Type 1 diabetes genetic risk score discriminates between monogenic and Type 1 diabetes in children diagnosed at the age of <5 years in the Iranian population.

AIM: To examine the extent to which discriminatory testing using antibodies and Type 1 diabetes genetic risk score, validated in European populations, is applicable in a non-European population. METHODS: We recruited 127 unrelated children with diabetes diagnosed between 9 months and 5 years from two centres in Iran. All children underwent targeted next-generation sequencing of 35 monogenic diabetes genes. We measured three islet autoantibodies (islet antigen 2, glutamic acid decarboxylase and zinc transporter 8) and generated a Type 1 diabetes genetic risk score in all children. RESULTS: We identified six children with monogenic diabetes, including four novel mutations: homozygous mutations in WFS1 (n=3), SLC19A2 and SLC29A3, and a heterozygous mutation in GCK. All clinical features were similar in children with monogenic diabetes (n=6) and in the rest of the cohort (n=121). The Type 1 diabetes genetic risk score discriminated children with monogenic from Type 1 diabetes [area under the receiver-operating characteristic curve 0.90 (95% CI 0.83-0.97)]. All children with monogenic diabetes were autoantibody-negative. In children with no mutation, 59 were positive to glutamic acid decarboxylase, 39 to islet antigen 2 and 31 to zinc transporter 8. Measuring zinc transporter 8 increased the number of autoantibody-positive individuals by eight. CONCLUSIONS: The present study provides the first evidence that Type 1 diabetes genetic risk score can be used to distinguish monogenic from Type 1 diabetes in an Iranian population with a large number of consanguineous unions. This test can be used to identify children with a higher probability of having monogenic diabetes who could then undergo genetic testing. Identification of these individuals would reduce the cost of treatment and improve the management of their clinical course.

Low-fouling biomimetic membranes fabricated by direct replication of self-cleaning natural leaf.

The membrane fouling has always been a big issue for developing membrane applications. Surface morphology and roughness affect remarkably on the membrane tendency to fouling. In this study, a biomimetic technique, as a simple, cost-effective and time-saving method was employed to replicate Tropaeolum majus (nasturtium) leaf surface on the surface of a commercial thin-film composite (TFC) reverse osmosis (RO) membrane using polyethersulfone (PES) moulds. Morphology of surface and hydrophilicity of membranes were investigated by scanning electron microscope (SEM), atomic force microscope (AFM) and water contact angle measurements. AFM and SEM photos of membrane surface declared that replication of nasturtium leaf improved the surface characteristics of membranes. The average roughness of membranes heated at 130°C and 150°C was 81.1 and 152.4 nm, respectively. The similar measurement was lower for the virgin membrane. Also, the roughened membranes showed higher hydrophilicity than the virgin membrane. In addition, the performance of the membrane was assessed by evaluating pure water flux (PWF) and flux recovery (FR) after the filtration of whey solution as a severe foulant for membranes. The findings exhibited that the replicated membranes had higher PWF and FR values, indicating the lower fouling tendency of modified membranes.

What is to be done? Controversies in the diagnosis and treatment of manic-depressive illness.

BACKGROUND: In recent years, much progress has been made in the diagnosis and treatment of schizophrenia and depression. Bipolar disorder, however, remains frequently misunderstood, leading to inconsistent diagnosis and treatment. Why is the case? What is to be done about it? METHODS: We critically review studies in the nosology of bipolar disorder and the effects of antidepressant agents. RESULTS: Bipolar disorder is underdiagnosed and frequently misdiagnosed as unipolar major depressive disorder. Antidepressants are probably overused and mood stabilisers underused. Reasons for underdiagnosis include patients' impaired insight into mania, failure to involve family members in the diagnostic process, and inadequate understanding by clinicians of manic symptoms. We propose using a mnemonic to aid in diagnosis, obtaining family report, and utilising careful clinical interviewing techniques given the limitations of patients' self-report. We recommend aggressive use of mood stabilisers, and less emphasis on antidepressants. CONCLUSIONS: The state of diagnosis and treatment in bipolar disorder is suboptimal. More diagnostic attention to manic criteria is necessary and the current pattern of use of antidepressant use in bipolar disorder needs to change.

Prevalence of transient hyperglycemia and diabetes mellitus in pediatric patients with acute leukemia.

BACKGROUND: The most common malignancy of children is Leukemia, accounting approximately one third of cancer diagnosis. Available data demonstrate improvement in survival of pediatric leukemia, so evaluation of side effects of treatment is very important. This study investigates hyperglycemia and diabetes mellitus prevalence in pediatric patients with acute leukemia. MATERIALS AND METHODS: This study was performed in children with acute leukemia. At the first admission, demographic data was collected and blood glucose and HbA1c levels were obtained. These tests examined at least two times during six months of follow up. Growth parameters and blood samples were obtained too. RESULT: Twenty nine patients were examined; three of them (10.3%) had diabetes mellitus and 5patients (17.2%) had transient hyperglycemia.Mean age of the patients was 6.26 years and nineteen Children (63%) were in preschool age. In preschool age children, incidence of hyperglycemia was meaningfully higher than school age children (p= 0.02). 24 of 29 patients (82.7%) were known case of acute lymphoblastic leukemia (ALL) and 5 patients (17.3%) were known case of acute myeloblastic leukemia (AML). No significant difference was found between sex groups. Also underweight was significant risk factor for hyperglycemia. CONCLUSION: The prevalence of hyperglycemia was in the range of other similar studies in different parts of the world. Underweight and preschool ages were significant predictors of hyperglycemia.

