could help in the selection of patients for induction chemotherapy in laryngeal cancers, with relatively good sensitivity and specificity in predicting lack of response. Statistical harmonization with ComBat and unsupervised clustering seems to improve the predictive value of features extracted in such a heterogeneous multicenter setting., (© 2021 American Association of Physicists in Medicine.)

Objective: To report outcome and predictive factors in patients with N3 (> 6 cm) non-metastatic locally advanced head and neck squamous cell carcinoma (LAHNSCC) treated with a conservative approach or with initial surgery., Methods: 104 patients were included: 69 treated with radiotherapy (RT) ± chemotherapy (CT) and 35 with nodal surgery with or without primary tumour resection, which was completed in 30 patients by adjuvant RT ± CT. Positron-emission tomography-computed tomography (PET-CT) guided surveillance after RT ± CT was standard., Results: Two-year overall survival (OS) and locoregional control (LRC) were 39.4% and 37.5%, respectively. In univariate analysis, body mass index (BMI), performance status (PS), p16 status and haemoglobin value influenced OS and disease-free survival (DFS). In multivariate analysis, p16 positive status and BMI ≥ 25 remained independent prognostic factors for better OS (p = 0.023) and DFS (p = 0.002). Only under/normal weight remained an independent and adverse significant prognostic factor in multivariate analysis for regional control (RC). Patients treated with primary RT ± CT had slightly better 2-year OS (43.5% versus 33.3%, p = 0.31)., Conclusions: Patients with N3 LAHNSCC have poor prognosis, but long term LRC is achievable, especially in overweight patients and those with a good PS., (Copyright © 2021 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Background: Adolescents with type1 diabetes appear to be at greater risk for developing eating disorders (ED) which are often associated with impaired metabolic control of diabetes., Aim: To estimate the prevalence of ED in a population of adolescents with type 1 diabetes (T1D) and to identify risk factors associated with this disorder in order to propose preventive measures., Methods: A cross-sectional, population-based study involved 102 adolescents with type 1 diabetes, aged 11-18 years, recruited from the National Institute of Nutrition in Tunis, Tunisia over a period of one-year January 2017-January 2018., Results: The prevalence of ED was 33.3%. It was significantly higher among girls (46.2% vs 20%, p = 0.005). Unspecified ED were predominant with a prevalence of 29.4%. Independent factors associated with ED were female sex, abdominal obesity and quality of life. The risk of developing ED was multiplied by 3.5 for women (adjusted OR = 3.5 and CI95% [1.4-8.6]) and by 5.6 for patients with abdominal obesity (Adjusted OR = 5.6 and CI95% [1.5-20.4]). Impaired quality of life and specifically anxiety about diabetes increased significantly the risk of developing ED in our patients. However, we didn't find significant association between ED and age, family characteristics, duration of diabetes, metabolic balance, treatment and complications of diabetes., Conclusion: We concluded that ED should be always suspected in adolescents with T1D especially in girls. Unspecified ED are more common in this group of patients. Treatment of diabetes requires a multidisciplinary care approach including diabetologist, dietician and psychiatrist in order to promote healthy eating and to improve quality of life of adolescents with T1D.

Competing Interests: Conflict of interest The authors declare that there is no conflict of interests.

Background: Research concerning factors of death after neonatal surgery is scarce. Insight into mortality might improve perioperative care. This study aimed to identify predictive factors of mortality after neonatal surgery in a low income country (LIC)., Methods: Charts of all newborn patients who underwent surgical procedures under general anesthesia during the neonatal period in our department of pediatric surgery between January 2010 and December 2017 were reviewed. We used univariate and multivariate analysis to evaluate perioperative variables potentially predictive of early postoperative mortality., Results: One hundred eighty-two cases were included in the study: 41 newborns (28.6%) were premature (<37 weeks of gestation) and 52 (22.5%) weighed less than 2.5 kg. The most commonly diagnosed conditions were esophageal atresia (24%) and bowel obstruction (19%). Forty-four patients (24%) died during hospitalization. The highest rate of mortality was observed for congenital diaphragmatic hernia. Univariate analysis showed that perinatal predictive variables of mortality were prematurity, low birth weight, the necessity of preoperative intubation, and duration of surgery more than 2 h. Logistic regression showed three independent risk factors, which are the duration of surgery, low birth weight and the necessity of preoperative intubation., Conclusion: The overall mortality in infants undergoing neonatal surgery is still high in LICs. Knowledge of independent risk factors of early mortality may help clinicians to more adequately manage the high-risk population., Type of the Study: Clinical research paper., Level of Evidence: III., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Fungi and bacteria associated to phytoparasitic nematodes Globodera rostochiensis and Meloidogyne spp. in Algeria were identified and characterized. Trichoderma spp. showed the highest prevalence in the cysts of G. rostochiensis . A number of isolates were identified through PCR amplification and the sequencing of the internal transcribed spacer (ITS)1-2 and Rpb2 gene regions. The most represented species were T. harzianum and T. afroharzianum . The latter and T. hirsutum were reported for the first time in Algeria. Fusarium spp., including F. oxysporum and F. solani , comprised a second group of fungi found in cysts. Taxa associated to females of Meloidogyne spp. included T. harzianum , Fusarium spp. and other hyphomycetes. To assess the efficacy of Trichoderma spp., two assays were carried out in vitro with the culture filtrates of two T. afroharzianum and T . harzianum isolates, to check their toxicity versus the second stage juveniles of M. incognita . After 24-48 h exposure, a mortality significantly higher than the control was observed for both filtrates at 1% dilutions. The TRI genes involved in the production of trichothecenes were also amplified with the PCR from some Trichoderma spp. isolates and sequenced, supporting a putative role in nematode toxicity. Bacteria isolated from the cysts of G. rostochiensis included Brucella, Rhizobium, Stenotrophomonas and Bacillus spp., identified through 16S rRNA gene sequencing. The potential of the microbial isolates identified and their mechanisms of action are discussed, as part of a sustainable nematode management strategy.

