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Background: Each subgroup of immune cells has a different prognostic role in breast cancer; however, the prognostic impact of tumor-infiltrating natural killer cells (TINKs) is still not well established. Our aim was to assess the prognostic impact of natural killer (NK) cells in breast carcinomas., Materials and Methods: NK cells infiltration were assessed by immunohistochemistry (IHC). Statistical analyses were performed to evaluate the correlation of NK cells with clinical-pathological features and outcome., Results: CD56 IHC was realized in 126 patients. NK cells infiltration showed significant and positive association with tumor high Scarff-Bloom-Richardson (SBR) grade. NK cells were significantly associated with HER2-positive breast cancer and triple-negative breast cancer subtypes. Analyses showed significant and inverse correlation with progesterone and estrogen receptors expression status. High NK cells were significantly related to high Ki-67 labeling index. Our data showed that high NK cells infiltrate was significantly associated with tumor-infiltrating lymphocytes in breast cancer tissues. At a median follow-up of 5.5 years, high CD56 expression (≥ 5 cells/10 high power field) was associated significantly with a good overall survival and with good disease-free survival., Conclusion: In this study, we assessed the important prognostic role of TINKs in breast carcinomas, which seems to be evident despite its association with aggressive pathological features. Thus evaluation of NK cells can be standardized and integrated in daily routine., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: CD155 is a ligand of the NK activating receptor DNAM-1, it has been described in a variety of human malignancies, but its expression in breast cancer remains unclear and poorly studied., Main Methods: CD155 expression and NK cells infiltration were investigated in 158 patients with breast cancer by immunohistochemistry (IHC). Statistical analyses were performed to evaluate correlations of CD155 expression with clinical-pathological features, prognosis and tumor immunity., Key Findings: Tumor cytoplasmic CD155 (cyt-CD155) was associated with lymphovascular invasion (p = 0.011), and membranous CD155 (m-CD155) was strongly correlated with the presence of Tumor Infiltrating natural killer cells (NK-TILs) (p = 0.0003). Survival analysis demonstrated that patients with high cyt-CD155 had a significantly worse overall survival (p < 0.001) and death free survival (p = 0.014) than those with low expression, while high levels of m-CD155 correlated with a better prognosis (p = 0.037). Furthermore, we found that patients with m-CD155 Low /NK Low tumors had a significantly reduced overall survival (p = 0.012). Multivariate analysis showed that positive tumor m-CD155 status was a significant independent marker of good prognosis. Meanwhile, high cyt-CD155 expression was identified as an independent poor prognostic predictor, suggesting a key role in this malignancy., Significance: Altogether, our results revealed that cyt-CD155 was associated with invasiveness and poorer prognosis, but the concomitant presence of m-CD155 and NK-TILs had an opposite prognostic relevance in breast cancer. These results raised the importance of CD155 IHC analysis to elucidate biomarker localization, leading to better understand and design therapeutic molecule targeting CD155 in breast tumors., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Imipenem is a beta-Lactam antibiotic characterized by a broad spectrum of activity. It is prescribed to treat severe infections. Our goal is to investigate toxicity induced in male rat reproductive systems following exposure to this drug (15, 50 or 100 mg/kg) compared to gentamicin (50 mg/kg) treatment. Effects of imipenem on reproductive organ weights, histoarchitecture, sperm parameters, and oxidative stress parameters were evaluated. Serum testosterone levels were measured. Apoptosis and inflammatory behaviors were investigated by immunohistochemical proteins expression analysis of apoptosis regulator BAX (Bax), B-cell lymphoma 2 (Bcl-2), and interleukin-1 beta (IL-1 beta) in testis. Results showed a significant decrease in male fertility parameters including sperm count, sperm motility, reproductive organ weights and serum testosterone levels after imipenem administration as compared to the control and gentamicin treated groups. Increased sperm abnormality was significant in animals treated with high doses of imipenem. Oxidative stress analysis revealed an expressed increase in lipid peroxidation and carbonyl groups levels in testicular tissues compared to control. Similar results were observed with superoxide dismutase and catalase activities from testicular tissues. In addition, severe testicular lesions were observed in the seminiferous tubules as well as important impairments in spermatogenesis testifying an inflammatory microenvironment confirmed by the intensive expression of IL1-beta and Bax protein by germinal cells and Bcl-2 by Leydig cells. In conclusion, imipenem treatment with high doses was found to lead to oxidative stress in male reproductive organs and an inflammatory microenvironment leading to spermatogenesis dysfunction and histopathological changes in the testis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We investigated at the single cell level during 16months (June 2012 to September 2013) the temporal distribution of picophytoplankton (picoeukaryotes, Synechococcus and Prochlorococcus) communities in two contrasted ecosystems: the Bay of Bizerte characterised by an oligotrophic regime typical of the Mediterranean Sea and the Bizerte Lagoon that exhibits a mesotrophic/eutrophic state. We aimed at depicting seasonal variations and quantifying the relationships between the environmental factors and the structure and abundance of picophytoplankton communities. Results showed that picophytoplankton groups were able to grow under a wide range of