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Introduction: Primary Sjögren's syndrome (pSS) is a chronic inflammatory disease primarily affects exocrine glands dysfunction. Oxidative stress (OS) is a phenomenon occurring as a result of an imbalance between the generation of free radicals and antioxidant defense system. Hence, we aimed to establish the status of OS and inflammatory response according to the pSS disease activity index. In this context, we investigated malondialdehyde (MDA), and antioxidant enzymes during pSS. The possible association between MDA and nitric oxide (NO) levels and between MDA and some pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IL-33)., Methods: The study has been conducted on 53 pSS patients. The antioxidant enzymes, represented by glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD), were estimated by a colorimetric activity kit. Whereas, MDA value was assessed by measuring thiobarbituric acid reactive substances. Moreover, pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IL-33) and NO were respectively quantified by enzyme-linked immunosorbent assays (ELISA) and the modified Griess., Results: Interestingly, we report a notable reduction in our pSS patients' antioxidant enzyme activity, while NO, MDA and proinflammatory cytokines values were significantly increased. pSS patients with higher disease activity had much stronger increases in NO and MDA levels. No significant difference was assessed in CRP level. Additionally, substantial significant correlations between plasmatic NO and MDA levels and between MDA, NO and IL-1β, IL-6, TNF-α cytokines were reported. However, no significant association was found between NO, MDA and IL-33 concentrations., Conclusion: Collectively, our data showed altered oxidant-antioxidant balance in pSS patients. MDA, NO, IL-1β, IL-6, TNF-α seem to be good indicators in monitoring disease activity. Oxidative stress was closely related to inflammation in pSS. Exploiting this relationship might provide valuable indicators in the follow-up and prognosis of pSS with a potential therapeutic value., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The detection of weld defects by using X-rays is an important task in the industry. It requires trained specialists with the expertise to conduct a timely inspection, which is costly and cumbersome. Moreover, the process can be erroneous due to fatigue and lack of concentration. In this context, this study proposes an automated approach to identify multi-class welding defects by processing the X-ray images. It is realized by an intelligent hybridization of the data augmentation techniques and convolutional neural network (CNN). The proposed data augmentation mainly performs random rotation, shearing, zooming, brightness adjustment, and horizontal flips on the intended images. This augmentation is beneficial for the realization of a generalized trained CNN model, which can process the multi-class dataset for the identification of welding defects. The effectiveness of the proposed method is confirmed by testing its performance in processing an industrial dataset. The intended dataset contains 4479 X-ray images and belongs to six groups: cavity, cracks, inclusion slag, lack of fusion, shape defects, and normal defects. The devised technique achieved an average accuracy of 92%. This indicates that the approach is promising and can be used in contemporary solutions for the automated detection and categorization of welding defects.

