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Background: Cardiac surgery can be traumatic and stressful, and as a result many people experience psychological difficulties following treatment., Aim: To assess the level of post-traumatic stress disorder (PTSD) 1 month after coronary artery bypass graft (CABG) surgery among Jordanian patients, and to examine the predictors of PTSD after 1 month., Method: A descriptive survey design was used., Findings: 149 patients participated in the study. Their mean age was 59 years (SD=10.2) and most were male (87%) and married (93%). Some 44% of patients had PTSD. Length of stay in hospital (c² (1)=6.598, P <0.05), and age (c² (1)=4.920, P <0.05), predicted the occurrence of PTSD after 1 month., Conclusions: Nurses, who are usually in the frontline with patients, should consider using a robust tool and clinical interview to assess and evaluate the presence and the risks of PTSD to promote early detection and optimal management. Follow-up studies after 6 and 12 months would be beneficial.

Background: Food-drug interactions may lead to suppression or induction of drug metabolizing enzymes. Pomegranate is a commonly used fruit in folk medicine all over the world. Data concerning the effect of pomegranate on the activity of UDP-glucuronosyltransferases (UGTs) is scarce., Objective: The purpose of this work was to investigate the effect of pomegranate juice ingestion on the transcription of ugt2b1, ugt2a3, and ugt1a9 in the liver and small intestine of male mice., Methods: Pomegranate juice was administered to 10 male mice for 14 days in drinking bottles instead of water. Ten control mice received water in the drinking bottles. On the 15th day, the mice were sacrificed and the liver and the small intestine were removed. The small intestine was divided into 3 parts. Total mRNA was extracted from samples of these specimens, and cDNA was synthesized by quantitative real-time polymerase chain reaction (RT-PCR) using specific primers for each ugt gene., Results: The ugt1a9 mRNA level was reduced by 2.25-fold in the liver and by 6-, 1.5-, and 3-folds in the first, second and third part of the small intestine, respectively. The ugt2b1 mRNA level in the liver and the third part of the small intestine was not affected, while it was reduced by 3.7- and 3-folds in the first and second parts of the small intestine, respectively. The ugt2a3 mRNA level was not affected in the liver and the 3 parts of the small intestine., Conclusion: Some ugt mRNA levels may be reduced by the ingestion of pomegranate juice, which may reduce the metabolism of their drug substrates. The consequences may be an accumulation of such drugs in the body and enhanced toxicity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Defects in the peroxisomes biogenesis and/or function result in peroxisomal disorders. In this study, we describe the largest Arab cohort to date (72 families) of clinically, biochemically and molecularly characterized patients with peroxisomal disorders. At the molecular level, we identified 43 disease-causing variants, half of which are novel. The founder nature of many of the variants allowed us to calculate the minimum disease burden for these disorders in our population ~1:30 000, which is much higher than previous estimates in other populations. Clinically, we found an interesting trend toward genotype/phenotype correlation in terms of long-term survival. Nearly half (40/75) of our peroxisomal disorders patients had documented survival beyond 1 year of age. Most unusual among the long-term survivors was a multiplex family in which the affected members presented as adults with non-specific intellectual disability and epilepsy. Other unusual presentations included the very recently described peroxisomal fatty acyl-CoA reductase 1 disorder as well as CRD, spastic paraparesis, white matter (CRSPW) syndrome. We conclude that peroxisomal disorders are highly heterogeneous in their clinical presentation. Our data also confirm the demonstration that milder forms of Zellweger spectrum disorders cannot be ruled out by the "gold standard" very long chain fatty acids assay, which highlights the value of a genomics-first approach in these cases., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A 2-yr-old boy presented profound developmental delay, failure to thrive, ataxia, hypotonia, and tonic-clonic seizures that caused the death of the patient. Targeted and whole exome sequencing revealed two heterozygous missense variants: a novel mutation in the KCNJ10 gene that encodes for the inward-rectifying K + channel Kir4.1 and another previously characterized mutation in KCNT1 that encodes for the Na + -activated K + channel known as Slo2.2 or SLACK. The objectives of this study were to perform the clinical and genetic characterization of the proband and his family and to examine the functional consequence of the Kir4.1 mutation. The mutant and wild-type KCNJ10 constructs were generated and heterologously expressed in Xenopus laevis oocytes, and whole cell K + currents were measured using the two-electrode voltage-clamp technique. The KCNJ10 mutation c.652C>T resulted in a p.L218F substitution at a highly conserved residue site. Wild-type KCNJ10 expression yielded robust Kir current, whereas currents from oocytes expressing the mutation were reduced, remarkably. Western Blot analysis revealed reduced protein expression by the mutation. Kir5.1 subunits display selective heteromultimerization with Kir4.1 constituting channels with unique kinetics. The effect of the mutation on Kir4.1/5.1 channel activity was twofold: a reduction in current amplitudes and an increase in the pH-dependent inhibition. We thus report a novel loss-of-function mutation in Kir4.1 found in a patient with a coexisting mutation in SLACK channels that results in a fatal disease. NEW & NOTEWORTHY We present and characterize a novel mutation in KCNJ10 Unlike previously reported EAST/SeSAME patients, our patient was heterozygous, and contrary to previous studies, mimicking the heterozygous state by coexpression resulted in loss of channel function. We report in the same patient co-occurrence of a KCNT1 mutation resulting in a more severe phenotype. This study provides new insights into the phenotypic spectrum and to the genotype-phenotype correlations associated with EAST/SeSAME and MMFSI., (Copyright © 2017 the American Physiological Society.)