It is of interest to assess the clinical and pathological aspects of Gallbladder and biliary tract carcinomas confirmed by histological data. It is also of further interest to evaluate the link between Helicobacter pylori and biliary tract cancers. Eighty-nine (89) cases (mean age 60±12 years) of Gallbladder and biliary tract cancer confirmed by histological data were enrolled for the study at the Department of Pathology in Mohammed VI University Hospital, in Morocco. The data such as age, sex, clinical and histo pathological features were collected. Bile duct specimens were investigated for H. pylori using Giemsa and immuno histo chemistry staining. Results show that bile duct stones were found in 53.9% of cases. It is known using histological data that adeno carcinoma is common accounting for 70 % of all bile duct tumors. Moreover, Helicobacter pylori was detected in 54% of cases linking with the presence of bile duct stones characterized by the histological subtype, the macroscopic classification and lymph node's presence (p<0.001). Thus, data collected suggest the potential association of Helicobacter pylori with gallbladder cancer possibly through the formation of bile duct stones., Competing Interests: The authors have no conflict of interest to disclose., (© 2019 Biomedical Informatics.)

Medicinal plants play an important role in the management of diabetes mellitus especially in developing countries where resources are lacking. Herbal of natural origin, unlike the synthetic compounds, are more effective, safer and have less side effects. For continuing research on biological properties of Moroccan medicinal plants, the present work was undertaken to evaluate the potential and mechanism of the antidiabetic activity of the Caralluma europaea methanolic extract in alloxan-induced diabetic mice. A high-performance liquid chromatography technique (HPLC) was used to identify and quantify the major phenolic compounds in the methanolic extract. The in vitro antioxidant property was evaluated using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging method, reducing power and ß -carotene-linoleic acid assays. The acute toxicity of the extract was evaluated by giving it orally to mice at single doses of 200, 500, 1000, 2000 mg/kg body weight. The antidiabetic effect was conducted on Swiss albino mice. Diabetes was induced with single intraperitonial injection of alloxan monohydrate (200 mg/kg body weight) and animals were treated with methanol extract at a dose of 250 mg/kg and 500 mg/kg body weight. The blood glucose levels were measured and histopathological analysis of pancreas was performed to evaluate alloxan-induced tissue injuries. The main phenols identified and quantified in the extract were ferulic acid, quercetine, 3,4 dihydroxybenzoic acid, rutin, epigallocatechin, and catechin. Ferulic acid was found to be the main phenolic compound ant its proportion was up to 52% of total phenolic compounds, followed by quercetin (36%). The result showed that methanol extract exhibited an antioxidant effect. Acute toxicity studies revealed that C. europaea extract was safe up 2000 mg/kg body weight and approximate LD 50 is more than 2000 mg/kg. Moreover, the methanol extract prevented the diabetogenic effect of alloxan and decreased significantly the blood glucose level ( P  < 0.001) in treated mice. Morphometric study of pancreas revealed that C. europaea extract protected significantly the islets of Langerhans against alloxan-induced tissue alterations.

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome resulting from acute or chronic hepatic impairments. The clinical features of HE include attention as well as a mild cognitive deficits associated with impaired attentional and executive networks in patients as well as in animal models of HE. The underlining pathomechanism of memory impairment in HE patients is still not fully understood; however, it may involve a possible gliopathy as well as neuropathy. The aim of the present investigation is to assess progression of short working memory deterioration in acute HE and to delineate the glial and the neuronal alteration which may underlie such cognitive impairment. The study was carried out in male Sprague-Dawley rats with acute liver failure induced by thioacetamide (TAA). The study was performed on different stages of acute HE; 12 h, 24 h and 36 h following administration of TAA. The liver functions were assessed via different biochemical markers (ALT, AST, bilirubin, urea and creatinine) and an histopathological examination of the liver tissue. While for the behavioral study, we used T-Maze test to assess short working memory using the percentage of alternation behavior, together with an immunohistochemical analysis of the Glial Fibrillary Acidic Protein (GFAP) as the key marker of astrocytes in the hippocampus, as well as serotonin (5-HT) for 5-HTergic neurons within the dorsal Raphe nucleus (DRN). Our data revealed a progressive loss of liver tissue integrity with inflammation and hepatocytes degeneration which was associated to obvious loss of the liver function. In parallel, we observed a gradual alteration of the alternation behavior, as a sign of altered short working memory in the acute HE rats. At the central level, the immunohistochemical study showed a time dependent region-specific changes of GFAP-immunoreactive astrocytes within the hippocampus. While within the DRN, serotonin levels declined progressively in a time-dependant manner. Our data revealed for the first time, a gradual loss of short memory function in acute HE, resulting from liver dysfunction. Such cognitive deterioration may involve a possible gliopathy as well as a 5-HTergic dysfunction which could be considered as a new key element for understanding the basis of memory and attention loss in HE patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The regulation of sugar metabolism and partitioning plays an essential role for a plant's acclimation to its environment, with specific responses in autotrophic and heterotrophic organs. In this work, we analyzed the effects of high salinity on sugar partitioning and vascular anatomy within the floral stem. Stem sucrose and fructose content increased, while starch reduced, in contrast to the response observed in rosette leaves of the same plants. In the stem, the effects were associated with changes in the expression of SWEET and TMT2 genes encoding sugar transporters, SUSY1 encoding a sucrose synthase and several FRK encoding fructokinases. By contrast, the expression of SUC2 , SWEET11 and SWEET12 , encoding sugar transporters for phloem loading, remained unchanged in the stem. Both the anatomy of vascular tissues and the composition of xylem secondary cell walls were altered, suggesting that high salinity triggered major readjustments of sugar partitioning in this heterotrophic organ. There were changes in the composition of xylem cell walls, associated with the collapse and deformation of xylem vessels. The data are discussed regarding sugar partitioning and homeostasis of sugars in the vascular tissues of the stem.

