Exploring the role of vitamin D-VDR pathway in pemphigus foliaceous: a novel perspective on disease pathogenesis.

Several auto-immune diseases have been linked to vitamin D deficiency as a contributing environmental factor. Its pleiotropic effects on the immune system, especially its essential role in maintaining immune tolerance, make the vitamin D pathway of great interest. In this study, we focused on Pemphigus foliaceous (PF) in Tunisian population. we aimed to quantify the Serum 25[OH]D levels using chemiluminescence assay and to analyze the differential expression of the VDR, CYP27B1 and CYP24A1 genes in the circulating blood cells and lesional skin tissue of PF patients using Q-PCR. A genetic explanation was then sought to explore any direct relationship between tag polymorphisms and the inherited features of PF. Results confirmed a vitamin D hypovitaminosis in Tunisian PF patients. Interestingly, a differential gene expression correlated to the disease stratification was noted. Indeed, at the systemic level, an upregulation of VDR and CYP27B1 genes was observed in healthy controls compared to PF patients. Notably, in lesional skin tissue, the clinical and serological remission phase was correlated with high transcriptional levels of the VDR gene and conversely a drop in expression of the CYP24A1 gene. Genetic analysis indicated the involvement of the most appealing polymorphisms, rs2228570 and poly (A) microsatellite, in PF etiopathogenesis. Indeed, CAC13 haplotype was associated with a higher risk of PF development. Our findings suggest that alterations in the vitamin D-VDR pathway may influence PF physiopathology, making this pathway a potential target for pharmacological modulation, especially for cortico-resistant PF patients.

Molecular characterization of Pseudomonas aeruginosa from diabetic foot infections in Tunisia.

Background. Pseudomonas aeruginosa is an invasive organism that frequently causes severe tissue damage in diabetic foot ulcers.Gap statement. The characterisation of P. aeruginosa strains isolated from diabetic foot infections has not been carried out in Tunisia.Purpose. The aim was to determine the prevalence of P. aeruginosa isolated from patients with diabetic foot infections (DFIs) in Tunisia and to characterize their resistance, virulence and molecular typing.Methods. Patients with DFIs admitted to the diabetes department of the International Hospital Centre of Tunisia, from September 2019 to April 2021, were included in this prospective study. P. aeruginosa were obtained from the wound swabs, aspiration and soft tissue biopsies during routine clinical care and were confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antimicrobial susceptibility testing, serotyping, integron and OprD characterization, virulence, biofilm production, pigment quantification, elastase activity and molecular typing were analysed in all recovered P. aeruginosa isolates by phenotypic tests, specific PCRs, sequencing, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing.Results. Sixteen P. aeruginosa isolates (16.3 %) were recovered from 98 samples of 78 diabetic patients and were classified into 6 serotypes (O:11 the most frequent), 11 different PFGE patterns and 10 sequence types (three of them new ones). The high-risk clone ST235 was found in two isolates. The highest resistance percentages were observed to netilmicin (69 %) and cefepime (43.8 %). Four multidrug-resistant (MDR) isolates (25 %) were detected, three of them being carbapenem-resistant. The ST235-MDR strain harboured the In51 class 1 integron (intI1 +aadA6+orfD+qacED1-sul1). According to the detection of 14 genes involved in virulence or quorum sensing, 5 virulotypes were observed, including 5 exoU-positive, 9 exoS-positive and 2 exoU/exoS-positive strains. The lasR gene was truncated by ISPpu21 insertion sequence in one isolate, and a deletion of 64 bp in the rhlR gene was detected in the ST235-MDR strain. Low biofilm, pyoverdine and elastase production were detected in all P. aeruginosa; however, the lasR-truncated strain showed a chronic infection phenotype characterized by loss of serotype-specific antigenicity, high production of phenazines and high biofilm formation.Conclusions. Our study demonstrated for the first time the prevalence and the molecular characterization of P. aeruginosa strains from DFIs in Tunisia, showing a high genetic diversity, moderate antimicrobial resistance, but a high number of virulence-related traits, highlighting their pathological importance.

