Predominant monomorphism of the RIT2 and GPM6B exceptionally long GA blocks in human and enriched divergent alleles in the disease compartment.

Across human protein-coding genes, the human neuron-specific genes, RIT2 and GPM6B, contain the two longest GA short tandem repeats (STRs) of 11 and 9-repeats, respectively, the length ranges of which are functional, and result in gene expression alteration. Here we sequenced the RIT2 and GPM6B STRs in 600 human subjects, consisting of late-onset neurocognitive disorder (n = 200), multiple sclerosis (n = 200), and controls (n = 200). Furthermore, we selected two large human databases, including the general-population-based gnomAD ( https://gnomad.broadinstitute.org ) and a mainly disease-phenotype-archiving database, TOPMed ( https://www.nhlbiwgs.org ), to compare allele frequencies in the general populations vs. the disease compartment. The RIT2 and GPM6B GA-repeats were monomorphic in the human subjects studied, at lengths of 11 and 9-repeats, respectively, and were predominantly human-specific in formula. Exception included a 9/11 genotype of the RIT2 GA-STR in an isolate case of female multiple sclerosis. Exceedingly rare alleles of the two GA repeats were significantly enriched in TOPMed vs. the gnomAD. We report prime instances of predominant monomorphism for specific lengths of STRs in human, and possible enrichment of rare divergent alleles in the disease phenotype compartment. While STRs are most attended because of their high polymorphic nature, STR monomorphism is an underappreciated feature, which may have a link with natural selection and disease.

Natural selection at the RASGEF1C (GGC) repeat in human and divergent genotypes in late-onset neurocognitive disorder.

Expression dysregulation of the neuron-specific gene, RASGEF1C (RasGEF Domain Family Member 1C), occurs in late-onset neurocognitive disorders (NCDs), such as Alzheimer's disease. This gene contains a (GGC)13, spanning its core promoter and 5' untranslated region (RASGEF1C-201 ENST00000361132.9). Here we sequenced the (GGC)-repeat in a sample of human subjects (N = 269), consisting of late-onset NCDs (N = 115) and controls (N = 154). We also studied the status of this STR across various primate and non-primate species based on Ensembl 103. The 6-repeat allele was the predominant allele in the controls (frequency = 0.85) and NCD patients (frequency = 0.78). The NCD genotype compartment consisted of an excess of genotypes that lacked the 6-repeat (divergent genotypes) (Mid-P exact = 0.004). A number of those genotypes were not detected in the control group (Mid-P exact = 0.007). The RASGEF1C (GGC)-repeat expanded beyond 2-repeats specifically in primates, and was at maximum length in human. We conclude that there is natural selection for the 6-repeat allele of the RASGEF1C (GGC)-repeat in human, and significant divergence from that allele in late-onset NCDs. STR alleles that are predominantly abundant and genotypes that deviate from those alleles are underappreciated features, which may have deep evolutionary and pathological consequences.

Evolving evidence on a link between the ZMYM3 exceptionally long GA-STR and human cognition.

The human X-linked zinc finger MYM-type protein 3 (ZMYM3) contains the longest GA-STR identified across protein-coding gene 5' UTR sequences, at 32-repeats. This exceptionally long GA-STR is located at a complex string of GA-STRs with a human-specific formula across the complex as follows: (GA)8-(GA)4-(GA)6-(GA)32 (ZMYM3-207 ENST00000373998.5). ZMYM3 was previously reported among the top three genes involved in the progression of late-onset Alzheimer's disease. Here we sequenced the ZMYM3 GA-STR complex in 750 human male subjects, consisting of late-onset neurocognitive disorder (NCD) as a clinical entity (n = 268) and matched controls (n = 482). We detected strict monomorphism of the GA-STR complex, except of the exceptionally long STR, which was architecturally skewed in respect of allele distribution between the NCD cases and controls [F (1, 50) = 12.283; p = 0.001]. Moreover, extreme alleles of this STR at 17, 20, 42, and 43 repeats were detected in seven NCD patients and not in the control group (Mid-P exact = 0.0003). A number of these alleles overlapped with alleles previously found in schizophrenia and bipolar disorder patients. In conclusion, we propose selective advantage for the exceptional length of the ZMYM3 GA-STR in human, and its link to a spectrum of diseases in which major cognition impairment is a predominant phenotype.

Breakfast consumption in relation to lowered risk of psychological disorders among Iranian adults.

