Neurological diagnostic tests for patients with and without delirium: a prospective observational study.

Since most of the precipitating factors of delirium are not due to neurological disorders, neurological diagnostic tests (NDTs) may be of limited value. We hypothesized that delirium has a high burden of NDTs with a low diagnostic yield. All patients admitted to the internal medicine wards of a single secondary teaching hospital between November 2019 and January 2020 were eligible. Within the first 48 h of their admission, they had a formal evaluation by a neuropsychologist to screen for presence of delirium. NDTs (brain MRI, brain CT, electroencephalography (EEG), and lumbar puncture) performed during the hospital stay were compared between patients with and without delirium using a logistic regression model stratified by a propensity score. The proportions of diagnostic yield (acute anomalies that changed the treatment management) provided by each type of examination were compared. Of 217 patients included, 19/32 patients (61%) with delirium had one or more NDTs, compared to 48/185 (26%) without delirium (adjusted OR 2.7; 95%CI 1.1-6.7; p = 0.027). The proportions of NDT results affecting management for patients with and without delirium were 13 and 20% for brain CT scans (p = 0.71), 29 and 38% for brain MRI (p = 0.99), and 20 and 10% for EEGs (p = 0.99), respectively. The higher proportion of NDTs performed on patients with delirium was associated with a low diagnostic yield, although not statistically different from those performed among inpatients without delirium. There is a need for restrictive, evidence-based guidelines to help with the work-up for patients with delirium.

The Synthesis of 2'-Hydroxychalcones under Ball Mill Conditions and Their Biological Activities.

Chalcones are polyphenols that belong to the flavonoids family, known for their broad pharmacological properties. They have thus attracted the attention of chemists for their obtention and potential activities. In our study, a library of compounds from 2'-hydroxychalcone's family was first synthesized. A one-step mechanochemical synthesis via Claisen-Schmidt condensation reaction under ball mill conditions was studied, first in a model reaction between a 5'-fluoro-2'-hydroxyacetophenone and 3,4-dimethoxybenzaldehyde. The reaction was optimized in terms of catalysts, ratio of reagents, reaction time, and influence of additives. Among all assays, we retained the best one, which gave the highest yield of 96% when operating in the presence of 1 + 1 eq. of substituted benzaldehyde and 2 eq. of KOH under two grinding cycles of 30 min. Thus, this protocol was adopted for the synthesis of the selected library of 2'-hydroxychalcones derivatives. The biological activities of 17 compounds were then assessed against Plasmodium falciparum, Leishmania donovani parasite development, as well as IGR-39 melanoma cell lines by inhibiting their viability and proliferation. Compounds 6 and 11 are the most potent against L. donovani, exhibiting IC50 values of 2.33 µM and 2.82 µM, respectively, better than the reference drug Miltefosine (3.66 µM). Compound 15 presented the most interesting antimalarial activity against the 3D7 strain, with IC50 = 3.21 µM. Finally, chalcone 12 gave the best result against IGR-39 melanoma cell lines, with an IC50 value of 12 µM better than the reference drug Dacarbazine (IC50 = 25 µM).

Knowledge, attitudes and mental health of sub-Saharan African migrants living in Tunisia during COVID-19 pandemic.

COVID-19 pandemic potentially impacted the mental health of migrants. Our objective was to measure the prevalence of psychological distress among a group of sub-Saharan African migrants living in Tunisia, and its association with knowledge about COVID-19. The Questionnaire of Knowledge towards COVID-19 (QK-COVID-19) was used to evaluate the level of Knowledge about COVID-19. The participants were asked about their attitudes for seeking information and healthcare services related to the pandemic using a multiple-choice questionnaire. The Hopkins Symptoms Checklist (HSCL-25)) was used to screen for anxiety and depression. A logistic regression was used to estimate the adjusted odds of having psychological distress across levels of QK-COVID-19 score. Among the 133 participants, 34.6% (95% CI: 26.5, 42.67) had psychological distress, 91% were unemployed and 96% uninsured. Of the respondants, 20% had low QK-COVID-19 score , and 44.36% had medium score. The adjusted odds of psychological distress for those with high and medium QK-COVID-19 scores were respectively 3.9 (95% CI: 1.08, 14.13) and 6.39 (95% CI: 1.79, 22.9) times that of those with low scores. Screening and early treatment of anxiety and depression among migrants during outbreaks is an imperative. Further investigations of the determinants of mental health of sub-Saharan African migrants are needed.