Co-occurrence of problematic facebook and video game use: prevalence and association with mental health disorders among adolescents.

INTRODUCTION: The rapid proliferation of technology and its impact on adolescents' lives have raised concerns about addictive behaviors and its potential consequences, including behavioral and mental health problems. This study investigates the prevalence and risk factors associated with the co-occurrence of Problematic Facebook Use and Problematic Video game Use among Tunisian adolescents. METHODOLOGY: We conducted a cross-sectional study in the urban area of Sousse governorate in Tunisia during the 2018/2019 school year. We selected a representative sample of high school students enrolled in public educational institutions in Sousse. Data collection was performed through a self-administered structured questionnaire, which gathered information on sociodemographic characteristics, lifestyle behaviors, and mental health disorders. Problematic Facebook Use was assessed using the validated Arabic version of the Bergen Scale, while Problematic Video Game Use was measured using the 21-point Lemmens Scale, which was translated into Arabic. Statistical analysis was carried out using the SPSS program (version 20). RESULTS: We enrolled a total of 1342 high school students in our study, of whom, 63.2% were female with a mean age of 17.5 ± 1.44 years. The prevalence of Problematic Facebook Use and Problematic Video Game Use was  28.3% and  13% respectively. Regarding the co-occurrence of the two problematic behaviors, 31.3% of participants faced a singular addictive behavior, either related to problematic Facebook or video game use, while 5% had both addictive behaviors simultaneously. In a multivariate analysis, risk factors for the co-occurrence of Problematic Facebook and Video Game Use, in decreasing order of significance, included severe depression (AOR = 4.527; p = 0.003), anxiety (AOR = 4.216; p = 0.001), male gender (AOR = 4.130; p < 0.001), problematic internet use (AOR = 3.477; p = 0.006), as well as moderate depression (AOR = 3.048; p = 0.007). CONCLUSION: Our study found that Problematic Facebook and Video Game Use were prevalent among Tunisian adolescents. The co-occurrence of these disorders is strongly linked to male gender, problematic internet use, depression, and anxiety disorders. These findings underscore the urgency of implementing tailored and effective awareness and prevention programs to address these emerging challenges.

A novel PIK3CA hot-spot mutation in breast cancer patients detected by HRM-COLD-PCR analysis.

BACKGROUND: The PI3K protein is involved in the PI3K/AKT/mTOR pathway. Deregulation of this pathway through PIK3CA mutation is common in various tumors. The aim of this work is to identify hotspot mutation at exons 9 and 20 in Tunisian patients with sporadic or hereditary breast cancer. METHODS: Hotspot mutations in exon 9 and exon 20 of the PIK3CA gene were identified by QPCR-High Resolution Melting followed by COLD-PCR and sequencing in 63 (42 sporadic cases and 21 hereditary cases) tumor tissues collected from Tunisian patient with breast cancer. MCF7, and BT20 breast cancer cell lines harboring the PIK3CA hotspot mutations E545K and H1047R in exon 9 and exon 20 respectively, were used as controls in HRM experiments. RESULTS: PIK3CA hotspot mutations were detected in 66.7% (28 out of 42) of sporadic BC cases, and in 14.3% (3 out of 21) of hereditary BC. The E545K and the H1048Y were the most prevalent mutations identified in patients with sporadic and hereditary BC, whereas the H1047R hotspot mutation was not found in our patients. Statistical analysis showed that PIK3CA mutation associated with an aggressive behavior in patients with sporadic BC, while it's correlated with age, tumor stage and tumor size in the group patients with hereditary breast cancer. CONCLUSIONS: Our results showed a novel PIK3CA hotspot mutation in Tunisian breast cancer patients detected by HRM-COLD-PCR. Moreover, the absence of PIK3CA hotspot mutation associated with good prognosis.