Background: Several studies documented that insulin-like growth factor-2 mRNA-binding protein 2 (IGF2BP2) contributes to carcinogenesis, and 1 report documented the association of IGF2BP2 rs4402960 with increased risk of breast cancer (BC). This study investigated the association of rs4402960 and rs1470579 IGF2BP2 variants with BC and triple negative BC (TNBC)., Materials and Methods: This case-control study included 488 BC patients comprising 130 TNBC and 358 non-TNBC patients, and 476 cancer-free controls. Genomic DNA was obtained from peripheral venous blood, and genotyping was done by allelic exclusion method on real-time PCR., Results: The rs440960, but not rs1470579, minor allele was significantly associated with BC, and significantly higher rs4402960 T/T genotype frequency was noted in BC patients than controls; the distribution of rs1470579 genotypes were comparable between BC patients and controls. In contrast, significantly lower rs1470579 minor allele frequency, and reduced rs1470579 A/C and C/C, and rs4402960 T/T genotype frequencies were seen in TNBC cases. Among TNBC cases, rs4402960 and rs1470579 correlated with menses pattern, histological type, breastfeeding, oral contraceptive use and hormonotherapy. Among non-TNBC patients, and rs1470579 correlated significantly with breast feeding, oral contraceptive use, hormonotherapy, and nodal status; rs4402960 also correlated with menses pattern. Two-locus (rs440960-rs1470579) haplotype analysis confirmed the positive association of TC, and negative association of GC and TA haplotypes with BC, while TC and GC haplotypes were negatively associated with TNBC., Conclusion: Whereas rs440960 was positively associated with BC, both rs4402960 and rs1470579 were negatively associated with TNBC, suggesting potential diagnostic/prognostic role in BC and its complications., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: We previously reported on the association between ESR1 and ESR2 gene variants and heightened risk of breast cancer (BC). Here we investigated the association of common ESR1 and ESR2 gene variants with triple negative BC (TNBC)., Methods: This retrospective case-control study involved 488 BC patients (130 TNBC, 358 non-TNBC patients). ESR1 (rs2234693, rs9340799, rs3020314, rs3798577) and ESR2 (rs928554, rs944459, rs4986938, rs1256049, rs1256030, rs1271572) genotyping was done by real-time PCR., Results: While minor allele frequencies (MAF) of ESR1 variants were comparable between TNBC and non-TNBC subjects, significantly higher ESR2 rs1256049 MAF was seen in TNBC patients. Significantly higher frequency of ESR1 rs3798577 T/C and C/C genotypes were noted in TNBC cases, and significant differences were seen in ESR2 rs928554, rs1256049, and rs1271572 genotype distribution. Increased TNBC risk was associated with ESR1 rs3798577 T/C and C/C genotypes according to codominant and dominant models, while positive association of ESR2 rs928554 with TNBC was seen according to codominant and recessive models, and positive association of ESR2 rs1256049 with TNBC was seen according to codominant and dominant models. Positive interactions were noted between ESR2 rs1271572-ESR1 rs3020314, ESR2 rs1271572-ESR1 rs9340799, and ESR2 rs1271572-ESR1 rs2234693, ESR2 rs4986938-ESR1 rs2234693, and ESR2 rs928554-ESR1 rs9340799. Haplotype analysis confirmed the positive association of ESR1 CATT with TNBC, while ACGGCTC and ACGGTT ESR2 haplotypes were positively associated with TNBC., Conclusion: Results of this study confirmed the association of unique ESR1 and ESR2 genetic variants with altered risk of TNBC. This suggests possible diagnostic and prognostic role of these variants with TNBC independent of their association with BC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: We investigated the association between CRP variants and chronic gastritis in H. pylori-infected patients at the allele, genotype, and haplotype levels. This was also assessed according to serum hs-CRP levels., Methods: Study subjects consisted of 77 H. pylori-infected patients and 96 H. pylori-negative controls. Genotyping of the CRP rs1572970, rs876537, rs2794520, rs2808630, rs1130864, rs1417938, rs7553007, and rs4285692 variants were analyzed by real-time PCR., Results: Significantly higher MAF and increased risk of chronic gastritis were associated with rs1130864, rs1417938, and rs7553007, which persisted after controlling for key covariates. Significant differences in the genotype distribution of rs1130864, rs1417938, and rs7553007 were also seen between H. pylori-infected patients and healthy controls. Increased risk of H. pylori-associated chronic gastritis was associated with carriage of rs1130864 C/T, and more with T/T genotype carriers, as well as with rs1417938 T/A and A/A genotype carriers. Functionally, the distribution of rs1130864 and rs1417938 genotypes were significantly different between H. pylori-infected patients and controls in the low hs-CRP (<6 mg/L) group. CRP haplotype analysis identified Block 1 (rs1572970, rs876537, rs2794520), and Block 2 (rs2808630, rs1130864, rs1417938) associated with H. pylori infection. Haplotypes ACC (Block 1) and TTA and TTT (Block 2) were positively associated with H. pylori-associated chronic gastritis with low hs-CRP levels., Conclusion: Altered serum levels of hs-CRP, stemming in part from the presence of specific genetic variants in CRP gene, modulate the risk of H. pylori infection., Competing Interests: Declaration of competing interest The authors state that there are no conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Ovarian cancer (OC) is one of the most common gynecologic cancers,with significant morbidity and mortality. The risk of OC is influenced by hormone status, of which sex hormone-binding globulin (SHBG), which influences the serum availability of steroid sex hormones, is implicated in the pathogenesis and evolution of OC. The aim of this study is to evaluate the involvement of common SHBG gene variants in OC susceptibility and evolution., Materials: A case control study including 71 OC patients and 74 cancer-free controls, who were genotyped for rs9898876, rs13894, rs1799941 and rs6257 SHBG SNP. Genotyping was done by the allelic discrimination method, using VIC- and FAM-labeled primers., Results: The minor allele frequencies of rs9898876, rs13894, rs1799941 and rs6257 SHBG SNP was comparable between OC cases and control women, implying no significant associations of the tested variants and overall OC risk. Taking homozygous wild-type genotype as reference (OR = 1.00), heterozygous rs9898876 (G/T), and minor allele-carrying genotypes [G/T + T/T] were associated with reduced risk of OC. While rs9898876 heterozygosity (G/T) was predictive of OC occurrence, no significant association of the remaining three tested SNPs was noted with altered risk of OC. Irrespective of FIGO staging, the four tested SHBG SNPs were not associated with the clinical progression of OC., Conclusions: In conclusion, SHBG rs9898876 is associated with a decreased risk of OC, and thus constitutes a potential diagnostic biomarker of OC., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: We aimed to assess and compare autonomic function in Parkinson's disease (PD) associated with the leucine-rich repeat kinase (LRRK2) G2019S mutation (LRRK2-PD) and non-LRRK2 PD, by the study of heart rate variability (HRV) and sympathetic skin responses (SSR)., Methods: In a cross-sectional three-year study, fifty LRRK2-PD and fifty clinically matched non-LRRK2 PD patients were included. Cardiac parasympathetic functions were assessed using heart rate variation to deep breathing (HR-DB), to the Valsalva maneuver (HR-V) and to standing (HR-S) and the sympathetic autonomic system by sympathetic skin responses (SSR)., Results: Neurophysiological, parasympathetic and sympathetic dysautonomia were found in 78%, 69% and 37% of all PD patients respectively. Rates of dysautonomia in the LRRK2-PD and non-LRRK2 PD patient subgroups were 76% vs 80% (p = 0.405) for neurophysiological, 62% vs 76% (p = 0.123) for parasympathetic and 38% vs 36% (p = 0.500) for sympathetic dysautonomia. HR-S was the most frequently altered parameter in both groups, and was significantly associated with the tremor-dominant (TD) motor phenotype of PD in the total cohort (p = 0.004) and in LRRK2-PD (p = 0.015). In LRRK2-PD patients, female gender was associated with parasympathetic dysfunction (p = 0.024), and with altered HR-DB (p = 0.022). Early-onset parkinsonism was also significantly associated with preserved neurophysiological autonomic functions (p = 0.044) in LRRK2-PD. In non-LRRK2 PD patients, male gender was associated with early parasympathetic (p = 0.043) and sympathetic dysfunction (p = 0.007)., Conclusion: Our study showed a roughly similar neurophysiological autonomic profile in non-LRRK2 PD and LRRK2-PD. The latter had some peculiarities with more marked parasympathetic dysfunction and more altered HR-DB in females, more altered HR-S in the TD-motor phenotype, and preserved autonomic functions in early-onset parkinsonism. These preliminary findings would require further investigations on larger genetically homogeneous cohorts to explore the multiple facets of autonomic dysfunction in PD., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Unverricht-Lundborg disease (ULD), also called progressive myoclonic epilepsy type 1, is usually characterized by the presence of ataxia associated with myoclonus and epileptic seizures without progressive cognitive deficit, presenting during late childhood and early adolescence. Currently, there is a growing body of evidence for atypical presentations of the disease with a milder phenotype or without the full symptomatology. We describe a case report of a late-onset phenotype with progressive myoclonus-ataxia syndrome accompanied by initial recurrent falls, resulting in specific phobia and agoraphobia starting at the age of 50 years old. The examination revealed multifocal myoclonus with cerebellar ataxia and electroencephalogram showed generalized polyspikes and spike-wave discharges. Electromyogram revealed positive myoclonus of 60-ms duration in the face and the presence of C reflex. A genetic study confirmed the diagnosis of ULD in the patient and other additional family members, presenting a wide range of intra-familial variability. We discuss the challenging differential diagnosis for such a misleading presentation and its possible underlying pathophysiological mechanisms. Our case report may contribute to broadening the age and clinical boundaries for this disease and emphasizes the intra-familial age and symptom variability. Based on a suggestive family history, the diagnosis of ULD should be considered in this context, even in older patients.

The reconfiguration of supply chain is becoming a crucial concept used to deal with market disruptions and changes such as the COVID-19 pandemic, demand uncertainty, and new technologies. It can be defined as the ability of the supply chain to change its structure and functions in order to adapt to new changes. Its assessment requires an understanding of its quantitative factors to provide indicators that are easy to interpret. Effective reconfigurability assessment can be achieved by measuring quantitatively its six characteristics (modularity, integrability, convertibility, diagnosability, scalability, and customization). This paper aims at identifying the quantitative factors of each characteristic and their inter-relationships by using Total Interpretive Structural Modelling (TISM). The structural model obtained by TISM is applied to understand the dependency quantitative factors. Based on TISM results, a classification of quantitative factors is determined using "Matrice d'Impacts Croisés, Multiplication Appliquée à un Classement" (MICMAC) analysis. This article provides a better understanding of the six characteristics previously mentioned to improve the reconfigurability of supply chains by considering the interactions between their factors. Thus, this analysis helps managers to understand the characteristics that influence the change of the supply chain structure and those that enable changing the supply chain functions in order to optimize the supply chain reconfiguration process., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature 2022.)