OBJECTIVES: This study aims to find whether breakfast consumption is associated with human mental health. STUDY DESIGN: This cross-sectional study was conducted to investigate the association between breakfast consumption and psychological disorders, including depression and anxiety, among Iranian adults. METHODS: This cross-sectional study was conducted on 4378 general public adults in Isfahan, Iran. Breakfast consumption was assessed using a validated detailed dietary habits' questionnaire. Depression and anxiety were screened using an Iranian validated Hospital Anxiety and Depression Scale questionnaire. Psychological distress was examined by means of Iranian validated version of General Health Questionnaire (GHQ-12 items). Depression, anxiety, and psychological distress were defined based on standard criteria. RESULTS: Overall, 13.95% (n = 611) of study participants had anxiety, 28.62% (n = 1253) were depressive, and 23.18% (n = 1015) had psychological distress. After controlling for potential confounding variables, participants with every day breakfast consumption had lower odds for depression (odds ratio [OR]: 0.49, 95% confidence interval [95% CI]: 0.36-0.66) compared with those with the least frequent intake of breakfast, even after further adjustment for body mass index [BMI] (OR: 0.47, 95% CI: 0.34-0.63). Frequent breakfast consumption was inversely associated with anxiety before (OR: 0.53, 95% CI: 0.37-0.76, P < 0.001) and after controlling for BMI (OR: 0.52, 95% CI: 0.36-0.75, P < 0.001). The same findings were obtained for psychological distress (OR: 0.46, 95% CI: 0.33-0.62, P < 0.001). CONCLUSION: We found an inverse association between breakfast consumption and depression, anxiety, and psychological distress among Iranian adults. Further prospective studies are needed to confirm these findings.

Dietary glycaemic index and glycaemic load and upper gastrointestinal disorders: results from the SEPAHAN study.

BACKGROUND: Little is known about the effects of carbohydrate, particularly any association between dietary glycaemic index or glycaemic load and uninvestigated heartburn or uninvestigated chronic dyspepsia in the community. The present study aimed to determine associations between dietary glycaemic index or glycaemic load and uninvestigated heartburn or uninvestigated chronic dyspepsia. METHODS: This cross-sectional study was conducted in 2987 adults. Dietary glycaemic index and glycaemic load were estimated using a validated food-frequency questionnaire. Uninvestigated heartburn and uninvestigated chronic dyspepsia were determined using a modified and validated version of the Rome III questionnaire. RESULTS: After controlling for various confounders, high glycaemic load was associated with an increased risk of uninvestigated heartburn [odds ration (OR) = 1.75; 95% confidence interval CI = 1.03, 2.97; P = 0.04] and uninvestigated chronic dyspepsia (OR = 2.14; 95% CI: 1.04, 4.37; P = 0.04) in men but not in women. In normal-weight individuals, high glycaemic index was related to an increased risk of uninvestigated heartburn (OR = 1.52; 95% CI: 1.07, 2.15; P = 0.02) and high glycaemic load to an increased risk of uninvestigated chronic dyspepsia (OR=1.78; 95% CI: 1.05, 3.01; P = 0.03). No significant associations were observed in subjects with excess body weight. CONCLUSIONS: Our data suggest that there are body mass index- and sex-specific associations between dietary carbohydrate quality with uninvestigated heartburn and uninvestigated chronic dyspepsia.

The relationship between tooth loss and psychological factors.

OBJECTIVES: Limited evidence is available regarding mutual interactions between psychological factors and tooth loss. This study aimed to investigate the association between these two issues. METHOD: In this 2011 cross-sectional study we obtained data from 4,585 adults who had completed information in 20 counties across Isfahan province, Iran, regarding tooth loss and psychological factors (depression, anxiety and stress level). To analyse the data ANOVA and multiple ordinal regression were applied. RESULTS: After adjusting socio demographic factors, the association between depression (OR 1.23; 95% CI = 1.01,1.49), anxiety (OR 1.19; 95% CI = 1.03,1.38), and high stress level (OR 95% CI = 1.19; 1.01,1.39) remained significant. CONCLUSION: We confirm the interaction between psychological factors and tooth loss, but recommend further studies on a national Iranian population.

Abnormal dentition in a boy with incontinentia pigmenti: case report.

Incontinentia pigmenti (IP) is an X-linked dominant genodermatosis characterized by typical skin lesions along Blaschko's lines and associated with ocular, dental, nails, hair, skeletal, central nervous system and cardiovascular anomalies. We report a 5-year-old boy with cutaneous hyperpigmentation along Blaschko's lines, atrophic streaks, strabismus and mental retardation. He showed the characteristic abnormal dentition seen in IP as partial hypodontia, peg-shaped anterior teeth and un-erupted teeth. The expression of IP in boys is exceptional as the disease is lethal in males.

Evaluation of Microleakage in Composite-Composite and Amalgam-Composite Interfaces in Tooth with Preventive Resin Restoration (Ex-viva).

