ZSCAN10 deficiency causes a neurodevelopmental disorder with characteristic oto-facial malformations.

Neurodevelopmental disorders are major indications for genetic referral and have been linked to more than 1,500 loci including genes encoding transcriptional regulators. The dysfunction of transcription factors often results in characteristic syndromic presentations, however, at least half of these patients lack a genetic diagnosis. The implementation of machine learning approaches has the potential to aid in the identification of new disease genes and delineate associated phenotypes. Next generation sequencing was performed in seven affected individuals with neurodevelopmental delay and dysmorphic features. Clinical characterization included reanalysis of available neuroimaging datasets and 2D portrait image analysis with GestaltMatcher. The functional consequences of ZSCAN10 loss were modelled in mouse embryonic stem cells (mESC), including a knock-out and a representative ZSCAN10 protein truncating variant. These models were characterized by gene expression and Western blot analyses, chromatin immunoprecipitation and quantitative PCR (ChIP-qPCR), and immunofluorescence staining. Zscan10 knockout mouse embryos were generated and phenotyped. We prioritized bi-allelic ZSCAN10 loss-of-function variants in seven affected individuals from five unrelated families as the underlying molecular cause. RNA-Seq analyses in Zscan10-/- mESCs indicated dysregulation of genes related to stem cell pluripotency. In addition, we established in mESCs the loss-of-function mechanism for a representative human ZSCAN10 protein truncating variant by showing alteration of its expression levels and subcellular localization, interfering with its binding to DNA enhancer targets. Deep phenotyping revealed global developmental delay, facial asymmetry, and malformations of the outer ear as consistent clinical features. Cerebral MRI showed dysplasia of the semicircular canals as an anatomical correlate of sensorineural hearing loss. Facial asymmetry was confirmed as a clinical feature by GestaltMatcher and was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations. Our findings provide evidence of a novel syndromic neurodevelopmental disorder caused by bi-allelic loss-of-function variants in ZSCAN10.

Comparison of shear bond strength of rebonded stainless steel brackets with three different enamel surface conditioning methods.

Background: During the orthodontic bonding process, the need for repositioning or rebonding of orthodontic brackets on the enamel surface occurs frequently. The aim of this study is to compare the shear bond strength (SBS) in rebonding orthodontic stainless steel brackets with three different methods of enamel surface conditioning methods. Materials and Methods: In this in vitro study, 80 human premolars that were extracted for orthodontic purposes were randomly divided into four groups and underwent orthodontic bonding procedure (N = 20). Except for the control group, three other groups underwent debonding and rebonding process in which after removing the remaining adhesive with tungsten-carbide bur, enamel surface conditioned by three different methods including re-etching with phosphoric acid, sandblasting + acid etching, and Erbium-doped Yttrium-Aluminum-Garnet laser. Then, the SBS of the bracket to the enamel surface was compared between different groups. Scanning Electron microscopy images were also obtained from a number of samples. Statistical analysis was performed by Kruskal-Wallis and Mann-Whitney tests. Results: The highest SBS was observed in the primary bond (control group) with an average of 29,440 MPa. There was a significant difference between the studied groups (P < 0.001) and only the group that was re-etched with phosphoric acid had no significant difference with the control group (P = 0.708) ∝ =0.05. Conclusion: Rebonding of brackets using phosphoric acid for reconditioning of the enamel surface creates bond strength comparable to the primary bond. Other groups had significantly lower SBS than the control group.

Comparison of Oral and Intravenous N-acetyl Cysteine in Preventing Contrast Nephropathy.

INTRODUCTION: Despite high rates of morbidity and mortality in patients with contrast-induced nephropathy (CIN), there is no consensus regarding prevention of this well-known complication of contrast media use. One agent that has been widely used in this regard is N-acetyl cysteine (NAC). Nevertheless, its efficacy is still controversial. The aim of this study was to assess the efficacy of NAC, both in the oral and intravenous forms, for the prevention of CIN. METHODS: This study is a double-blind randomized placebo controlled clinical trial. We randomized 434 adult patients with chronic kidney disease (constant serum creatinine ≥1.5 mg/dL) who were candidates for coronary angiography/plasty. The patients were categorized into three groups. One group received 1,200 mg NAC intravenously half an hour before the procedure and oral placebo starting 3 days before angiography. The second group received oral NAC 600 mg twice daily for 3 days, starting the day before the intervention and intravenous placebo half an hour before intervention. The third group received both oral and intravenous placebo. CIN was defined as a 25% relative increase in serum creatinine from baseline value, 48 h after use of contrast medium. RESULTS: Of the 434 patients, 149 received intravenous NAC, 145 received oral NAC, and the remaining 140 received placebo. The incidence of CIN in the three groups was 6.1%, 7.6%, and 10.8%, respectively (p = 0.34). CONCLUSION: In patients with chronic kidney disease, neither intravenous nor oral NAC is superior to placebo for preventing CIN.

