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This paper deals with an Integrated Elective Surgery-Scheduling Problem (IESSP) that arises in a privately operated healthcare facility. It aims to optimize the resource utilization of the entire surgery process including pre-operative, per-operative and post-operative activities. Moreover, it addresses a specific feature of private facilities where surgeons are independent service providers and may conduct their surgeries in different private healthcare facilities. Thus, the problem requires the assignment of surgery patients to hospital beds, operating rooms and recovery beds as well as their sequencing over a 1-day period while taking into account surgeons' availability constraints. We present two Mixed Integer Linear Programs (MILP) that model the IESSP as a three-stage hybrid flow-shop scheduling problem with recirculation, resource synchronization, dedicated machines, and blocking constraints. To assess the empirical performance of the proposed models, we conducted experiments on real-world data of a Tunisian private clinic: Clinique Ennasr and on randomly generated instances. Two criteria were minimised: the patients' average length of stay and the number of patients' overnight stays. The computational results show that the proposed models can solve instances with up to 44 surgical cases in a reasonable CPU time using a general-purpose MILP solver.

We tested the performance of MRZ-reaction, an intrathecal humoral immune response against-Measles (M), Rubella (R) and Varicella Zoster (Z) viruses, in multiple sclerosis (MS) diagnosis. The MRZ-reaction was significantly more positive in MS than in non-MS group with a specificity of 91.9%. In MS group, the RZ-profile was the most prevalent and the R-specific antibody-index was correlated to the number of oligoclonal bands (OCB) in CSF. Interestingly, the MRZ-reaction was detected in 53% of OCB-negative-MS patients. The MRZ-reaction seems to be a relevant CSF diagnostic marker of MS disease. The likely relation between its positivity and the vaccination status deserves to be investigated., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Objectives: Short tandem repeats (STR) are usually used as informative polymorphic markers for genetic mapping and for disease susceptibility analysis. The involvement of these microsatellite markers localized in the MHC region was reported in many auto-immune diseases. In this study we analyzed for the first time eight polymorphisms of microsatellite loci at the HLA region: D6S291, D6S273, TNFa, b and c, MICA, D6S265 and D6S276, in Tunisian systemic lupus erythematosus (SLE) patients., Materials and Methods: We performed a case control study in which the microsatellite loci were amplified using specific primers labeled with NED, VIC, PET or 6-FAM and analyzed using GeneScan software 3.7. For the statistical analysis, we used SPSS software and we performed a sub-haplotype scoring test using the haplo.stats software developed in the R language., Results: We found that two mean associated regions existed; the most statistically significant encompassed the 3 TNF markers (p = 0.0003, OR = 19.34); the latter covered the DR region. In fact, when scoring haplotypes in 3 marker- sliding windows, the p value increased as we moved away from the TNF region and decreased again when we approached the DRB1 locus. We also established for the first time the negative association between alleles of D6S291 and SLE. The majority of clinical and serological correlations were noted with TNF alleles., Conclusion: Our results confirm the association between TNF and DRB1 polymorphisms and SLE. The association between alleles of D6S291 and SLE needs however to be verified by the analysis of other markers beyond this region., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease with various presentations. This variation is due to the interaction of hormonal, environmental, and genetic factors. Associations between human leukocyte antigens and SLE have long been recognized in different ethnic populations and have been suggested to represent the most important association., Objectives: The objectives of this paper were to determine susceptibility and protection human leukocyte antigens (HLA) Class II markers for SLE and to highlight, for the first time, associations between HLA alleles and clinical and serological features in South Tunisia., Methods: We conducted a case-control study on 75 SLE patients and 123 healthy controls. The HLA Class II DRB1/DQB1 of all patients and controls was genotyped using polymerase chain reaction-sequence specific primer technique. Statistical analysis was performed using SPSS software., Results: HLA-DRB1*03 was the principal Class II allele associated with the genetic susceptibility to SLE (pc = 0.02; OR = 2.57; CI = [1.39-4.75]; this allele was also associated with anti-SSB production ( P = 0.016; OR = 4.00; CI = [1.24-12.96]). HLA-DRB1*01 was significantly more expressed in SLE patients with neurologic disorders ( P = 0.013; OR = 20.25; CI = [1.87-219.21]). No allele was found to be protective against SLE in our study group., Conclusion: Our results show that in South Tunisia SLE is associated with HLA-DRB1*03 and that some clinical features of SLE may be influenced by specific DRB1 and DQB1 alleles.