The COVID 19 pandemic, fluctuating demand, market uncertainty and the emergence of new technologies explain the need for a more flexible and agile supply chain. In fact, several important factors should be taken into account in the process of building an adaptive and reconfigurable supply chain. Reconfigurability is used to measure quantitatively the capability of supply chain to change easily their structure and functions. The aim of this work is to evaluate the level of reconfigurability of a supply chain. Quantitative measures of six indicators that characterize reconfigurability are presented in this paper. Then, an index of reconfigurability in supply chain is developed based on The Multi-Attribute Utility Theory in order to choose the most reconfigurable configuration. An illustrative example is also given. From the discussion, it is deduced that the characteristics of the reconfigurable supply chain impacts positively on the degree of reconfigurability., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

Introduction: Data on epidemiology of atypical parkinsonian syndromes (APS) in North African countries are limited. Our objective was to study the epidemiological features of APS in a Tunisian population., Methods: We conducted a 17-year retrospective cross-sectional descriptive study in the Department of Neurology at Razi University Hospital. We included all patients responding to consensus diagnosis criteria of APS. We recorded demographic and clinical data. Group differences were assessed with a post hoc ANOVA with a Bonferroni error correction., Results: We included 464 APS patients. Hospital prevalence of APS among all parkinsonism cases was 20.6%. Mean annual increase of incidence defined as newly diagnosed APS cases per year reached 38.8%/year. APS were divided into 4 etiological subgroups: dementia with Lewy bodies (DLB; 56.7%); progressive supranuclear palsy(PSP; 16.2%); multiple system atrophy (MSA; 14.6%); and finally corticobasal syndrome (CBS; 12.5%). Sex-ratio was 1.2. This male predominance was found in all subgroups except MSA (p = .013). Mean age at onset was 68.5 years, most belated in DLB (69.7 years; p < .001). Young-onset parkinsonism (<40 years) was found only in MSA subgroup (p = .031). Parkinsonism was of late onset (>70 years) in 50.7% of patients and was significantly associated with DLB subgroup (p = .013). Inaugural parkinsonism was associated with CBS and MSA (p = .0497), and gait disorders at disease onset were associated with PSP and MSA (p = .0062). Cognitive and mood disorders were more marked in DLB and most preserved in MSA. Consanguinity was more marked in CBS (p = .037), and family history of dementia and psychiatric diseases was more common in DLB. Thirty-seven families with similar cases of APS were identified., Conclusions: This is the largest African epidemiological study on APS. In our population, APS were frequent and dominated by DLB. The age of onset of parkinsonism was the most decisive feature for differential diagnosis., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

With technological progress in particular telemedicine and health care, the information should meet and serve as well the needs of people and in particular whom with reduced mobility, the elderly as well as people with difficulties to access to medical resources and services. These services should be achieved in a fast and reliable manner based on case priorities. One of the major challenges in health care is the routing and scheduling problem to meet people's needs. Of course, the objective is to considerably minimize costs while respecting priorities according to cases that will face. Through this article, we propose a new technique for home healthcare routing and scheduling problem purely based on an artificial intelligence technique to optimize the offered services within a distributed environment. The automatic learning and search method seem to be interesting to optimize the allocation of visits to beneficiaries. The proposed approach has several advantages in terms of especially cost, efforts, and gaining time. A comparative study was carried out to evaluate the effectiveness of the planned technique compared to previous work., (© King Fahd University of Petroleum & Minerals 2020.)

Status matrimonial, cigarette smoking and hormonal contraceptive (HC) use have been associated with cervical cancer (CC) establishment by influencing the CC carcinogenesis process. In the present study, we aim to confirm this correlation between these factors and the risk of CC occurrence among Tunisian population. To evaluate the role of matrimonial status, smoking and HC as cofactors of CC installation, we performed a random selection of 600 women from Salah Azeiz institute in Tunisia and a questionnaire was conducted by doctors for each patient. Logistic regression after adjustment for potential confounding factors, relative excess risk due to interaction (RERI) and synergy index (S) were used to evaluate the additive interaction. Subgroup analysis was conducted to examine whether the relative risks changed with CC stages. There were an excess risk among smoker patients and patient with HC use (p < 0.001) for CC installation. Women who are smokers have a 14 times greater risk of suffering from cervical cancer and approximately 24 times greater to develop an advanced form of CC malignancy. Having a history of using birth control pills increase CC occurrence and aggravation (OR~2). The matrimonial status seems an important factor for CC appearance (OR = 3.58 and 2.46) among CC Tunisian patient. However, no significant biological interaction from this three joint exposure was observed in the early FIGO stages but the risk increase in advanced FIGO stages. In our Tunisian cohort, oral contraception, smoking habit and matrimonial status are associated with an overall increased risk of CC development. Indeed, it may damage the local immunity system and may affect the disease severity in patient carriers of some genetic risk biomarkers. The balance of cancer risks may vary among Tunisian CC patient, depending on some environmental co-factors.

Introduction: We investigated the association between common variants in TGF- β 1, IL-6 and the risk of ovarian cancer (OC) in Tunisian patients and control women., Material Methods and Results: Study subjects comprised 71 OC cases and 74 control women. Genotyping of TGF- β 1 and IL-6 SNPs was done by real-time PCR. No differences were noted in the minor allele frequencies of the three TGF- β 1 SNPs between OC patients and controls. However, marked differences in the distribution of TGF- β 1 rs1800469 genotypes were seen between OC cases and controls (p < 0.001), with TGF- β 1 rs1800469 heterozygous (C/T) genotype being negatively associated with OC (OR [95% CI] = 0.24 [0.15-0.58]). The allelic and genotypic distributions at IL-6 polymorphisms showed a positive association between minor allele (G) at IL-6 rs1880242 variant (p = 0.0275; R [95% CI] = 1.88 [1.03-3.46]) and the occurrence of OC. In fact, the presence of T allele [G/T + T/T] decrease the risk of OC (p = 0.021; OR [95% CI] = 0.38 [0.17-0.88]). In addition, the Haploview analysis demonstrated high linkage disequilibrium (LD) between IL-6 SNPs and eight-locus haplotype analysis identified that GGAGGGGA and GGAGGGTA haplotypes are positively associated with OC risk. A negative association was shown between IL-6 haplotype (TGGGCCTA) and OC occurrence., Conclusions: Our results suggest that TGF- β 1 rs1800469, IL-6 rs1880242 variants and IL-6 haplotype (TGGGCCTA) have protective roles of OC risk. IL-6 haplotypes (GGAGGGGA and GGAGGGTA) increase OC susceptibility among Tunisian women., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Termedia.)

Background: Chronic infection with hepatitis B (HBV) and C virus (HCV) is linked with a pro-inflammatory state, predisposing to cirrhosis and liver cancer, particularly hepatocellular carcinoma (HCC). A role for Toll-like receptor (TLR) signalling in hepatocarcinogenesis was recently documented. We hypothesised a link TLR3 and TLR4 polymorphisms and HCC, as surrogates for the significance of TLR signalling in the promotion and initiation of HCC., Materials and Methods: We recruited 174 HCV-infected patients, 100 HBV-infected patients and 360 healthy control subjects. TLR3 (rs3775290) and TLR4 (rs4986790) genotyping was done by PCR-restriction fragment length polymorphisms (PCR-RFLP), LFTs and AFP by standard routine techniques. Liver fibrosis was assessed clinically by the Fibrotest and Actitest., Result: The TLR3 rs3775290 minor T genotype was linked with increased risk of chronic HBV (P = 0.05) and HCV (P = 0.031) infection. The TLR4 rs4986790 minor G genotype was linked with significantly increased risk for HBV/HCV chronic infection (P < 0.001). Subgroups analyses indicated decreased risk of HBV-related HCC in relation to TLR3 rs3775290 CC/CT genotype (P = 0.022), with increased risk ascribed to the minor (T) allele (P = 0.04). Likewise, TLR4 rs4985790 minor (GG) genotype was positively associated with HBV-linked HCC (P < 0.001). Furthermore, a link between TLR3 TT (P < 0.001) andTLR4 GG (P = 0.04) minor genotypes was noted in relation to increased risk of HCV-related disease., Conclusion: TLR3 and TLR4 polymorphisms are promising biomarkers of liver cirrhosis and cancer associated with HBV and HCV infection.

