Glioblastoma Multiforme heterogeneity profiling with solid-state micropores.

Glioblastoma multiforme (GBM) is the most common and lethal type of brain cancer. It is characterized by widespread heterogeneity at the cellular and molecular levels. The detection of this heterogeneity is valuable for accurate diagnosis. Herein, solid-state 20 µm diameter micropore made in thin suspended silicon dioxide membrane is used as cell sensor device. The device relies on a cell's mechano-physical properties as an indicator to differentiate between the subtypes of GBM. A library of GBM cell lines (U251, U87, D54 EGFRviii, and G55) was created by measuring the differences in cell's micropore translocation properties from their distinct electrical profiles. Each GBM subtype has distinct phenotype and this was delineated in their cell translocation behaviors. The library was used to distinguish cells from samples of brain tumor patients. The micropore device accurately profiled GBM patient samples for cell subtypes by comparing data with the GBM library. The micropore approach is simple, can be implemented at low cost and can be used in the clinical setups and operation theaters to detect and identify GBM subtypes from patient samples.

Application of lactic acid bacteria in removing heavy metals and aflatoxin B1 from contaminated water.

In this study selected lactic acid bacteria (LAB, Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus plantrium and Streptococcus thermophiles) and probiotic bacteria (Bifidobacterium angulatum) were tested for their ability in removing heavy metals (HM) including cadmium (Cd), lead (Pb) and arsenic (As) as well as aflatoxin B1 (AFB1) from contaminated water. The biosorption parameters (pH, bacterial concentration, contact time and temperature) of removal using individual as well as mixed LAB and probiotic bacteria were studied. Removal of HM and AFB1 depended on the strain, wherein the process was strongly pH-dependent with high removal ability at a pH close to neutral. The increase in bacterial concentration enhanced the removal of Cd, Pb and As. Also, increasing of contact time and temperature increased the ability of LAB to remove HM. The effect of contact time on Cd removal was slightly different when freshly cultured cells were used. The removal of Cd, Pb and As decreased with the increase in the initial metal concentration. The most effective HM removers were Lactobacillus acidophilus and Bifidobacterium angulatum. The system was found to be adequate for concentrations of HM under investigation. At the end of the operation, the concentration of HM reached the level allowed by the World Health Organization regulations.

Infantile and childhood onset PLA2G6-associated neurodegeneration in a large North African cohort.

BACKGROUND AND PURPOSE: Mutations in the PLA2G6 gene are causative of PLA2G6-associated neurodegeneration (PLAN), a spectrum of neurodegenerative conditions including infantile, childhood and adult onset forms. METHODS: Seventeen North African patients with a clinical suspicion of infantile-onset PLAN underwent clinical, neurophysiological and neuroimaging examinations, and PLA2G6 sequencing. Haplotype analysis was performed to date the identified founder mutation. RESULTS: All patients carried biallelic mutations in PLA2G6. Sixteen children had the commonest form of infantile-onset PLAN, with early onset of psychomotor regression, hypotonia, pyramidal and cerebellar signs, and abnormal ocular movements. The phenotype was highly homogeneous, with rapid development of severe spastic tetraparesis, cognitive impairment and optic atrophy. Neuroimaging showed cerebellar atrophy and claval hypertrophy to be the commonest and earliest signs, whilst cerebellar cortex hyperintensity and pallidal iron deposition were later findings. Motor or sensory-motor neuropathy and electroencephalogram fast rhythms were also frequent. Nine patients from six families shared the same founder mutation (p.V691del) which probably arose by the late seventeenth century. Only one patient fitted the diagnosis of the much rarer childhood-onset PLAN. Despite the early onset (18 months), clinical progression was slower, with behavioral disturbances and dystonia. Typical features of infantile-onset PLAN such as hypotonia, nystagmus/strabismus, optic atrophy, electroencephalogram fast rhythms and motor neuropathy were absent. Cerebellar atrophy, claval hypertrophy and pallidal hypointensity were evident at brain magnetic resonance imaging. This patient carried a missense variant predicted to be less deleterious. CONCLUSIONS: The PLAN-associated phenotypes and the challenges of diagnosing the childhood-onset form are delineated, and a common North African founder mutation is identifed.

[Acute disseminated encephalomyelitis in Tunisia: Report of a pediatric cohort]. / Encéphalomyélite aiguë disséminée en Tunisie: étude d'une cohorte pédiatrique.

