Prevalence of ATP7B Gene Mutations in Iranian Patients With Wilson Disease

Background

Wilson disease (WD) is an autosomal recessive disorder. The WD gene, ATP7B, encodes a copper-transporting ATPase involved in the transport of copper into the plasma protein ceruloplasmin and in excretion of copper from the liver. ATP7B mutations cause copper to accumulate in the liver and brain.

Objectives

We examined the ATP7B mutation spectrum in Wilson disease patients in Iran.

Patients and Methods

Genomic DNA was extracted from patients with Wilson disease. The entire coding region of the ATP7B gene was amplified using PCR and analyzed using direct sequencing.

Results

We identified five novel mutations in 5 Iranian patients with Wilson disease. The first was a transversion, c.2363C > T, which led to an amino acid change from threonine to isoleucine. The second mutation was a deletion, c.2532delA (Val845Ser), which occurred in exon 10. The third mutation was a transition mutation, c.2311C > G (Leu770Leu), which occurred in the TM4 domain of the ATP7B protein. The fourth mutation was a transversion, (c.3061G > A) (Lys1020Lys), in exon 14. Lastly, we identified a transversion, c.3206C > A (His1069Asn) in exon 14 which led to a change in function of the ATP loop domain of the ATP7B protein. The H1069Q mutation was identified as the most common mutation in our study population.

Conclusions

Based on our findings, the H1069Q may be a biomarker that can be used in a rapid detection assay for diagnosing WD patients     

Metabolism and toxicity of menthofuran in rat liver slices and in rats

Menthofuran is a monoterpene present in mint plants that is oxidized by mammalian cytochrome P450 (CYP) to hepatotoxic metabolites. Evidence has been presented that p-cresol and other unusual oxidative products are metabolites of menthofuran in rats and that p-cresol may be responsible in part for the hepatotoxicity caused by menthofuran [ Madyastha, K. M. and Raj, C. P. (1992) Drug Metab. Dispos. 20, 295 - 301]. In the present study, several oxidative metabolites of menthofuran were characterized in rat and human liver microsomes and in rat liver slices exposed to cytotoxic concentrations of menthofuran. Metabolites that were identified were monohydroxylation products of the furanyl and cyclohexyl groups, mintlactones and hydroxymintlactones, a reactive γ-ketoenal, and a glutathione conjugate. A similar spectrum of metabolites was found in urine 24 h after the administration of hepatotoxic doses of menthofuran to rats. In no case was p-cresol (or any of the other reported unusual oxidative metabolites of menthofuran) detected above background concentrations that were well below concentrations of p-cresol that cause cytotoxicity in rat liver slices. Thus, the major metabolites responsible for the hepatotoxic effects of menthofuran appear to be a γ-ketoenal and/or epoxides formed by oxidation of the furan ring.     

Psychometric properties of a Persian-language version of the Automatic Thoughts Questionnaire: ATQ-Persian

AIMS: To examine the psychometric properties of a Persian-language version of Hollon and Kendall's (1980) Automatic Thoughts Questionnaire (ATQ-Persian)--a measure of negative automatic thoughts in depression. METHODS: In a sample of 125 student volunteers from two Iranian universities we assessed the internal consistency and test-retest reliability of ATQ-Persian, and examined its concurrent validity against the Beck Depression Inventory (Beck et al., 1996). We also examined the factor structure of the test through comparing the fit of various proposed factor-analytic models to the data using confirmatory factor analysis. RESULTS: ATQ-Persian had excellent internal consistency (Cronbach's alpha = 0.96), test-retest reliability (r = 0.84) and correlation with the Beck Depression Inventory (r = 0.77). Using a receiver operating characteristics curve, a score of 53 on ATQ-Persian was associated with a sensitivity of 89% and a specificity of 78% for detecting moderate to severe depression defined through Beck Depression Inventory. None of the proposed factorial models fitted the data well. However, models with correlated factors generally provided better fit than models with orthogonal factors, suggesting that the latent factors underlying ATQ-Persian are highly correlated. CONCLUSIONS: These data support the reliability and validity of ATQ-Persian as a measure of negative automatic thoughts in depression.     