Docosahexaenoic acid, eicosapentaenoic acid, arachidonic acid, and neural tube defects in Tunisian population.

OBJECTIVE: To determine the effect of maternal status in (plasma and red blood cell) folate, vitamin B12, homocysteine, and vitamin D, as well as their interaction with MTHFR (C677T and A1298C) and MTRR A66G polymorphisms, on maternal plasma docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) levels and the risk of neural tube defects (NTDs). METHODS: ARA, EPA, and DHA composition was assessed using capillary gas chromatography. RESULTS: ARA and DHA levels were higher in controls than in case mothers for low plasma folate status. For low red blood cell folate status, DHA levels were higher in controls than in case mothers. For high homocysteine levels, ARA and DHA levels were higher in controls than in case mothers. NTD mothers had lower EPA and DHA levels for low vitamin B12 levels. NTD mothers had lower DHA levels for low vitamin D levels. For low plasma folate status, DHA levels in the MTHFR C677T gene and ARA and EPA levels in MTHFR A1298C gene were different among the three genotypes in case mothers. DHA levels in the MTHFR C677T gene were different among the three genotypes in case mothers for both low and high homocysteine levels. For low vitamin B12 levels, ARA and DHA levels were different among the three genotypes of the MTHFR C677T gene in case mothers. In the MTHFR C677T gene, ARA and DHA levels were different among the three genotypes in case mothers for low vitamin D levels. CONCLUSIONS: More advanced research is required to verify a suitable biochemical parameter status in relation to the genotypes in pregnant women.

A Knowledge, attitude and practice (KAP) study on sheep owners regarding fasciolosis in northwest of Tunisia.

Fasciolosis is a worldwide zoonotic snail-borne infection that affects ruminants, it causes high economic losses among livestock. A participatory epidemiological survey was conducted on 204 sheep owners of Sejnane region (District of Bizerte, Northwest Tunisia) to assess their knowledge, attitude and practice regarding fasciolosis. All interviewed sheep owners are aware of this parasitic infection (100%, 204/204), among them, 81% (165/204) reported history of clinical cases in their sheep flocks. According to 33.73% (113/335) of them, sheep get infected by fasciolosis mainly by grazing in wet areas, 79.9% (163/204) of these farmers think that wet climate is the most favourable for the infection. Weight loss (28.40%, 121/426) and submandibular oedema (20.42%, 87/426) are the main clinical signs of fasciolosis cited by interviewed sheep owners and the majority of them (98.53%; 201/204) confirmed that fasciolosis causes significant economic losses. Fasciolosis infection persists in Sejnane region despite the use of antiparasitic drugs, this is due mainly to the fact that animals graze in moist grass (39.88%, 132/331). Treat animals (51.47%, 193/375), prohibit grazing on moist grass (15.20%, 57/357), prohibit grazing on wet soils (14.33%, 53/357) and avoid pastures (10.93%, 41/357) are the main prevention measures cited by interviewed sheep owners. Only 18,14% (37/204) of responders knew that fascioliasis is a zoonotic disease. These results could be considered by animal health decision makers and field veterinarians when implementing control programmes in order to increase breeders' knowledge of fasciolosis.

Cystic echinococcosis (Echinococcus granulosus sensu lato infection) in Tunisia, a One Health perspective for a future control programme.

The emergence of pandemics with dramatic consequences for human health has obscured endemic diseases that continue to pose a problem for human and animal health in several regions of the world. Among these diseases, cystic echinococcosis, a zoonotic parasitic infection caused by a group of cestodes, Echinococcus granulosus sensu lato, remains a real human and animal health problem in several regions of the world, including the Mediterranean Basin. Despite the implementation of a number of governmental control programmes using several tools (dog treatment, meat inspection, etc.), this infection is still highly prevalent in North Africa. Here we present a review of the epidemiology of cystic echinococcosis in Tunisia, an analysis of the constraints limiting the effectiveness of the control programmes implemented, and finally argue for the use of the One Health framework to improve the effectiveness of future programmes.