INTRODUCTION: Acute disseminated encephalomyelitis (ADEM) is an inflammatory, demyelinating disorder of the central nervous system whose clinical features, management and outcome are incompletely understood in Tunisian population. OBJECTIVE: To describe clinical, neuroimaging and laboratory features; treatment and outcome in a cohort of Tunisian children with ADEM. METHODS: We conducted a retrospective review of the medical records of all children attending the Department of Child and Adolescent Neurology (Tunis) with ADEM between 2005 and 2015. Clinical, neuroimaging and laboratory features, therapeutic data and outcome were analyzed. RESULTS: There were 15 children (7 males and 8 females). The mean age at onset was 6.9 years. Thirteen (86.6%) patients had a prodromal event. The onset of neurological symptoms occurred within 17.6 days (4-30). Limb weakness was the most common presenting symptom (53.3%). Extrapyramidal syndrome was noticed in 6 patients (40%). Initial MRI showed a deep gray matter involvement in 7 cases (46.6%). Gadolinium enhancement at acute stage was observed in only 2 patients (13%). Cerebrospinal fluid findings did not show intrathecal oligoclonal bands. The use of high-dose IV methylprednisolone followed by oral steroid taper was associated with rapid recovery. Additional treatment with intravenous immunoglobulin was necessary in 2 patients. Complete recovery was obtained in 11 patients (73.3%). A monophasic course was noticed in 14 cases. Only one patient (5%) developed multiple sclerosis. CONCLUSION: The high frequency of prodromal events and extrapyramidal syndrome in addition to the low rate of gadolinium enhancement at acute stage seem to be the main features in our patients. Larger ADEM multicenter cohort studies in Tunisia and North Africa could provide more detailed information about this entity.

[Botulinum toxin in the management of spasticity in children]. / Place de la toxine botulique dans le traitement de la spasticité de l'enfant.

INTRODUCTION: Spasticity is a motor disorder, which can be treated by botulinum toxin (BT). We found no studies describing BT management of spasticity in Tunisian children. The aim of our study was to determine the frequency of spastic children treated with BT in the Tunisian hospital population and to evaluate treatment efficacy. METHODS: We conducted a prospective study over a 5-year period including all children diagnosed with spasticity treated with BT and attending the "Movement Disorders and Botulinum Toxin" outpatient clinic of the National Institute of Neurology of Tunis. RESULTS: Hundred and fifteen patients were included (31% of patients attending the "Movement Disorders and Botulinum Toxin" outpatient clinic). Mean age was 7.6years and M:F sex ratio 1.7. Main clinical features were: spastic quadriplegia (48%), equinus deformity (70.4%) and cerebral palsy (88%). All patients were evaluated with the modified Ashworth score and were treated with BT. Other treatments were associated with BT: baclofene, physiotherapy, ortheses, plaster, and sometimes surgical treatment. The average percentage of improvement after BT was>50%. The Ashworth score was significantly lower for the majority of injected muscles. DISCUSSION AND CONCLUSION: Our study is the first to describe BT management of spasticity in Tunisian children. Treatments of spasticity are numerous and vary according to location and extent of spasticity. BT is the main treatment for focal spasticity. Associated with physical therapy, BT allows optimal management of spastic children.

Awareness and Knowledge of Medical Interns in the Diagnosis and Management of Anaphylaxis in Medina Region, Saudi Arabia.

Background Anaphylaxis is a severe hypersensitivity reaction caused by IgE-mediated mechanisms. This life-threatening condition affects multiple body systems. Global lifetime prevalence estimates for anaphylaxis range from 0.3% to 5.1%, with increasing incidence noted, particularly among young individuals. Symptoms range from mild skin manifestations like urticaria and pruritus to severe respiratory distress and hypotension. Objectives This study aimed to assess the knowledge level of medical interns in the Medina region, Saudi Arabia, regarding the diagnosis and management of anaphylaxis. Method A prospective cross-sectional study was conducted in hospitals in Saudi Arabia by delivering a questionnaire designed to assess the level of awareness and knowledge (including signs, symptoms, and management of anaphylaxis) among medical interns in the Medina region. The data collected were coded and analyzed using IBM SPSS Statistics for Windows, Version 22.0 (released 2013, IBM Corp., Armonk, NY). Results The study involved 291 interns from the universities in the Medina region. Most participants (275, 94.5%) correctly defined anaphylaxis and identified food allergies or insect stings as the main triggers (254, 87.3%). The participants demonstrated good knowledge of health education practices and anaphylaxis symptoms, such as the importance of carrying an adrenaline auto-injector (269, 92.4%) and recognizing syncope as a cardiovascular symptom (196, 67.4%). Regarding management, most correctly identified the initial step as removing the allergen (226, 77.7%) and epinephrine as the preferred medication (256, 88.0%). Significant gender differences were observed in the knowledge of management aspects (P = 0.001, P = 0.002, P = 0.049, P = 0.004, P = 0.001). Conclusion The study found that most participants had a good understanding of the definition of anaphylaxis and its most common triggers. The participants also demonstrated knowledge of symptoms and signs associated with anaphylaxis and the appropriate management of anaphylaxis. However, there were some differences in knowledge between females and males, suggesting that further education and awareness campaigns may be needed to ensure an accurate and consistent understanding of anaphylaxis among both genders. Overall, the study highlights the importance of education and awareness in effectively managing anaphylaxis and preventing its complications.