Autosomal recessive congenital hereditary corneal dystrophy associated with a novel SLC4A11 mutation in two consanguineous Tunisian families.

BACKGROUND: Autosomal recessive congenital hereditary corneal dystrophy (CHED) is a rare isolated developmental anomaly of the eye characterised by diffuse bilateral corneal clouding that may lead to visual impairment requiring corneal transplantation. CHED is known to be caused by mutations in the solute carrier family 4 member 11 (SLC4A11) gene which encodes a membrane transporter protein (sodium bicarbonate transporter-like solute carrier family 4 member 11). METHODS: To identify SLC4A11 gene mutations associated with CHED (OMIM: #217700), genomic DNA was extracted from whole blood and sequenced for all exons and intron-exon boundaries in two large Tunisian families. RESULTS: A novel deletion SLC4A11 mutation (p. Leu479del; c.1434_1436del) is responsible for CHED in both analysed families. This non-frameshift mutation was found in a homozygous state in affected members and heterozygous in non-affected members. In silico analysis largely support the pathogenicity of this alteration that may leads to stromal oedema by disrupting the osmolarity balance. Being localised to a region of alpha-helical secondary structure, Leu479 deletion may induce protein-compromising structural rearrangements. CONCLUSION: To the best of our knowledge, this is the first clinical and genetic study exploring CHED in Tunisia. The present work also expands the list of pathogenic genotypes in SLC4A11 gene and its associated clinical diagnosis giving more insights into genotype-phenotype correlations.

TIPS-Diazoacetone Aldol Addition: Mechanistic Aspects and Contribution to the Synthesis.

Aldol addition of α-triisopropylsilyl-α-diazoacetone (TIPS-diazoacetone), promoted by excess lithium diisopropylamide (LDA), was developed and applied to the synthesis of original C-TIPS diazoaldols, C-TIPS diazoketols, and a related Mannich-type product. An unprecedented mechanistic pathway has been proposed, involving a lithiated triazene intermediate resulting from the nucleophilic addition of LDA on the diazo moiety, supported by experimental results and DFT calculations.

Novel BEST1 gene mutations associated with two different forms of macular dystrophy in Tunisian families.

BACKGROUND: Epidemiological studies of hereditary eye diseases allowed us to identify two Tunisian families suffering from macular dystrophies: Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB). The purpose of the current study was to investigate the clinical characteristics and the underlying genetics of these two forms of macular dystrophy. METHODS: Complete ophthalmic examination was performed including optical coherence tomography, electroretinography, electrooculography and autofluoresence imaging in all patients. Genomic DNA was extracted from peripheral blood collected from patients and family members. RESULTS: Sanger sequencing of all exons of the BEST1 gene in both families identified two new mutations: a missense mutation c.C91A [p.L31 M] at the N-terminal transmembrane domain within the ARB family and a nonsense mutation C1550G (p.S517X) in the C-terminal domain segregating in the BVMD family. CONCLUSIONS: Several mutations of the BEST1 gene have been reported which are responsible for numerous ocular pathologies. To the best of our knowledge, it is the first time we report mutations in this gene in Tunisian families presenting different forms of macular dystrophy. Our report also expands the list of pathogenic BEST1 genotypes and the associated clinical diagnosis.

Enterobius vermicularis: A Cause of Abdominal Pain Mimicking Acute Appendicitis in Children. A Retrospective Cohort Study.

