A disorder clinically resembling cystic fibrosis caused by biallelic variants in the AGR2 gene.

PURPOSE: We sought to describe a disorder clinically mimicking cystic fibrosis (CF) and to elucidate its genetic cause. METHODS: Exome/genome sequencing and human phenotype ontology data of nearly 40 000 patients from our Bio/Databank were analysed. RNA sequencing of samples from the nasal mucosa from patients, carriers and controls followed by transcriptome analysis was performed. RESULTS: We identified 13 patients from 9 families with a CF-like phenotype consisting of recurrent lower respiratory infections (13/13), failure to thrive (13/13) and chronic diarrhoea (8/13), with high morbidity and mortality. All patients had biallelic variants in AGR2, (1) two splice-site variants, (2) gene deletion and (3) three missense variants. We confirmed aberrant AGR2 transcripts caused by an intronic variant and complete absence of AGR2 transcripts caused by the large gene deletion, resulting in loss of function (LoF). Furthermore, transcriptome analysis identified significant downregulation of components of the mucociliary machinery (intraciliary transport, cilium organisation), as well as upregulation of immune processes. CONCLUSION: We describe a previously unrecognised autosomal recessive disorder caused by AGR2 variants. AGR2-related disease should be considered as a differential diagnosis in patients presenting a CF-like phenotype. This has implications for the molecular diagnosis and management of these patients. AGR2 LoF is likely the disease mechanism, with consequent impairment of the mucociliary defence machinery. Future studies should aim to establish a better understanding of the disease pathophysiology and to identify potential drug targets.

Ultrasound-assisted surface treatment of ZrO2 with BSA and incorporating in PVC to improve the properties of the obtained nanocomposites: Fabrication and characterization.

This paper describes the preparation of poly(vinyl chloride) (PVC) nanocomposites (NCs) reinforced with modified zirconia (ZrO2) nanoparticles (NPs). The ZrO2 NPs were defined as efficient filler for PVC NCs. For achieving the best dispersion and improvement of properties, the surface of ZrO2 NPs was modified by Bovine Serum Albumin (BSA). Carboxylic acids and amines are important functional groups of BSA which handle the grafting BSA on the surface of ZrO2 NPs. The PVC/ZrO2-BSA NCs were fabricated by incorporation of various amounts of the ZrO2-BSA NPs (3, 6 and 9wt%) into PVC matrix. All the above processes were accomplished by ultrasonication asa green and environmentally-friendly method. Also, the magnetic and mechanical stirrer was used for the preparation of samples but the results are not suitable and the aggregation was observed which indicated the use of ultrasonic irradiation is the best method for the preparation of NC. The products were characterized by Fourier transform infrared spectroscopy, Transmission electron microscopy, Field emission scanning electron microscopy, X-ray diffraction, Thermogravimetric analysis, Ultraviolet-visible spectroscopy, photoluminescence spectroscopy, energy dispersive X-ray spectroscopy, wettability, and mechanical tests. The achieved PVC/ZrO2-BSA NCs showed high thermal stability, good mechanical, optical and wettability properties compared to the pure PVC. In addition, among the obtained NCs, the PVC/ZrO2-BSA NC 6wt% showed the best improvement.

Borderline Personality Features in Students: the Predicting Role of Schema, Emotion Regulation, Dissociative Experience and Suicidal Ideation.

BACKGROUND: Numerous studies have demonstrated that early maladaptive schemas, emotional dysregulation are supposed to be the defining core of borderline personality disorder. Many studies have also found a strong association between the diagnosis of borderline personality and the occurrence of suicide ideation and dissociative symptoms. OBJECTIVES: The present study was designed to investigate the relationship between borderline personality features and schema, emotion regulation, dissociative experiences and suicidal ideation among high school students in Shiraz City, Iran. PATIENTS AND METHODS: In this descriptive correlational study, 300 students (150 boys and 150 girls) were selected from the high schools in Shiraz, Iran, using the multi-stage random sampling. Data were collected using some instruments including borderline personality feature scale for children, young schema questionnaire-short form, difficulties in emotion-regulation scale (DERS), dissociative experience scale and beck suicide ideation scale. Data were analyzed using the Pearson correlation coefficient and multivariate regression analysis. RESULTS: The results showed a significant positive correlation between schema, emotion regulation, dissociative experiences and suicide ideation with borderline personality features. Moreover, the results of multivariate regression analysis suggested that among the studied variables, schema was the most effective predicting variable of borderline features (P < 0.001). CONCLUSIONS: The findings of this study are in accordance with findings from previous studies, and generally show a meaningful association between schema, emotion regulation, dissociative experiences, and suicide ideation with borderline personality features.

Predicting addiction potential on the basis of early traumatic events, dissociative experiences, and suicide ideation.

BACKGROUND: There is a great deal of medical literature suggesting that substance use disorder is a serious clinical concern, affecting general population and associated with considerable economic, societal, and personal costs. OBJECTIVES: This study sought to clarify the relationship between early trauma, dissociative experience, and suicide ideation as predictive factors of active and passive addiction potential (A/PAP) in high-school students. PATIENTS AND METHODS: Three hundred students with the mean age of 15.72 y were selected via multistage random sampling. All participants were asked to complete Iranian addiction potential scale, early trauma inventory, dissociative experiences scale, and Beck's suicide ideation scale. Analyzing data was done using canonical correlation. RESULTS: Structural coefficients showed that the pattern of high scores in A/PAP correlates with the pattern of high scores in early trauma, dissociative experience and suicide ideation. The findings of the study showed that the combination of low A/PAP can probably decrease the likelihood of early trauma, dissociative experience and suicide ideation. CONCLUSIONS: Early trauma, dissociative experience, and suicide ideation can predict A/PAP and explain the considerable variance of survival index.