LYRM7-associated mitochondrial complex III deficiency with non-cavitating leukoencephalopathy and stroke-like episodes

Defects of respiratory chain complex III (CIII) result in characteristic but rare mitochondrial disorders associated with distinct neuroradiological findings. The underlying molecular defects affecting mitochondrial CIII assembly factors are few and yet to be identified. LYRM7 assembly factor is required for proper CIII assembly where it acts as a chaperone for the Rieske iron–sulfur (UQCRFS1) protein in the mitochondrial matrix and stabilizing it. We present here the seventeenth individual with LYRM7-associated mitochondrial leukoencephalopathy harboring a previously reported rare pathogenic homozygous LYRM 7 variant, c.2T>C, (p.Met1?). Like previously reported individuals, our 5-year-old male proband presented with recurrent metabolic and lactic acidosis, encephalopathy, and fatigue. Further, he has additional, previously unreported features, including an acute stroke like episode with bilateral central blindness and optic neuropathy, recurrent hyperglycemia and hypertension associated with metabolic crisis. However, he has no signs of psychomotor regression. He has been stable clinically with residual left-sided reduced visual acuity and amblyopia, and no more metabolic crises for 2-year-period while on the mitochondrial cocktail. Although the reported brain MRI findings in other affected individuals are homogenous, it is slightly different in our index, revealing evidence of bilateral almost symmetric multifocal periventricular T2 hyperintensities with hyperintensities of the optic nerves, optic chiasm, and corona radiata but with no cavitation or cystic changes. This report describes new clinical and radiological findings of LYRM7-associated disease. The report also summarizes the clinical and molecular data of previously reported individuals describing the full phenotypic spectrum.     

Adipocyte-fatty acid binding protein induces apoptosis in DU145 prostate cancer cells

Adipocyte-fatty acid binding protein (A-FABP) is a 14-15 kDa cytoplasmic protein that binds unesterified fatty acids (FA). It is believed that A-FABP is present in normal cells and disappears in cancer cells. Prostate cancer DU145 cells lack expression of A-FABP. Here, we report that transfection of A-FABP blocked growth of DU145 cells suggesting its role as a tumor suppressor. A-FABP transfected- prostate cancer DU145 cells underwent apoptosis when induced to overexpress A-FABP using an ecdysone-controlled expression system. DU145 cell cultures in complete medium exhibited a maximum of approximately 28% of apoptotic cells after 96 h of exposure to an ecdysone analog, Ponasterone A. We found that the possible mechanisms leading to the observed apoptotic effect may be due, in part, to an overexpression of tumor necrosis factor-alpha (TNF-alpha) and a moderate downregulation of transforming growth factor-alpha (TGF-alpha) in DU145 cells overexpressing A-FABP. The epidermal growth factor receptor (EGFR)/phosphatidyl inositol 3-kinase (PI 3-kinase) signaling pathway was not altered in these cells, suggesting that A-FABP may cause apoptosis by inducing downregulation of essential autocrine growth factors and/or upregulation of pro-apoptotic ones.     

Tumor necrosis factor-α production from mononuclear cells in nephrotic syndrome

Tumor necrosis factor-alpha (TNF-alpha) levels in supernatant fluid from cultured peripheral blood mononuclear cells (PBMC) were measured by ELISA in 54 children with active non-inherited forms of primary nephrotic syndrome (PNS), 10 nephrotics in remission, and 10 healthy controls. Children with active PNS included 21 patients with steroid-sensitive (SS) minimal change nephrotic syndrome (MCNS), 5 patients with steroid-resistant (SR) MCNS, 11 with SR focal segmental glomerulosclerosis (FSGS), 6 patients with SS diffuse mesangial proliferation (DMP), 5 patients with SR DMP, and 6 patients with mesangiocapillary glomerulonephritis (MCGN). Patients with active PNS had elevated TNF-alpha production compared with controls. Remission was associated with normalization of TNF-alpha production. There was a positive correlation between TNF-alpha production and the degree of proteinuria ( r=0.34, P=0.013), mesangial hypercellularity ( r=0.42, P=0.028), and glomerulosclerosis ( r=0.46, P=0.001). By using ROC curve, TNF-alpha production greater or equal to a cut-off point of 50 pg/ml could be used to predict resistance to steroid therapy (predictability 93.2%). By discriminate analysis, TNF-alpha production could be used to discriminate between patients with SR MCNS, SR FSGS, and SR DMP (predictability 100%). In conclusion, TNF-alpha from cultured PBMC might be involved in the pathogenesis of proteinuria as well as the pathological changes that occur in non-inherited forms of PNS. TNF-alpha levels in PBMC culture could be used to predict the pathological type of PNS and the response of these patients to steroid therapy.     

The effect of bread making steps on the degradation of aflatoxins produced as a result of single inoculation with Aspergillus flavus and combined inoculation with Aspergillus flavus and Aspergillus ochraceus

This study aimed to determine the effect of bread making steps on the stability of aflatoxin. Sakha 8 wheat and Gemaiza 5 wheat cultivars, were used in the present study. They were inoculated with a dense spore suspension of toxigenic fungal species of Aspergillus flavus and a non toxigenic species of Aspergillus ochraceus singly and combined. Aflatoxin concentration was determined in the whole wheat grain, after milling, after fermentation, and after bread-baking process. Results showed that the highest reduction percentage for the total aflatoxins (81, G1 and G2), was in Sakha 8 (32.96%) (single treatment), Gemaiza 5 (19.54%) (single treatment ), Gemaiza 5 (18.65%) (combined treatment), and finally in Sakha 8 (16.49%) (combined treatment). There was no significant difference (p < 0.05) in aflatoxins content between Sakha 8 and Gemaiza 5 treated singly and in a combined way before and after milling process. In the mean time, the percentage of AFB1, AFG1 and AFG2 were reduced by 31.98%, 44.53% and 35.35%, respectively, while the total aflatoxins concentration were reduced by 41.17% after baking. Results also showed the presence of a significant difference at p < 0.05 among the whole grain, after milling and after baking concerning AFG1, AFG2 and the total aflatoxins content. No significant difference was found in case of AFB1.     