OBJECTIVE: This study addresses the question of whether conservative methods of restoration may be applied efficaciously in permanent posterior teeth with proximal lesions and intact occlusal preventive resin restoration (PRR). The purpose of the present study was to assess the microleakage at amalgam-composite interface and composite-composite interface in permanent tooth with PRR. MATERIALS AND METHODS: Thirty-five premolar teeth extracted for orthodontic reasons were selected. The occlusal surfaces were sealed as preventive resin restoration. Then the teeth were stored in incubator for 6 months. After this period, two single boxes were prepared in mesial and distal surfaces in each tooth and filled with amalgam. Another class I composite restoration was prepared in occlusal surface in contact with the first PRR. Then samples were thermocycled and marginal leakage was assessed by the degree of dye penetration on sections of the restored teeth. Friedman and Wilcoxon signed-rank tests served for statistical analyses. RESULTS: In 51.4% of amalgam-composite interfaces the dye reached the pulpal wall. The corresponded figures for amalgam-tooth and composite-composite interfaces were 31.4% and 14.3%, respectively. The differences in microleakage among the three interfaces were statistically significant (P<0.05). CONCLUSION: In the teeth restored with PRR technique, restoring proximal lesions with a conservative technique may lead to favorable results concerning microleakage.

Topiramate add-on treatment in schizophrenia: a randomised, double-blind, placebo-controlled clinical trial.

Glutamate antagonists such as topiramate have been proposed based on the glutamate hypothesis of schizophrenia because its properties encourage its exploration and possible development as a medication for the treatment of schizophrenia. A randomised, double-blind, placebo-controlled clinical trial was performed on 18- to 45-year-old patients with schizophrenia. Baseline information including vital signs, height, weight, smoking status, demographic characteristics, (past) psychiatric history, medication history and medication-related adverse effects were collected. Patients were randomly assigned to a topiramate or placebo group. Efficacy of medication was measured by administering Positive and Negative Syndrome Scale (PANSS), and tolerability of treatment was recorded on day 0 (baseline), day 28 and day 56. PANSS values (95% confidence interval) at baseline, day 28 and day 56 in the topiramate group were 96.87 (85.37-108.37), 85.68 (74.67-96.70) and 76.87 (66.06-87.69), respectively; compared with 101.87 (90.37-113.37), 100.31 (89.29-111.32) and 100.56 (89.74-111.37) in the placebo group. General linear model for repeated measures analysis showed that topiramate has lowered PANSS values significantly compared with the placebo group. Similar significant decline patterns were found in all three subscales (negative, positive and psychopathology sign). Clinical response (more than 20% reduction in PANSS) was significantly higher in topiramate-treated subjects than controls (50% vs 12.5%). Topiramate can be an effective medication in controlling schizophrenic symptoms, considering its effect on negative symptoms and controlling antipsychotic-associated weight gain.

Predictors of conversion to sinus rhythm using ibutilide for atrial fibrillation or flutter.

To determine what factors can predict conversion to sinus rhythm, we retrospectively studied 201 consecutive patients who received ibutilide for treatment of atrial fibrillation or flutter. On multivariate analysis, the following factors were significantly associated with conversion: recent onset of arrhythmia, an underlying atrial flutter rhythm, lack of a history of congestive heart failure, and lack of concomitant digoxin therapy.

Cryoablation of incessant ventricular tachycardia: case report and long-term follow-up.

We report the case of a 52-year-old man who had incessant ventricular tachycardia despite treatment with antiarrhythmic agents. Placement of an implantable cardioverter/defibrillator, radiofrequency ablation, and antitachycardia pacing were ineffective. He underwent intraoperative arrhythmia mapping and cryoablation at our institution. Eighteen months later, he remained free of arrhythmia. He was in New York Heart Association functional class II with an ejection fraction of 30%.

Gendering the millennium: globalising women.

As the century has just changed for the Western calendar it should be borne in mind that for a vast part of the world the centuries are rolling at a different time and under different conditions. So, although we live and trade in a "global village", we are yet divided by time, space, and ideologies. The hope is that the 21st century will enable us to have a closer look at each other and that the global networks, the web sites, and the electronic mailing systems, will work as a bridge rather than as a new means of widening the gaps. This article is a plea for a better understanding of the different priorities and views that Islamist women have of themselves, of their place in history, and what it is that they need to fight for. It is also a call for the universality of sisterhood and a wish that the solidarity that was forged in the latter part of the 20th century will not be fragmented into smithereens in the new millennium.

Low-energy internal cardioversion of atrial fibrillation after failed external cardioversion: Texas Heart Institute experience and review of the literature.

In patients with atrial fibrillation, low-energy internal cardioversion may be used to restore sinus rhythm after external cardioversion fails. We used this method in 8 consecutive patients with a mean age of 69.5+/-8.3 (SD) years, 7 (87.5%) of whom were successfully treated with a mean 9.1 J (range, 4 to 14 J). No patient had ventricular arrhythmias at the time of cardioversion, or local groin complications afterward. One patient had recurrent atrial fibrillation the morning after cardioversion, and another patient had an embolus to the renal artery 20 days posttreatment. After 1 month, 5 patients were still in sinus rhythm, and 1 patient was lost to follow-up. This study confirms the efficacy of internal cardioversion in this setting and stresses the importance of a standard anticoagulation protocol before and after cardioversion.