The aim of this study is to investigate management and outcome in esophageal atresia (EA) and to identify early predictive factors of morbidity and mortality in a developing country. Charts of neonates with repaired EA from 2007 to 2016 were reviewed. Patients' characteristics, operative details, and postoperative outcomes were collected. Statistical analyses were performed to identify predictors of complicated evolution. Forty-two cases were collected. There were 14 girls and 28 boys. Only one patient had antenatal diagnosis (2.3%). The mean gestational age was 38 weeks. Nine patients (21.4%) weighed less than 2.5 kg. Seventeen (40.4%) patients had associated malformations most commonly cardiac (9/17). Thirteen patients had delayed diagnosis (30.9%). Thirty-nine (92.8%) patients underwent primary esophageal anastomosis. Overall survival was 76.2%. Nineteen patients (57% of survivals) had complicated evolution before the age of one year and 15 patients (46.8% of survivals) developed complications after the age of one year. Perinatal variables associated with mortality were prematurity (p = 0.004, OR = 5.4, IC95% = [1.13-25.80]), low birth weight (p = 0.023, OR = 7, IC95% = [1.38-35.47]), cardiac malformations (p = 0.006, OR = 10.5, IC95% = [2.03-54.27]) and delayed diagnosis (p = 0.005, OR = 10.11, IC95% = [2.005-50.980]). Variables associated with short-term and middle-term complications were duration of intubation (p = 0.019, OR = 0.118, IC95% = [0.019-0.713]) and the presence of short-term complications (p = 0.016, OR = 7.33, IC95% = [1.467-36.664]) respectively. These factors may be used to identify patients who will benefit from more intensive follow-up program., (© The Author(s) 2019. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Plant responses to abiotic stresses entail adaptive processes that integrate both physiological and developmental cues. However, the adaptive traits that are involved in the responses to a high soil salinity during reproductive growth are still poorly studied. To identify new clues, we studied the halophyte, Thellungiella salsuginea , and three Arabidopsis accessions, known as tolerant or salt-sensitive. We focused on the quantitative traits associated with the stem growth, sugar content, and anatomy of the plants subjected to the salt treatment, with and without a three-day acclimation, applied during the reproductive stage. The stem growth of Thellungiella salsuginea was not affected by the salt stress. By contrast, salt affected all of the Arabidopsis accessions, with a natural variation in the effect of the salt on growth, sugar content, and stem anatomy. In response to the high salinity, irregular xylem vessels were observed, independently of the accession's tolerance to salt treatment, while the diameter of the largest xylem vessels was reduced in the tolerant accessions. The stem height, growth rate, hexoses-to-sucrose ratio, and phloem-to-xylem ratio also varied, in association with both the genotype and its tolerance to salt stress. Our findings indicate that several quantitative traits for salt tolerance are associated with the control of inflorescence growth and the adjustment of the phloem-to-xylem ratio.

Competing Interests: There are no conflicts of interest.

Bacillus thuringiensis Vip3A protein has been widely used for crop protection and for delay resistance to existing insecticidal Cry toxins. During current study, a fusion between vip3Aa16 and the toxic core sequence of cry1Ac was constructed in pHT Blue plasmid. Vip3Aa16-Cry1Ac protein was expressed in the supernatant of B. thuringiensis with a size of about 150 kDa. Bioassays tested on Ephestia kuehniella showed that the use of the chimera toxin as biopesticide improved the toxicity to reach 90% ± 2 with an enhancement of 20% compared to the single Vip3Aa16 protein. The findings indicated that the fusion protein design opens new ways to enhance Vip3A toxicity against lepidopteran species and could avoiding insect tolerance of B. thuringiensis delta-endotoxins. Through computational study, we have predicted for the first time the whole 3D structure of a Vip3A toxin. We showed that Vip3Aa16 structure is composed by three domains like Cry toxins: an N-terminal domain containing hemolysin like fold as well as two others Carbohydrate Binding Module (CBM)-like domains. Molecular docking analysis of the chimera toxin and the single Vip3Aa16 protein against specific insect receptors revealed that residues of CBM like domains are clearly involved in the binding of the toxin to receptors., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The synthesis and characterization of di-aqua-bis-[2-(2-hy-droxy-eth-yl)pyridine-κ 2 N , O )nickel(II) dinitrate, [Ni(C 7 H 9 NO) 2 (H 2 O) 2 ](NO 3 ) 2 , under ambient conditions is reported and compared with catena -poly[[bis-[2-(2-hy-droxy-eth-yl)pyridine-κ 2 N , O ]copper(II)]-μ-sulfato-κ 2 O : O '], [Cu(C 7 H 9 NO) 2 (SO 4 )] n [Zegh-ouan et al. (2016 ▸). Private communication (refcode 1481676). CCDC, Cambridge, England]. In the two complexes, the 2-(2-hy-droxy-eth-yl)pyridine ligands coordinate the metal ions through the N atom of the pyridine ring and the O atom of the hy-droxy group, creating a chelate ring. The Ni II or Cu II ion lies on an inversion centre and exhibits a slightly distorted M O 4 N 2 octa-hedral coordination geometry, build up by O and N atoms from two 2-(2-hy-droxy-eth-yl)pyridine ligands and two water mol-ecules or two O atoms belonging to sulfate anions. The sulfate anion bridges the Cu II ions, forming a polymeric chain. The photoluminescence properties of these complexes have been studied on as-synthesized samples and reveal that both compounds display a strong blue-light emission with maxima around 497 nm. From DFT/TDDFT studies, the blue emission appears to be derived from the ligand-to-metal charge-transfer (LMCT) excited state. In addition, the IR spectroscopic properties and thermogravimetric behaviours of both complexes have been investigated.