Introduction: Previous studies have highlighted the importance of polymorphisms of toll-like receptors (TLRs) in the pathogenesis of certain cancers, including head and neck cancers (HNC)., Aim of the Study: The aim of this study was to evaluate the association of TLR2 (-196 to -174 ins/del) and TLR3 (1377 C>T) as potential risk factors for HNC in Tunisians., Material and Methods: A case-control study including 246 HNC patients (174 nasopharyngeal carcinoma - NPC and 72 laryngeal cancer - LC) and 250 healthy controls. Genotyping was done by using PCR and PCR-RFLP methods., Results: Higher minor allele frequencies of TLR2 (-196 to -174 ins/del) and TLR3 1377 C>T polymorphisms were seen in HNC, NPC, and LC compared to controls. In addition, higher increased HNC, NPC, and LC risk was associated with TLR2 ins/del and TLR2 del/del genotypes (p < 0.0001). Positive association with HNC, NPC, and LC risk was seen with TLR2 del-containing genotypes (ins/del + del/del) (p < 0.0001). The T/T genotype of TLR3 is associated with HNC, NPC, and LC susceptibility (p < 0.0001). Positive association with HNC and NPC risk was seen with TLR3 T allele carriers (C/T + T/T) (p < 0.0001). Increased frequency of T-ins, C-del, and T-del haplotypes was revealed in HNC and NPC cases than healthy controls; however, T-del was significantly higher in LC cases., Conclusions: Our results demonstrate an increased risk of HNC, NPC, and LC with TLR2 ins/del, TLR2 del/del, and TLR3 T/T genotypes. And positive association with T-ins, C-del, and T-del haplotypes with HNC and NPC and T-del haplotype with LC., Competing Interests: The authors declare no conflict of interest.

Background: Primary Sjögren's syndrome (pSS) represents a chronic, systemic autoimmune disorder, characterized by lymphocytic infiltration of exocrine glands, inducing compromised secretory function and tissue destruction. Increasing evidence had revealed that inflammatory mediators, such as nitric oxide (NO) and pro-inflammatory cytokines, are critical in the development and perpetuation of pSS systemic manifestations. In our current study, we aimed to investigate the ex vivo immunomodulatory effect of interferon (IFN)-β on iNOS expression, as well as on pro-inflammatory (tumor necrosis factor (TNF)-α, interleukin (IL)-6) and immunoregulatory (IL-10) cytokine production. Furthermore, we examined potential associations between the influence of IFN-β treatment on NO production, and pSS clinical and serological manifestations., Methods: In 41 pSS patients documented for their clinical and serological features, NO and cytokines levels were measured by the Griess method and enzyme-linked immunosorbent assay, respectively. Inducible nitric oxide synthase expression was analyzed by fluorescence immunostaining assay, using peripheral blood mononuclear cells (PBMCs) isolated from healthy controls and pSS patients., Results: Our results revealed a strong down-modulating effect of IFN-β in the secretion of pro-inflammatory mediators including TNF-α, IL-6, and NO production. Interestingly, IFN-β exerts an increase in IL-10 levels. The most suppressive effect exerted by IFN-β on NO production was importantly reported for patients with neurological manifestation. This immunomodulatory effect of IFN-β on NO production is highly related to the decrease of inducible nitric oxide synthase (iNOS) expression., Conclusion: Our findings highlight a consistent ex vivo inhibitory effect of IFN-β on pro-inflammatory cytokine production and NO pathway in pSS patients. Our data suggest that IFN-β could represent a potential candidate for targeting inflammation during pSS.

Pterygium is a common ocular surface disease observed in humans. Chronic ultraviolet (UV) exposure is extensively recognized as an aetiological factor in the pathogenesis of this disease. This hypothesis is sustained by epidemiological and histopathological data in relation to UV injured skin. Although some findings have indicated that genetic factors, anti-apoptotic and immunological mechanisms are involved in the pathogenesis of pterygium, the mechanism by which it develops remains poorly understood. In this study, we analysed the in vivo production of IL-17A, IL-6, IL-10 and nitric oxide (NO) in the tears and sera from Algerian patients. Interestingly, we observed that IL-6, IL-17A and NO production in the tears and sera of all patients was strongly associated with inflammatory infiltration, NOS2, NF-κB and Bcl2 expression in pterygia biopsies. Collectively, our results indicate a relationship between local inflammation and anti-apoptotic processes in pterygium disease, leading to both tissue damage and enhanced cellular proliferation.

Background/aim: We evaluated the association of TLR2 (-196 to -174 Ins/Del) and TLR3 (1377 C>T) as potential risk factors for nasopharyngeal carcinoma (NPC) in Tunisians. Material and methods: The study subjects comprised 137 NPC patients and 164 cancer-free control subjects. TLR2 genotyping was done by PCR and TLR3 genotyping was performed by PCR-RFLP. Results: Minor allele frequency (MAF) and genotypes of TLR3 (1377 C>T) were comparable between NPC patients and controls. Significantly higher MAF and TLR2-containing Del allele genotypes of TLR2 (-196 to -174 Ins/Del) were seen in NPC patients compared to controls [OR (95% CI) = 2.10 (1.43-3.08), P < 0.001 and OR (95% CI) = 2.07 (1.27-3.37), P = 0.003]. In addition, higher increased NPC risk was associated with the TLR2-Del/Del genotype [OR (95% CI) = 2.74 (1.37-5.48), P = 0.004]. An increased frequency of the Del-T haplotype was seen in NPC cases compared to controls. Conclusion: Our results demonstrate an increased risk of NPC with the TLR2-Del/Del genotype and Del-T TLR2 and TLR3 haplotype, suggesting their potential use as biomarkers to evaluate NPC risk in Tunisians.

For the first time in the word, we investigated the association between five FSHR polymorphisms with the risk of cervical cancer among Tunisians. Study subjects comprised 112 Cervical Cancer (CC) patients and 164 control women. Genotyping of FSHR rs6166, rs1007541, rs11692782, rs2055571 and rs1394205 variants was done by realtime PCR, with defined clusters. The allelic distributions of the tested FSHR SNPs were comparable between CC patients and control women. In contrast, the heterozygous genotype of rs1007541 was associated with 1.8-fold increased risk of CC. Stratification according to FIGO staging revealed that the minor allele of rs1007541 was more frequent among advanced tumor stage patients, with 11-fold increased risk of CC [P < 0.0001; OR (95 % CI) = 11.32 (7.46-17.18)]. However, no significant allelic association was revealed in the rest of analyzed FSHR SNPs. Haploview analysis showed high Linkage disequilibrium (LD) between rs2055571 and rs1394205. Haplotype analysis revealed a lack of association between cases and controls. However, analysis of CC patient subgroups demonstrated enrichment of GGTAG haplotype in early tumor stage [P = 0.025; OR (95 % CI) = 0.07 (0.01-0.70)]. The FSHR variants and haplotypes may be a genetic markers for CC susceptibility and evolution among Tunisian women.

