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"A Theory of Justice" is a project in the Kantian school by John Rawls, the twentieth-century philosopher. The "Veil of Ignorance" is one of the prominent notions of his theory of justice, which is born in another abstract concept as the "Original Position". Rawls seeks to establish fairness or impartiality in the laws and administration of society by using such a tool. The present article has tried descriptively and analytically to emphasize the capacity of applying the theory of veil of ignorance in criminal law by applying this doctrine. Finally, the writing of this article demonstrates that an applied approach to Rawls' explanatory model can lead to a better understanding of the legal principles and rules of a legal system (descriptively), and to the extent that the theory is immune from subjectivity, it may criticize criminal justice and its rules.

Background: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive disorder characterized by macrocephaly, and slowly progressive clinical course marked by ataxia, spasticity and mental decline. MLC is caused by mutations in the gene MLC1 which encodes a novel protein, MLC1. Conclusion: A 4-year-old girl with macrocephaly, spasticity, ataxia and abnormal cerebral white matter and subcortical cysts in brain MRI diagnosed with MLC. This is the first report of MLC in an Iranian family. Conclusion: MLC1 should be considered in children with macrocephaly and slowly progressive psychomotor decline. This disease can be prenatally diagnosed and genetic counseling offered for future pregnancies. [ABSTRACT FROM AUTHOR]

Background: The cesarean scar niche, a consequence of incomplete wound healing, can lead to gynecological complications and affect future pregnancies. While internal niches have been well-studied, external and bidirectional niches are also important., Objective: We aimed to conduct a comparative analysis of the prevalence and measurements of different types of niches., Study Design: This cross-sectional study examined 200 patients with prior cesarean delivery undergoing hysterectomy due to abnormal uterine bleeding. It evaluated internal, external, and bidirectional niche prevalence, measurements (height, residual myometrial thickness, and adjacent myometrial thickness), and classification in hysterectomy specimens compared to prehysterectomy transvaginal sonography reports. The secondary outcome was to determine niche presence in uterine tissue samples based on the number of previous cesarean deliveries., Results: The mean age of the study participants was 48.19 years, with 30% having undergone only one cesarean delivery. Notably, 83.5% had niches detected via sonography, while 91% had niches identified in uterine tissue samples posthysterectomy (P value=.008). Internal niches were common, with significant associations between niche presence and the number of previous cesarean deliveries. 23.3% of patients with one cesarean delivery had internal niches. Additionally, external niches were detected in 4% of hysterectomy samples but not observed in ultrasound reports. Key parameters such as residual myometrium thickness and adjacent myometrial thickness differed notably between ultrasound and tissue samples, highlighting discrepancies in niche detection methods. Residual myometrium thickness ranged from 2.8 to 24 mm (7.68±3.09 mm) in ultrasound reports vs 0 to 25 mm (4.28±2.71 mm) in tissue samples (P<.001). Adjacent myometrial thickness ranged from 6 to 29 mm (17.08±4.53 mm) in ultrasound reports vs 7.5 to 30 mm (16±5.03 mm) in tissue samples (P<.001). This study underscores the importance of accurate niche assessment in patients with prior cesarean delivery., Conclusion: We performed a comparative analysis of niche prevalence and measurements in gross specimens and transvaginal sonography reports. The results highlight the importance of considering external and bidirectional niches, in addition to internal niches. These niches can reduce residual myometrial thickness and increase future pregnancy complications. Furthermore, we demonstrated that niche formation can occur after a single cesarean delivery., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Next-generation sequencing (NGS) has been proven to be one of the most powerful diagnostic tools for rare Mendelian disorders. Several studies on the clinical application of NGS in unselected cohorts of Middle Eastern patients have reported a high diagnostic yield of up to 48%, correlated with a high level of consanguinity in these populations. We evaluated the diagnostic utility of NGS-based testing across different clinical indications in 1436 patients from Iran, representing the first study of its kind in this highly consanguineous population. A total of 1075 exome sequencing and 361 targeted gene panel sequencing were performed over 8 years at a single clinical genetics laboratory, with the majority of cases tested as proband-only (91.6%). The overall diagnostic rate was 46.7%, ranging from 24% in patients with an abnormality of prenatal development to over 67% in patients with an abnormality of the skin. We identified 660 pathogenic or likely pathogenic variants, including 241 novel variants, associated with over 342 known genetic conditions. The highly consanguineous nature of this cohort led to the diagnosis of autosomal recessive disorders in the majority of patients (79.1%) and allowed us to determine the shared carrier status of couples for suspected recessive phenotypes in their deceased child(ren) when direct testing was not possible. We also highlight the observations of recessive inheritance of genes previously associated only with dominant disorders and provide an expanded genotype-phenotype spectrum for multiple less-characterized genes. We present the largest mutational spectrum of known Mendelian disease, including possible founder variants, throughout the Iranian population, which can serve as a unique resource for clinical genomic studies locally and beyond., (© 2024. The Author(s).)

