A novel PAX6 mutation causes congenital aniridia with or without retinal detachment

Background: Aniridia is a rare developmental eye disorder characterized by complete or partial iris hypoplasia often accompanied with other ocular changes that affect the cornea, anterior chamber, lens, retina, and optic nerve. Most cases of aniridia are inherited with an autosomal dominant mode of inheritance caused by PAX6 mutations or deletions. To reveal the underlying genetic defect in a four-generation Iranian family with aniridia, we carried out a genetic screening of PAX6.

Methods: Complete ophthalmic examinations were performed for available affected family members. All PAX6 exons and their flanking regions were sequenced for affected individuals. Candidate variation was screened for segregation in the pedigree by Sanger sequencing. Bioinformatics prediction was done to evaluate the deleterious effects of the mutation on protein product. Real-time PCR was used to investigate the impact of the variant on PAX6 mRNA expression.

Results: All patients were diagnosed with isolated aniridia associated with variable phenotypic features including retinal detachment. A novel heterozygous deletion c.320_348delTGTCCGAGGGGGTCTGTACCAACGATAAC (p.Leu107HisfsX16) on PAX6 gene was detected. Decreased mRNA level of PAX6 in the affected individuals indicated that the mutation caused nonsense-mediated mRNA decay (NMD).

Conclusions: To the best of our knowledge, it is the first report on the genetics of aniridia in Iran. Segregation analysis, bioinformatics prediction and confirmation of NMD, all support the proposition that the novel observed PAX6 mutation is the cause of aniridia in the pedigree. Retinal detachment in some of the affected members, which is a rare reported phenotypic feature of aniridia patients, may be associated with this mutation.     

Vaccine-associated paralytic poliomyelitis in a patient with MHC class II deficiency.

Vaccine-associated paralytic poliomyelitis (VAPP) is a rare complication of oral polio vaccine. We describe a fatal case of VAPP in an 8-month-old boy with Major Histocompatibility Class II deficiency. The isolated poliovirus was a Sabin type 2-type 1 recombinant that showed 1.4% VP1 divergence from Sabin type 2.     

Effects of diode low-level laser therapy on healing of tooth extraction sockets: a histopathological study in diabetic rats

Lasers in Medical Science - Diabetes mellitus is mostly interrelated to deficiency in wound healing. Low-level laser therapy has been shown to exert reliable effects on the acceleration of wound...     

A randomized,double-blind placebo-controlled add-on trial to assess the efficacy,safety, and anti-atherogenic effect of spirulina platensis in patients with inadequately controlled type 2 diabetes mellitus

The efficacy of spirulina platensis (S. platensis) as an add-on therapy to metformin and its effect on atherogenic keys in patients with uncontrolled Type 2 Diabetes Mellitus (T2DM) was evaluated. Sixty patients were randomly assigned to S. platensis (2 g/day) or placebo group for three months while continuing metformin as their usual treatment. The efficacy of S. platensis was determined using the pre- and post-intervention HbA1c levels (primary outcome) as well as tracking FBS and lipid profiles levels (TC, LDL-C, TG, and HDL-C) as secondary outcomes at the different treatment time points (0,30,60,90 days). During the three–month intervention period, supplementation with S. platensis resulted in a significant lowering of HbA1c (↓1.43, p < 0.001) and FBS (↓ 24.94 mg/dL, p < 001) levels. Mean TG in the intervention group was found to be significantly lower in the intervention group than in controls (p < 0.001). Total cholesterol (TC) and its fraction, LDL-C, exhibited a fall (↓41.36 mg/dL and ↓38.4 mg/dL, respectively; p < 0.001) coupled with a marginal increase in the level of HDL-C (↑3 mg/dL; p < 0.001). Add-on therapy with S. platensis was superior to metformin regarding long-term glucose regulation and controlling blood glucose levels of subjects with T2DM. Also, as a functional supplement, S. platensis has a beneficial effect on atherogenic keys (TG and HDL-C) with no adverse events.     

Establishment of a formal program for retinoblastoma: Feasibility of clinical coordination across borders and impact on outcome

Retinoblastoma is an ocular tumor that occurs in young children, in either heritable or sporadic manner. The relative rarity of retinoblastoma, and the need for expensive equipment, anesthesia, and pediatric ophthalmologic expertise, are barriers for effective treatment in developing countries. Also, with an average age‐adjusted incidence of two to five cases per million children, patient number limits development of local expertise in countries with small populations. Lebanon is a small country with a population of approximately 4.5 million. In 2012, a comprehensive retinoblastoma program was formalized at the Children's Cancer Institute (CCI) at the American University of Beirut Medical Center, and resources were allocated for efficient interdisciplinary coordination to attract patients from neighboring countries such as Syria and Iraq, where such specialized therapy is also lacking. Through this program, care was coordinated across hospitals and borders such that patients would receive scheduled chemotherapy at their institution, and monthly retinal examinations and focal laser therapy at the CCI in Lebanon. Our results show the feasibility of successful collaboration across borders, with excellent patient and physician adherence to treatment plans. This was accompanied by an increase in patient referrals, which enables continued expertise development. However, the majority of patients presented with advanced intraocular disease, necessitating enucleation in 90% of eyes in unilateral cases, and more than 50% of eyes in bilateral cases. Future efforts need to focus on expanding the program that reaches to additional hospitals in both countries, and promoting early diagnosis, for further improvement of globe salvage rates.     

