Molecular Epidemiology of SARS-CoV-2 in Tunisia (North Africa) through Several Successive Waves of COVID-19

Documenting the circulation dynamics of SARS-CoV-2 variants in different regions of the world is crucial for monitoring virus transmission worldwide and contributing to global efforts towards combating the pandemic. Tunisia has experienced several waves of COVID-19 with a significant number of infections and deaths. The present study provides genetic information on the different lineages of SARS-CoV-2 that circulated in Tunisia over 17 months. Lineages were assigned for 1359 samples using whole-genome sequencing, partial S gene sequencing and variant-specific real-time RT-PCR tests. Forty-eight different lineages of SARS-CoV-2 were identified, including variants of concern (VOCs), variants of interest (VOIs) and variants under monitoring (VUMs), particularly Alpha, Beta, Delta, A.27, Zeta and Eta. The first wave, limited to imported and import-related cases, was characterized by a small number of positive samples and lineages. During the second wave, a large number of lineages were detected; the third wave was marked by the predominance of the Alpha VOC, and the fourth wave was characterized by the predominance of the Delta VOC. This study adds new genomic data to the global context of COVID-19, particularly from the North African region, and highlights the importance of the timely molecular characterization of circulating strains.     

CDK13-related disorder: Report of a series of 18 previously unpublished individuals and description of an epigenetic signature

PurposeRare genetic variants in CDK13 are responsible for CDK13-related disorder (CDK13-RD), with main clinical features being developmental delay or intellectual disability, facial features, behavioral problems, congenital heart defect, and seizures. In this paper, we report 18 novel individuals with CDK13-RD and provide characterization of genome-wide DNA methylation.MethodsWe obtained clinical phenotype and neuropsychological data for 18 and 10 individuals, respectively, and compared this series with the literature. We also compared peripheral blood DNA methylation profiles in individuals with CDK13-RD, controls, and other neurodevelopmental disorders episignatures. Finally, we developed a support vector machine–based classifier distinguishing CDK13-RD and non–CDK13-RD samples.ResultsWe reported health and developmental parameters, clinical data, and neuropsychological profile of individuals with CDK13-RD. Genome-wide differential methylation analysis revealed a global hypomethylated profile in individuals with CDK13-RD in a highly sensitive and specific model that could aid in reclassifying variants of uncertain significance.ConclusionWe describe the novel features such as anxiety disorder, cryptorchidism, and disrupted sleep in CDK13-RD. We define a CDK13-RD DNA methylation episignature as a diagnostic tool and a defining functional feature of the evolving clinical presentation of this disorder. We also show overlap of the CDK13 DNA methylation profile in an individual with a functionally and clinically related CCNK-related disorder.     

Endogenous competition against binding of [18F]DMFP and [18F]fallypride to dopamine D2/3 receptors in brain of living mouse

Aim . Molecular imaging studies with benzamide radioligands can reveal competition from endogenous binding at D_2/3‐receptors in living brain. However, single photon emission computed tomography (SPECT) methods suffer from limited spatial resolution, and [¹¹C]‐labeled ligands are only available at positron emission tomography (PET) research sites with cyclotron‐radiochemistry facilities, whereas [¹⁸F] can be transported, due to its longer physical half‐life. Therefore, we endeavored to characterize the vulnerabilities of the benzamide antagonist [¹⁸F]desmethoxyfallypride (DMFP) and its high‐affinity congener [¹⁸F]fallypride (FP) to competition from endogenous dopamine in living mouse brain. Methods . Groups of awake mice were pretreated with saline, amphetamine (10 mg/kg), or reserpine (5 mg/kg), followed by i.v. tracer injections. Mice were killed at 2.5–90 min (DMFP) or 2.5–180 min (FP) circulation times. Brains were dissected and regional radioactivity concentration measured by gamma counting. Other groups of mice were anesthetized for dynamic microPET recordings with DMFP or FP. Binding potentials (BP_ND) were calculated using cerebellum as reference region. Results . With 90‐min circulation, DMFP BP_ND in striatum was 2.4 by dissection and 2.2 by microPET, which showed a 62% decrease in response to amphetamine‐evoked dopamine release and a 33% increase after reserpine‐evoked dopamine depletion. With 120‐min circulation, FP BP_ND in striatum was 24.1 by dissection and 9.2 by microPET, which showed a 31% decrease in the amphetamine group, but no effect of reserpine. Dissection showed similar sensitivities for FP binding, but only a 29% amphetamine‐evoked reduction for DMFP. Conclusions . Relative to gold standard ex vivo results, microPET estimates of DMFP BP_ND were unbiased, whereas FP BP_ND in striatum was substantially underestimated. Both tracers proved suitable for revealing pharmacologically evoked changes in competition at D_2/3‐receptors in striatum of living mice. Synapse 64:313–322, 2010. © 2009 Wiley‐Liss, Inc.     