Comparison of therapeutic effect of mucoadhesive Nanotriamcinolone gel and conventional triamcinolone gel on recurrent aphthous stomatitis / Comparação do efeito terapêutico do gel mucoadesivo de nano-triancinolona e do gel convencional de triancinolona na estomatite aftosa recorrente

Objective: Recurrent aphthous stomatitis (RAS) is characterized by recurring ulcers, with well-defined margins. The lesions are confined to the oral mucosa (usually seen in non-keratinized mucosa). The disease manifests in the form of outbreaks, with a chronic and self-limiting course in most cases. Since the cause of the disease is unknown, many drugs have been studied to palliate the symptoms. Treatment used is multifocal and varies according to the predisposing factors. The aim of this study was to investigate the effect of recombinant Nano-based triamcinolone acetonide gel and compare it with conventional triamcinolone gel on RAS. Material and methods: In this triple-blind randomized clinical trial study, sixty patients with minor aphthous lesions were divided into two groups receiving conventional triamcinolone (CT) and Nano-based triamcinolone (NT). The patients were requested to apply drug four times a day for a week. The severity of pain (through VAS) and the size of the lesions (mean of the largest diameter of the lesions) were evaluated on starting day and days 2, 4, 6 after the intervention. Statistical analysis was performed using chi square and independent t-test. Findings were significant with P < 0.05. Results: Of the 60 patients enrolled in the study, 5 patients did not continue; 21 (38.2%) cases were female and 34 (61.8%) cases were male (P=0.6). The severity of pain in NT group before and after the study was 1.4 ± 5.2 and 1.8 ± 1.3 cm, respectively and in CT group was 48.1 ± 1 and 1.8 ± 1.3 cm. The size of the lesions in NT group before and at the end of the study was 0.96 ± 0.1 and 0.18 ± 0.1 cm, respectively and in CT group was 0.93 ± 0.1 and 0.19 ± 0.1 cm. Among the mentioned variables, only size of lesions on the 2nd and 4th days had a significant reduction in NT group in comparison with CT group. Conclusion: The size of lesions showed a significant reduction on the 2nd and 4th days in NT group in comparison with CT group, therefore NT has a better impact on RAS in comparison with CT. (AU)

Objetivos: A estomatite aftosa recorrente (EAR) é caracterizada por úlceras recorrentes, com margens bem definidas. As lesões estão confinadas à mucosa oral (geralmente vista em mucosa não queratinizada). A doença se manifesta na forma de surtos, com um curso crônico e autolimitado na maioria dos casos. Como a causa da doença é desconhecida, muitos medicamentos foram estudados para aliviar os sintomas. O tratamento utilizado é multifocal e varia de acordo com os fatores predisponentes. O objetivo deste estudo foi investigar o efeito do gel acetonido de triancinolona recombinante baseado em Nano e compará-lo com o gel de triancinolona convencional no EAR. Material e métodos: Neste estudo clínico randomizado triplocego, sessenta pacientes com lesões aftosas menores foram divididos em dois grupos que receberam triancinolona convencional (CT) e triancinolona Nano (NT). Os pacientes foram solicitados a aplicar droga quatro vezes ao dia durante uma semana. A gravidade da dor (por meio da EVA) e o tamanho das lesões (média do maior diâmetro das lesões) foram avaliados no dia inicial e nos dias 2, 4 e 6 após a intervenção. A análise estatística foi realizada utilizando teste qui quadrado e teste t independente. Os achados foram significativos com P < 0.05. Resultados: Dos 60 pacientes incluídos no estudo, 5 pacientes não deram continuidade; 21(38,2%) casos foram mulheres e 34 (61,8%) casos foram homens (P=0,6). A gravidade da dor no grupo NT antes e depois do estudo foi de 1,4 ± 5,2 e 1,8 ± 1,3 cm. O tamanho das lesões no grupo NT antes e ao final do estudo foi de 0,96 ± 0,1 e 0,18 ± 0,1 cm, respectivamente, e no grupo de TC foi de 0,93 ± 0,1 e 0,19 ± 0,1 cm. Entre as variáveis mencionadas, somente o tamanho das lesões no segundo e quarto dias tiveram uma redução significativa no grupo NT em comparação com o grupo CT. Conclusão: O tamanho das lesões mostrou uma redução significativa nos 2º e 4º dias no grupo NT em comparação ao grupo CT, portanto o NT tem um impacto melhor no RAS em comparação com o TC. (AU)

Long-term consequences of iron-fortified flour consumption in nonanemic men.

BACKGROUND/AIMS: Despite the advantages of fortifying flour with iron, there are still special concerns regarding the possible adverse effects of the extra iron consumed by nonanemic individuals. This study aimed to investigate the oxidative stress and iron status following 8 and 16 months of consumption of iron-fortified flour in nonanemic men. METHODS: In a before-and-after intervention study, 78 nonanemic apparently healthy 40- to 65-year-old men were randomly selected from Semnan, in the northeast of Iran. Data were collected at three time points. Evaluation of oxidative stress biomarkers as well as the assessment of iron status was performed in all three stages. After baseline data collection, the flour fortification program was started with 30 mg/kg iron as ferrous sulfate. RESULTS: After 16 months, serum iron levels had significantly increased from 102.9 ± 31.5 µg/dl (baseline) to 117.2 ± 29.8 µg/dl (p < 0.001). The mean total antioxidant capacity (1.71 ± 0.10 µM) was significantly lower than that at baseline (1.83 ± 0.17 µM; p < 0.01). Among other oxidative stress biomarkers, only superoxide dismutase and glutathione peroxidase activity increased significantly compared to the beginning of the study (p < 0.001 and p < 0.001, respectively). The results of this study did not show any symptoms of iron overload after 8 and 16 months. CONCLUSIONS: Our data did not support the safety of flour fortification with 30 mg/kg iron as ferrous sulfate as a community-based approach to control iron deficiency in nonanemic healthy men.