BACKGROUND: Enterobius vermicularis (EV) is the most common helminthic infection in the world. This small parasite is predominant in the pediatric population. The presence of EV in the appendix can cause or mimick appendicitis. The aim of our study was to compare patients with EV infection and those without EV infection, and to identify predictive factors that may help the diagnosis of EV infection in patients presenting with right iliac fossa pain and avoid negative appendectomy. METHODS: A retrospective analysis of all the appendices removed between January 2012 and December 2016 was conducted at the department of pediatric surgery, Hedi Chaker Hospital, Sfax, Tunisia. According to the final histopathological diagnosis, patients with EV infection were compared to those without EV infection. Data including age, sex, white blood cell (WBC) count, neutrophil count, eosinophil count, C-reactive protein, and ultrasound results for both groups were analyzed and compared. The study protocol was approved by the local hospital ethics committee. Statistical analysis was performed using IBM SPSS, version 20. Descriptive analysis in the form of mean and standard deviation was performed on demographic information. Differences between groups were assessed using the student t-test for continuous variables and the χ2 test and Fisher exact test where appropriate for categorical variables. RESULTS: In total, 540 pediatric appendectomies were performed. Overall, 63.5% of patients were male and 36.5% were female. Mean age was 9.28 ± 2.77 years. 22.2% of procedures were completed laparoscopically, 76.5% were open and 1.3% were converted. The negative appendectomy rate was 11.1%. EV was present in 9.8% of cases. Comparison of clinical, biological, and ultrasound findings between two groups of patients with EV (EV+) and those without EV (EV-) shows a statistical significance for pruritus ani (P < 0.001), WBC count (P < 0.001), neutrophil count (P < 0.001), C-reactive protein (CRP) (P = 0.001), positive ultrasound (P < 0.001), perforation rate (P = 0.009), and negative appendectomy rate (P < 0.001). No significant difference between the two groups was seen when comparing gender (P = 0.271), vomiting (P = 0.130), eosinophil count (P = 0.915), and procedure (P = 0.536). CONCLUSION: EV was seen in 9.8% of pediatric appendectomies in our study. Pruritus ani, normal WBC count, normal neutrophil count, and normal CRP level at presentation could predict EV infection in children who present with right iliac fossa pain.

Ocular involvement associated with varicella in adults.

BACKGROUND: Varicella is a common infectious disease primarily of childhood that is usually benign and self-limited. It is, however, increasingly seen in adults who are at a higher risk of severe infection. Ocular complications of varicella are relatively uncommon and have been rarely described in adults. We describe herein five adults who developed ocular involvement in association with primary varicella-zoster virus infection. FINDINGS: Ocular manifestations included acute anterior uveitis in four eyes, with associated stromal keratitis in one of them, epithelial ulcerative keratitis in the two eyes of one patient, and acute retinal necrosis in one eye. One patient with acute anterior uveitis was treated with topical steroids and cycloplegic agents. The four other patients received topical or systemic antiviral drugs, with subsequent resolution of acute ocular inflammatory disease. CONCLUSIONS: The spectrum of chickenpox-associated ocular complications in adults is wide. Early diagnosis and appropriate management are mandatory to improve visual outcome.

TBAF-Triggered Aldol-Type Addition of α-Triethylsilyl-α-diazoacetone.

Aldol-type addition of α-triethylsilyl-α-diazoacetone was achieved under nucleophilic activation by tetrabutylammonium fluoride (TBAF). The use of a semistoichiometric amount of TBAF (protocol P1) provided the corresponding ß-hydroxy-α-diazoacetone as the sole product. Alternatively, the use of a catalytic amount of TBAF led to a mixture of ß-hydroxy- and ß-silyloxy-α-diazoacetone products, which was cleanly desilylated with Et3N·3HF (protocol P2). The weakly basic conditions employed tolerate a wide range of substrates and constitute a high-yielding, convenient complementary procedure to the low-temperature LDA-promoted aldol-type addition of diazoacetone.