The following work presents a new, rapid, potential to be portable, convenient, and low-cost method using hollow fiber membrane-protected solid phase microextraction followed by corona discharge ion mobility spectrometry which was used for determining dimethyl methylphosphonate in beverages. Response surface methodology based on the design of Box-Behnken was implemented for optimizing the different factors influencing the proposed method for obtaining the best results. Optimal extractions were calculated with 65 µm polydimethylsiloxane-divinylbenzene fiber, fiber equilibration time of 10 min, stirring rate of the sample solution at 750 rpm, and extraction temperature of 50 °C. The proposed technique provided linear range (0.5-50 µg mL -1 ), good linearity (>0.991), and repeatability (the relative standard deviations of 5.42% and 8.37% of intra- and inter-day analyses, respectively) under the optimized extraction conditions. Finally, the developed method was successfully used for determining dimethyl methylphosphonate in beverages such as coffee mix, fruit juice, tap water, milk, and tea., Competing Interests: Declaration of Competing Interest There are no conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

In this paper, a novel solid phase microextraction fiber based on Co 3 O 4 quantum dot incorporated polyacrylamide-co-ethylene glycol dimethacrylate followed by corona discharge ion mobility spectrometry is presented for the trace determination of organophosphorus pesticides in environmental water samples. Ion mobility spectrometry is a comparatively inexpensive, well-known, robust, and easy to operate analytical instrument. This combination would provide a low-cost, fast, selective, and sensitive quantitative system for detection of organophosphorus pesticides. In order to obtain the best extraction efficiency, the optimization of parameters affecting this method was carried out. After optimization, a solution pH of 7.0, extraction temperature of 60 °C, adsorption temperature of 260 °C, extraction time of 30 min, stirring speed of 750 rpm, and ionic strength of 10% w/w were obtained. Consequently, the presented method showed low limits of detection (0.3-0.6 ng mL -1 ), excellent enrichment factors (PF = 221-263), good linearity (R 2 > 0.995), and repeatabilities (intra-day: 3.4 to 4.8%) and (inter-day: 4.7 to 6.1%). The reproducibility (RSD% of fiber to fiber) was also investigated by analyzing three as-prepared fibers under the same conditions and was found to be less than 7.6%. Finally, the developed fiber was used for determination of organophosphorus pesticides in the field samples.

In many printing technologies involving multicomponent liquids, the deposition and printing quality depend on the small-scale transport processes present. For liquids with dispersed particles, the internal flow within the droplet and the evaporation process control the structure of the deposition pattern on the substrate. In many situations, the velocity field inside microdroplets is often subject to either thermal or solutal Marangoni convection. Therefore, to achieve more uniform material deposition, the surface tension-driven flow should be controlled and the effect of different fluid and chemical parameters should be identified. Here, we employ an axisymmetric numerical model to study droplet spreading and evaporation on isothermal and heated substrates. For ethanol-water droplets, the effects of the initial contact angle and initial ethanol concentration inside the droplet (solutal Marangoni number) have been studied. We explore the role of the initial ethanol concentration on the magnitude and structure of the internal flows for binary mixture droplets. In addition, we show that certain combinations of initial contact angle and initial ethanol concentration can lead to a more uniform deposition of dispersed particles after all of the liquid has been evaporated., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

This study focuses on the synthesis of carbon nanotubes decorated with nickel-zinc ferrites and fabrication of polyurethane (PU) nanofiber containing CNT-ferrite composites as highly efficient adsorbents for removal of hydrogen sulfide. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transformed infrared (FTIR) spectroscopy, and powder X-ray diffraction (PXRD) are used to perform microstructural and morphological characterization of the electrospun nanofibrous composites. To show the efficiency of the composite as an adsorbent, a breakthrough test is carried out. It is shown that the PU-CNT-ferrite composites are fabricated almost uniformly with an average fiber diameter of 320 nm and exhibit significant H 2 S breakthrough capacity (498 mgH 2 S/g) compared to both the pristine PU and PU-CNT nanofibers. These electrospun nanofibers based on CNT-ferrite composites, already studied for H 2 S adsorption with promising results, open up new and interesting perspective into the design and fabrication of highly efficient membrane for practical application in the processes of air purification.

Sjögren-Larsson syndrome (SLS) is a rare autosomal recessive disorder characterized by ichthyosis, spasticity and intellectual disability. The disease is caused by mutations in the ALDH3A2 gene that encodes fatty aldehyde dehydrogenase. We describe 7 Iranian SLS patients from 5 unrelated consanguineous families. Sequencing of ALDH3A2 identified 4 novel mutations, including a 26-bp deletion (c.25&#95;50del), small in-frame deletion (c.370&#95;372del; p.G124del), a termination (p.Q35Ter) and a missense mutation (p.Lys211Glu). Bacterial expression of the p.Lys211Glu and p.G124del mutations showed little or no detectable enzyme activity. Three of the patients exhibited an unusual neuro-regressive clinical course associated with seizures, which may reflect the presence of unidentified genetic or environmental modifiers in this consanguineous population. This cohort represents the largest group of Iranian patients with molecularly confirmed SLS and expands the mutational and clinical spectrum of this disease., (Copyright © 2017. Published by Elsevier Masson SAS.)

Kaufman oculo-cerebro-facial syndrome (KOS) is caused by recessive UBE3B mutations and presents with microcephaly, ocular abnormalities, distinctive facial morphology, low cholesterol levels and intellectual disability. We describe a child with microcephaly, brachycephaly, hearing loss, ptosis, blepharophimosis, hypertelorism, cleft palate, multiple renal cysts, absent nails, small or absent terminal phalanges, absent speech and intellectual disability. Syndromes that were initially considered include DOORS syndrome, Coffin-Siris syndrome and Dubowitz syndrome. Clinical investigations coupled with karyotype analysis, array-comparative genomic hybridization, exome and Sanger sequencing were performed to characterize the condition in this child. Sanger sequencing was negative for the DOORS syndrome gene TBC1D24 but exome sequencing identified a homozygous deletion in UBE3B (NM&#95;183415:c.3139&#95;3141del, p.1047&#95;1047del) located within the terminal portion of the HECT domain. This finding coupled with the presence of characteristic features such as brachycephaly, ptosis, blepharophimosis, hypertelorism, short palpebral fissures, cleft palate and developmental delay allowed us to make a diagnosis of KOS. In conclusion, our findings highlight the importance of considering KOS as a differential diagnosis for patients under evaluation for DOORS syndrome and expand the phenotype of KOS to include small or absent terminal phalanges, nails, and the presence of hallux varus and multicystic dysplastic kidneys.