Navigating the Factors Affecting Functional Impairment in Spondyloarthritis.

Objectives: This study aimed to assess the predictive factors of functional impairment in spondyloarthritis (SpA) patients assessed with bath ankylosing spondylitis functional index (BASFI) and Lequesne Index (LI). Methods: This retrospective study was conducted at the Rheumatology Department of Mohamed Kassab Institute of Orthopedics, Manubah, Tunisia, and collected data from 2008 to 2019 over a period of 4 months (August to November 2019). Socio-demographic and disease-related data of SpA patients were collected. Disease activity was assessed using the bath ankylosing spondylitis-global score (BASG-s) and the bath ankylosing spondylitis disease activity index (BASDAI). The spinal mobility was evaluated by the bath ankylosing spondylitis metrology index (BASMI). Structural progression was evaluated with the bath ankylosing spondylitis radiologic index (BASRI) and modified stoke ankylosing spondylitis spine score (mSASSS). A multivariate analysis was done to search for predictive factors associated with BASFI and LI. Results: A total of 263 patients were included. The mean age was 38.9 ± 12.7 years and the gender ratio was 2.7. The mean age of onset of SpA was 27.6 ± 10.8 years and disease duration was 11.3 ± 9.5 years. Occupation was significantly associated with BASFI and LI scores. A significant functional impact was notably correlated with a long duration of the disease. The two scores were correlated with a limitation of spinal mobility (BASMI), a greater disease activity (BASDAI and erythrocyte sedimentation rate) and a greater impact of the disease on health status (BASG-s). Significant functional impairment was also correlated with structural impairment (mSASSS, BASRI and sacroiliitis grade). The variables independently related to BASFI were the mSASSS score and the BASDAI. The variables independently related to LI were profession (unemployed subjects had higher scores), the mSASSS score and the BASMI. Conclusion: Occupation, disease activity, mobility and structural progression predicted functional impairment in Tunisian SpA patients.

Critical care ultrasound among Tunisian intensive care residents: A Cross-sectional Survey.

INTRODUCTION: Critical Care ultrasound (CCUS) is more and more used in Tunisian critical care units. An objective assessment of this training has not yet been performed. AIM: To assess the theoretical and practical knowledge about CCUS among Intensive Care Unit (ICU) residents. METHODS: This is a cross-sectional study conducted during the period from January to June 2021. Data were collected using a French language questionnaire distributed on the day of the selection of the residents' posts for the next training period (at the end of June 2021). RESULTS: Out of 75 residents, 37 accepted to answer to the survey (Participation rate =49 %). The majority were female (66.4%). The mean age was 29±12.36 years. Only 5.4% of participants (n=2) had previously received training concerning echocardiography and only 8.1% of the participants have received dedicated training for lung ultrasound (LU). Among the participants, 80.1% of residents (n=30) had never performed a transthoracic echocardiography (TTE). Competence in performing echocardiography was self-assessed quite good and bad by 5.4% and 43.2% of responders respectively. Most of the residents (86%) did not insert before ultrasound-guided central venous catheters. Views known by the participants using TTE were mainly parasternal long axis section (56.8%) and apical 4/5 chambers section (52.8%). All participants (100%) thought that teaching CCU is a necessary part of the training of intensivists. CONCLUSION: Our study highlighted the lack of training of Tunisian ICU residents regarding CCUS learning. Therefore, it is crucial to integrate such learning and training into their training programs.

Evaluation de l'enseignement par les étudiants : Exemple d'un atelier de simulation sur l'ECG.