We investigated the association between six common and novel interleukin-6 (IL-6) polymorphisms with the risk of cervical cancer (CC) among Tunisians. Study subjects comprised 112 CC cases and 164 control women. Genotyping of IL-6 rs2069845, rs2069840, rs1474348, rs1800795, rs1800797, rs2069827 variants was done by real-time PCR, with defined clusters. The allelic and genotypic distributions of the tested IL-6 SNPs were comparable between CC patients and control women. Stratification according to FIGO staging revealed that rs1800795 homozygous major allele genotype (P = 0.033; OR =0.49(0.25-0.95)) and major allele (P = 0.037; OR = 0.57 (0.33-0.97)) were protective of CC. Moreover, carriage of rs1474348 major allele was also protective of CC (P = 0.014; OR = 0.53(0.32-0.88)), while higher rs1474348 minor allele frequency was seen in CC patients with early FIGO stage (P = 0.044; OR = 0.39 (0.15-1.00)), thus implicating rs1474348 in CC evolution and progression of angiogenesis. Haploview analysis demonstrated high linkage disequilibrium (LD) between rs2069845, rs2069840, rs1474348 and rs1800795, and 6-locus haplotype analysis identified GACCCA haplotype to be positively associated with increased CC, while GAGGGG haplotype was negatively associated with CC, thus suggesting a protective role for this haplotype in CC. Furthermore, there was a significant association between the incidence of CC and the use hormonal contraception (P = 0.047; OR = 1.97 (0.94-4.13)) and smoking (P < 0.001; OR = 7.12 (2.97-17.04)). The IL-6 variants rs1800795 and rs1474348, and haplotypes GACCCA and GAGGGG, along with use of hormonal contraceptives and smoking, are major risk factors of CC susceptibility and evolution among Tunisian women.

Aim of the Study: Several studies implicated altered inflammatory response in the susceptibility to ovarian cancer, and polymorphisms in inflammatory cytokines were shown to play an important role in the development of malignancies, including ovarian cancer (OC). Here we investigated the relationship between polymorphisms in IL-1 β (-511C>T), IL-1RN VNTR, TNF- α (-308G>A), and TNF RII (-322 VNTR) and OC risk in Tunisian women., Methods and Results: Study subjects comprised 62 OC patients and 126 healthy women. Genotyping was done from genomic DNA obtained from blood simple by PCR. Positive association between IL-1RN (-VNTR) A1 allele (p = 0.0069; OR = 2.04; 95% CI:1.17-3.58) and OC risk, while negative association was seen with the A3 allele (P = 0.0034; OR = 0.09; 95% CI: 0.00-0.64), suggesting a protective role by the A3 allele. For IL-1 β (-511C>T), homozygous C/C genotype was associated with significantly increased risk of OC (p = 0.0002; OR = 4.14; 95% CI: 1.77-9.76), while heterozygote C/T genotype was linked with reduced risk of OC (p = 0.0033; OR = 0.40; 95% CI: 0.20-0.78). Furthermore, TNF- α -308A allele was significantly associated with heightened risk of OC (p = 0.016; OR = 1.70; 95% CI: 1.08-2.69), and homozygote G/G genotype was associated with decreased risk of OC (p = 0.0018; OR = 0.25; 95% CI: 0.09-0.66). In contrast, TNFRII (-322 VNTR) polymorphism was not associated with altered OC risk in the studied group., Conclusions: The significant association between IL-1RN VNTR, IL1- β (-511), TNF- α (-308) and OC susceptibility in Tunisian women confirms a role for altered inflammatory response in ovarian cancer pathogenesis., Competing Interests: The authors declare no conflict of interest.

Accumulative epidemiological evidence suggests that polymorphisms of Toll-like receptors signaling pathway elucidated the cellular and molecular mechanisms of human diseases whose gaining a primordial importance. The aim of our study is to identify the role of TLR 2 (-196 to -174 del), TLR 3 (1377 C>T), TLR 4 (Asp299Gly) and TLR 9 (G2848A) gene polymorphisms with the evolution of cervical cancer in Tunisian women. Blood samples were collected from histopathologically confirmed patients with cervical cancer and unrelated healthy female controls of similar ethnicity. Genotyping of the analyzed polymorphisms were done using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism. For the TLR 2, Ins/Ins genotype is a protector factor [p = 0.006; OR: 0.35(0.16-0.73)] and the dominant genotype of TLR 3 increased the risk of CC in stage (III+IV); C/C versus C/T [p = 0.033; OR: 2.03(1.00-4.13)] and C/C versus C/T+T/T [p = 0.036; OR: 1.93(1.00-3.74)]. For TLR 4, the dominant genotype Asp/Asp is implicated in the occurrence of CC in stage (I+II) [p = 0.000; OR: 4.55(1.58-13.06)], [p = 0.001; OR: 3.49(1.44-8.45)] and in stage (III+IV) [p = 0.038; OR: 3.77(0.87-16.29)], [p = 0.007; OR: 5.21(1.65-16.46)] and the major allele Asp is a risk factor for the development of tumor in stage (I+II). The TLR2 Ins/Del genotype is associated with tumor evolution to stage (III+IV) [p = 0.003; OR: 3.00 (1.22-7.35)] and the genotypes Gly/Gly and Asp/Gly+Gly/Gly and Gly allele of TLR 4 are implicated in tumor evolution to the advanced stages. Further, TLR 2, TLR 3, TLR 4 and TLR 9 gene polymorphisms are implicated in the modulation of CC risk due to tobacco usage and statue of menopause among cases. Our study suggests a relationship between the incidence of the TLR2, TLR 3, TLR 4 and TLR9 mutations and the clinical progression of CC according to the FIGO classification. However, future studies with different demographic and clinical characteristics in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in cervical cancer etiology in women worldwide.