[Clinical and therapeutic aspects in Tunisian patients with dystonia: a 5-year prospective study]. / Aspects cliniques et thérapeutiques des dystonies en Tunisie : étude prospective sur cinq ans.

INTRODUCTION: Studies of dystonia are heterogeneous and there are no studies on this disease in Tunisia. The aim of our study was to determine the frequency of dystonia in the hospital population, to identify different forms of dystonia according to age of onset, distribution, to determine etiologies and to describe treatment. METHODS: We conducted a prospective study over a 5-year period (from January 2005 to November 2009) including all patients diagnosed with dystonia and followed at the Child and Adolescent Neurology Department and "Movement Disorders and Botulinum Toxin" consultation of the National Institute of Neurology of Tunis. RESULTS: Two hundred patients were included (2.2% of our patients). Mean age was 26.4±21.4 years and sex ratio H:F 1.3. Consanguinity rate was 29%. Main features of dystonia were action dystonia (78.5%), generalized forms (47%) and secondary forms (58%). A pyramidal syndrome and other movement disorders were the most common signs associated with dystonia (36.5% and 33.5% respectively). In the group of secondary dystonia, mains etiologies were dystonia due to exogenic agent (56%), neuro-metabolic diseases (26%), hereditary degenerative disease (13%) and psychogenic dystonia (5%). Dystonia was primary in 44% (84 patients). Different treatments were used and a dramatic improvement in some patients was noted with levodopa and botulinum toxin injections. A multidisciplinary approach associated with medical treatment led to recovery or improved prognosis. DISCUSSION AND CONCLUSION: Very few studies have been devoted to reporting a large series of dystonic patients. Our study is the first to describe both primary and secondary dystonia in 200 Tunisian patients. The presence of familial dystonia in our country suggests a genetic origin. Further work including genetic analysis with a screening of known mutations responsible for dystonia and the informative families with unknown mutations would be useful. Specific studies designed to identify new genes causal in dystonia are needed.

The Impact of Allergic Rhinitis on Asthma and Its Effect on the Quality of Life of Asthmatic Patients.

Background Allergic rhinitis (AR) and asthma are one of the most common diseases in the Kingdom of Saudi Arabia. Asthma and AR patients report significant reductions in their daily activities due to this condition. Therefore, measuring health-related quality of life (HRQOL) in adult asthmatic and AR patients and evaluating the use of allergic rhinitis treatment modalities to improve asthma control may help prevent future respiratory complications, improve patient quality of life, and reduce morbidity. Methods This cross-sectional observational study was conducted through an online self-administrated questionnaire distributed electronically on social media through "Survey Monkey" (http://www.surveymonkey.com) from April 2 to September 18, 2021. The study targeted adult patients with asthma and/or allergic rhinitis residing in the Riyadh region of Saudi Arabia. The study compared and evaluated HRQOL between three groups: asthmatic patients with concomitant AR, patients with asthma only, and patients with AR only. Results A total of 811 questionnaires were analyzed. Of those, 23.1% were diagnosed with asthma and 64% were diagnosed with allergic rhinitis; from those who were diagnosed with AR, 27.2% were asthmatics. A statistically significant association was observed between receiving AR medications and asthma control in respondents with intermittent AR (P < 0.001). However, no association was observed between asthma control and receiving medications for AR in respondents with persistent AR (P = 0.589). The average scores for all eight-item short-form (SF-8) QOL dimensions were lower in patients with combined asthma and AR than in patients with AR only and asthma only (P < 0.001). Conclusions This study suggested that AR was associated with more severe asthma and quality of life impairment.