Cutis laxa is a heterogeneous condition characterized by redundant, sagging, inelastic, and wrinkled skin. The inherited forms of this disease are rare and can have autosomal dominant, autosomal recessive, or X-linked inheritance. Three of the autosomal recessive cutis laxa syndromes, namely cutis laxa IIA (ARCL2A), cutis laxa IIB (ARCL2B), and geroderma osteodysplastica (GO), have very similar clinical features, complicating accurate diagnosis. Individuals with these conditions often present with cutis laxa, progeroid features, and hyperextensible joints. These conditions also share additional features, such as short stature, hypotonia, and congenital hip dislocation, but the severity and frequency of these findings are variable in each of these cutis laxa syndromes. The characteristic features for ARCL2A are abnormal isoelectric focusing and facial features, including downslanting palpebral fissures and a long philtrum. Rather, the clinical phenotype of ARCL2B includes severe wrinkling of the dorsum of the hands and feet, wormian bones, athetoid movements, lipodystrophy, cataract and corneal clouding, a thin triangular face, and a pinched nose. Normal cognition and osteopenia leading to pathological fractures, maxillary hypoplasia, and oblique furrowing from the outer canthus to the lateral border of the supraorbital ridge are discriminative features for GO. Here we present 10 Iranian patients who were initially diagnosed clinically using the respective features of each cutis laxa syndrome. Each patient's clinical diagnosis was then confirmed with molecular investigation of the responsible gene. Review of the clinical features from the cases reported from the literature also supports our conclusions.

Unlabelled: The present study aimed to optimize the electrospinning parameters for polyacrylonitrile (PAN) nanofibers containing MgO nanoparticle to obtain the appropriate fiber diameter and mat porosity to be applied in air filtration. Optimization of applied voltage, solution concentration, and spinning distance was performed using response surface methodology. In total, 15 trials were done according to the prepared study design. Fiber diameter and porosity were measured using scanning electron microscopic (SEM) image analysis. For air filtration testing, the nanofiber mat was produced based on the suggested optimum conditions for electrospinning. According to the results, the lower solution concentration favored the thinner fiber. The larger diameter gave a higher porosity. At a given spinning distance, there was a negative correlation between fiber diameter and applied voltage. Moreover, there were curvilinear relationships between porosity and both spinning distance and applied voltage at any concentration. It was also concluded that the developed filter medium could be comparable to the high-efficiency particulate air (HEPA) filter in terms of collection efficiency and pressure drop. The empirical models presented in this study can provide an orientation to the subsequent experiments to form uniform and continuous nanofibers for future application in air purification., Implications: High-efficiency filtration is becoming more important, due to decreasing trends air quality. Effective filter media are increasingly needed in industries applying clean-air technologies, and the necessity for developing the high-performance air filters has been more and more felt. Nanofibrous filter media that are mostly fabricated via electrospinning technique have attracted considerable attention in the last decade. The present study aimed to develop the electrospun PAN-containing MgO nanoparticle (using the special functionalities such as absorption and adsorption characteristics, antibacterial functionality, and as a pore-forming agent) filter medium through experimental investigations for application in high-performance air filters.

Objective: To establish a diagnosis and provide counseling and treatment for 3 adult patients from one family presenting with peripheral osteolysis., Methods: Following clinical and radiographic assessment, exome sequencing, targeted gene resequencing, and determination of enzyme activity in cultured fibroblasts were performed., Results: The proband (age 40 years) had a history of episodic fever and pain in childhood that subsided around puberty. He and 2 of his older sisters (ages 58 and 60 years, respectively) showed adult-onset progressive shortening of fingers and toes with redundancy of the overlying skin. Radiographs showed severe osteolysis of the distal radius and ulna, carpal bones, metacarpal bones, and phalanges. Sequencing of the known genes for recessively inherited osteolysis, MMP2 and MMP14, failed to show pathogenic mutations. Exome sequencing revealed compound heterozygosity for mutations c.505T>C (p.Trp169Arg) and c.760A>G (p.Arg254Gly) in ASAH1, the gene coding for acid ceramidase. Sanger sequencing confirmed correct segregation in the family, and enzyme activity in fibroblast cultures from the patients was reduced to ∼8% of that in controls, confirming a diagnosis of Farber's disease., Conclusion: Our findings indicate that hypomorphic mutations in ASAH1 may result in an osteoarticular phenotype with a juvenile phase resembling rheumatoid arthritis that evolves to osteolysis as the final stage in the absence of neurologic signs. This observation delineates a novel type of recessively inherited peripheral osteolysis and illustrates the long-term skeletal manifestations of acid ceramidase deficiency (Farber's disease) in what appear to be the oldest affected individuals known so far., (© 2016, American College of Rheumatology.)