Extrastriatal dopamine D(2) receptor binding in Huntington's disease

Huntington's disease (HD) is a neurodegenerative disorder, primarily affecting medium spiny neurones in the striatum. The density of striatal dopamine D(2) receptors is reduced in HD but there is little known about this biomarker in brain regions outside the striatum. The primary objective of this study was to compare extrastriatal dopamine D(2) receptor binding, in age-matched control subjects and patients with HD. All subjects were examined using a high-resolution positron emission tomography system and the high-affinity dopamine D(2) receptor radioligand [(11) C]FLB 457. A ROI based analysis was used with an atrophy correction method. Dopamine D(2) receptor binding potential was reduced in the striatum of patients with HD. Unlike the striatum, dopamine D(2) receptor binding in thalamic and cortical subregions was not significantly different from that in control subjects. A partial least square regression analysis which included binding potential values from all investigated cortical and subcortical regions revealed a significant model separating patients from controls, conclusively dependent on differences in striatal binding of the radioligand. Some clinical assessments correlated with striatal dopamine D(2) receptor binding, including severity of chorea and cognitive test performance. Hence, the present study demonstrates that dopamine D(2) receptors extrinsic to the striatum are well preserved in early to mid stage patients with HD. This observation may have implication for the development of therapy for HD.     

The effects of extraction method on the measured tocopherol level and antioxidant activity of L. nobilis vegetative organs

Tocopherol contents of Tunisian Laurus nobilis vegetative organs were screened for antioxidant activity. Tocopherol isomers extracted by probe sonication and micro-scale saponification were analysed by reversed-phase high performance liquid chromatography (RP-HPLC) with UV detection to determine the optimum extraction method. Total phenolic, flavonoid and proanthocyanidin contents were determined spectrophotometrically. Significant variations in the amounts of α-, γ- and δ-tocopherols were observed with the two different extraction methods as well as with different plant parts. Leaf extract contained the highest amount of α-tocopherol (139 mg/100 g fresh weight), but root extract contained the highest content of flavonoids (11.12 mg catechin equivalents (CE)/g dry weight or DW), total phenolics (55.45 ± 2.9 mg GAE/g DW) and condensed tannins (9.76 ± 0.1 mg CE/g DW). Acetonic extract of laurel leaf exhibited the highest antioxidant activity response to lipid peroxidation in the β-carotene-linoleic acid system, which may have been due to the high content of α-tocopherol. These findings suggest that laurel leaf may be a source of natural α-tocopherol and that it may be increasingly important for human consumption, as well as for the agro-food, cosmetic and pharmaceutical industries.     

Quand et comment conduire une nutrition entérale au cours de l’anorexie mentale ?

Lifesaving treatment in patients with anorexia nervosa and compromised nutritional status is controversial. Enteral nutrition, via a nasogastric tube can be useful in this situation. The digestive tract can be used better than parenteral nutrition. Enteral nutrition can also be used in a situation with moderate malnutrition and stable body weight despite an adequate psychological treatment. In all cases, this treatment should be discussed and accepted with the patient. Polymeric standard solutions can be used, taking care of the level of protein which should not be too high. The start of enteral nutrition is progressive, in order to avoid the risk of Refeeding Syndrome. Vitamins and phosphorus should be added to the enteral nutrition during the first few days. Complications of treatment is not frequent with these patients and are presented. Enteral nutrition should be not too long and should be decreased in the same time that oral nutrition progressively increases. The results of literature show that, enteral nutrition does not deteriorate the psychological state of the patients and is found to be accepted more positively than forced feeding orally in the initial critical phases, and is less dangerous in terms of metabolic tolerance. For these reasons, enteral nutrition should be included in the armament of treatment of anorexia nervosa.     