Objective: We investigated the association between polymorphisms in the promoter and intron regions of the interleukin-10 (IL-10) gene with the risk of cervical cancer (CC) in Tunisian patients and control women., Methods: Study subjects comprised 86 CC cases and 126 control women. Genotyping of IL-10 intron (rs3024491, rs3024490) and promoter (rs1800872, rs1800871, rs1800896) variants was done by real-time PCR, with defined clusters., Results: The minor allele frequencies of the five tested IL-10 SNPs were not significantly different between cervical cancer cases and control women. However, significantly higher frequencies of homozygous minor allele-carriers in cases was seen for rs3024490 (P=0.023), rs1800872 (P=0.037), and rs1800871 (P=0.028). IL-10 serum levels were significantly reduced in rs3024490 T/T vs. G/G genotype carriers, and in rs1800871 T/T than C/C genotype carriers. While carriage of rs1800872 and rs3024491 minor allele was associated with reduced IL-10 secretion, this was not statistically significant. Haploview analysis demonstrated high linkage disequilibrium (LD) among the IL10 SNPs studied, and only seven haplotypes were common, capturing 98.8% of the total possible haplotypes. Reduced frequency of haplotypes GTCCA (P<0.001) and TGATG (P<0.001) was seen in cervical cancer cases than in control women, thus conferring disease protection nature to these haplotype. This association remained significant for GTCCA (Pc=0.006) and TGATG (P=0.045) after correcting for multiple comparisons., Conclusion: Specific IL-10 variants (rs3024490, rs1800872, and rs1800871) and haplotype (GTCCA and TGATG) may contribute to the development of cervical cancer among Tunisian women., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The present study was undertaken to investigate the association between Hepatitis B Virus (HBV) infection and polymorphisms of tumour necrosis factor alpha TNF-α -308 G>A, TNF-α -238 G>A and TNF RII VNTR (p75) gene promoter in a Tunisian population. Blood samples were collected from 100 Tunisian patients with HBV infection, 45 with Chronic Hepatitis (CH), 36 with Liver Cirrhosis (LC), 15 with Hepatocellular Carcinoma (HCC) and 200 healthy individuals of similar ethnicity. Genomic DNA was extracted from peripheral blood leukocytes. Genotyping of the analysed polymorphisms was performed using Amplified Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR), Restriction Fragment Length Polymorphism (RFLP) and Variable Number Tandem Repeat PCR (PCR-VNTR). The variant homozygotes -308 GG were associated with 50% decreased risk of HBV chronic infection (GG vs AA+GA; p=0.010; OR=0.50; 95%CI=0.29-0.85). However, the carriers of minor allele -308 A have higher risk (1.5 times) to develop a chronic infection than other patients (p=0.027; OR=1.46; 95%CI=1.04-2.06). The minor allele of -238 polymorphism was positively associated with virus resistance and the development of chronic infection (p=0.043; OR=1.42; 95%CI =1.01 1.99). The distribution of -308, -238 and TNF RII VNTR (p75) among the three groups differed significantly. For HCC groups, there were statistically significant differences in allele distribution in -308, -238 respectively in which A allele remains a risk factor for HBV evolution to HCC (p=0.008 and p=0.026). Haplotype analysis revealed that TNF-α (-308A; -238A) was significantly associated to HBV chronic infection and moreover to disease aggravation to HCC stage. Our findings imply that variations in the genes governing the levels of constitutive and inducible TNF-α and TNF RII might be an important risk factor, which could explain the variable outcomes of HBV infection., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to investigate the role of IL-1β (-511C>T), TNFα (-308 G>A), IL-10 (-1082 G>A) and IL-1RN VNTR polymorphisms in the susceptibility to rheumatoid arthritis (RA) in Tunisians., Patients and Methods: Using PCR-based methods, 104 RA patients and 150 healthy controls were investigated. We compared allele and genotype frequencies in RA patients versus controls and analyzed their correlations with erosive form (EF)., Results: IL1-RN VNTR A1A3 genotype is associated with higher risk of RA (P=0.012, OR=4.31). Among the cases, males who carry this genotype were more exposed to RA (P=0.044, OR=8, 47). For IL1- β gene, a significantly higher frequency of the -511C/C genotype was observed in RA patients in comparison to controls (P=0.013, OR=2.45). This higher frequency was especially observed in women (P=0,003, OR=3.42). In contrast, IL10-1082G/G genotype was less common in patients (P=0.046, OR=0.46). According to EF, men carrying IL1-RN VNTR A1A3 (P=0.005 OR=5.28) and IL1-β-511C/C (P=0.015 OR=2.61) genotypes develop non EF of RA. Moreover, TNFα-308 A allele (P=0.024, OR=1.84) and A/A genotype (P=0.033, OR=3.1) were positively associated to EF of RA. However, G allele (P=0.024, OR=0.31) and GG genotype (P=0.31, OR=0.031) of the TNFα-308 were protectors., Conclusion: Our results indicated that IL-1RN VNTR, IL-1β (-511C>T) and IL-10 (-1082 G>A) are associated with susceptibility to RA, and that IL-1RN VNTR, IL-1β (-511C>T) and TNFα (-308 G>A) are associated with severity of RA., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Our study aimed to evaluate the association between IL-1α (4845 G/T), IL-1β (-511C/T) and IL-1RN (VNTR) polymorphisms and risk of cervical cancer. This case-control study investigates three polymorphisms in 130 patients and 260 controls by PCR-restriction fragment length polymorphism (RFLP). The IL-1RN (VNTR) A1/A3 genotype appear as a cervical cancer risk factor (p = 0.048; OR = 2.92; 95 % CI = 1.00-8.74), moreover, the L/2* decreased the risk (p = 0.011; OR = 0.47; 95 % CI = 0.25-0.88) and may be a protective factor against this pathology. Stratified analysis according to the FIGO stage subgroup revealed that the IL-1β-511 T/T genotype and T allele may be a protective factors against cervical cancer development for patients with early stage (p = 0.030; OR = 0.46; 95 % CI = 0.22-0.96) (p = 0.020; OR = 0.68; 95 % CI = 0.48-0.97). However, for the patients with advanced FIGO stage, IL-1RN-VNTR L/2* genotype appear as a protective factor for this pathology (p = 0.023; OR = 0.29; 95 % CI = 0.08-0.99). The (G-T-L) haplotype showed a significant decreased frequency in cervical cancer patients as compared to controls (p = 0.032; OR = 0.53; 95 % CI = 0.29-0.95). In contrast, the (T-T-2*) combination appear a risk factor for the development of cervical cancer (p = 0.018; OR = 1.57; 95 % CI = 1.07-2.30). Our study suggested that IL1 cluster polymorphisms and haplotypes may be a genetic risk factor for cervical cancer.

Objective: We investigated the association between common vascular endothelial growth factor (VEGF) single nucleotide polymorphisms (SNPs) and the risk of cervical cancer (CC) in Tunisian patients and control women., Methods: Study subjects comprised 86 CC cases and 124 control women. Genotyping of VEGF rs699947, rs833061, rs1570360, rs2010963, rs25648, rs833068, rs833070, rs3025039 SNPs was done by real-time PCR., Results: Higher minor allele frequencies (MAF) of rs699947 (-2578C/A) [P=0.04; OR (95% CI)=1.52 (1.02-2.29)], and rs1570360 (-1154G/A) [P=0.04; OR (95% CI)=1.58 (1.01-2.47)] were seen in CC cases compared to control women. Marked differences in the distribution of rs699947 (P=9×10(-4)) and rs1570360 (P=0.03) genotypes were seen between CC cases and control groups; the distribution of the remaining SNPs was comparable between CC cases and control women. The association of rs699947 and rs1570360 with heightened CC risk with was seen in the heterozygous, and more so in the homozygous states. Haploview analysis revealed high LD between rs699947, rs833061, rs1570360, rs2010963, rs25648, rs833068 and rs833070 but weak or no LD between rs3025039 and the other SNPs. Seven-locus (rs699947/rs833061/rs1570360/rs2010963/rs25648/rs833068/ rs833070) haploview analysis identified only CTGCCAG haplotype to be positively associated with CC [P=0.022; OR(95% CI)=1.74 (1.08-2.79)]., Conclusion: Specific VEGF variants (rs699947, rs1570360) and haplotype (CTGCCAG) may contribute to the development of CC among Tunisian women., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Host genetic factors may confer susceptibility to Cervical Cancer. TNF-α as pro-inflammatory cytokine participates in the maintenance of immune homeostasis. Allelic variation of immuno-modulatory genes is associated with alteration in immune function. This study investigated the associations between TNF-α-308G>A, -238G>A, and TNFRII - VNTR-322 and cervical cancer in Tunisian women. Genotypes of those polymorphisms were detected in 130 cases and 260 controls. The variant heterozygote -308 G/A was associated with a 41% decreased risk of cervical cancer (GG vs A/A; p = 0.002; OR = 0.41; 95% CI =0.23-0.76). Furthermore, compared with dominant variant G/G, the (G/A+A/A) genotypes was significantly associated with a decreased risk of CC (GG vs G/A+A/A; p = 0.026; OR = 0.62; 95% CI = 0.40-0.97). The FIGO stratified analysis showed that the minor variant A/A and combined G/A+A/A of TNFα-238 G>A and TNFα-308 G>A increased the risk of the tumor evolution, respectively, (P = 0.011; OR = 2.98; 95% CI = 1.16-7.72) (P = 0.008; OR = 2.76; 95% CI = 1.20-6.41), (P = 0.000; OR = 16.33; 95% CI = (5.10-55.23) (P = 0.000; OR = 7.54; 95% CI = 2.68-22.29). There was statistically significant relationship between the incidence of the TNF-α mutations and the clinical progression of cancer according to the FIGO classification. In our study, the haploview analysis revealed no LD between rs1800629 and rs361525. TNF-α and TNFRII polymorphisms might be genetic risk factors for cervical cancer in Tunisian population.