Insight into appropriate medication prescribing for elderly in the COVID-19 era

Coronavirus disease 2019 (COVID-19) complicates clinical management in elderly population. There is an additional need to properly treat and monitor elderly COVID-19 patients. This paper discusses the inappropriate medication prescribing in the elderly and suggests an updated valid assessment tool considering COVID-19 and its treatment.     

A case of basidiobolomycosis mimicking rhabdomyosarcoma: A diagnostic challenge

Basidiobolomycosis is a rare curable fungal infection caused by the saprophytic fungus Basidiobolus ranarum. It often causes skin infections but rarely infects visceral tissues in humans. Gastrointestinal basidiobolomycosis is an emerging form, which is rare but is increasingly reported. Due to its ability to mimic more common diagnoses such as chronic inflammatory disorders and malignancies, Basidiobolomycosis imposes a diagnostic challenge on most physicians. Therefore, a timely and correct diagnosis by laboratory tests and careful review of images along with proper medical management can save patients from invasive treatments and reduce both morbidity and mortality. Here, we present a rare case of an 8-year-old boy with basidiobolomycosis initially misdiagnosed as rhabdomyosarcoma. We aim to highlight basidiobolomycosis as a potential differential from masses on imaging under the right clinical circumstances and to provide radiologists with key imaging details to help recognize this infectious etiology and reduce its associated morbidity.     

DETECTION OF R576 INTERLEUKIN-4 RECEPTOR AN ALLELE GENE, SERUM INTERLEUKIN-4, AND EOSINOPHILIC CATIONIC PROTEIN IN ATOPIC DERMATITIS PATIENTS

Atopic dermatitis (AD) is a chronic pruritic skin disease. It results from a complex interplay between strong genetic and environmental factors. The aim of this work was to study some biochemical markers of the dermatosis. This included detection of R576 interleukin-4 receptor alpha allele gene. Twenty five patients with AD and 25 controls participated in this study.     

Longitudinal assessment of hepatic fibrosis in responders to direct‐acting antivirals for recurrent hepatitis C after liver transplantation using noninvasive methods

Successful eradication of recurrent hepatitis C virus (HCV) infection following liver transplantation (HCV) improves graft survival. This study aimed at evaluation of hepatic fibrosis changes among long‐term responders to DAA therapy for recurrent HCV after liver transplantation using noninvasive methods. Patients with significant hepatic fibrosis (≥F2) who achieved SVR12 after treatment with DAAs for recurrent HCV were included (n = 52). Hepatic fibrosis status was assessed, noninvasively, by calculation of fibrosis‐4 score (FIB‐4) and Aspartate Aminotransferase Platelet Ratio Index (APRI) and by measurement of graft stiffness using FibroScan at baseline and 12 and 18 months post‐treatment. Acoustic radiation force imaging (ARFI) was done for all patients 12 and 18 months post‐treatment. Patients were classified into two groups based on baseline liver stiffness measurement (LSM) by FibroScan; significant fibrosis (F2; n = 28) and advanced fibrosis groups (≥F3). Over 18‐month follow‐up period, there was serial improvement of FIB‐4, APRI, and LSM by FibroScan in both groups. Higher baseline LSM and delayed initiation of antiviral therapy were significant predictors of lack of fibrosis regression (P‐value 0.01 and 0.04, respectively). Fibroindices and LSM improved over time in liver transplant recipients who responded to DAAs. Baseline LSM can predict post‐treatment fibrosis regression.     

Mechanisms of Dendritic Cell Trafficking Across the Blood–brain Barrier

Although the central nervous system (CNS) is considered to be an immunoprivileged site, it is susceptible to a host of autoimmune as well as neuroinflammatory disorders owing to recruitment of immune cells across the blood–brain barrier into perivascular and parenchymal spaces. Dendritic cells (DCs), which are involved in both primary and secondary immune responses, are the most potent immune cells in terms of antigen uptake and processing as well as presentation to T cells. In light of the emerging importance of DC traficking into the CNS, these cells represent good candidates for targeted immunotherapy against various neuroinflammatory diseases. This review focuses on potential physiological events and receptor interactions between DCs and the microvascular endothelial cells of the brain as they transmigrate into the CNS during degeneration and injury. A clear understanding of the underlying mechanisms involved in DC migration may advance the development of new therapies that manipulate these mechanistic properties via pharmacologic intervention. Furthermore, therapeutic validation should be in concurrence with the molecular imaging techniques that can detect migration of these cells in vivo. Since the use of noninvasive methods to image migration of DCs into CNS has barely been explored, we highlighted potential molecular imaging techniques to achieve this goal. Overall, information provided will bring this important leukocyte population to the forefront as key players in the immune cascade in the light of the emerging contribution of DCs to CNS health and disease.