Differential Expression of ATM, NF-KB, PINK1 and Foxo3a in Radiation-Induced Basal Cell Carcinoma.

Research in normal tissue radiobiology is in continuous progress to assess cellular response following ionizing radiation exposure especially linked to carcinogenesis risk. This was observed among patients with a history of radiotherapy of the scalp for ringworm who developed basal cell carcinoma (BCC). However, the involved mechanisms remain largely undefined. We performed a gene expression analysis of tumor biopsies and blood of radiation-induced BCC and sporadic patients using reverse transcription-quantitative PCR. Differences across groups were assessed by statistical analysis. Bioinformatic analyses were conducted using miRNet. We showed a significant overexpression of the FOXO3a, ATM, P65, TNF-α and PINK1 genes among radiation-induced BCCs compared to BCCs in sporadic patients. ATM expression level was correlated with FOXO3a. Based on receiver-operating characteristic curves, the differentially expressed genes could significantly discriminate between the two groups. Nevertheless, TNF-α and PINK1 blood expression showed no statistical differences between BCC groups. Bioinformatic analysis revealed that the candidate genes may represent putative targets for microRNAs in the skin. Our findings may yield clues as to the molecular mechanism involved in radiation-induced BCC, suggesting that deregulation of ATM-NF-kB signaling and PINK1 gene expression may contribute to BCC radiation carcinogenesis and that the analyzed genes could represent candidate radiation biomarkers associated with radiation-induced BCC.

Is Intussusception in an Adult with Active COVID-19 Infection a Surprise?

The severe acute respiratory syndrome coronavirus 2 (SARS COV2) had rapidly spread and caused a global pandemic worldwide. The most common symptoms in adults are respiratory with dry cough, dyspnea, and fever. Occasionally, extra-respiratory presentations may be seen such as gastrointestinal involvement with diarrhea, vomiting or abdominal pain. Acute intestinal intussusception is the most common cause of bowel obstruction in infants (2-4 months of age) but rarely could it be encountered in adult. It is a very rare gastro-intestinal manifestation of COVID-19 with an invagination of a segment of the bowel within a more distal one. The part that prolapses into the other is called the intussusceptum, and the part that receives it is called the intussuscipiens. Most of COVID-19 cases of AII are reported in the pediatric population between 4 and 10 months. Only a single case of small bowel obstruction secondary to ileo-colic intussusception in a COVID-19 infection adult was published on April 2021. We present here a challenging case of intussusception secondary to COVID-19 infection in an adult in the absence of respiratory symptoms. Our study presents the first case in Africa of AII in adult patients due to COVID-19.

Prevalence of comorbid asthma in Tunisian patients with COVID-19: clinical features and outcomes.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in around 1 million COVID-19 infection cases and over 29,000 deaths in Tunisia thus far. There is great variability in the prevalence of asthma among patients with COVID-19, but the impact of asthma on patients with COVID-19 is not clear. We sought to describe the clinical features of Tunisian patients with COVID-19 and to compare asthmatic and non-asthmatic patients. METHODOLOGY: This retrospective study included 675 Tunisian patients who were hospitalized with COVID-19. Clinical characteristics were collected from medical records. Bivariate analyses and multivariate regression models were used to assess the associations between asthma and the risk of severe symptoms, including death/recovery. RESULTS: The prevalence of asthma in the sample was 14.5%. The results show that asthmatic patients with COVID-19 have significantly less severe symptoms and better outcomes than non-asthmatic patients. CONCLUSIONS: Asthma was not found to be associated with higher severity or worse prognosis among patients with COVID-19 in Tunisia.

Expanding the clinical phenotype associated with NIPAL4 mutation: Study of a Tunisian consanguineous family with erythrokeratodermia variabilis-Like Autosomal Recessive Congenital Ichthyosis.

Erythrokeratodermia variabilis (EKV) is a rare disorder of cornification usually associated with dominant mutations in the GJB3 and GJB4 genes encoding connexins (Cx)31 and 30.3. Genetic heterogeneity of EKV has already been suggested. We investigated at the clinical and genetic level a consanguineous Tunisian family with 2 sisters presenting an autosomal recessive form of EKV to better characterize this disease. Mutational analysis initially screened the connexin genes and Whole-exome sequencing (WES) was performed to identify the molecular aetiology of the particular EKV phenotype in the proband. Migratory shaped erythematous areas are the initial presenting sign followed by relatively stable hyperkeratotic plaques are the two predominates characteristics in both patients. However, remarkable variability of morphological and dominating features of the disease were observed between patients. In particular, the younger sister (proband) exhibited ichthyosiform-like appearance suggesting Autosomal Recessive Congenital Ichthyosis (ARCI) condition. No causative mutations were detected in the GJB3 and GJB4 genes. WES results revealed a novel missense homozygous mutation in NIPAL4 gene (c.835C>G, p.Pro279Ala) in both patients. This variant is predicted to be likely pathogenic. In addition, in silico analysis of the mutated 3D domain structure predicted that this variant would result in NIPA4 protein destabilization and Mg2+ transport perturbation, pointing out the potential role of NIPAL4 gene in the development and maintenance of the barrier function of the epidermis. Taken togheter, these results expand the clinical phenotype associated with NIPAL4 mutation and reinforce our hypothesis of NIPAL4 as the main candidate gene for the EKV-like ARCI phenotype.