Previous studies underscored the importance of genetic factors in the pathogenesis of certain cancers, including cervical cancer. Epidemiological evidence supports an association between specific polymorphisms of Toll-like receptors (TLR) with several human pathological states, including cervical cancer. The aim of this study was to investigate the link between specific gene variants in TLR2 (-196 to -174 del), TLR3 (c.1377 C>T), TLR4 (Asp299Gly), and TLR9 (2848 G>A) and susceptibility to cervical cancer in Tunisian women. Study subjects comprised 122 women with histopathologically-confirmed cervical cancer, and 260 unrelated age- and ethnically-matched healthy females, who served as controls. TLR genotyping was done using PCR-restriction fragment length polymorphism. The C/C genotype of TLR3 (c.1377 C>T) is associated with cervical cancer susceptibility (OR: 1.71, CI: 1.08-2.70). For TLR4 (Asp299Gly), the Asp/Asp genotype and the Asp allele were associated with higher risk of developing cervical cancer (OR: 4.95, CI: 1.97-13.22) and (OR: 5.17, CI: 2.11-13.50) respectively. We demonstrated no association between the TLR2 (-196 to -174 del) and the TLR 9 (2848 G>A) polymorphisms and the susceptibility of cervical cancer among Tunisian women. However, the C/C genotype for the TLR3 (c.1377 C>T) polymorphism and the Asp/Asp genotype and the Asp allele for (Asp299Gly) TLR4 polymorphism were found to be associated with a higher risk of cervical cancer.

The variability in host immunogenetic background, especially in human major histocompatibilty genes, has been shown to influence the susceptibility to human papillomavirus (HPV) infection and cervical neoplasia. Here, we conducted a case-control study in Tunisian women to examine the effect of genetic variation in HLA class II DRB1 and DQB1 genes on invasive cervical cancer (ICC) and squamous cell carcinoma (SCC). HLA genotyping was performed by PCR sequence-specific primers technique. The data revealed significant positive and negative associations, suggesting either predisposing or protective effects of these genes in the disease outcome. DRB1*15, alone or linked to DQB1*06, was associated with a 2.7- and 3.5-fold increase in risk for ICC, respectively. DRB1*13-DQB1*03 showed a similar 3.5 risk effect. Concerning SCC, we observed a relatively higher, about 1.2 times more, risk effect for these genetic markers. In contrast, only one haplotype - DRB1*13-DQB1*06 - provides evidence for a weak protection (about 0.3-fold reduction) of ICC and SCC. In conclusion, we suggest that HLA class II polymorphisms are involved in the genetic susceptibility to cervical cancer in Tunisian women.

Hemophagocytic syndrome (HPS), whether familial or acquired, is a clinico-pathological entity, characterized by uncontrolled hyper-inflammation, leading sometimes to a lifethreatening condition. Liver dysfunction is central in HPS: hepatomegaly is discovered in half cases, liver enzyme elevation and/or cholestasis are very frequent, cholestasis is a prognostic factor, and liver biopsy is often necessary to confirm HPS and to diagnose the underlying disorders in secondary HPS. The spectrum is large from acquired SAM than can be cured with the treatment of his trigger, to genetic cases only cured by stem cell transplantation.

Objective: Primary epiploic appendicitis is an uncommon, self-limited disease with spontaneous resolution. Diagnosis is usually made at surgery as the disease is generally mistaken for acute appendicitis or sigmoid diverticulitis. CT allows a non-invasive diagnosis, thus avoiding unnecessary surgery. The condition can be managed conservatively with the use of analgesic drugs only, and clinical evolution is uneventful. The aim of this study is to report the CT features of this pathologic process before and after medical treatment by analgesics., Patients and Method: Six patients (4 men and 2 women aged from 23 to 70 year old mean; 29 year old) underwent abdominal CT scan because of acute abdominal pain located in the left lower quadrant (n = 3) and right lower quadrant (n = 3). No patient had fever. Laboratory findings were normal in all cases. Follow-up CT scans were obtained in 4 patients respectively at 2, 4, 8 and 80 weeks., Results: CT scan showed in all cases a fatty mass located to the anterolateral wall of the colon, delineated by an hyper attenuating rim. Infiltration of the pericolic fat was noted in all cases. Follow up CT scans obtained in 4 patients showed that the inflammatory signs had cleared in all cases, the lesion had disappeared (n = 2), decreased in size (n = 1) or a residual paracolic node was observed (n = 1)., Conclusion: Primary epiploic appendicitis is a rare disease. Knowledge of CT signs allowed the correct diagnosis and a conservative management.

Background: Magnetic resonance cholangiography (MRC) is currently under investigation for non-invasive biliary tract imaging., Aim: To compare MRC with endoscopic retrograde cholangiography (ERC) for pretreatment evaluation of malignant hilar obstruction., Methods: Twenty patients (11 men, nine women; median age 74 years) referred for endoscopic palliation of a hilar obstruction were included. The cause of the hilar obstruction was a cholangiocarcinoma in 15 patients and a hilar compression in five (one hepatocarcinoma, one metastatic breast cancer, one metastatic leiomyoblastoma, two metastatic colon cancers). MRC (T2 turbo spin echo sequences; Siemens Magnetomvision 1.5 T) was performed within 12 hours before ERC, which is considered to be the ideal imaging technique. Tumour location, extension, and type according to Bismuth's classification were determined by the radiologist and endoscopist., Results: MRC was of diagnostic quality in all but two patients (90%). At ERC, four patients (20%) had type I, seven (35%) had type II, seven (35%) had type III, and two (10%) had type IV strictures. MRC correctly classified 14/18 (78%) patients and underestimated tumour extension in four (22%). Successful endoscopic biliary drainage was achieved in 11/17 attempted stentings (65%), one of which was a combined procedure (endoscopic + percutaneous). One patient had a percutaneous external drain, one had a surgical bypass, and in a third a curative resection was attempted. Effective drainage was not achieved in six patients (30%). If management options had been based only on MRC, treatment choices would have been modified in a more appropriate way in 5/18 (28%) patients with satisfactory MRC., Conclusion: MRC should be considered for planning treatment of malignant hilar strictures. Accurate depiction of high grade strictures for which endoscopic drainage is not the option of choice can preclude unnecessary invasive imaging.

Background: Magnetic resonance cholangiography (MRC) is a new technique for non-invasive imaging of the biliary tract., Aim: To assess the results of MRC in patients with suspected bile duct stones as compared with those obtained with reference imaging methods., Patients/methods: 70 patients (34 men and 36 women, mean (SD) age 71 (15.5) years; median 75) with suspected bile duct stones were included (cholangitis, 33; pancreatitis, three; suspected post-cholecystectomy choledocholithiasis, nine; cholestasis, six; stones suspected on ultrasound or computed tomography scan, 19). MR cholangiograms with two dimensional turbo spin echo sequences were acquired. Endoscopic retrograde cholangiography with or without sphincterotomy (n = 63), endosonography (n = 5), or intraoperative cholangiography (n = 2) were the reference imaging techniques used for the study and were performed within 12 hours of MRC. Radiologists were blinded to the results of endoscopic retrograde cholangiography and previous investigations., Results: 49 patients (70%) had bile duct stones on reference imaging (common bile duct, 44, six of which impacted in the papilla; intrahepatic, four; cystic duct stump, one). Stone size ranged from 1 to 20 mm (mean 6.1, median 5.5). Twenty seven patients (55%) had bile duct stones smaller than 6 mm. MRC diagnostic accuracy for bile duct lithiasis was: sensitivity, 57.1%; specificity, 100%; positive predictive value, 100%; negative predictive value, 50%., Conclusions: Stones smaller than 6 mm are still often missed by MRC when standard equipment is used. The general introduction of new technical improvements is needed before this method can be considered reliable for the diagnosis of bile duct stones.