In adults, anti-neutrophil cytoplasmic antibodies (ANCA) are considered as serological markers of several diseases, especially vasculitis and glomerulonephritis. Since ANCA are rarely positive in children, few data about the clinical relevance of these auto-antibodies in pediatric population have been reported. Therefore, our study aims to describe the spectrum of disorders associated with positive ANCA in Tunisian children. This study had been carried out over a period of 12 years and a half. All patients under the age of 15 for whom ANCA screening was performed in our laboratory were included. Clinical data were collected retrospectively. Indirect immunofluorescence (IFI) technique for ANCA detection was performed using PNN smears fixed with ethanol, formalin and, if necessary, methanol. Positive results were tested using immunodot to characterize the antigenic targets (myeloperoxydase (MPO) and proteinase 3 (PR3)). Our results showed that 410/5,990 (6.8%) laboratory requests for ANCA screening were for children. Forty (9.7%) requests were positive (24 children). Clinical data were available for 19 patients only. Sex-ratio (F/M) was 1.25. The mean age was 9 years and a half (3-15 years). The most frequent IIF patterns were x-ANCA (n=12) and p-ANCA (n=7). In our patients, the most frequent conditions associated to ANCA were treatment with benzylthiouracil for hypothyroidism (n=6), inflammatory bowel disease (n=4) and hemolytic anemia (n=4). In conclusion, the positivity of ANCA in children seems to be a rare event. Associated conditions include clinical disorders specific to the pediatric population. Treatment with benzylthiouracil is an etiology to be taken into consideration.

Objective: The common association between NOD2/CARD15 and TLR4 gene variants with inflammatory bowel disease (IBD) has not been replicated in all studies. We studied the polymorphism of these two genes in Tunisian patients with IBD., Methods: Polymorphisms of NOD2 (R702W, G908R and L1007fs) and TLR4 (Asp299Gly and Thr399Ile) genes were analyzed in 106 patients with IBD (68 with ulcerative colitis [UC], 38 with Crohn's disease [CD]) and 160 healthy controls using polymerase chain reaction-restriction fragment length polymorphism. Genotypes and phenotypes were correlated., Results: The mutated allele of TLR4-Thr399Ile was strongly associated with IBD (9.4% in IBD, 7.4% in UC and 13.2% in CD vs 2.5% in controls; P = 0.0004, 0.014 and 0.00006, respectively). Heterozygous genotypes were significantly more frequent in patients with IBD (17.0%), UC (14.7%) and CD (21.1%) than in controls (5.0%) (P = 0.0012, 0.012 and 0.001, respectively). Interestingly, the wild genotype was found to be protective (odds ratio 0.24). The mutated allele of TLR4-Asp299Gly was more frequent in controls (6.8%) than in patients with IBD (2.9%). A phenotypic correlation of Asp299Gly-AG genotype with arthritis in UC patients was detected (P = 0.003). Regarding the NOD2 gene, the common variations studied were not polymorphic and there was no genetic association with IBD., Conclusion: The TLR4-Thr399Ile variant was strongly associated with susceptibility to IBD, whereas TLR4-Asp299Gly seems to play a role in the clinical expression of UC. The rarity and non-association of NOD2 mutations with IBD may reveal a genetic characteristic of the population in our region., (© 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objective: The aim of this work was to establish human leukocyte antigen (HLA) class I and hereditary hemochromatosis gene (HFE) mutation associations with recurrent aphthous oral ulcers (RAOU) and Behçet disease (BD) in a cohort of Southern Tunisian patients., Subjects and Methods: A total of 232 patients with RAOU and 123 healthy controls (HCs) were enrolled in this study. The patients were divided into 2 groups based on the presence (BD+: n = 62) or absence of BD (BD-, n = 170). In the BD+ group, 28 patients had severe manifestations of BD. In the BD- group, RAOU was isolated in 81 patients, associated with mucocutaneous manifestations in 58 and with joint symptoms in 25. Complement-dependent microlymphocytotoxicity assay and polymerase chain reaction-restriction fragment length polymorphism were used to study HLA class I polymorphism and HFE mutations, respectively., Results: HLA-B51 was positively associated with BD, particularly in those with severe manifestations. No association was detected with HLA class I polymorphism among the BD group. Based on stratification to clinical manifestations, the isolated RAOU was negatively associated with HLA-A1 with a difference close to significance (12 [14.81%] vs. 32 [26.02%] in HCs; p = 0.06). Furthermore, patients with mucocutaneous features had a higher frequency of HLA-B51 (14, 24.14%) than patients without mucocutaneous involvement (11, 11.37%). Considering HFE mutations, patients with isolated RAOU had a higher frequency of H63D when compared with other subgroups, especially after limiting the comparison to 27 patients of at least 5 years of follow-up., Conclusion: This study showed that, unlike BD, RAOU were not associated with HLA-B51. Moreover, we suggest that H63D mutation was positively associated with isolated RAOU., (© 2017 The Author(s) Published by S. Karger AG, Basel.)

Objectives: The aims of this study were to determine predictive factors of paradoxical reaction in patients with cervical lymph node tuberculosis (TB) and to discuss the therapeutic management of this condition., Materials and Methods: A retrospective study was performed of 501 patients managed for cervical lymph node TB over a period of 12 years (from January 2000 to December 2011). Statistical data were analyzed using IBM SPSS Statistics version 20.0., Results: Paradoxical reaction occurred in 67 patients (13.4%), with a median delay to onset after starting TB treatment of 7 months. Lymph node size ≥3cm and associated extra-lymph node TB were independently associated with paradoxical reaction. Treatment consisted of surgical excision (71.6%), restarting quadruple therapy (10.4%), reintroduction of ethambutol (23.8%), and addition of ciprofloxacin (20.8%); steroids were given in two cases . All patients recovered after an average treatment duration of 14.91±7.03 months., Conclusion: The occurrence of paradoxical reaction in cervical lymph node TB seems to be predicted by associated extra-lymph node TB and a swelling size ≥3cm. The treatment of paradoxical reaction remains unclear and more randomized trials are necessary to improve its management., (Copyright © 2016. Published by Elsevier Ltd.)