Background: Epidermal growth factor (EGF) plays a fundamental role in the healing of wounds relating to skin damage, the cornea, and the gastrointestinal tract., Objectives: The aim of this study is the cloning, expression, and purification of recombinant human EGF (rhEGF), and an assessment of its activity., Materials and Methods: In the present experimental study, a synthetic pET28a (+) -hEGF construct was prepared. In order to ligate hEGF into pET24a (+), the PCR technique was performed, using special primers that possess restriction enzyme sites, which are also located in appropriate sites in pET24a (+). After transferring this construct into E. coli cells, protein expression was performed under standard conditions. Protein solubilization was done by urea. hEGF purification and refolding were carried out using gradient dialysis against the urea. We used RP-HPLC to compare between rhEGF and commercial rhEGF as a control. Finally, an MTT assay was performed to assess the viability of the NIH 3T3 cells treated with various concentrations of rhEGF., Results: Dialysis after urea solubilization caused precipitation of unwanted proteins, resulting in achievement of purified EGF with > 90% purity, without the need for expensive and time-consuming process. The MTT assay results showed that our rhEGF activate significantly higher proliferation of NIH 3T3 cells in comparison to the control (P-values were < 0.0001), in total concentrations and times evaluated, Conclusions: Via our purification protocol, a sufficient amount of bioactive recombinant human epidermal growth factor was obtained in just a few affordable steps, with superlative purity.

In this paper, carbon-coated Fe3 O4 nanoparticles were successfully synthesized and used as a magnetic solid-phase extraction absorbent for the preconcentration and extraction of organophosphorus pesticides in environmental water samples. The carbon-coated Fe3 O4 nanoparticles were characterized by transmission electron microscopy, X-ray powder diffraction, Fourier transform infrared spectroscopy, and vibrating sample magnetometry. The determination of organophosphorus pesticides in water samples with carbon-coated Fe3 O4 nanoparticles was investigated by high-performance liquid chromatography with a diode array detector. Furthermore, the response surface model based on the central composite design was applied to quantitatively investigate the effect of some important variables influencing the extraction efficiency, such as pH, treatment time, amount of nanoparticle sorbents, and amount of salt and to find the optimized conditions providing the highest extraction efficiency. Under optimized conditions, the calibration curve was linear in the range of 0.5-15.0 ng/mL with a regression coefficient of 0.9948, 0.9958, and 0.9931 for fenitrothion, diazinon, and ethion, respectively. The obtained results showed that this analytical method would be useful for the analysis of fenitrothion, diazinon, and ethion in tap water with high precision and accuracy., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A highly sensitive chemiluminescence (CL) method for the determination of 2-chloroethyl ethyl sulfide (2-CEES) was presented. It was found that 2-chloroethyl ethyl sulfide (2-CEES) could inhibit the CL of the luminol-AgNO3 system in the presence of silver nanoparticles in alkaline solution, which made it applicable for determination of 2-CEES. The presented method is simple, convenient, rapid and sensitive. Under the optimized conditions, the calibration curve was linear in the range of 0.0001-1ngmL(-1), with the correlation coefficient of 0.992; while the limit of detection (LOD), based on signal-to-noise ratio (S/N) of 3, was 6×10(-6)ngmL(-1). Also, the relative standard deviation (RSD, n=5) for determination of 2-CEES (0.50ngmL(-1)) was 3.1%. The method was successfully applied for the determination of 2-CEES in environmental aqueous samples., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) (MIM #604004) is a rare autosomal recessive neurological disorder characterized by macrocephaly, motor and cognitive decline, ataxia, spasticity and occasional seizures. Magnetic resonance imaging (MRI) shows diffusely abnormal and swollen white matter of the cerebral hemispheres and subcortical cysts in the anterior temporal and frontoparietal region. Mutations in MLC1(22q13.33) and GLIALCAM have been identified in patients with MLC. Mutations in MLC1 account for approximately 75% of the cases. MLC was suspected in eighteen Iranian patients from sixteen families based on positive clinical findings including macrocephaly beginning in the first year, neurocognitive deterioration, seizure or loss of consciousness after minor head trauma. All except two were born to consanguineous parents. Brain MRI images were compatible with MLC and confirmed the diagnosis. Sequencing of entire coding region of MLC1 was performed for seventeen patients and mutations in MLC1 were detected in all of them. Eight novel mutations and seven previously reported mutations were identified. This report shows that MLC is relatively common in Iranian population, as expected for rare diseases with high inbreeding, with a surprisingly high frequency of novel mutations., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Gamma-glutamyl carboxylase (GGCX) mutations have been reported in patients with a pseudoxanthoma elasticum (PXE)-like phenotype, loose redundant skin, and multiple vitamin K-dependent coagulation factor deficiencies. We report on the clinical findings and molecular results in 13 affected members of two families who had a uniform phenotype consisting of (PXE)-like skin manifestations in the neck and trunk, loose sagging skin of the trunk and upper limbs, and retinitis pigmentosa confirmed by electroretinographies in 10 affected individuals. There were no coagulation abnormalities. Molecular investigations of the ATP-binding cassette subfamily C member 6 did not yield causative mutations. All 13 affected family members were found to be homozygous for the splice-site mutation c.373+3G>T in the GGCX gene. All tested parents were heterozygous for the mutation, and healthy siblings were either heterozygous or had the wild type. We suggest that the present patients represent a hitherto unreported phenotype associated with GGCX mutations. Digenic inheritance has been suggested to explain the variability in phenotype in GGCX mutation carriers. Consequently, the present phenotype may not be explained only by the GGCX mutations only but may be influenced by variants in other genes or epigenetic and environmental factors.