environmental conditions varying seasonally, although their abundances and contributions to the total chlorophyll biomass significantly varied and showed importance in the Bay of Bizerte. Synechococcus was the most abundant group reaching 225∗10 3 cells·cm -3 in the Bay and 278∗10 3 cells·cm -3 in the lagoon. This group was present all over the year in both ecosystems. Structural equation model results pointed out a different configuration regarding the picophytoplankton environmental drivers. The complexity of the configuration, i.e. number of significant links within the system, decreased under enhanced eutrophication conditions. The less exposure to anthropogenic stress, i.e. in the Bay of Bizerte, highlight a larger role of nutrient and hydrological conditions on the seasonal variations of picophytoplankton, whereas a negative effect of eutrophication on picophytoplankton communities was unveiled in the Bizerte Lagoon. We stress that such influence may be exacerbated under expected scenarios of Mediterranean warming conditions and nutrient release in coastal ecosystems., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The effects of two plastic-derived chemicals: Bisphenol A (BPA) and di-2-ethylhexyl phthalate (DEHP) were assessed on abundance and physiological responses of the marine toxic dinoflagellate Alexandrim pacificum. During 7days experiment, A. pacificum was exposed to different levels of BPA and DEHP (separately and in mixture). The responses were evaluated and compared with controls. Results showed that A. pacificum was highly sensitive to this contaminants comparing to other phytoplankton species. BPA and DEHP caused the decrease of the biomass (1.2 to 50 times lower relative to the controls), as well as the perturbation of the photosystem and the photosynthetic activity. Nevertheless, our results show a recovery of contaminated cells activity depending on exposure time and BPA and DEHP contamination. This could be related to an adaptation to induced stress or a degradation of BPA and DEHP in the medium., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: The main objective of this study was to assess the prevalence of IgG antibodies against Toscana virus (TOSV) by an ELISA test and to determine the extent of its circulation in Tunisia., Methods: An indirect ELISA test was performed to detect anti-TOSV IgG. The results were compared to those of an indirect fluorescent antibody (IFA) test., Results: The survey tested 494 healthy people from various regions of Tunisia by ELISA for anti-TOSV IgG; 47 people (9.5%) were found to be positive. Seroprevalence varied by bioclimatic region and gender. Two hundred and twelve samples, randomly chosen from the same selected population and tested with ELISA, were retested using an IFA for IgG antibodies. An 85% concordance between the IFA and ELISA was obtained (kappa=0.650)., Conclusions: These serological data confirm the circulation of TOSV in different bioclimatic zones in Tunisia where the vector sand flies are found. The detection of IgG against TOSV suggests that the diagnosis of TOSV infection is often neglected, as this virus often causes asymptomatic infections, with only a few patients developing severe illnesses involving neurological manifestations., (Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: To detect the presence of Toscana virus (TOSV) circulation in Tunisia and to study its role in viral meningo-encephalitis., Patients and Methods: A total of 315 (167 sera and 178 cerobrospinal fluid [CSF]) samples was investigated. These samples are colleted from Tunisian patients with neurological diseases during the period between January 2003 and December 2009. All samples were tested negative for enterovirus, Herpes Simplex virus and West Nile virus. Detection for IgM and IgG specific to TOSV was done by ELISA tests., Results: Specific IgM for TOSV were detected in 10 % of patients with neurological diseases (31 cases). These recent infections were distributed throughout the study period and predominated during summer and automn. Patients were originated, in the majority from the coastal region. IgG were isolated in 22 cases (7 %) corresponding to previous infection., Conclusion: This is the first report of TOSV circulating in Tunisia and its frequent implication in neurological diseases. These results incited to include TOSV as one of the viral etiologies to target in the diagnosis of viral meningitis and encephalitis in the country., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Aim of Study: Recombination is one of the major mechanisms of evolution in poliovirus. In this work, recombination was assessed in children during vaccination with OPV and among circulating vaccine strains isolated in Tunisia during the last 15 years in order to identify a possible role of recombination in the response to the vaccine or the acquisition of an increased transmissibility., Material and Methods: This study included 250 poliovirus isolates: 137 vaccine isolates, excreted by children during primary vaccination with OPV and 113 isolates obtained from acute flaccid paralytic (AFP) cases and healthy contacts. Recombination was first assessed using a double PCR-RFLP, and sequencing., Results: Nineteen per cent of recombinant strains were identified: 20% of strains excreted by vaccinees among 18% of circulating strains. The proportion of recombinant in isolates of serotype1 was very low in the two groups while the proportions of recombinants in serotypes 2 and 3 were different. In vaccinees, the frequency of recombinants in serotype3 decreased during the course of vaccination: 54% after the first dose, 32% after the second and 14% after the third dose., Conclusion: These results suggest that recombination enhances the ability of serotype3 vaccine strains to induce an immune response. Apart from recent vaccination, it may contribute to a more effective transmissibility of vaccine strains among human population., (Copyright © 2009 Elsevier Masson SAS. All rights reserved.)