Benign fronto-orbital osteoblastoma arising from the orbital roof: case report and literature review

BACKGROUND: Osteoblastoma is an uncommon benign osteogenic neoplasm that rarely involves the orbit. Intracranial and intraorbital extension causing neurologic and ophthalmologic symptoms and signs is very unusual. We report the case of an osteoblastoma of the orbital cavity with ethmoidal and anterior cranial fossa extension presenting as unilateral proptosis. Manifestations and management of this rare fronto-orbital lesion are discussed, and the relevant literature is reviewed. CASE DESCRIPTION: This 22-year-old man experienced a 3-month history of progressive left proptosis without neurologic symptoms. Computed tomography and magnetic resonance imaging scans demonstrated a bony mass involving the roof of the left orbit and extending laterally to the adjacent ethmoid cells and upward to the lower part of the homolateral frontal convexity without parenchymal abnormality. A presumptive diagnosis of osteoma was considered. A left fronto-orbital craniotomy was performed. At surgery, the tumor was well circumscribed by a sclerotic margin. It was granular with bony spicules, destroying the orbital roof and involving the orbital cavity, ethmoidal cells, and anterior cranial fossa. The lesion was totally removed, and the anterior cranial base reconstructed. The histologic features were typical of benign osteoblastoma. After a follow-up period of 12 months, the patient has remained well without evidence of recurrence. CONCLUSION: Osteoblastoma should be considered in the differential diagnosis with other fronto-orbital bone-forming lesions. Although generally regarded as benign, a complete resection is recommended to prevent the possibility of postoperative recurrence and malignant transformation. Twelve previously reported cases were also reviewed.     

The type III aortic dissection. Diagnosis, outcome, contribution of the endovascular therapies to their management--a case report

The dissection of the descending aorta is a serious affection regarding to its mortality and its complications. It becomes chronic after the 14th day following the first signs of dissection. The authors report the case of a 55 years old patient who has presented a type III dissection diagnosed at the chronic period. The persistance of the pain has indicated the implantation of a stent at the intimal tear. This new endovascular treatement of the aorta diseases is a promising and less invasive alternative to the surgical treatement. It may reduce the morbidity and the mortality of this pathology but it needs an accurate and performant imaging techniques.     

Prevention of central venous line-related thrombosis by continuous infusion of low-dose unfractionated heparin, in patients with haemato-oncological disease. A randomized controlled trial

We have conducted a prospective randomized controlled trial to evaluate the role of low-dose unfractionated heparin prophylaxis in preventing central venous line-related thrombosis in patients with haemato-oncological disease. Patients were randomly assigned to receive either prophylactic intravenous unfractionated heparin (continuous infusion of 100 IU/kg/daily) or 50 ml/daily of normal saline solution as a continuous infusion. CVLs were externalized, non tunneled, double lumen catheters. All CVLs were placed percutaneously by the same physician in the subclavian vein. Upper limb veins were systematically examined by ultrasonography just before, or <24 hours after, catheter removal, and in case of clinical signs of thrombosis. One hundred and twenty-eight CVLs were inserted. Catheter-related thrombosis occurred in 1.5% of the catheters inserted in patients of the heparin group, and in 12.6% in the control group (p = 0.03). No other risk factors were found for the development of catheter-related thrombosis. Two and three patients experienced severe bleeding in the heparin group, and in the control group, respectively (p = 0.18). There were no other side-effects clearly ascribable to the use of unfractionated heparin. This is the first prospective, randomized study, which shows that low-dose of unfractionated heparin is safe and effective to prevent catheter-related thrombosis in patients with haemato-oncological disease.