Background: Intellectual Disabilities (ID), defined as a state of developmental deficit, result in significant limitation of intellect and poor adaptation behavior. A number of genetic factors can result in ID, such as chromosomal abnormalities, copy number variation, and single gene defect. Karyotyping is the routine method for detecting chromosomal abnormalities in patients with ID. More recently, the Multiplex Ligation-dependent Probe Amplification (MLPA) method has been applied for detecting microdeletion/duplication in patients with dysmorphism and ID., Methods: A total of 100 patients with dysmorphism and ID have been referred to us since 2011. All patients were first evaluated clinically and a number of these individuals had normal karyotypes. We investigated duplications and deletions for 21 different microdeletion syndromes using MLPA kit (MRC-Holland)., Results: We were able to identify aberrations in 12 (12%) patients clinically ascertained as follows: 5 Williams syndromes, 3 Miller- Dieker syndromes, 1 Sotos syndrome, 1 Angelman Syndrome, 1 Di-George syndrome and one patient with an abnormal 4p chromosomal region., Conclusion: Our MLPA results indicate a high degree of concordance between the clinical data and the genotype. We suggest MLPA as the first screening method for children suffering from MR with normal karyotypes. In those cases where clinical findings were not compatible with the microdeletion syndrome identified by MLPA investigation, further studies such as FISH and aCGH were performed.

Purpose: The aim of this study was to evaluate the association between a Mediterranean dietary pattern (MeDi) and Vitamin D levels on dry eye syndrome (DES)., Methods: This was a cross-sectional study. Male patients seen in the Miami Veterans Affairs eye clinic with normal eyelid, corneal, and conjunctival anatomy were recruited to participate in the study. The patients filled out the 2005 Block Food Frequency Questionnaire and the Dry Eye Questionnaire 5 and underwent measurement of tear film parameters. The serum level of 25-hydroxy vitamin D was also measured. The main outcome measures included the association among MeDi, Vitamin D levels, and DES., Results: Two hundred forty-seven men underwent DES testing. The mean patient age was 69 years (range, 55-95). Using latent class analysis to categorize the presence or absence of disease and quantify its severity, we found that adherence to the MeDi was positively associated with the risk of having DES (odd ratio 1.25, 95% confidence interval, 1.06-1.47, P = 0.007) and with increasing disease severity. Vitamin D levels were not significantly associated with the presence or severity of disease. However, higher levels of vitamin D were associated with decreased DES symptoms, with a -1.24 decrease in median Dry Eye Questionnaire 5 score for every 10-U increase in Vitamin D levels (P = 0.01)., Conclusions: Adherence to the MeDi was not associated with a beneficial effect on DES. Higher vitamin D levels had a small but favorable effect on DES symptoms.

Johanson-Blizzard syndrome (JBS) is a rare, autosomal recessive disorder characterized by exocrine pancreatic insufficiency, typical facial features, dental anomalies, hypothyroidism, sensorineural hearing loss, scalp defects, urogenital and anorectal anomalies, short stature, and cognitive impairment of variable degree. This syndrome is caused by a defect of the E3 ubiquitin ligase UBR1, which is part of the proteolytic N-end rule pathway. Herein, we review previously reported (n = 29) and a total of 31 novel UBR1 mutations in relation to the associated phenotype in patients from 50 unrelated families. Mutation types include nonsense, frameshift, splice site, missense, and small in-frame deletions consistent with the hypothesis that loss of UBR1 protein function is the molecular basis of JBS. There is an association of missense mutations and small in-frame deletions with milder physical abnormalities and a normal intellectual capacity, thus suggesting that at least some of these may represent hypomorphic UBR1 alleles. The review of clinical data of a large number of molecularly confirmed JBS cases allows us to define minimal clinical criteria for the diagnosis of JBS. For all previously reported and novel UBR1 mutations together with their clinical data, a mutation database has been established at LOVD., (© 2014 WILEY PERIODICALS, INC.)

Proteoglycans are important components of cell plasma membranes and extracellular matrices of connective tissues. They consist of glycosaminoglycan chains attached to a core protein via a tetrasaccharide linkage, whereby the addition of the third residue is catalyzed by galactosyltransferase II (β3GalT6), encoded by B3GALT6. Homozygosity mapping and candidate gene sequence analysis in three independent families, presenting a severe autosomal-recessive connective tissue disorder characterized by skin fragility, delayed wound healing, joint hyperlaxity and contractures, muscle hypotonia, intellectual disability, and a spondyloepimetaphyseal dysplasia with bone fragility and severe kyphoscoliosis, identified biallelic B3GALT6 mutations, including homozygous missense mutations in family 1 (c.619G>C [p.Asp207His]) and family 3 (c.649G>A [p.Gly217Ser]) and compound heterozygous mutations in family 2 (c.323&#95;344del [p.Ala108Glyfs(∗)163], c.619G>C [p.Asp207His]). The phenotype overlaps with several recessive Ehlers-Danlos variants and spondyloepimetaphyseal dysplasia with joint hyperlaxity. Affected individuals' fibroblasts exhibited a large decrease in ability to prime glycosaminoglycan synthesis together with impaired glycanation of the small chondroitin/dermatan sulfate proteoglycan decorin, confirming β3GalT6 loss of function. Dermal electron microcopy disclosed abnormalities in collagen fibril organization, in line with the important regulatory role of decorin in this process. A strong reduction in heparan sulfate level was also observed, indicating that β3GalT6 deficiency alters synthesis of both main types of glycosaminoglycans. In vitro wound healing assay revealed a significant delay in fibroblasts from two index individuals, pointing to a role for glycosaminoglycan defect in impaired wound repair in vivo. Our study emphasizes a crucial role for β3GalT6 in multiple major developmental and pathophysiological processes., (Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Objective: Ullrich congenital muscular dystrophy (UCMD) corresponds to the severe end of the clinical spectrum of neuromuscular disorders caused by mutations in the genes encoding collagen VI (COL VI). We studied four unrelated families with six affected children that had typical UCMD with dominant and recessive inheritance., Materials & Methods: Four unrelated Iranian families with six affected children with typical UCMD were analyzed for COLVI secretion in skin fibroblast culture and the secretion of COLVI in skin fibroblast culture using quantitative RT-PCR (Q-RT-PCR), and mutation identification was performed by sequencing of complementary DNA., Results: COL VI secretion was altered in all studied fibroblast cultures. Two affected sibs carried a homozygous nonsense mutation in exon 12 of COL6A2, while another patient had a large heterozygous deletion in exon 5-8 of COL6A2. The two other affected sibs had homozygote mutation in exon 24 of COL6A2, and the last one was homozygote in COL6A1., Conclusion: In this study, we found out variability in clinical findings and genetic inheritance among UCMD patients, so that the patient with complete absence of COLVI was severely affected and had a large heterozygous deletion in COL6A2. In contrast, the patients with homozygous deletion had mild to moderate decrease in the secretion of COL VI and were mildly to moderately affected.