A Novel Mutation p.A59P in N-Terminal Domain of Methyl-CpG-Binding Protein 2 Confers Phenotypic Variability in 3 Cases of Tunisian Rett Patients: Clinical Evaluations and In Silico Investigations.

Rett syndrome is a monogenic X-linked dominant neurodevelopmental disorder related to mutation in MECP2, which encodes the methyl-CpG-binding protein MeCP2. The aim of this study was to search for mutations of MECP2 gene in Tunisian Rett patients and to evaluate the impact of the found variants on structural and functional features of MeCP2. The result of mutation analysis revealed that 3 Rett patients shared the same novel heterozygous point mutation c.175G>C (p.A59P). The p.A59P mutation was located in a conserved amino acid in the N-terminal segment of MeCP2. This novel mutation confers a phenotypic variability with different clinical severity scores (3, 8, and 9) and predicted by Sift and PolyPhen to be damaging. Modeling results showed that p.A59P adds 2 hydrogen bonds and changes the structural conformation of MeCP2 with a significant root mean square deviation value (9.66 Å), suggesting that this mutation could probably affect the conformation, function and stability of MeCP2.

[Study of a Tunisian population of children with learning disorders]. / Etude d'une population tunisienne d'enfants en difficultés scolaires.

BACKGROUND: Learning disorders are increasingly a concern for Tunisians parents. These difficulties are divided into two groups: specific learning disabilities and non-specific learning disorders. AIM: Our work is part of a federated research project. Our aim is to determine the incidence, etiology and management of learning disorders in the region of Sfax. METHODS: We conducted a descriptive cross-sectional study on a population of 304 children assessed by their teachers as having academic difficulty. A multidisciplinary assessment including a neurological examination, an assessment of score of intelligence and language assessment has been performed for 209 children. RESULTS: Referring to our sample, learning disorders affect 21.3% of children in the region Sfax. The frequency of specific learning disorder is estimated at 10.3% (reading disorder 5.9%, dyscalculia 2.4%, reading disorder associated with dyscalculia 2%). Non-specific learning disorders were found in 11% of children. Etiologies in this group were dominated by mental retardation (2.1%), inappropriate education (2.3%). CONCLUSION: Our study revealed the high frequency of learning difficulties. It allows us to distinguish between specific learning disabilities and non specific learning disorders secondary to neurological or precarious socio-economic conditions. However, the profile and severity of specific learning disorders could not be studied due to the lack of standardized Arabic tests in Tunisia. In countries with a lack of professional and specialized unit care as in Tunisia, reading interventions in school should be proposed. Only children with remaining difficulties after this training will be sent to specialized professionals.

A novel mutation in FGD4/FRABIN causes Charcot Marie Tooth disease type 4H in patients from a consanguineous Tunisian family.

Charcot-Marie-Tooth (CMT) disease constitutes a clinically and genetically heterogeneous group of hereditary neuropathies characterized by progressive muscular and sensory loss in the distal extremities with chronic distal weakness, deformation of the feet, and loss of deep tendon reflexes. CMT4H is an autosomal recessive demyelinating subtype of CMT, due to mutations in FGD4/FRABIN, for which nine mutations are described to date. In this study, we describe three patients from a consanguineous Tunisian family, presenting with severe, early onset, slowly progressive, autosomal recessive demyelinating CMT, complicated by mild to severe kyphoscoliosis, consistent with CMT4H. In these patients, we report the identification of a novel homozygous frameshift mutation in FGD4: c.514_515insG; p.Ala172Glyfs*27. Our study reports the first mutation identified in FGD4 in Tunisian patients affected with CMT. It further confirms the important clinical heterogeneity observed in patients with mutations in FGD4 and the lack of phenotype/genotype correlations in CMT4H. Our results suggest that FGD4 should be screened in other early-onset CMT subtypes, regardless of the severity of the phenotype, and particularly in patients of consanguineous descent. In Tunisians, as in other populations with high consanguinity rates, screening of genes responsible for rare autosomal recessive CMT subtypes should be prioritized.