Enterobacterial components in the joints of patients are believed to contribute to a perpetuating inflammation leading to a reactive arthritis (ReA), a condition in which microbial agents cannot be recovered from the joint. At present, it is unclear whether nucleic acids from Shigella spp. are playing a pathogenic role in causing not only ReA but also other forms of arthritis. Quantitative real-time polymerase chain reaction assay (qPCR) is the method of choice for the identification of bacteria within the synovium. The aim of our study was to detect the presence of Shigella spp. nucleic acids in the synovial tissue (ST) of Tunisian arthritis patients. We investigated 57 ST samples from rheumatoid arthritis (RA) n = 38, undifferentiated oligoarthritis (UOA) n = 12, and spondyloarthritis (SpA) n = 7 patients; 5 ST samples from healthy individuals were used as controls. Shigella spp. DNA and mRNA transcripts encoding the virulence gene A (VirA) were examined using an optimized qPCR with newly designed primers and probes. Using qPCR, Shigella spp. DNA was found in 37/57 (65%) ST samples (24/38, i.e., 63.2% of RA, 8/12, i.e., 67% of UOA, and 5/7, i.e., 71.4% of SpA patients). Paired DNA and mRNA were extracted from 39 ST samples, whose VirA cDNA was found in 29/39 (74.4%) patients. qPCR did not yield any nucleic acids in the five healthy control ST samples. The qPCR assay was sensitive and showed a good intra- and inter-run reproducibility. These preliminary findings generated by an optimized, highly sensitive PCR assay underline a potential role of past gastrointestinal infections. In Tunisian patients, a bacterial etiology involving Shigella spp. in the manifestation of arthritic disorders including RA might be more common than expected.

The entomopathogenic Photorhabdus luminescens TT01 is a promoting bacterium that controls effectively many insect pests. Indeed, it exhibited a mortality rate of 32.36% against the first instar larvae of the turnip moth Agrotis segetum, when it was used at a concentration of 5 × 10 7  cells/ml but no toxicity against the second instar larvae in the same condition. P. luminescens TT01 oral toxicity is associated to septicaemia since cells fraction exhibited the highest mortality rate of 34%. In order to enhance P. luminescens TT01 insecticidal potential, combination with Bacillus thuringiensis Vip3Aa16 toxin was tested. An improvement of insecticidal activity was shown. Indeed, 100% mortality of A. segetum first instar larvae was obtained after 2 days of treatment, when using TT01 cells and Vip3Aa16 toxin at a concentration of 5 × 10 7  cells/ml and 9.025 ng/cm 2 , respectively. Moreover, growth inhibition rate of 45% of the second instar larvae was observed, when using the same combination. A. segetum mortality could be the result of several alterations in the midgut epithelium caused by Vip3Aa16 toxin, allowing a rapid invasion of the hemocoel by TT01 cells as demonstrated by histopathological study. Clear symptoms of intoxication were observed for all combinations tested, including swelling, vesicle formation, cytoplasm vacuolization and brush border membrane lysis. Taken together, these results promote the use of P. luminescens TT01 as a potent bioinsecticide to control effectively A. segetum by oral treatment in a mixture with Vip3Aa16 toxin., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The aim of this study was to examine the relationship between bone mass and bone turnover markers with lean mass (LM) in pubescent soccer players. Two groups participated in this study, which included 65 elite young soccer players who trained for 6-8 hours per week and 60 controls. Bone mineral density; bone mineral content in the whole body, lower limbs, lumbar spine, and femoral neck; biochemical markers of osteocalcin; bone-specific alkaline phosphatase; C-telopeptide type I collagen; and total LM were assessed. Young soccer players showed higher bone mineral density and bone mineral content in the whole body and weight-bearing sites (P < .001). Indeed, the total LM correlated with whole-body bone mineral density and bone mineral content (P < .001). There were significant differences within the bone formation markers and osteocalcin (formation)/C-telopeptide type I collagen (resorption) ratio between young soccer players compared with the control group, but no significant difference in C-telopeptide type I collagen was observed between the 2 groups. This study showed a significant positive correlation among bone-specific alkaline phosphatase, osteocalcin, and total LM (r = .29; r = .31; P < .05) only for the young soccer players. Findings of this study highlight the importance of soccer practice for bone mineral parameters and bone turnover markers during the puberty stage.

Objectives: The dynamic nature of the skeleton is achieved by a remodeling process. Receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) stimulates bone resorption by activating RANK signaling. Therefore it is considered as a candidate gene regulating susceptibility to osteoporosis. In the current study, we have investigated the association between the RANKL gene -693G > C and -643 C > T polymorphisms and bone mineral density (BMD) in a population of postmenopausal Tunisian women., Methods: Polymorphic sites in RANKL gene (rs9533155 -693G > C and rs9533156 -643 C > T polymorphisms) were determined using PCR-RFLP analysis in 566 postmenopausal Tunisian women. All statistical analysis were examined by SPSS software., Results: We have detected a significant difference in lumbar spine and hip BMD for -643C > T genotypes. For -693G > C genotypes, a significant difference was detected only in hip BMD. The distribution of -643C > T genotypes and alleles between three groups (osteoporotic, osteopenic and normal women) revealed a significant association of the TT genotype with development of osteoporosis (p = 0.01; odds ratio 2.15), although for the -693G > C polymorphism, no significant results were found., Conclusion: We have demonstrated the association of the -643C > T polymorphism with BMD variation and osteoporosis risk in postmenopausal Tunisian women.