Endothelial Cells Promote Pigmentation through Endothelin Receptor B Activation.

Findings of increased vascularization in melasma lesions and hyperpigmentation in acquired bilateral telangiectatic macules suggested a link between pigmentation and vascularization. Using high-magnification digital epiluminescence dermatoscopy, laser confocal microscopy, and histological examination, we showed that benign vascular lesions of the skin have restricted but significant hyperpigmentation compared with the surrounding skin. We then studied the role of microvascular endothelial cells in regulating skin pigmentation using an in vitro co-culture model using endothelial cells and melanocytes. These experiments showed that endothelin 1 released by microvascular endothelial cells induces increased melanogenesis signaling, characterized by microphthalmia-associated transcription factor phosphorylation, and increased tyrosinase and dopachrome tautomerase levels. Immunostaining for endothelin 1 in vascular lesions confirmed the increased expression on the basal layer of the epidermis above small vessels compared with perilesional skin. Endothelin acts through the activation of endothelin receptor B and the mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK)1/2, and p38, to induce melanogenesis. Finally, culturing of reconstructed skin with microvascular endothelial cells led to increased skin pigmentation that could be prevented by inhibiting EDNRB. Taken together these results demonstrated the role of underlying microvascularization in skin pigmentation, a finding that could open new fields of research for regulating physiological pigmentation and for treating pigmentation disorders such as melasma.

A case of linear atrophoderma of Moulin successfully treated with methotrexate.

Linear atrophoderma of Moulin is an acquired rare and self-limited skin condition. It is characterized by atrophic bandlike skin lesions that often show hyperpigmentation and always follow the lines of Blaschko. Usually it begins in childhood or adolescence and there is no evidence of any long term progression. We describe a case of a 21-year-old woman with clinical and histological features of linear atrophoderma of Moulin. The patient was successfully treated with methotrexate 20 mg/week during 6 months with an improvement of skin pigmentation and atrophy. Approximately, 30 cases of linear atrophoderma of Moulin were described in the literature. There is not a proven effective treatment of this dermatosis. High dose penicillin, topical corticosteroids, heparin, and oral potassium aminobenzoate have been used but found to be uneffective. To our knowledge, this is the first case of extensive linear atrophoderma of Moulin treated with methotrexate.

[Psoas abscess of the adult: study of 38 cases]. / L'abces du psoas de l'adulte: etude de 38 cas.

OBJECTIVE: Our aim is to report the clinical aspects, the etiologies, the treatment and the evolution of the psoas abscess in the adult. METHODS: Our retrospective study concerns 38 cases of psoas abscesses collected in the Department of Infectious Diseases of Sfax (Tunisia), over a period of 16 years (January 1990 - December 2005). RESULTS: The average age is 44 years (extremes: 16-76 years). The sex-ratio is 1.4. Six patients were diabetics and one had a chronic renal injury at the stage of hemodialysis. The clinical manifestations were: a fever (76.4%), an abdomino-pelvic ache (84.2%) and a psoitis (34.2%). All patients had a biologic inflammatory syndrome with a hyperleucocytosis in 28 cases. The abscess was one-sided in 29 cases and bilateral in 9 cases. After microbiological study and/or histological study, pathogens were identified in 31 patients, they were Staphylococcus aureus (10 cases), Staphylococcus lugdunensis (1 case), Streptococci (3 cases), Escherichia coli (2 cases), Bacteroides fragilis (1 case), Actinomyces (2 cases), Brucella (3 cases), Mycobacterium tuberculosis (8 cases) and Candida glabrata (1 case). The psoas abscess was primary in 10 cases and secondary in 28 cases. All the patients received an antibiotherapy or an antifungal therapy adapted to the micro-organism in cause, with a drainage of the abscess in 25 cases (surgical in 9 cases and percutaneous in 16 cases). The evolution was favourable in 36 cases. One patient presented recurrences and one patient died. CONCLUSION: The psoas abscess of the adult is characterized by a polymorphe clinical presentation. Germs in cause are very variable.