Joubert syndrome (JS) is a recessive neurodevelopmental disorder characterized by hypotonia, ataxia, abnormal eye movements, and variable cognitive impairment. It is defined by a distinctive brain malformation known as the "molar tooth sign" on axial MRI. Subsets of affected individuals have malformations such as coloboma, polydactyly, and encephalocele, as well as progressive retinal dystrophy, fibrocystic kidney disease, and liver fibrosis. More than 35 genes have been associated with JS, but in a subset of families the genetic cause remains unknown. All of the gene products localize in and around the primary cilium, making JS a canonical ciliopathy. Ciliopathies are unified by their overlapping clinical features and underlying mechanisms involving ciliary dysfunction. In this work, we identify biallelic rare, predicted-deleterious ARMC9 variants (stop-gain, missense, splice-site, and single-exon deletion) in 11 individuals with JS from 8 families, accounting for approximately 1% of the disorder. The associated phenotypes range from isolated neurological involvement to JS with retinal dystrophy, additional brain abnormalities (e.g., heterotopia, Dandy-Walker malformation), pituitary insufficiency, and/or synpolydactyly. We show that ARMC9 localizes to the basal body of the cilium and is upregulated during ciliogenesis. Typical ciliopathy phenotypes (curved body shape, retinal dystrophy, coloboma, and decreased cilia) in a CRISPR/Cas9-engineered zebrafish mutant model provide additional support for ARMC9 as a ciliopathy-associated gene. Identifying ARMC9 mutations as a cause of JS takes us one step closer to a full genetic understanding of this important disorder and enables future functional work to define the central biological mechanisms underlying JS and other ciliopathies., (Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) is an autosomal dominant disease caused by mutations in the SERPING1 gene. A Jordanian family, including 14 individuals with C1-INH-HAE clinical symptoms, was studied. In the propositus and his parents, SERPING1 had four mutations leading to amino acid substitutions. Two are known polymorphic variants (c.167T>C; p.Val34Ala and c.1438G>A; p.Val458Met), the others are newly described. One (c.203C>T; p.Thr46Ile) is located in the N-terminal domain of the C1-inhibitor protein and segregates with angioedema symptoms in the family. The other (c.800C>T; p.Ala245Val) belongs to the serpin domain, and derives from the unaffected father. DNA from additional 24 family members were screened for c.203C>T mutation in the target gene. All individuals heterozygous for the c.203C>T mutation had antigenic and functional plasma levels of C1-inhibitor below 50% of normal, confirming the diagnosis of type I C1-INH-HAE. Angioedema symptoms were present in 14 of 16 subjects carrier for the c.203T allele. Among these subjects, those carrying the c.800T variation had more severe and frequent symptoms than subjects without this mutation. This family-based study provides the first evidence that multiple amino acid substitutions in SERPING1 could influence C1-INH-HAE phenotype., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: The production of camel heavy-chain antihuman IgE (huIgE) that has the potential to block IgE-FcεRI interaction and histamine release by basophils., Methods: Camels were immunized with a synthetic loop peptide (SLP) designed in a multiple antigen peptide system (MAPS) forming SLP-MAPS immunogen. Camel polyclonal antibodies (PCAs) were produced, purified, characterized using Protein A & G, ELISA, and SDS-PAGE, and tested for their potency to block passive sensitization and histamine release of human basophils using flow cytometry (FCM) and ELISA, respectively., Results: FCM data indicated that camel conventional (IgG1) and heavy chain antibodies (HCAbs; IgG2, and IgG3) had blocking activities of 43.9%, 72%, and 96.6%, respectively. Moreover, both IgG2 and IgG3 achieved remarkable inhibition rates of 93.98% and 97.05% in histamine release, respectively, whereas the IgG1inhibiting activity was 60.05%., Conclusions: Camel PCAs produced against SLP-MAPS were capable of blocking the IgE-receptor interaction and the release of histamine by basophils with superiority to HCAbs. These findings may pave the way toward the possible use of camel anti-huIgE HCAbs as blocking antibodies in the treatment of IgE-mediated allergy and asthma.