Purpose: To investigate inter-device agreement between the Pentacam (Optikgerate GmbH, Wetzlar, Germany) and IOLMaster (Carl Zeiss Meditec, Jena, Germany) in measuring corneal power, cylinder, and axis of astigmatism., Methods: Retrospective case series reviewing the status of eyes after toric IOL implantation to evaluate inter-device agreement in measuring corneal power, cylinder, and axis of astigmatism., Results: Forty-nine eyes from 41 patients were evaluated. Agreement for corneal power and cylinder were deemed good and moderate, with 95% limits of agreement of -1.02 to +1.13 and -1.37 to +1.09 diopters (D), respectively. Agreement for axis of astigmatism was only fair, with a mean absolute difference of 8.9 degrees (range: 0.3 to 37.7 degrees, standard deviation: 8.79 degrees). Thirty percent of eyes had a 10-degree or greater difference in axis measurements, and 13% of eyes had a 20-degree or greater difference in measurements. Analysis by multivariate logistic regression showed higher cylinder powers associated with discrepant corneal power measurements (odds ratio: 3.46, P = .02), and increasing age was associated with discrepant axis measurements (odds ratio: 1.09, P = .03). Overall, there was no significant difference in accuracy predicting postoperative spherical equivalent refraction., Conclusions: Pentacam and IOLMaster agree well for corneal power but less so for cylinder and axis of astigmatism and thus cannot be used interchangeably., (Copyright 2013, SLACK Incorporated.)

In this study, a method for extraction and preconcentration trace amounts of organophosphorus pesticides (OPPs) in environmental water was developed using magnetic solid phase extraction (magnetic-SPE) followed by high performance liquid chromatography (HPLC) with UV detection. Magnetite octadecylsilane nanoparticles were synthesized and characterized by X-ray diffraction, FTIR spectroscopy, vibrating sample magnetometry and scanning electron microscopy. These nanoparticles were applied for extraction and preconcentration of OPPs (residues of diazinon and fenitrothion, which are the most-widely used for pest control in Iran) in environmental water samples at low ng mL(-1) concentration as magnetic-SPE adsorbent. The extraction conditions and efficiency of the nanoparticles for OPPs were investigated. The method was evaluated according to the reproducibility, enrichment factor, linearity range and limits of detection. Under optimized conditions, method showed good linearity between 0.03-0.06 and 30 ng mL(-1) with regression coefficients (R(2)) of 0.997 and 0.998. Limits of detection were 0.019 and 0.014 ng mL(-1). The enrichment factors of this method were 172 and 184 and the analysis yielded good reproducibility with the RSD values 7.2% and 5.4% at the 10 ng mL(-1) level (n=5) for diazinon and fenitrothion, respectively. Determination of OPPs can be easily carried out with this fast, accurate, sensitive and simple method procedure., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the impact of ocular surface symptoms on quality of life in a veteran population receiving eye care services., Design: Cross-sectional survey study., Methods: setting: Miami Veterans Affairs Medical Center (VAMC). patient population: Patients seen at the eye clinic between June and August 2010 were asked to fill out the Dry Eye Questionnaire 5 (DEQ5) and the Impact of Dry Eye on Everyday Life (IDEEL) questionnaire. main outcome measures: Correlation between ocular surface symptoms and functionality., Results: Four hundred eighty-nine patients elected to fill out the DEQ5 questionnaire (36% response rate). The mean age of respondents was 66 years (standard deviation 12). Ninety-four percent were male; 62% were white and 37% were black. Using the DEQ5 as a surrogate measure of ocular surface symptoms, 65% of respondents reported at least mild ocular surface symptoms (DEQ5 ≥6) and 27% of them reported severe symptoms (DEQ5 ≥12). Black subjects had a 2-fold increased risk of severe symptoms compared to white subjects (odds ratio 2.06, 95% confidence interval 1.33-3.19). Several medications were associated with a significantly increased risk of severe symptoms, including glaucoma medications (1.7-fold increase), antidepressants (2.3-fold increase), and antihistamines (2.1-fold increase). There was an inverse correlation between DEQ5 and IDEEL scores with regard to ability to perform activities of daily living (n = 391, r = -0.54, P < .001), emotional well-being (n = 386, r = -0.63, P < .001), and the ability to work (n = 205, r = -0.57, P < .001). Fifty percent of patients with severe symptoms had documentation that their symptoms were addressed during the visit., Conclusion: Severe ocular surface symptoms reduce the quality of life of Miami VAMC veterans. Eye care professionals should be vigilant in eliciting ocular surface complaints from their patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous group of inherited disorders of the neuromuscular junction. A difficult to diagnose subgroup of CMS is characterised by proximal muscle weakness and fatigue while ocular and facial involvement is only minimal. DOK7 mutations have been identified as causing the disorder in about half of the cases. More recently, using classical positional cloning, we have identified mutations in a previously unrecognised CMS gene, GFPT1, in a series of DOK7-negative cases. However, detailed description of clinical features of GFPT1 patients has not been reported yet. Here we describe the clinical picture of 24 limb-girdle CMS (LG-CMS) patients and pathological findings of 18 of them, all carrying GFPT1 mutations. Additional patients with CMS, but without tubular aggregates, and patients with non-fatigable weakness with tubular aggregates were also screened. In most patients with GFPT1 mutations, onset of the disease occurs in the first decade of life with characteristic limb-girdle weakness and fatigue. A common feature was beneficial and sustained response to acetylcholinesterase inhibitor treatment. Most of the patients who had a muscle biopsy showed tubular aggregates in myofibers. Analysis of endplate morphology in one of the patients revealed unspecific abnormalities. Our study delineates the phenotype of CMS associated with GFPT1 mutations and expands the understanding of neuromuscular junction disorders. As tubular aggregates in context of a neuromuscular transmission defect appear to be highly indicative, we suggest calling this condition congenital myasthenic syndrome with tubular aggregates (CMS-TA).