INTRODUCTION: The electrocardiogram (ECG) is a fundamental tool in medical practice. At the Faculty of Medicine of Tunis (FMT), it is usually taught during a lecture. FMT's Physiology Department has innovated its teaching by introducing simulation workshops. AIM: This study aimed to assess the students' satisfaction with teaching ECG by simulation. METHODS: This was a cross-sectional descriptive study, carried out in April 2018, including 160 students in the first year of the first cycle of medical studies, divided into 10 groups. The students attended an ECG simulation workshop at the FMT media library and then answered a satisfaction form and a self-assessment questionnaire for the workshop. RESULTS: More than 50% of the students answered either satisfied or very satisfied with the duration of the course, the room, the method of the teacher, and their participation in the course of the session. Regarding teaching support, 19.3% of the students were very satisfied with the practice of the ECG on a mannequin versus 25% for the practice on a voluntary student. For the number of students per group, 42.1% of students were dissatisfied. CONCLUSION: This study highlights the weak points of this simulation workshop in order to improve it. Then, it helps to build students' confidence and encourage their adherence to the feedback process. Finally, it shows students' enthusiasm for new teaching methods such as simulation. It would be interesting to generalize this evaluation process for the improvement of medical education and the training of future doctors.

Assessment of knowledge and perceptions of Tunisian psychiatrists regarding telepsychiatry.

INTRODUCTION: Telemedicine has become a fundamental pillar of the evolution of healthcare worldwide. In Tunisia, the challenges of the health system, amplified by the COVID-19 pandemic, have highlighted the urgency to adopt innovative solutions. In this regard, the publication of Presidential Decree No. 318/2022 on April 8 in the Official Journal of the Tunisian Republic represents a significant advance in the regulation of telemedicine. AIM: To assess the knowledge of Tunisian psychiatrists and child psychiatrists regarding telemedicine, its legal framework, and their perceptions of this new medical practice. METHODS: A descriptive cross-sectional study was conducted 8 months after the issuance of the presidential decree. The survey was conducted online through an electronic questionnaire on Google Forms. RESULTS: A total of 68 participants were included in this survey. The median number of professional years was 5±7 years. Among the participants, 82% worked in psychiatry and 18% worked in child psychiatry. The sector of practice was public in 69% and private in 31% of cases. Most of them (62%) did not know about the different telemedicine acts, and 57% of doctors were unaware of the existence of the presidential decree. The majority of doctors (84%) expressed a favorable opinion regarding the adoption of telepsychiatry, regardless of sex (p=0.69), professional status (p=0.512), specialty (p=1), years of experience (p=0.83), and practice sector (p=1). CONCLUSION: Despite a low level of knowledge regarding telemedicine, the study highlights the interest of the participants in integrating telepsychiatry into their clinical practices.

Doctoral theses at the medical faculty of Tunis from 2015 to 2017: Scientific publication rates and associated factors.

INTRODUCTION: Medical doctoral thesis publication is a way to ensure knowledge dissemination and to increase the scientific research visibility. AIM: To determine thesis-related publication's rate at the Faculty of Medicine of Tunis (FMT), and identify associated factors. METHODS: Cross-sectional retrospective study including medical theses registered at the FMT over the study period (2015-2017). All publications related to the defended thesis were collated by scanning Scopus and Google scholar databases, up to April 2022. Binary logistic regression was performed to assess associated factors to publication. Adjusted Odds Ratios (AOR) were presented with 95% confidence interval. RESULTS: Out of 878 defended theses, 11.8% (n=104) were published. Out of 130 publications in total, 90 (69.2%) interested Scopus-indexed journals with a mean Scimago Journal Rank (SJR) of 0.70. The publication was in English in 73.1% of cases. The median time between the thesis defense and the first scientific publication was 15 months. In multivariable analysis, associated factors to "at least one thesis-related publication" were the resident status of the candidate (AOR=2.35 [1.2-4.7]) and the grade assistant professor of the thesis supervisor (AOR=2.48 [1.1-5.6]). CONCLUSION: Compared to the number of defended theses, the thesis-related publication's rate at the FMT is relatively low. Thus, enhanced support for doctoral students to optimize their engagement in research and to consequently promote scientific publication is highly recommended.