Objective: This study had for aim to study the serological and molecular patterns of hepatitis delta infection in Tunisian patients., Design: Our study was carried out in 215 HBs antigen positive patients, including 176 asymptomatic carriers originated from regions of variable hepatitis B virus (HBV) endemicities, and 39 hepatitis B chronic patients with delta positive serology. Delta antigen, delta antibodies and HBe antigen were investigated for all patients; detection and genotyping of hepatitis delta virus (HDV) RNA and detection of HBV DNA were conducted in the second group patients., Results: Twelve patients (6.8%) out of 176 asymptomatic carriers had HDV positive serology. Delta prevalence was relatively more elevated in regions of high HBV endemicity than on those with moderate or weak endemicity. The mean age of patients was 5 years higher in the delta positive subjects than in the global population. For hepatitis B chronic patients with delta positive serology, HDV RNA was detected in 53.8% of cases; HBV-HDV co-replication was observed in 38.4% of cases. Genotype 1 was found for one of the amplified samples., Conclusions: The results of our study enrich the limited data on HDV prevalence in Tunisia and on the molecular epidemiology of circulating isolates.

Objective: To evaluate the seroprevalence and the risk factors of hepatitis B virus (HBV) infection in 2303 Tunisian pregnant women and to estimate the risk of perinatal transmission in women positive for hepatitis B surface antigen (HBsAg) but negative for hepatitis B e-antigen (HBeAg)., Material and Methods: Positive samples were tested for HBeAg and anti-HBe antibody using enzyme immunoassays. Serum HBV-DNA was determined by real time PCR assay., Results: Overall, 4% of women were HBsAg positive and for the majority of them (96.8%) this status was unknown. Only 1.4% of studied population were vaccinated previously against hepatitis B. Study of risk factors revealed association between the HBsAg status and presence of intrafamilial hepatitis cases (p<0.05). Only four women were positive for HBeAg. Among patients with HBeAg negative status, only 11% were negative for HBV DNA. For the others, DNA level ranged from 34 to 10(8)copies/ml; it was greater than 10(4)copies/ml in 26.5% of them., Conclusion: Hepatitis B virus (HBV) prevalence in pregnant women is of intermediate endemicity in Tunisia. Universal vaccination before pregnancy and antenatal screening is recommended. Pregnant women who are found to be HBsAg positive and HBeAg negative should be tested systematically for DNA level to evaluate the risk of perinatal infection and to prevent it by sero-prophylactic for babies or by treatment during the third trimester of pregnancy.

Objective: Viral hepatitis A (HAV) and E (HEV) infections are still frequent in many regions of the world, particularly in developing countries where sanitary conditions and socioeconomic level are frequently low. In this work, we have studied seroprevalences of these two infections in Tunisian children, teenagers and young adults., Material and Methods: The studied population included 3357 individuals from different regions of Tunisia and distributed in three groups 1 (n=1145), 2 (n=707) and 3 (n=1505) with a mean of age of 6.94, 12.84 and 20.71 years, respectively., Results: Rates of HAV infection prevalence of 84.0, 90.5 and 91.7% were found within groups 1, 2 and 3, respectively. These rates are lower than those previously found in the country; thus, primary infection with HAV in Tunisia is progressively shifting to older ages, which is probably due to the improvement of sanitary conditions. Lower anti-HAV prevalences were found in costal regions as compared to the rest of the country. This difference may be due to the higher socioeconomic level of the population living in costal regions. Antibodies against HEV were assessed in individuals of group 3. A seroprevalence of 4.3% was found which indicates that, despite the absence of epidemics, the virus is circulating among the Tunisian population as sporadic cases., Conclusion: The present work contributes to a better knowledge of HAV and HEV infections in Tunisia and highlights the need of the establishment of a national program for virological surveillance of hepatitis cases and of further studies to monitor changes in the epidemiology of these infections.