Central neurocytomas are defined as neoplasms composed of round, uniform cells, with neural immunophenotypic profile and low proliferation index. They account for 0.5% of intracranial tumors. They usually occur near the foramen of Monro and can cause obstructive hydrocephaly. We conducted a retrospective data collection from records of 12 patients with central neurocytomas in the Anatomopathological Laboratory at the Mohammed VI University Hospital, Marrakech, between January 2006 and June 2015. This study aimed to report and describe the radiopathological features of this rare histologic type. The male/female sex-ratio was 1.4. The average age at diagnosis was 22.3 years. The revealing symptomatology was dominated by intracranial hypertension associated with decreased visual acuity and diplopia in all patients. Our study concerned about simple biopsy in one case, subtotal resection in seven cases and total resection in four cases. Histopathological examination showed tumor proliferation with endocrine architecture. Tumor cells are more often small and uniform. Mitotic index was low. Tumor proliferation was associated with fibrillary fundus and vascular network with three types of trees. Immunohistochemical examination was identical in all patients. It showed tumor cells positive for anti-synaptophysin antibodies, chromogranine and NSE. In all patients the radio-pathologic correlation suggested central neurocytoma (grade II - WHO 2016). This study highlights the anatomo-clinical, radiological and evolutionary features of these rare tumors.

The economically important crop pest Ephestia kuehniella was tested at two stages of larval development for susceptibility to Bacillus thuringiensis Cry1Aa toxin. Bioassays showed that toxicity decreased during the development of larvae stage. In fact, Cry1Aa toxins from BNS3-Cry - (pHT-cry1Aa) showed low toxicity against the first-instar larvae (L1) with a LC 50 value of about 421.02μg/g of diet and was not toxic against the fifth-instar (L5), comparing to the BLB1 toxins used as positive control which represent a LC 50 value of about 56.96 and 84.21μg/g of diet against L1 and L5 instars larvae, respectively. Effects of Cry1Aa toxins were reflected in histopathological observations by the weak destruction of midgut epithelium, slight hypertrophy of epithelial cells, and minor alteration of brush border membrane (BBM) detected mainly in L1 larvae stage comparing to the more extensive damage caused by BLB1 toxins. Interestingly, in vitro proteolysis of Cry1Aa toxins was found to correlate with the difference of toxicity during larval stage development. In fact, the weak proteinase activity detected inside the L1 midgut has led to the persistence of the Cry1Aa active forms (65 and 58kDa) during prolonged incubations, causing the alterations described previously. Three subfamilies of aminopeptidase (APN) receptors were detected in both larvae instars with different intensities and molecular weights (150kDa and 55kDa for APN1, and 90kDa for APN2 and APN4). Remarkably, binding assay using Cry1Aa toxin seems to have no direct correlation with larval stages toxicity differences, since same putative receptors were detected. Understanding the reasons for the clear differences in the effectiveness of Cry1Aa toxins during larval development stages of E. kuehniella is very important for the design of future improvement insecticidal approaches and for the accomplishment of resistance prevention strategies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The basis of the different susceptibility of Ephestia kuehniella to the Cry1Aa and Cry1Ac δ-endotoxins from Bacillus thuringiensis kurstaki BNS3 was studied. Both toxins bound specifically to the BBMV of E. kuehniella. The result of the ligand blot showed that Cry1Ac bound to three putative receptors of about 100, 65 and 80 kDa and Cry1Aa interacted only with a 100 kDa protein. Pronase digestion of the BBMV-bound toxins was used to analyze the toxin insertion. Both toxins inserted into the BBMV as monomers however, a 14 kDa peptide of α4-α5 which correspond to the oligomeric form of this peptide was detected in case of Cry1Ac only. Analysis of the in vitro oligomerisation of these toxins in the presence of the BBMV of E. kuehniella showed reduced oligomer formation in case of Cry1Aa in comparison with Cry1Ac. Taken together, these results strongly suggest that the difference of toxicity between Cry1Aa and Cry1Ac to E. kuehniella is due to a deficient oligomerisation of Cry1Aa., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Bacillus species are attractive due to their potential use in the biological control of fungal diseases. Bacillus amyloliquefaciens strain BLB369, Bacillus subtilis strain BLB277, and Paenibacillus polymyxa strain BLB267 were isolated and identified using biochemical and molecular (16S rDNA, gyrA, and rpoB) approaches. They could produce, respectively, (iturin and surfactin), (surfactin and fengycin), and (fusaricidin and polymyxin) exhibiting broad spectrum against several phytopathogenic fungi. In vivo examination of wheat seed germination, plant height, phenolic compounds, chlorophyll, and carotenoid contents proved the efficiency of the bacterial cells and the secreted antagonist activities to protect Tunisian durum wheat (Triticum turgidum L. subsp. durum) cultivar Om Rabiia against F. graminearum fungus. Application of single bacterial culture medium, particularly that of B. amyloliquefaciens, showed better protection than combinations of various culture media. The tertiary combination of B. amyloliquefaciens, B. subtilis, and P. polymyxa bacterial cells led to the highest protection rate which could be due to strains synergistic or complementary effects. Hence, combination of compatible biocontrol agents could be a strategic approach to control plant diseases., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