Knowledge of Tunisian physicians about electronic cigarettes.

INTRODUCTION: The electronic cigarette is a new-generation smoking product whose mechanism of use could, in theory, minimize adverse health effects. AIM: Determine the knowledge and perceptions of a sample of Tunisian doctors regarding electronic cigarettes. METHODS: We conducted a descriptive cross-sectional study over a two-month period with a sample of Tunisian doctors. We used an online self-questionnaire on physicians' knowledge and perceptions of e-cigarettes. RESULTS: Data were obtained from 216 physicians. Of the participants, 97.2% were familiar with e-cigarettes, 56.5% reported low knowledge, and 83.4% expressed motivation to learn more about e-cigarettes. Overall, 83.8% of doctors felt that electronic cigarettes are harmful to the user's health. Use of this product would increase the risk of cancer according to 73.1% of participants, the risk of cardiovascular disease according to 68.5% of participants, and the risk of chronic lung disease according to 79.2% of participants. The perception of e-cigarettes as harmful to the user's health was associated with the physicians' medical specialty (p=0.032). The recommendation of e-cigarettes as a smoking cessation tool was negatively correlated with addictology training (p=0.027). CONCLUSIONS: Physicians' knowledge of electronic cigarettes is heterogeneous, reflecting the current lack of information and consensus.

Multivariate investigation of Moringa oleifera morpho-physiological and biochemical traits under various water regimes.

BACKGROUND: The climatic changes crossing the world menace the green life through limitation of water availability. The goal of this study was to determine whether Moringa oleifera Lam. trees cultivated under Tunisian arid climate, retain their tolerance ability to tolerate accentuated environmental stress factors such as drought and salinity. For this reason, the seeds of M. oleifera tree planted in Bouhedma Park (Tunisian arid area), were collected, germinated, and grown in the research area at the National Institute of Research in Rural Engineering, Waters and Forests (INRGREF) of Tunis (Tunisia). The three years aged trees were exposed to four water-holding capacities (25, 50, 75, and 100%) for 60 days to realise this work. RESULTS: Growth change was traduced by the reduction of several biometric parameters and fluorescence (Fv/Fm) under severe water restriction (25 and 50%). Whereas roots presented miraculous development in length face to the decrease of water availability (25 and 50%) in their rhizospheres. The sensitivity to drought-induced membrane damage (Malondialdehyde (MDA) content) and reactive oxygen species (ROS) liberation (hydrogen peroxide (H2O2) content) was highly correlated with ROS antiradical scavenging (ferric reducing antioxidant power (FRAP) and (2, 2'-diphenyl-1-picrylhydrazyle (DPPH)), phenolic components and osmolytes accumulation. The drought stress tolerance of M. oleifera trees was associated with a dramatic stimulation of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), ascorbate peroxidase (APX), and glutathione peroxidase (GPX) activities. CONCLUSION: Based on the several strategies adopted, integrated M. oleifera can grow under drought stress as accentuated adverse environmental condition imposed by climate change.

Impact of an educational intervention on patient safety culture among gynecology-obstetrics' healthcare professionals.