7-Piperazinylquinolones with methylene-bridged nitrofuran scaffold as new antibacterial agents

Quinolone class of antibacterial agents has considerable attention to find new useful antibacterial agents. Therefore, a series of N-substituted piperazinylquinolones bearing (5-nitrofuran-2-yl)methyl moiety were synthesized and evaluated against a variety of bacteria. The methylene-bridged nitrofuran functionality has been recently used in oxazolidinone class of antibacterial agents containing piperazinyl moiety by introducing ranbezolid as a 5-nitrofuran analog of eperzolid. The results of antibacterial evaluation revealed that the influence of (5-nitrofuran-2-yl) attachment to the 7-piperazinylquinolones against different bacterial species depends on the type of substituents at the N-1 and C-8 positions. Better results were obtained with ethyl at N-1 and CF at C-8 in the term of activity against Bacillus subtilis and E. coli. While, the optimum activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumonia was entailed by a molecule possessing cyclopropyl at N-1 and CH at C-8.     

Bilateral Optic Nerve Head Angiomas and Retrobulbar Haemangioblastomas in von Hippel-Lindau Disease

A 39-year-old man presented with progressive visual loss in both eyes. His past medical history was remarkable for biopsy-proven bilateral adrenal phaeochromocytomas. Ophthalmoscopy revealed an optic nerve head angioma and macular lipid exudates in the right eye and a regressed optic nerve head angioma in the left eye. A fluorescein angiogram revealed a lobulated pattern of leakage and venous staining from the optic nerve head angioma. Brain and orbital magnetic resonance imaging showed haemangioblastomas of the right intraorbital and left paraclinoid optic nerves and in the left cerebellopontine angle area. These findings were consistent with a clinical diagnosis of von Hippel-Lindau disease.     

Practical development and operationalization of a 12-hour hospital census prediction algorithm

Hospital census prediction has well-described implications for efficient hospital resource utilization, and recent issues with hospital crowding due to CoVID-19 have emphasized the importance of this task. Our team has been leading an institutional effort to develop machine-learning models that can predict hospital census 12 hours into the future. We describe our efforts at developing accurate empirical models for this task. Ultimately, with limited resources and time, we were able to develop simple yet useful models for 12-hour census prediction and design a dashboard application to display this output to our hospital’s decision-makers. Specifically, we found that linear models with ElasticNet regularization performed well for this task with relative 95% error of +/− 3.4% and that this work could be completed in approximately 7 months.     

Sleep hygiene behaviours mediate the association between health/e-health literacy and mental wellbeing

Background

Health literacy and e-health literacy are important factors helping people shape awareness of health behaviours in different aspects, including sleep hygiene behaviours. Good sleep hygiene behaviours promote sleep quality and are beneficial to overall mental wellbeing.

Objective

We aimed to examine if sleep hygiene behaviours may mediate the association between health literacy/e-health literacy and mental wellbeing.

Methods

Adult Iranian subjects (n = 9775; mean [SD] age = 36.44 [11.97] years; 67.3% females) completed the Health Literacy Instrument for Adults, eHealth Literacy Scale, three items on sleep hygiene behaviour that have been used in prior research and the Short Warwick Edinburgh Mental Wellbeing Scale. Data were then subjected to structural equation modelling (SEM) including 500 bootstrapping resampling to examine whether sleep hygiene is a mediator in the relationship between health literacy/e-health literacy and mental wellbeing.

Findings

Both health literacy and e-health literacy were significantly associated with mental wellbeing (r = .63 for health literacy and .39 for e-health literacy; p < .001) and sleep hygiene behaviours (r = .58 for health literacy and .36 for e-health literacy; p < .001). Sleep hygiene behaviours were significantly associated with mental wellbeing (r = .42; p < .001). Moreover, SEM that incorporated bootstrapping approaches indicated that sleep hygiene behaviours were significant mediators in the association between health literacy/e-health literacy and mental wellbeing.

Conclusions

We conclude that health literacy and e-health literacy are associated with mental health wellbeing in the Iranian population. Additionally, the association could be mediated via sleep hygiene behaviours.

Patient or Public Contribution

The study was co-designed with healthcare providers from the vice-Chancellor's Office for Health Affairs of Qazvin University of Medical Sciences as equal partners. Moreover, the women's health volunteers were involved in the design of the study.