The Bacillus thuringiensis S1/4 strain was previously found to harbour vip1S, vip2S, and vip3 genes. Its plasmid curing led to the obtaining of four partially cured strains S1/4-2, S1/4-3, S1/4-7, and S1/4-9 (vip2S-vip1S (-), vip3 (+)), one strain S1/4-4 (vip2S-vip1S (+), vip3 (-)), and S1/4-0 strain lacking the three genes. Using these derivative strains as templates, PCR amplification and southern blot assay revealed that vip2S-vip1S operon and vip3 gene were localized on two different large plasmids. Bioinformatics studies showed that vip2S (1.356 kb), and vip1S (2.637 kb) genes are encoding by an operon consisting of two ORFs separated by an intergenic spacer of 4bp. Using the InterPro tool, Vip2S was found to belong to the family of Binary exotoxin A and Vip1S to bacterial exotoxin B. In silico modeling indicated that the 3D structure of Vip2S is a mixed α/β protein and proposed 3D-model of Vip1S. Bioassays of the partially cured strains supernatants showed a weak toxicity of S1/4-4 to the lepidopteran Spodoptera littoralis comparing to a better effect of S1/4-2, S1/4-3, S1/4-7, and S1/4-9, suggesting its eventual contribution to the toxicity. Nevertheless, the concentrated supernatant of S1/4-4 strain was not toxic against the coleopteran Tribolium castaneum., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The aim of the present study was to evaluate the phytotoxicity of olive mill wastewater (OMW) after being treated by the white-rot fungus Coriolopsis gallica. For this, the effect of irrigation with treated OMW (TOMW) and untreated OMW (UOMW) on tomato plants (Lycopersicon esculentum) for 3 weeks was studied. The control plants were irrigated with distilled water. Agronomic tests were performed in pot experiments in a greenhouse using the randomized complete block (RCB) experimental design. The relative leaf height (RLH), as a morphological parameter, and the content of total phenols in the roots and total chlorophyll [Cha + Chb] and reducing sugars in the leaves, as physiological parameters, were selected as responses of the experimental design. The results obtained showed that [Cha + Chb] in the leaves of tomato growth under TOMW was enhanced by 36.3 and 19.4 % compared to the plant growth under UOMW and to the controls, respectively. Also, reducing sugar concentrations were closed to those of the control plants, ranging from 0.424 to 0.678 g/L for the different dilutions tested. However, the plants irrigated with UOMW showed lower reducing sugar concentrations ranging from 0.042 to 0.297g/L. The optimum RLH (0.537) was observed in the plants irrigated with TOMW diluted at (1:4), this value being higher than that observed in the controls (0.438). Our study proved that the irrigation with TOMW significantly improved tomato growth and photosynthesis activity over those irrigated with UOMW. Optimization of TOMW as a fertilizer was obtained for a dilution of 1:4. From the obtained results, it can be concluded that OMW treated by C. gallica holds potential to be used as a fertilizer for tomato plants. Graphical Abstract ᅟ Please provide a caption for the graphical abstract.The graphical abstract is improved and sent as attachment Please replace it.

The tomato leaf miner Tuta absoluta is one of the most devastating pests for tomato crops. Digestive proteases and β-glucosidase enzymes were investigated using general and specific substrates and inhibitors. Maximal β-glucosidase and proteolytic activities occurred at temperature and pH optima of 30 and 40°C, 5 and 10-11 unit of pH, respectively. Zymogram analysis showed the presence of distinguished β-glucosidase exhibiting a specific activity of about 183 ± 15 µmol min-1 mg-1. In vitro inhibition experiments suggested that serine proteases were the primary gut proteases. Gel based protease inhibition assays demonstrated that the 28 and 73 kDa proteases might be trypsin-like and chymotrypsin-like enzymes, respectively. Overall gut trypsin-like and chymotrypsin-like activities were evaluated to be about 27.2 ± 0.84 and 1.68 ± 0.03 µmol min-1 mg-1, respectively. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis showed that T. absoluta gut serine proteases are responsible for Bacillus thuringiensis Cry insecticidal proteins proteolysis. Additionally, bioassays showed that T. absoluta larvae development was more affected by the β-glucosidases inhibitor (D-glucono-δ-lactone) than the serine proteases inhibitor (soybean trypsin inhibitor). These results are of basic interest since they present interesting data of β-glucosidases and gut serine proteases of T. absoluta larvae.