BACKGROUND: In recent years, patient safety has begun to receive particular attention and has become a priority all over the world. Patient Safety Culture (PSC) is widely recognized as a key tenet that must be improved in order to enhance patient safety and prevent adverse events. However, in gynecology and obstetrics, despite the criticality of the environment, few studies have focused on improving PSC in these units. This study aimed at assessing the effectiveness of an educational program to improve PSC among health professionals working in the obstetric unit of a Tunisian university hospital. METHODS: We conducted a quasi-experimental study in the obstetric unit of a university hospital in Sousse (Tunisia). All the obstetric unit's professionals were invited to take part in the study (n = 95). The intervention consisted of an educational intervention with workshops and self-learning documents on patient safety and quality of care. The study instrument was the French validated version of the Hospital Survey on Patient Safety Culture. Normality of the data was checked using Kolmogorov-Smirnov test. The comparison of dimensions' scores before and after the intervention was carried out by the chi2 test. The significance level was set at 0.05. RESULTS: In total, 73 participants gave survey feedback in pre-test and 68 in post-test (response rates of 76.8% and 71.6, respectively). Eight dimensions improved significantly between pre- and post-tests. These dimensions were D2 "Frequency of adverse events reported" (from 30.1 to 65.6%, p < 0.001), D3 "Supervisor/Manager expectations and actions promoting patient safety" (from 38.0 to 76.8%, p < 0.001), D4 "Continuous improvement and organizational learning" (from 37.5 to 41.0%, p < 0.01), D5 "Teamwork within units" (from 58.2 to 79.7%, p < 0.01), D6 "Communication openness" (from 40.6 to 70.6%, p < 0.001), and D7 "Non-punitive response to error" (from 21.1 to 42.7%, p < 0.01), D9 "Management support for patient safety" (from 26.4 to 72.8%, p < 0.001), and D10 "Teamwork across units" (from 31.4 to 76.2%, p < 0.001). CONCLUSIONS: Educational intervention, including workshops and self-learning as pedagogical tools can improve PSC. The sustainability of the improvements made depends on the collaboration of all personnel to create and promote a culture of safety. Staff commitment at all levels remains the cornerstone of any continuous improvement in the area of patient safety.

Catalyzing precision: unraveling the diagnostic conundrum of tunisian familial hypophosphatasia case through integrative clinical and molecular approaches.

Familial Hypophosphatasia presents a complex diagnostic challenge due to its wide-ranging clinical manifestations and genetic heterogeneity. This study aims to elucidate the molecular underpinnings of familial Hypophosphatasia within a Tunisian family harboring a rare c.896 T > C mutation in the ALPL gene, offering insights into genotype-phenotype correlations and potential therapeutic avenues. The study employs a comprehensive approach, integrating biochemical examination, genetic analysis, structural modeling, and functional insights to unravel the impact of this rare mutation. Genetic investigation revealed the presence of the p.Leu299Pro mutation within the ALPL gene in affected family members. This mutation is strategically positioned in proximity to both the catalytic site and the metal-binding domain, suggesting potential functional consequences. Homology modeling techniques were employed to predict the 3D structure of TNSALP, providing insights into the structural context of the mutation. Our findings suggest that the mutation may induce conformational changes in the vicinity of the catalytic site and metal-binding domain, potentially affecting substrate recognition and catalytic efficiency. Molecular dynamics simulations were instrumental in elucidating the dynamic behavior of the tissue-nonspecific alkaline phosphatase isozyme (TNSALP) in the presence of the p.Leu299Pro mutation. The simulations indicated alterations in structural flexibility near the mutation site, with potential ramifications for the enzyme's overall stability and function. These dynamic changes may influence the catalytic efficiency of TNSALP, shedding light on the molecular underpinnings of the observed clinical manifestations within the Tunisian family. The clinical presentation of affected individuals highlighted significant phenotypic heterogeneity, underscoring the complex genotype-phenotype correlations in familial Hypophosphatasia. Variability in age of onset, severity of symptoms, and radiographic features was observed, emphasizing the need for a nuanced understanding of the clinical spectrum associated with the p.Leu299Pro mutation. This study advances our understanding of familial Hypophosphatasia by delineating the molecular consequences of the p.Leu299Pro mutation in the ALPL gene. By integrating genetic, structural, and clinical analyses, we provide insights into disease pathogenesis and lay the groundwork for personalized therapeutic strategies tailored to specific genetic profiles. Our findings underscore the importance of comprehensive genetic and clinical evaluation in guiding precision medicine approaches for familial Hypophosphatasia.

Functional analysis of MMR gene VUS from potential Lynch syndrome patients.