SQSTM1 mutation: Description of the first Tunisian case and literature review.

BACKGROUND: Mutations in SQSTM1 gene have been recently identified as a rare cause of progressive childhood neurodegenerative disorder. So far, only 25 patients from 10 unrelated families were reported. METHODS AND RESULTS: We report on the first Tunisian case of an 11-year-old girl with cerebellar ataxia, chorea and ophthalmoparesis. Brain MRI was normal. Whole-exome sequencing revealed a homozygous mutation c.823_824del(p.Ser275Phefs*17) in SQSTM1 gene (GenBank: NM_003900.4). CONCLUSION: By pooling our data to the data of literature, we delineated the phenotypic spectrum and stressed on genetic heterogeneity of this rare neurodegenerative disease.

[Cerebromediastinal tuberculosis in a child with a probable Say-Barber-Miller syndrome: a causative link?]. / Tuberculose cérébromédiastinale chez un enfant atteint de syndrome de Say-Barber-Miller probable : un lien de causalité ?

INTRODUCTION: Tuberculosis continues to be a public health problem in emerging countries with a recent evidence of increased incidence of extrapulmonary localization in developed countries probably linked to HIV. To our knowledge the occurrence of cerebro-mediastinal tuberculosis in an immuno-competent child has not been previously described; moreover the child we describe has a probable Say-Barber-Miller syndrome. We discuss a putative causative link between this syndrome and the occurrence of tuberculosis. CASE REPORT: A seven-year-old girl presented to our department with a history of infantile encephalopathy since birth characterized by a facial dysmorphy (evocative of a bird face), microcephaly, and mental retardation, and with recurrent infections. The child had complained of back pain for several months; the parents reported anorexia, loss of weight. Spinal and cerebral MRI showed a mediastinal mass involving the spine and cerebral lesions evocative of tuberculomas. The tuberculin interdermal reaction was positive. Culture of a vertebral biopsy was positive for Koch bacillus. Anti-tuberculosis treatment improved general and local status. An extensive immunological work-up was normal. CONCLUSION: [corrected] This observation is exceptional in many aspects: very early age of onset of extrapulmonary tuberculosis, no immune deficit, association with a rare congenital neurological syndrome. We discuss the possible link between this entity and the occurrence of tuberculosis.

[An overview of neurometabolic diseases in Tunisia. a 3-year prospective study]. / Diagnostic et prise en charge des maladies neurométaboliques en Tunisie. Etude prospective sur trois ans.

INTRODUCTION: Neurometabolic diseases are a large group of genetic diseases. In our country, the diagnostic and therapeutic approach to theses diseases is rather difficult. The aim of our study was to determine the frequency of neurometabolic diseases in the hospital population, to describe the problems in diagnosing these conditions and difficulties encountered during patient care. Our goal was to propose guidelines for a practical diagnostic and therapeutic approach to neurometabolic disorders in our country. METHODS: We have conducted a prospective study over a 3-year period including all patients diagnosed with "metabolic disease" and followed at the Child and Adolescent Neurology Department of the National Institute of Neurology of Tunis. RESULTS: One hundred and thirty-six patients were included (2.4% of our patients). Mean age was 7.3 +/- 5.1 years. Mean age at onset was 4.3 years. There was a high consanguinity rate. Respiratory chain defects were the most frequently suspected diseases (16.9%), followed by lysosomal diseases (8.8%). Chromatography, initially systematically prescribed, became targeted with a higher diagnostic efficacy. Metabolic diseases diagnosed as certain, represented 22% of the studied cases. This can be explained by the insufficiency of available laboratory tests of confirmation. The prescription of specific treatment was insufficient, even for confirmed pathologies (14.7%) because of the high cost of these therapies. CONCLUSION: The diagnostic approach has to be rational, targeted, multidisciplinar and conducted within a care network. Diagnostic priority should focus on treatable neurometabolic diseases. The establishment of a systematized registry and neonatal screening for the main treatable neurometabolic diseases constitute the final objective of our work to prepare for biochemical and genetic studies.

Genetically engineered colorimetric single-chain antibody fusion protein for rapid diagnosis of rabies virus.