To study the importance of N- and C-terminus of Bacillus thuringiensis Vip3Aa16 (L121I) toxin (88 kDa), a number of mutants were generated. The addition of two (2R: RS) or eleven (11R: RSRPGHHHHHH) amino acid residues at the Vip3Aa16 (L121I) C-terminus allowed to an unappropriated folding illustrated by the abundant presence of the 62 kDa proteolytic form. The produced Vip3Aa16 (L121I) full length form was less detected when increasing the number of amino acids residues in the C-terminus. Bioassays demonstrated that the growth of the lepidopteran Ephestia kuehniella was slightly affected by Vip3Aa16 (L121I)-2R and not affected by Vip3Aa16 (L121I)-11R. Additionally, the fusion at the Vip3Aa16 (L121I) N-terminus of 39 amino acids harboring the E. coli OmpA leader peptide and the His-tag sequence allowed to the increase of protease sensitivity of Vip3Aa16 (L121I) full length form, as only the 62 kDa proteolysis form was detected. Remarkably, this fused protein produced in Escherichia coli (E. coli) was biologically inactive toward Ephestia kuehniella larvae. Thus, the N-terminus of the protein is required to the accomplishment of the insecticidal activity of Vip3 proteins. This report serves as guideline for the study of Vip3Aa16 (L121I) protein stability and activity., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Cry2 proteins play an essential role in current Bacillus thuringiensis (Bt) applications and in the prevention of insect resistance to Cry1A toxins. This paper reports on the screening and characterisation of novel Bt strains harbouring effective cry2A-type genes and higher insecticidal activity to Ephestia kuehniella., Results: A total of 29 native Bt strains were screened to search for the potent strain against E. kuehniella. The plasmid pattern of the selected strains showed interesting variability. PCR-RFLP analysis of two amplified regions showed high sequence identity within the selected cry2A-type genes. SDS-PAGE and western blot analysis revealed the presence of Cry2Aa toxin only in the MEB4 and BLB240 strains. The activation of Cry2Aa protoxins by larval midgut juice, trypsin or chymotrypsin enzymes revealed significant differences in terms of proteolysis profiles. Interestingly, a 49 kDa band was detected in the proteolysis pattern of BLB240, suggesting the presence of a chymotrypsin cleavage site that might have affected its insecticidal activity. Further, bioassays demonstrated that MEB4 (103.08 ± 36 µg g(-1)) was more active than BLB240 (153.77 ± 45.65 µg g(-1)) against E. kuehniella., Conclusion: Based on its potent insecticidal activity, the MEB4 strain could be considered to be an effective alternative agent for the control of E. kuehniella., (© 2015 Society of Chemical Industry.)

Insecticides derived from Bacillus thuringiensis are gaining worldwide importance as environmentally desirable alternatives to chemicals for the control of pests in public health and agriculture. Isolation and characterization of new strains with higher and broader spectrum of activity is an ever growing field. In the present work, a novel Tunisian B. thuringiensis isolate named BLB459 was characterized and electrophoresis assay showed that among a collection of 200 B. thuringiensis strains, the plasmid profile of BLB459 was distinctive. SmaI-PFGE typing confirmed the uniqueness of the DNA pattern of this strain, compared with BUPM95 and HD1 reference strains. PCR and sequencing assays revealed that BLB459 harbored three cry genes (cry30, cry40 and cry54) corresponding to the obtained molecular sizes in the protein pattern. Interestingly, PCR-RFLP assay demonstrated the originality of the BLB459 cry30-type gene compared to the other published cry30 genes. Insecticidal bioassays showed that BLB459 spore-crystal suspension was highly toxic to both Ephestia kuehniella and Spodoptera littoralis with LC50 values of about 64 (53-75) and 80 (69-91) μg of toxin cm(-2), respectively, comparing with that of the commercial strain HD1 used as reference. Important histopathological effects of BLB459 δ-endotoxins on the two tested larvae midguts were detected, traduced by the vacuolization of the apical cells, the damage of microvilli, and the disruption of epithelial cells. These results proved that BLB459 strain could be of a great interest for lepidopteran biocontrol., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Tuta absoluta is a destructive moth of Solanaceae plants and especially tomatoes. Here, we considered the entomopathogenic activity of the Bacillus thuringiensis Vip3Aa16 protein heterologously produced by Escherichia coli against T. absoluta. Purified Vip3Aa16 showed lower lethal concentration 50 % against third instar larvae (Toxin/tomato leaf) (335 ± 17 ng/cm(2)) compared to that of B. thuringiensis kurstaki HD1 δ-endotoxins (955 ± 4 ng/cm(2)) (P < 0.05). Action mode examination showed that Vip3Aa16 (88 kDa) was more sensitive to proteolysis activation by the chymotrypsin than the trypsin or the larvae gut soluble proteases, yielding derivative proteins essentially of about 62 and 33 kDa. The gut-soluble proteases could contain trypsin-like enzymes implicated in Vip3Aa16 activation since the proteolysis was inhibited using specific protease inhibitors. Additionally, we showed that the histopathological effect of Vip3Aa16 on T. absoluta larva midguts consisted on a microvillus damage and an epithelial cell rupture.

Objectives: Osteopenia is characterized by intermediate values of bone mineral density (BMD) as compared to normal and osteoporotic subjects. BMD, a surrogate phenotype for osteoporosis, is influenced in part by genetic factors. Among the genes associated with BMD, the vitamin D receptor (VDR) was the first gene studied as a potential candidate associated with BMD in adult and postmenopausal bone loss. However, results are controversial., Methods: To determine whether VDR polymorphisms ApaI and TaqI are associated with BMD, osteopenia, osteoporosis and low-impact fracture risk in North Africans, these genotypes were analyzed in 566 postmenopausal Tunisian women., Results: In postmenopausal Tunisian women, the GT ApaI genotype seems to be protective against osteoporosis development (p = 0.02; odds ratio = 0.54). Moreover, the presence of the combined GT/TT genotype of ApaI and TaqI polymorphisms is more frequent in normal BMD women than in osteoporotic women (p = 0.00; odds ratio = 0.41). Interestingly, the GG ApaI genotype is associated with osteopenia development (p = 0.02; odds ratio = 1.86) and also the TT TaqI polymorphism (p = 0.02; odds ratio = 1.53). The GG ApaI genotype is associated with a three times risk of vertebral fracture., Conclusions: The ApaI polymorphism showed an association with osteopenia and low-impact vertebral fracture incidence but not with osteoporosis. The TaqI polymorphism is associated specifically with the osteopenia phenotype. The presence of the two polymorphisms increases the risk to develop osteopenia in postmenopausal Tunisian women. Osteopenia seems to be genetically determined. However, osteoporosis is the result of interaction between genetic and environmental factors.