Preparation,characterization and catalytic application of nano-Fe3O4@SiO2@(CH2)3OCO2Na as a novel basic magnetic nanocatalyst for the synthesis of new pyranocoumarin derivatives

We present a study on the synthesis, characterization and application of sodium carbonate tag silica-coated nano-Fe₃O₄ (Fe₃O₄@SiO₂@(CH₂)₃OCO₂Na) as a novel and efficient heterogeneous basic catalyst. The described catalyst was fully characterized via FT-IR, X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDS), and field emission scanning electron microscopy (FE-SEM). The reported novel magnetic nanocatalyst presents an excellent activity and catalytic performance for the synthesis of a novel series of pyranocoumarins through the reaction of dialkyl acetylenedicarboxylates and 5,7-dihydroxy coumarin derivatives at 100 °C under solvent-free conditions.

We present a study on the synthesis, characterization and application of sodium carbonate tag silica-coated nano-Fe₃O₄ (Fe₃O₄@SiO₂@(CH₂)₃OCO₂Na) as a novel and efficient heterogeneous basic catalyst.     

Genetic variant association of PTPN22, CTLA4, IL2RA,as well as HLA frequencies in susceptibility to alopecia areata

ABSTRACT

Alopecia areata (AA) is characterized by a genetically complex inheritance. HLA frequencies, as well as the single nucleotide polymorphism (SNP) in PTPN22, CTLA4, and IL2RA genes, have been described to be associated with AA susceptibility. So far, no independent replication of these studies has been reported, and no data exist on a possible association between AA disease and these SNPs or influence of HLA frequencies in Iranian population. A possible association between HLA-DRB1*11 alleles as well as a single variation in PTPN22, CTLA4, and IL2RA genes and patchy AA disease have been investigated in a cohort from Iran. Patient and control subjects were genotyped for PTPN22 (rs2476601), CTLA4 (rs3087243), and IL2RA (rs3118470) variations as well as HLA frequencies. Gene expression levels were analyzed by real-time RT-PCR. In contrast to PTPN22 and CTLA4 gene polymorphisms, a significant association was found between IL2RA SNP and susceptibility to AA in Iranian cohort. While gene expression levels of IL2RA and PTPN22 were higher in the patients than that of controls, CTLA4 expression levels found significantly lower in the patients. Despite a significant association between AA and HLA-DRB1*11 frequencies, the presence of DRB1*11 is not associated with PTPN22, CTLA4, or IL2RA gene SNPs. Although the minor allele in IL2RA SNP can be a significant determinant of AA disease development in Iranian population, reported an association between the PTPN22 and CTLA4 variations was not confirmed by our study. Furthermore, these genetic risk factors might act independently from HLA alleles.     

In vitro investigation of fluorescence of carious dentin observed with a Soprolife® camera

Objectives

Our aim was to determine the origin of the red fluorescence of carious dentine observed with the Soprolife® camera.

Methods

We conducted in vitro studies to evaluate the origin of the red fluorescence using acids and matrix metalloproteinase (MMP) to mimic caries and methylglycoxal (MGO) to evaluate the effect of glycation reactions on the red fluorescence. In every step of these models, we detected the changes of dentin photonic response with Soprolife® in daylight mode and in treatment mode. A Raman spectroscopy analysis was performed to determine the variations of the dentin organic during the in vitro caries processes. Raman microscopy was performed to identify change in the collagen matrix of dentine.

Results

The red fluorescence observed in carious dentine using a Soprolife® camera corresponds to the brownish color observed using daylight. Demineralization using nitric acid induces a loss of the green fluorescence of dentine. The red fluorescence of carious dentine is resistant to acid treatment. Immersion of demineralized dentine in MGO induces a change of color from white to orange-red. This indicates that the Maillard reaction contributes to lesion coloration. Immersion of demineralized dentine in an MMP-1 solution followed by MGO treatment results in a similar red fluorescence. Raman microspectroscopy analysis reveals accumulation of AGE's product in red-colored dentine.

Conclusions

Our results provide important information on the origin of the fluorescence variation of dentine observed with the Soprolife® camera. We demonstrate that the red fluorescence of carious dentine is linked to the accumulation of Advanced Glycation End products (AGE).

Clinical relevance

The study provides a new biological basis for the red fluorescence of carious dentine and reinforces the importance of the Soprolife® camera in caries diagnostics.     

The effect of different surface treatments of demineralised enamel on microleakage under metal orthodontic brackets

Background

The aim of this investigation was to assess the effects of different treatments of demineralised enamel on microleakage under orthodontic brackets.

Methods

Seventy-five intact premolars were randomly assigned to five groups. The teeth in groups 2 through 5 were immersed in a demineralising solution for 16 weeks. In groups 1 (control) and 2 (demineralised/control), conventional acid etching was used. In group 3, sodium hypochlorite (NaOCl) was applied on the enamel surface for 1 min after acid etching, and in group 4, Transbond Plus (3M Unitek, Monrovia, CA, USA) self-etching primer (SEP) was used. The teeth in group 5 were treated with 2% sodium fluoride (NaF) for 4 min before etching. After bracket bonding, the specimens were thermocycled, sealed with nail varnish, immersed in 0.5% basic fuchsine solution for 24 h and sectioned. Microleakage was measured under a stereomicroscope for the enamel-adhesive and adhesive-bracket interfaces of both occlusal and gingival sides.

Results

Demineralised teeth showed more microleakage at the enamel-adhesive interface on both occlusal and gingival sides compared to sound teeth, but the difference was not significant (P > 0.005). Treating the demineralised enamel with 5% NaOCl or Transbond Plus SEP was not effective in reducing microleakage. NaF treatment followed by acid etching of demineralised enamel resulted in significantly lower microleakage in most comparisons (P < 0.005).

Conclusions

The use of 2% NaF on hypomineralised enamel before the bracket bonding procedure is an effective way to decrease microleakage.