Purpose: To evaluate the prevalence of dry eye syndrome (DES) and its associated risk factors in a US Veterans Affairs population receiving ocular care services., Design: Retrospective study., Methods: settings: Patients were seen in the Miami and Broward Veterans Affairs eye clinics between 2005 and 2010. patients population: Patients were divided into cases and controls with regard to their dry eye status (cases = ICD9 code for DES plus dry eye therapy; controls = patients without ICD9 code plus no therapy). main outcome measures: The prevalence of DES and its associated risk factors., Results: A total of 16 862 patients were identified as either a dry eye case (n = 2056) or control (n = 14 806). Overall, 12% of male and 22% of female patients had a diagnosis of DES, with female gender imparting a 2.40 increased risk (95% confidence interval [CI] 2.04-2.81) over male gender. Several medical conditions were found to increase DES risk including post-traumatic stress disorder (odds ratio [OR] 1.97, 95% CI 1.75-2.23), depression (OR 1.91, 95% CI 1.73-2.10), thyroid disease (OR 1.81, 95% CI 1.46-2.26), and sleep apnea (OR 2.20, 95% CI 1.97-2.46) (all analyses adjusted for gender and age). The use of several systemic medications, including anti-depressant medications (OR 1.97, 95% CI 1.79-2.17), anti-anxiety medication (OR 1.74, 95% CI 1.58-1.91), and anti-benign prostatic hyperplasia medications (OR 1.68, 95% CI 1.51-1.86), was likewise associated with an increased risk of DES., Conclusions: The prevalence of DES was found to be high in both men and women in our eye care population. This is the first study to demonstrate that in a veteran population, several diagnoses were significantly associated with DES, including post-traumatic stress disorder and depression., (Published by Elsevier Inc.)

Purpose: To evaluate the refractive and surgical outcomes of cataract surgery with toric intraocular lens (IOL) implantation performed at a teaching institution., Setting: Miami Veterans Affairs Medical Center, Miami, Florida, USA., Design: Retrospective case series., Methods: All data were obtained by a retrospective chart review and entered into a standard computerized database for analysis. Main outcome measures included refractive and surgical outcomes after Acrysof toric IOL placement, including the deviation from the expected spherical and cylindrical correction and the incidence of ocular complications., Results: The study comprised 94 eyes (80 patients). The mean deviation from the anticipated spherical correction (94 eyes) was +0.06 diopter (D) ± 0.8 (range -2.6 D to +3.6 D), with 80% of eyes achieving a spherical equivalent within ±1.00 D of the target refraction. The postoperative refractive cylinder was significantly reduced from baseline, with 79% of eyes having at least a 0.50 D improvement in astigmatism after surgery (P<.0005). The mean deviation from the anticipated refractive cylinder (85 eyes) was -0.48 ± 1.2 D (range -5.0 to +2.8 D). The IOL was placed in an incorrect position in 2 patients, requiring a reoperation with IOL rotation into the proper axis. The mean follow-up was 7 months (range 1 to 28 months)., Conclusion: The added complexity associated with toric IOL placement resulted in spherical and astigmatic improvements without compromising patient safety beyond a level inherent in resident-based cataract surgery., (Published by Elsevier Inc.)