The effectiveness of 10 low-cost UV-absorbers in protecting Bacillus thuringiensis subsp. kurstaki BLB1 toxins against inactivation by UV-A and UV-B irradiation was evaluated in this study. Among them, two by-products, molasses and olive mill wastewater (OMW) were selected for further studies. They were tested at different concentrations of 0.05, 0.1, 0.15 and 0.2% using the para-aminobenzoic acid (PABA) as a common UV protectant. Interestingly, addition of PABA and OMW to BLB1 formulations was found to be most effective in protecting BLB1 spores at 90.8 and 76.4% respectively and in preserving delta-endotoxin concentration at a level of 81.7 and 72.2%, respectively when used at a concentration of 0.2%. The lowest preserved spores (46.3%) and delta-endotoxin level (12.4%) was found using molasses. In contrast, spore count and delta-endotoxin concentration were completely reduced after an exposure of unprotected Bt strain BLB1 to UV radiations up to 96h. SDS-PAGE analysis of protected and unprotected samples revealed that delta-endotoxin bands (130, 65-70kDa) were conserved until 96h of UV exposure in presence of PABA or OMW compared with their disappearance in presence of molasses after 72h of exposure and their dramatically decline from 8h of exposure in unprotected mixture. A complete loss of larvicidal toxicity against Ephestia kuehniella was found after 24h of exposure in absence of any UV-absorber. Addition of OMW or PABA offered the highest levels of insecticidal activity with 63.2 and 74.7% of residual toxicity, respectively. Whereas, molasses addition, as UV protectant retained only 26.3% of residual activity after 96h of exposure. Therefore, addition of OMW by-product to Bt formulation may be a suitable alternative to others synthetic chemical compounds. OMW may also provided added value, be environmentally friendly and less hazardous, when used at low concentration., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Aims: To investigate the association between type II collagen fragments and the presence of knee osteoarthritis (OA) in the Tunisian population and to determine whether this biomarker can predict X-ray progression of this disease., Methods: Type II collagen C-telopeptide (uCTX-II) and helical peptide (sHelix-II) were assessed in 125 female patients with knee osteoarthritis aged 54 ± 8 years over 2 years and 57 female age-matched controls. The markers were measured at baseline, 1 and 2 yrs' follow-up corresponding to x-ray time points., Results: Only urinary CTX-II values were significantly 48% higher in knee OA patients compared with controls (p=0.001). The longitudinal changes over 2 yrs in Helix-II were also significantly associated with Joint Space Narrowing: JSN (p=0.03). Over the 2-yr study period average CTX-II levels were not significantly higher in progressor compared with non-progressor (339.96 vs 256.00; NS)., Conclusion: The data presented here suggest that CTX-II may be useful to identify patients with knee OA. These results demonstrate significantly association between progression of this disease and alterations levels of Helix-II.

Background: Osteoporosis is a highly heritable trait. Among the genes associated with bone mineral density (BMD), the low-density lipoprotein receptor-related protein 5 gene (LRP5) has been consistently identified in Caucasians. However LRP5 contribution to osteoporosis in populations of other ethnicities remains poorly known., Methods: To determine whether LRP5 polymorphisms Ala1330Val and Val667Met are associated with BMD in North Africans, these genotypes were analyzed in 566 post-menopausal Tunisian women with mean age of 59.5 ± 7 .7 years, of which 59.1% have low bone mass (T-score<-1 at spine or hip)., Results: In post-menopausal Tunisian women, 1330Val was weakly associated with reduced BMD T-score at lumbar spine (p=0.047) but not femur neck. Moreover, the TT/TC genotypes tended to be more frequent in women with osteopenia and osteoporosis than in women with normal BMD (p=0.066). Adjusting for body size and other potential confounders, LRP5 genotypes were no longer significantly associated with aBMD at any site., Conclusions: The less common Val667Met polymorphism showed no association with osteoporosis. The Ala1330Val polymorphism is weakly associated with lower lumbar spine bone density and osteopenia/osteoporosis in postmenopausal Tunisian women. These observations expand our knowledge about the contribution of LRP5 genetic variation to osteoporosis risk in populations of diverse ethnic origin.

Context: Osteoarthritis (OA) is an articular disorder leading to the degradation of articular cartilage phenotypical chondrocytes modifications, including the acquisition of a fibroblast-like morphology, decreased expression of collagen type II, and increased expression of fetal collagen type I, metalloproteinase 13 and nitric oxide synthase. This promotes matrix degradation and unsuccessful cartilage repair. WNT signaling constitutes one of the most critical biological processes during cell fate assignment and homeostasis., Objectives: This review aims to give an insight on results from the studies that were interested in the involvement of WNT in OA., Methods: Studies were selected through a pubmed search., Results: Recent genetic data showed that aberration in WNT signaling may be involved in OA. WNT signals are transduced through at least three cascades: the canonical WNT/β-catenin pathway, the WNT/Ca(2+) pathway and the WNT/planar cell polarity pathway. Most of the studies used in-vitro models to elucidate the involvement of WNT in the physiopathology of OA. These studies analyzed the expression pattern of WNT pathway components during OA such as WNT5, WNT7, co-receptor LRP, β-catenin, WNT target genes (c-jun, cyclins) and/or the interaction of these components with the secretion of OA most important markers such as IL-1, collagens, MMPs. Results from these studies are in favor of a deep involvement of the WNT signaling in the physiopathology of OA either by having a protective or a destructive role., Conclusion: Deeper researches may eventually allow scientists to target WNT pathway in order to help develop efficient therapeutic approaches to treat OA.