The molecular pathogenesis of hepatocellular carcinoma, a tumour characterized by a vast clinical heterogeneity, remains unexplored outside Europe and Eastern Asia. We analysed by direct sequencing or loss of heterozygosity assay, the common targets of genomic alterations in 42 hepatocellular carcinomas collected in western North-Africa. Overall, genomic instability was uncommon, allelic losses affecting mostly chromosomes 1p, 4q, 8p and 17p (24-28% of cases). CTNNB1 and TP53 were infrequently mutated (9 and 17% of cases, respectively). Surprisingly, TP53 mutation R249S, diagnostic of aflatoxin B1 exposure, usually frequent in Africa, was exceptional (one case), indicating that in western North-Africa, hepatocellular carcinoma genetics differs markedly from that of the remainder of the continent.

This study reports the genetic characteristics of coxsackievirus A24 isolates from Tunisia, including a coxsackievirus A24 variant (CVA24v) that caused an outbreak of acute haemorrhagic conjunctivitis (AHC) between September and November 2003. The virus genome was detected by PCR from conjunctival swabs obtained from patients with AHC. Four virus isolates were obtained from PCR-positive samples and were serotyped by sequence analysis of the VP1 and VP4 genomic region and by seroneutralisation. Phylogenetic analysis of the VP1, VP4 and 3C genomic regions was performed. Other Tunisian CVA24 isolates from paralytic cases and healthy individuals were also amplified, sequenced and included in the phylogenetic analysis. The epidemic strain belonged to the CVA24 serotype. Phylogenetic analysis of the 3C region of the genome revealed a strong relationship between the Tunisian epidemic strain and strains that caused outbreaks in Korea (2002) and Guadeloupe and French Guiana (2003). Phylogenetic analysis of the VP1 and VP4 regions showed a clear distinction between serotype CVA24 isolates from conjunctivitis and non-conjunctivitis cases. This is the first study to report an outbreak of AHC caused by CVA24v in the North African region.

Human adenoviruses (ADV) are distributed worldwide; they are associated with a variety of diseases. Some ADV can be implicated in large epidemics of conjunctivitis, gastroenteritis and respiratory infections. Classical diagnosis of ADV infections is based on virus isolation on cell culture and identification of the serotype by neutralization test or hemagglutination inhibition assay. However, these methods have a lack of rapidity that makes them impractical in clinical situations. With the advent of PCR, the diagnosis of ADV was improved. In this work, we have used molecular techniques for the identification of ADV serotypes implicated in conjunctivitis in Tunisia. A total of 199 conjunctival swabs received between October 2000 and May 2005 were investigated. Serotype identification was performed using a PCR followed by restriction enzyme analysis in the hexon gene. Typing by sequencing of the PCR product was used to confirm the serotype identification. Among the 199 tested clinical specimens, 24% were positive for ADV. Two different profiles were observed: one predominant corresponding to the majority of the detected ADV; this profile is in favour of two distinct serotypes, ADV37 or ADV8; the second profile was specific of ADV4 and was found in one case observed in 2005. Sequencing confirmed two serotypes: ADV8 with an endemoepidemically circulation in our country and ADV4 that appeared sporadic. The present work showed the importance of molecular techniques not only for ADV detection but also for identification of the circulating serotypes. These techniques are practical and interesting mainly for the rapid virological investigation during epidemics.

Rubella is a worlwide common infection; its importance in public health relates to the risk of malformation when primary infection occurs during pregnancy. This serosurvey was conducted to assess the kinetics of rubella infection in Tunisian children and teenagers and to determine the proportion of girls who remain seronegative at childbearing age. The studied population included 2481 individuals aged seven (N =1136), 13 (N =711) and 19 years (N =634), this sample was collected in 1996 and is representative of all geographical regions of the country. Our results indicate that 42% of tunisians are infected before seven years, 73% before 13 and 89% before 19 years of age. These rates are lower than those previously reported in the country. The proportion of seronegatives at 19 years of age was higher in costal regions than in the rest of the country: 14 vs 5% (p =0,0008). This difference should be due to the higher socio-economic level of the population living in costal regions. Our study indicates that primary infection with rubella virus in Tunisia is progressively shifting to older ages, which may increase the risk of congenital rubella syndrome. The introduction of rubella vaccination in the national program of vaccination may be considered, however only very high coverage levels will have a positive effect. Beside the reduction of the risk of congenital rubella syndrome, rubella vaccination will reduce the incidence of febrile rush cases and thus facilitate the surveillance activities conducted as part of the national program of measles elimination.

Low power Laser irradiation is used in medical practice for different indications. Several firms which commercialise Laser claim that Laser irradiation may be beneficial towards Herpes virus pathogenicity. We observe that, in the ear experimental model of HSV latency [3], repeated exposure to infrared Laser radiation of cervical ganglia following HSV inoculation appears to specifically hinder the establishment of virus latency in mouse.