Lynch syndrome is caused by inactivating variants in DNA mismatch repair genes, namely MLH1, MSH2, MSH6 and PMS2. We have investigated five MLH1 and one MSH2 variants that we have identified in Turkish and Tunisian colorectal cancer patients. These variants comprised two small deletions causing frameshifts resulting in premature stops which could be classified pathogenic (MLH1 p.(His727Profs*57) and MSH2 p.(Thr788Asnfs*11)), but also two missense variants (MLH1 p.(Asn338Ser) and p.(Gly181Ser)) and two small, in-frame deletion variants (p.(Val647-Leu650del) and p.(Lys678_Cys680del)). For such small coding genetic variants, it is unclear if they are inactivating or not. We here provide clinical description of the variant carriers and their families, and we performed biochemical laboratory testing on the variant proteins to test if their stability or their MMR activity are compromised. Subsequently, we compared the results to in-silico predictions on structure and conservation. We demonstrate that neither missense alteration affected function, while both deletion variants caused a dramatic instability of the MLH1 protein, resulting in MMR deficiency. These results were consistent with the structural analyses that were performed. The study shows that knowledge of protein function may provide molecular explanations of results obtained with functional biochemical testing and can thereby, in conjunction with clinical information, elevate the evidential value and facilitate clinical management in affected families.

[Placenta accreta: a retrospective descriptive study of 46 patients treated in the Obstetrics and Gynaecology Department of the Farhat Hached University Hospital in Sousse, Tunisia]. / Placenta accreta: étude descriptive rétrospective de 46 cas pris en charge au Service de Gynécologie-obstétrique du Centre Hospitalier Universitaire Farhat Hached de Sousse, Tunisie.

Placenta accreta is a rare but serious placental attachment abnormality. The aim of this study is to analyze the epidemiological, clinical, para-clinical and evolutionary features of placenta accreta, to investigate the therapeutic management and to assess maternal and neonatal morbidity and mortality. We conducted a retrospective, descriptive study of patients with histologically confirmed placenta accreta in the obstetrics and gynaecology department of the Farhat Hached University Hospital in Sousse, over a 4-year period from 1st January 2015 to 31st December 2019. The epidemiological, clinical, paraclinical, therapeutic and evolutionary data were collected from patients´ medical records and operative reports. In our series, we identified 46 cases of placenta accreta. The average age of our patients was 35±4.61 years. Each of our patients had a scarred uterus. The average term of delivery was 34 weeks of amenorrhoea and the mode of delivery was caesarean section for all our patients. First-line hysterectomy was performed in 40 patients and conservative treatment in 6. Sixteen patients developed maternal complications. No maternal death was observed. Placenta accreta is a rare condition associated with significant maternal and foetal morbidity.

Isolation and Molecular Evidence of Tunisian Sheep-like Pestivirus (Pestivirus N) in Persistently Infected Sheep in Northern Italy, 2023.

Over the last few decades, several pestiviruses have been discovered in ruminants, pigs, and, more recently, in non-ungulate hosts. Consequently, the nomenclature and taxonomy of pestiviruses have been updated. The Tunisian sheep-like pestivirus (TSV, Pestivirus N) is an additional ovine pestivirus genetically closely related to classical swine fever virus (CSFV). In this study, during a survey of pestivirus infections in ovine farms in the Lombardy region of Northern Italy, we identified and isolated a pestivirus strain from a sheep that was found to belong to Pestivirus N species based on its genomic nucleotide identity. The sheep itself and its lamb were found to be persistently infected. We performed molecular characterization and phylogenetic analysis of three viral genomic regions (a fragment of 5'-UTR, partial Npro, and the whole E2 region). In conclusion, these results confirmed circulating TSV in Northern Italy after notification in Sicily, Italy, and France. Correlation with Italian, Tunisian, and French strains showed that detection might have resulted from the trading of live animals between countries, which supports the need for health control measures.