The most widely used test for rabies diagnostics is the fluorescent antibody test, which is recommended by both the World Health Organization and the World Organisation for Animal Health (OIE). This test may be used directly on a smear, and can also be used to confirm the presence of rabies antigen in cell culture or in brain tissue for diagnosis. The colorimetric enzymes are usually coupled to an antibody by chemical means using cross-linking reagents. However, such non-specific procedures lead to heterogeneous conjugates, sometimes with reduced activity and specificity. To bypass these problems, genetic engineering has provided a way to create chimeric bifunctional molecules in which the variable domains of an antibody are genetically linked to unrelated protein tracers. In this study, we describe the successful production of a bifunctional chimeric protein based on alkaline phosphatase-fused anti-rabies virus glycoprotein scFv antibody fragment. We also report the antigen binding properties and the alkaline phosphatase activity of the recombinant conjugate protein. We established its value as a novel in vitro tool for detecting the rabies virus in brain smear in a one-step procedure; it presents a similar sensitivity and specificity to that obtained using standard reagents.

Expression of Cell-Penetrating Peptides Fused to Protein Cargo.

Cell-penetrating peptides (CPPs) are short peptides that can cross cell membranes. CPPs enable the delivery of biomolecules into cells and can act as drug-delivery vectors. Because recombinant production of CPPs as fusions to protein "cargo" leads to low yields for some CPP-cargo fusions, approaches to enhance the recombinant expression of peptide-cargo fusions need to be identified. We optimized expression conditions in Escherichia coli for fusions of CPPs (SynB, histatin-5, and MPG) to the cargo proteins biotin carboxyl carrier protein, maltose-binding protein, and green fluorescent protein. We used Western blotting to evaluate induction temperatures of 37, 30, and 20°C, and induction times of 6, 10, and 24 h. Glutathione-S-transferase was incorporated as a fusion partner to improve expression. In general, expression at 37°C for 6 and 10 h led to the highest levels of expression for the different CPP-cargo constructs. The improvements in expression of CPP-cargo fusions will allow higher yields of CPP-cargo fusions for studies of their translocation into cells.

Pyridoxine-dependent epilepsy: A novel mutation in a Tunisian child.

Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive metabolic disease characterized by seizures in neonates or infants, which is unresponsive to antiepileptic drugs but controlled by pyridoxine. Without prompt treatment, continued seizures and severe encephalopathy result. Mutations in the ALDH7A1 gene encoding α-amino-adipic semialdehyde (α-AASA) dehydrogenase (antiquitin) have been identified as the cause of PDE. We report on a novel ALDH7A1 mutation in a Tunisian child with PDE.

[Type I glutaric aciduria: an unrecognized cause of progressive dystonia]. / L'acidurie glutarique type I: une cause méconnue de dystonie progressive.

INTRODUCTION: Glutaric acidemia type I is one of the least rare organic acidemias. The number of diagnosed causes is however still low because the presentation is variable and often confusing. The disease may sometimes have a slowly progressive course. Typically, it presents in infancy, mimicking acute encephalitis, leaving a previously healthy child severely handicapped with generalized dystonia, spastic quadriplegia or choreoathetosis. Cerebral MRI shows large CSF-containing spaces (sylvian fissures and anterior to the temporal lobes) and basal ganglia abnormal signal. CASE REPORT: An eight year-old boy had begun at 18 months with motor difficulties and abnormal posture of upper and lower left limbs. When examined, he had generalized dystonia more pronounced at the left side, severe dysarthria and tongue dystonia. IQ was normal. MRI showed high T2 signal in basal ganglia and enlarged CSF containing spaces. Urinary organic acids chromatography confirmed glutaric acidemia type I. Two of his sisters deceased before the age of two years with a clinical picture of fever, seizures and hypotonia. Another sister had the same symptoms at the same age. She lived until 10 year with severe quadriplegia. COMMENTS: Our observation shows variability of clinical picture and course of glutaric acidemia type I in the same kindred. We propose systematic organic acides chromatography in all children with acute or progressive dystonia with basal ganglia abnormalities on MRI. This seems an imperative attitude because appropriate diet could slow the progression of the illness.

[Malignant paraganglioma with vertebral and skull metastasis]. / Paragangliome malin avec métastases vertébrales et de la voûte crânienne.

A paraganglioma is a rare tumor composed of chromaffin cells. Malignant paraganglioma is a very rare presentation diagnosed by local recurrence after total resection of the primary mass or findings of distant metastasis. We report a case of a 30-year-old man who had undergone a carotid body tumor resection 10 years before and who presented to us with recurrence of the tumor associated with lymph node, vertebra and skull metastasis. The diagnosis of malignant paraganglioma was based on loco-regional and distant metastasis.