The study and analysis of the mating behavior and sound production of male cicada Psalmocharias alhageos (Kol.) (Homoptera:Cicadidae) to make disruption in mating.

Psalmocharias alhageos is an important pest of vine in most parts of Iran, Afghanistan, Pakistan, southern areas of Russia, Turkey and Iraq. This cicada is spread in most provinces in Iran such as Esfahan, Hamedan, Qazvin, Markazi, Lorestan, Qom, Kerman, Tehran and Kordestan. In addition to vine, this insect damages some other fruit trees, such as apple, sour cherry, quince, peach, pomegranate and pear trees and some non-fruit trees, namely white poplar, ash, elm, eglantine, silk and black poplar trees. The nymphs of cicada damage the trees by feeding on root, adult insects on young bud and by oviposition under branch barks. Nourishing root by nymph leads to the weakness of the tree and hinder its growth. The high density oviposition of adult insects inside young barks causes withering of branches. The resulted damage on vine products is 40% which is one of the most important factors in product reduction in vineyard. This research was conducted in Takestan in Qazvin. It was conducted for the first time to study the behaviors of the mates of this vine cicada in order to manage it. Two systems were used to record the sound of male cicada called analog voice-recorder and digital voice recorder. To analyze the recorded sound of the male cicada we used of spectrum analyzer, digital storage oscilloscope and protens 7 computer softwares. We could call the attention of natural enemies an disturb the male insect's attracting sound by producing natural and artificial sound in the range of 1-6 kHz in two different ripeness status of the fruits and could prevent mating and oviposition of female cicadas.

A natural variant of Bacillus licheniformis alpha-amylase isolated from flour mill wastewaters sheds light on the origin of high thermostability.

AIMS: Understanding the origin of high thermostability exhibited by the alpha-amylase produced by a natural strain of Bacillus licheniformis. METHODS AND RESULTS: The MSH320 alpha-amylase gene has been cloned from a native strain of B. licheniformis isolated from flour mill wastewaters in Kashan, central Iran, and its nucleotide sequence was determined (GenBank Accession Number AF438149). Whereas previously cloned B. licheniformisalpha-amylase (BLA) genes are nearly identical, the MSH320 gene coding sequence presents only 93% identity with the reference 'wild-type' BLA gene, most of the nucleotide changes leading to silent mutations. Amino acid substitutions occurred at 19 of the 483 residues of the matured protein, distributed all along the protein sequence. Nevertheless, the natural BLA variant presents thermoinactivation kinetics similar to that of the reference BLA. Protein modelling and structural predictions at the substitution sites suggest that half of the mutations may have a significant stabilizing or destabilizing effect on the protein structure. Compensatory mutations thus occurred in the natural variant in order to maintain thermostability to the level of the reference enzyme. CONCLUSIONS: The exceptional high thermostability of BLA, although produced by a nonthermophilic organism, is not fortuitous but subject to a selective pressure still at work in natural environments. SIGNIFICANCE AND IMPACT OF THE STUDY: BLA thermal performances are not naturally maximized and can be substantially improved by protein engineering.

Expression and secretion of an alpha-amylase gene from a native strain of Bacillus licheniformis in Escherichia coli by T7 promoter and putative signal peptide of the gene.

The gene encoding a hyperthermostable alpha-amylase from a Bacillus licheniformis native strain was cloned in pET24d transcription vector containing T7 promoter, and expressed in Escherichia coli BL21(DE3) cells. Having confirmed the alpha-amylase activity through activity staining method on SDS-PAGE gel, the yields of production were determined in two separated intra and inter-cellular phases and compared using enzymatic assay methods. Extracellular production of the active recombinant enzyme implies the recognition of the putative signal peptide of this Bacillus sp. by E. coli secretory system. This may be because of the amino acid sequence of this signal peptide which covers all the structural parameters of a standard signal peptide processed by Lep B, the major signal peptidase in E. coli secretory system. This study recommends the use of this signal peptide for extracellular production of other foreign proteins in E. coli.

Fluoxetine treatment of anger attacks: a replication study.

"Anger attacks" are outbursts of anger which are accompanied by intense autonomic arousal and are clearly inappropriate to the situation in which they occur. The Anger Attacks Questionnaire, designed to assess these attacks, was administered to 164 consecutive patients (78 men and 86 women; mean age, 40.5 +/- 11.0 years) diagnosed as having major depression with the Structured Clinical Interview for DSM-III-R. These patients were treated openly with fluoxetine, 20 mg/day for 8 weeks, and the prevalence of anger attacks was assessed before and after treatment. At baseline, 64 (39%) (26 men and 38 women) of these patients reported having anger attacks according to our criteria. Forty-one (64%) of the 64 depressed patients with anger attacks at baseline did not report anger attacks following fluoxetine treatment, while 7 (7%) of the 100 patients who did not have anger attacks at baseline reported these attacks following treatment, with this difference being statistically significant (chi 2 = 22.7, p < .0005).