Pyrroline-5-carboxylate reductase 1 (PYCR1) catalyzes the last step in proline synthesis. Deficiency of PYCR1, caused by a defect in PYCR1, was recently described in patients with cutis laxa, intrauterine growth retardation, developmental dysplasia of the hips and mental retardation. In this paper, we describe additional six patients (ages ranging from 4 months to 55 years) from four Iranian families with clinical manifestations of a wrinkly skin disorder. All patients have distinct facial features comprising triangular face, loss of adipose tissue and thin pointed nose. Additional features are short stature, wrinkling over dorsum of hand and feet, visible veins over the chest and hyperextensible joints. Three of the patients from a large consanguineous family do not have mental retardation, while the remaining three patients from three unrelated families have mental and developmental delay. Mutation analysis revealed the presence of disease-causing variants in PYCR1, including a novel deletion of the entire PYCR1 gene in one family, and in each of the other patients the homozygous missense mutations c.616G > A (p.Gly206Arg), c.89T > A (p.Ile30Lys) and c.572G > A (p.Gly191Glu) respectively, the latter two of which are novel. Light- and electron microscopy investigations of skin biopsies showed smaller and fragmented elastic fibres, abnormal morphology of the mitochondria and their cristae, and slightly abnormal collagen fibril diameters with irregular outline and variable size. In conclusion, this study adds information on the natural course of PYCR1 deficiency and sheds light on the pathophysiology of this disorder. However, the exact pathogenesis of this new disorder and the role of proline in the development of the clinical phenotype remain to be fully explained.

Neuromuscular junctions (NMJs) are synapses that transmit impulses from motor neurons to skeletal muscle fibers leading to muscle contraction. Study of hereditary disorders of neuromuscular transmission, termed congenital myasthenic syndromes (CMS), has helped elucidate fundamental processes influencing development and function of the nerve-muscle synapse. Using genetic linkage, we find 18 different biallelic mutations in the gene encoding glutamine-fructose-6-phosphate transaminase 1 (GFPT1) in 13 unrelated families with an autosomal recessive CMS. Consistent with these data, downregulation of the GFPT1 ortholog gfpt1 in zebrafish embryos altered muscle fiber morphology and impaired neuromuscular junction development. GFPT1 is the key enzyme of the hexosamine pathway yielding the amino sugar UDP-N-acetylglucosamine, an essential substrate for protein glycosylation. Our findings provide further impetus to study the glycobiology of NMJ and synapses in general., (Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

We report on two apparently unrelated girls with Johanson-Blizzard syndrome (JBS), in both children caused by a homozygous IVS26+5G>A mutation in the UBR1 gene. In both cases the parents are consanguineous and more sibs are affected. The somewhat mild phenotype (with no or slight mental retardation) in these two JBS families might be explained by residual UBR1 activity. One case has a dilated cardiomyopathy, a symptom only rarely reported in JBS, but of important clinical significance., (Copyright (c) 2008 Wiley-Liss, Inc.)

We report on a 25-year-old man with ectrodactyly and genital anomalies whose parents are first cousins. Their second child died 4 days after birth with severe limb defects and imperforate anus. Our patient may represent clinical variability of the acro-cardio-facial syndrome., (Copyright 2008 Wiley-Liss, Inc.)

A multiwavelength spectrophotometric titration method was applied to study the acidity constants of some azo dyes in water. The UV-vis absorption spectra of azo dye solutions were recorded in the course of their pH-metric titration with a standard base solution. The protolytic equilibrium constants, spectral profiles, concentration diagrams and also the number of components have been calculated. The quantitative effects of the substituents on the acidity of the studied azo dyes were investigated by the linear free energy relationship (LFER) using Hammet sigma constant (sigma) and field and resonance effects of Kamlet and Taft (f and Re, respectively).

A highly selective poly(vinyl chloride)-based membrane sensor produced by using N,N-diethyl-N-(4-hydroxy-6-methylpyridin-2-yl)guanidine (GD) as active material is described. The electrode displays Nernstian behavior over the concentration range 7.0 x 10(-5) - 1.0 x 10(-1) M. The detection limit of the electrode is 5.0 x 10(-5) M. The best performance was obtained with the membrane containing 30% PVC, 55% benzyl acetate, 5% GD and 10% oleic acid. The response of the sensor is pH-independent in the range of 3.0 - 7.0. The sensor possesses satisfactory reproducibility, fast response time (< 20 s), and specially excellent discriminating ability for Eu(III) ion with respect to the alkali, alkaline earth, transition and heavy metal ions. The membrane sensor was used as an indicator electrode in potentiometric titration of Eu(III) ion with EDTA. It was also applied in determination of fluoride ions in mouth wash preparations.

The 2,6-diphenyl-4-benzo-9-crown-3-pyridine (DPCP) was used as an excellent ionophore in construction of a coated graphite poly(vinyl chloride) (PVC)-based membrane sensor. The best performance was obtained with a membrane composition of 30% poly(vinyl chloride), 60% o-nitrophenyloctyl ether (NPOE), 5% 2,6-diphenyl-4-benzo-9-crown-3-pyridine and 5% sodium tetraphenyl borate (TBP). This sensor shows very good selectivity and sensitivity towards beryllium ion over a wide variety of cations, including alkali, alkaline earth, transition and heavy metal ions. The sensor revealed a great enhancement in selectivity coefficients and sensitivity for beryllium, in comparison with the previously reported beryllium electrodes. The electrode exhibits a Nernstian behavior (with slope of 29.6mV per decade) over a very wide concentration range (1.0x10(-7) to 1.0x10(-1)) with a detection limit of 4.0x10(-8)M (360pgml(-1)). It shows relatively fast response time, in whole concentration range (<10s), and can be used for at least 12 weeks in the pH range of 4.5-8.0. The proposed sensor was successfully used to determination of beryllium in mineral ore.