Neonatal lupus (NL) is a rare syndrome caused by placental transfer of maternal anti-SSA/Ro (60 and 52kDa) or anti-SSB/La antibodies. The aim of this study was to evaluate the clinical and biological profile of NL at the neonatal unit of Sfax, Tunisia, over a 10-year period. Six mother-NB pairs (two sets of twins and two sisters) had positive ANA by transplacental transmission during the study period. The ANA pattern was speckled and the NBs' sera titer was half that of their mothers'. Anti-SSA, anti-Ro52, and anti-SSB were found in 100%, 33%, and 50% of the mothers' sera, respectively. The transmission of anti-SSA was observed in four pregnancies out of six, anti-Ro52 in two pregnancies out of two, and anti-SSB in one pregnancy out of three. The patients' clinical records showed that two NBs had a congenital heart block: one with anti-SSA, whose mother had Sjögren syndrome, and another with anti-SSA, anti-SSB, anti-Ro52, and anti-mitochondrial antibodies (M2 type), whose mother had no diagnosis at the child's birth (cutaneous erythema and positive ANA with the same profile). Cutaneous signs (erythema, petechia) were described in three NBs out of six. The two sets of fraternal twins had cutaneous signs with the same ANA titer and profile (no anti-SSA transmission from their mother with lupus and anti-phospholipid syndrome). The two sisters' (two pregnancies 3 years apart) mother had Sjögren syndrome, one of them had heart block with positive anti-SSA, and the other was asymptomatic with anti-SSA and anti-Ro52. The same mother had a history of three pregnancies with two NBs who died of heart block., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Type 1 diabetes (T1D) is an autoimmune disease (AID) with both genetic and environmental components. We aimed to investigate the genetic association of polymorphisms in genes previously linked with other AIDs, namely BANK1, IL15 and IL2/IL21 region. A total of 76 T1D patients and 162 controls from Southern Tunisia were recruited for a case-control association study investigating the relationship between sixteen SNPs of the BANK1, IL15 and IL2/IL21 gene region and T1D. In the BANK1 gene, G allele and GG genotype of rs3733197 were significantly increased in the group of T1D patients compared to controls. In addition, in the IL15 gene, the minor allele A of rs10519613 polymorphism was significantly higher in patients than in controls. No significant association was found for SNPS in IL2/IL21 gene region. The analysis of the haplotype structure revealed the G-C-A-C-T haplotype of the IL15 gene as associated with a reduction in the risk of developing T1D, while A-T-A-C-T haplotype increased the risk of developing the disease. Furthermore, in the IL2/IL21 region, only one haplotype consisting of eight SNPs was markedly associated with T1D susceptibility. Moreover, G-C combination of the BANK1/IL15 was significantly increased in T1D patients, compared to controls. Our results establish BANK1 and IL15 as new T1D genetic susceptibility factors and replicate the association of the 4q27 region with T1D. Our data agree with the effect previously observed for other autoimmune conditions and delineate a shared underlying mechanism., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Primary immunodeficiency disorders (PID) are a heterogeneous group of diseases, characterized by an increased susceptibility to infections., Aim: To determine the frequency of PID in south of Tunisia to collect information on clinical experience with these disorders., Methods: Over a period of 16 years (1995 - 2010), primary immunodeficiency was confirmed in 51 patients (31 boys and 20 girls). The immunological investigation included a study of specific and/or non specific humoral and cellular immunity., Results: These 51 patients belonged to 47 families among which 37 were consanguine (80%). The immunological investigations revealed a cellular or combined immunodeficiency in 21 cases, with a majority of ataxia-telangiectasia syndromes (11 cases), HLA class II deficiency (9 cases). A predominant antibody defect was found in 3 patients and a chronic granulomatous disease in seven cases. Deaths occurred So far in 19 patients (37 %)., Conclusions: PID are relatively frequent in Tunisia, probably because of the high rate of consanguinity among the general population. The distribution of the different groups of primary immunodeficiencies is characterized by high frequency of ataxia - telangiectasia and HLA class II deficiency.

Rhinoscleroma is a rare chronic granulomatous infection caused by Klebsiella rhinoscleromatis. Because of its mundane clinical presentation as chronic rhinits, it is frequently unrecognized. The authors report the cases of two female patients with pseudotumoral rhiniscleromas located in the septum and in the rhinopharynx respectively CT scan permitted a precise evaluation of the extent of the lesion. Among the various para-clinical examinations required, bacteriological studies are very important and should be performed comcomitantly with biopsy.