Purpose: The objective of our study was to reassess the value of CT scan in the preoperative evaluation of gastric adenocarcinoma, using surgical and pathologic findings as the reference standard., Materials and Methods: Forty-five patients who had preoperative CT scan for gastric carcinoma were retrospectively included in the study. Images were analyzed by two readers working in consensus with respect to tumor detection, tumor location, depth of invasion, involvement of adjacent organs, lymph node involvement and presence of peritoneal carcinomatosis., Results: Gastric tumor was visible in 91% of cases. Accurate tumor localization was obtained in 50% of cases. Depth of tumor penetration was correctly evaluated in 40% of the cases. Evaluation of regional and distant lymph node metastases was correct in 54% and 64% of cases, respectively. Peritoneal carcinomatosis was depicted in 17% of cases., Conclusion: CT scan allows detection of gastric adenocarcinoma in the majority of cases. However, this technique markedly underscores the extent of gastric adenocarcinoma. Therefore, CT scan should not be used to determine the preoperative staging of gastric adenocarcinoma.

The case of a 50-year-old woman with pathologically proven tuberculous colitis is reported. Clinical course, single-contrast barium enema, and colonoscopy suggested Crohn's disease. Computed tomography allowed the correct diagnosis of tuberculous colitis as it showed asymmetric thickening of the colonic wall and enlarged necrotic lymph nodes. This case suggests that the diagnosis of tuberculous colitis may be difficult and raises the differential diagnosis with Crohn's disease. Our observation suggests that computed tomography can be helpful for the diagnosis and may avoid unnecessary exploratory laparotomy.

Objective: To compare the digestibility and tolerance of lactose from three semi-solid fermented dairy products with the same amount of lactose but different lactase contents and bacterial cultures in lactase deficient adults., Design: Measurement of breath hydrogen (H2) concentration and of clinical symptoms after consumption of the test meals., Setting: Metabolic ward for healthy volunteers, INSERM U290, Hôpital St. Lazare, Paris., Subjects: Fifteen lactase-deficient healthy adult volunteers (20-45 y) started the study. One subject became a non-H2-producer during the study; therefore the results of 14 subjects are presented., Intervention: Each subject consumed, on four different days and in random order, after a 12 h fast, three semisolid test meals containing 18 g of lactose, and a 10 g dose of lactulose which allowed calculation of lactose malabsorption. The three meals were: traditional yoghurt, fermented milk (Ofilus) that contained Lactobacillus acidophilus and Bifidobacterium sp., and a similar product 'Bulgofilus' enriched with Lactobacillus bulgaricus to increase the lactase content., Results: Compared with lactulose, the sum of symptoms was significantly lower for Bulgofilus (P = 0.05), and bloating was less severe for Ofilus (P = 0.06). Between the fermented milks, there were no differences. The area under the breath H2 curve was significantly lower for each fermented milk when compared to lactulose (P < 0.0001). The degree of maldigestion of lactose did not differ significantly between the products; it was 21 +/- 3% (range 6-52) for Ofilus, 21 +/- 3% (range 6-44) for Bulgofilus, and 18 +/- 3% (range 3-43) for yoghurt., Conclusion: Despite the differences in the lactase and bacterial content, lactose was as well digested and tolerated from the three different semi-sold fermented dairy products. This could be due to a slow gastric emptying of the semi-solid milk.

In order to determine how soya-bean proteins are digested and metabolized in the human intestine before colonic bacterial fermentation and to estimate their true digestibility, the gastro-jejunal behaviour of soya-bean proteins in water and in two other forms (a concentrated soya-bean-protein solution (isolate) and a drink composed of crude soya-bean proteins (soymilk)) was studied in humans. Experiments were carried out in eight healthy volunteers using a double-lumen steady-state intestinal perfusion method with polyethyleneglycol (PEG) as a non-absorbable volume marker. Gastric emptying and N and electrolyte contents of the jejunal digesta were analysed. Gastric half-emptying time (min) of the liquid phase after water ingestion (12.59 (SE 0.12)) was shorter (P < 0.05) than those for soymilk (37.74 (SE 11.57)) and isolate (36.52 (SE 11.23)). Electrolytic balances showed that for all meals, Na+, Cl- and K+ were secreted when Ca2+ was efficiently absorbed from the jejunal lumen. Gastro-jejunal N absorption for isolate and soymilk were 63 and 49% respectively, and were not significantly different from one another; after water ingestion, endogenous N was estimated to be 21 mmol. An estimate of the exogenous:endogenous values for the effluents was obtained from the amino acid compositions of soymilk and effluents after water or soymilk ingestion, indicating that 70% of the total N was exogenous and 30% endogenous. Under these conditions the endogenous fraction represented 31 mmol after soymilk ingestion and the gastro-jejunal N balance indicated that 54% of the soymilk was absorbed. This finding indicates that the true gastrojejunal digestibility of soya-bean proteins is similar to that of milk proteins.

Enteritis cystica profunda and diffuse colitis cystica profunda are exceedingly rare conditions. We report here the first case in which these two entities are associated in one patient. This 48-year-old woman presented initially with a solitary ulcer of the rectum and developed later deep ileal and colonic ulcerations with intervening normal mucosa, polypoid masses, and a dense fibrosis of the bowel wall. Colon and ileum specimens demonstrated submucosal mucous cysts and occasionally herniation of mucosal epithelium into the submucosa, which led to the diagnosis of enteritis and colitis cystica profunda. The exact nature of the underlying ileocolonic disease, which necessitated colectomy and extensive ileal resection, remained undetermined although an aggravating role of iterative surgical procedures is possible. Enteritis cystica profunda and diffuse colitis cystica profunda therefore seem to share a common pathogeny and have to be considered as lesions complicating an underlying disease rather than specific and autonomic diseases.

Oro-ileal intubation was performed in 6 healthy volunteers who ingested, either 100 g of a fermented milk containing 10(8)/g Lactobacillus acidophilus and 10(7)/g Bifidobacterium sp or sterilized fermented milk along with a meal in random order. Lactobacillus acidophilus and Bifidobacterium were counted in the ileal fluid which was aspirated continuously for 8 h, and flow rates were calculated using the constant slow infusion of PEG 4000. After ingestion of fermented milk but not after control, hourly ileal flow rates of Lactobacillus acidophilus and Bifidobacterium increased form 4.8 +/- 0.2 and 4.9 +/- 0.6 to 7.2 +/- 0.3 and 8.0 +/- 0.3, respectively (mean +/- SE log10 CFU). 8.3 +/- 0.2 Lactobacillus acidophilus and 8.8 +/- 0.1 Bifidobacterium were recovered in the ileum which represented 1.5 percent and 37.5 percent of the ingested bacteria, respectively. In conclusion, under usual conditions of fermented milk ingestion, a large number of living Lactobacillus acidophilus and Bifidobacterium pass through the upper gastrointestinal tract and reach the colon.