Early child health in Lahore, Pakistan: XIII. Primary teeth emergence

The aim of this study was to investigate the number of emerged primary teeth at various ages from 6 to 24 months in 1347 longitudinally followed Pakistan infants sampled from four socio-economically different areas in Lahore, Pakistan; from a very poor periurban slum to a privileged upper middle class group. The emergence of the primary teeth was found to be little, or not all related to sex or to the area of living. However, in comparison with studies conducted in other continents, the Indo-Pak subcontinent population lags behind in primary teeth emergence, especially in early life. This genetic difference makes it necessary to create specific standards of primary teeth emergence for this population.     

Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients

Classical citrullinemia (CTLN1), a rare autosomal recessive disorder, is caused by mutations of the argininosuccinate synthetase (ASS) gene, localized on chromosome 9q34.1. ASS functions as a rate-limiting enzyme in the urea cycle. Previously, we identified 32 mutations in the ASS gene of CTLN1 patients mainly in Japan and the United States, and to date 34 different mutations have been described in 50 families worldwide. In the present study, we report ASS mutations detected in 35 additional CTLN1 families from 11 countries. By analyzing the entire coding sequence and the intron-exon boundaries of the ASS gene using RT-PCR and/or genomic DNA-PCR, we have identified 16 novel mutations (two different 1-bp deletions, a 67-bp insertion, and 13 missense) and have detected 12 known mutations. Altogether, 50 different mutations (seven deletion, three splice site, one duplication, two nonsense, and 37 missense) in 85 CTLN1 families were identified. On the basis of primary sequence comparisons with the crystal structure of E. coli ASS protein, it may be concluded that any of the 37 missense mutations found at 30 different positions led to structural and functional impairments of the human ASS protein. It has been found that three mutations are particularly frequent: IVS6-2A>G in 23 families (Japan: 20 and Korea: three), G390R in 18 families (Turkey: six, U.S.: five, Spain: three, Israel: one, Austria: one, Canada: one, and Bolivia: one), and R304W in 10 families (Japan: nine and Turkey: one). Most mutations of the ASS gene are "private" and are distributed throughout the gene, except for exons 5 and 12-14. It seems that the clinical course of the patients with truncated mutations or the G390R mutation is early-onset/severe. The phenotype of the patients with certain missense mutations (G362V or W179R) is more late-onset/mild. Eight patients with R86H, A118T, R265H, or K310R mutations were adult/late-onset and four of them showed severe symptoms during pregnancy or postpartum. However, it is still difficult to prove the genotype-phenotype correlation, because many patients were compound heterozygotes (with two different mutations), lived in different environments at the time of diagnosis, and/or had several treatment regimes or various knowledge of the disease.     

Cloning and sequence analysis of the pfl gene encoding pyruvate formate-lyase from Streptococcus mutans.

We have isolated a sorbitol-negative mutant of Streptococcus mutans GS-5 following random mutagenesis with plasmid pVA891 clone banks. This mutant did not metabolize sorbitol anaerobically but did so aerobically. A 10-kb chromosomal DNA fragment flanking the pVA891 insertion was deleted in this mutant. The corresponding region from the parental strain GS-5 was then recovered by a marker rescue method with Escherichia coli. The pyruvate formate-lyase gene, pfl, was identified within a 3-kb PstI-XbaI fragment located in the middle of the deleted region of the chromosome, and its inactivation in S. mutans produced the same sorbitol-negative phenotype. Nucleotide sequence analysis of the pfl gene revealed a 2.3-kb open reading frame (ORF) preceded by potential ribosome-binding and promoter-like sequences. The ORF specified a putative protein of 775 amino acid residues with a calculated molecular weight of 87,533. The amino acid sequence deduced from the ORF exhibited significant similarity to that of the E. coli pfl gene.     

Adult-onset type II citrullinemia and idiopathic neonatal hepatitis caused by citrin deficiency: involvement of the aspartate glutamate carrier for urea synthesis and maintenance of the urea cycle

Citrin is a mitochondrial aspartate glutamate carrier primarily expressed in the liver, heart, and kidney. We found that adult-onset type II citrullinemia is caused by mutations in the SLC25A13 gene that encodes for citrin. In this report, we describe the frequency of SLC25A13 mutations, the roles of citrin as a member of the urea cycle and as a member of the malate-aspartate shuttle, the relationship between its functions and symptoms of citrin deficiency, and therapeutic issues.     

Plasma Free Fatty Acids and Metabolic Effect in Type 2 Diabetes,an Ancillary Study from a Randomized Clinical Trial

Most nutrition studies looking at the association of food with cardiometabolic markers rely on food frequency questionnaires, which are prone to recall bias. Pentadecanoic acid, heptadecanoic acid and trans-palmitoleic acid are fatty acids that are not synthesized endogenously but are obtained from the diet, particularly dairy, making them reasonable biomarkers of dairy consumption. We investigated the association of dairy fatty acid biomarkers with glycated hemoglobin (HbA1c) and cardiovascular risk factors in type 2 diabetes (T2D). In a clinical trial, 111 participants with T2D (age 58.5 ± 8.9 years, HbA1c 8.09 ± 0.96%) were randomized into three groups: a control group that maintained baseline dairy intake, a low-fat (LF) group that incorporated ≥3 servings/day of LF dairy and a high-fat (HF) group that incorporated ≥3 servings/day of HF dairy. We compared the fatty acids (FA) composition between the three groups at 24 weeks. Pentadecanoic acid and trans-palmitoleic acid increased in the HF group by 14.1% ± 5.4% and 17.5% ± 5.1%, respectively, but not in the control and LF groups (p = 0.0474 and p = 0.0025 for group-by-time interaction, respectively). Those increases were positively associated with changes in total cholesterol, very-low-density lipoprotein cholesterol VLDL-C and triglycerides but were not associated with changes in HbA1c from baseline to 24 weeks. These results suggest that the intervention was successful and that participants were likely compliant, which supports the validity of the main trial.     

Hemorrhoid Disorder and Anal Intercourse: Is There a Solution?

Archives of Sexual Behavior -     

The turmoil around the drug-eluting stents

Of 141 hospital survivors after intracardiac repair of tetralogy of Fallot, eight died suddenly 6–23 years later. Compared with the other 133 patients, these eight were older at operation, with higher post-repair systolic right ventricular pressure and more often complete atrioventricular block; ventricular arrhythmia was diagnosed before death in three cases. In follow-up totalling 2255 patient years, the linearized rate of sudden death was 0.35%/year. The instantaneous risk of sudden death showed continuous increase with the length of follow-up. Of 80 survivors electrocardiographically evaluated 13–26 (median 20) years postoperatively, none had complete block, but 79 had complete right bundle branch block, including seven with left anterior hemiblock. Ventricular extrasystoles were recorded in 1% at rest, in 34% during exercise and in 83% during 24-hour ambulatory monitoring, with Lown Grade ≥II in 27%. Old age and possibly presence of fibrosis and/or fibroelastosis in right ventricular outflow tract muscle correlated independently with high Lown Grade. A patient with Lown grade III died suddenly 2 years after our follow-up. Old age at repair thus was associated with increased risk of late sudden death and with frequent ventricular arrhythmia in long-term survivors.     

Invagination intestinale sur métastase d’un mélanome cutané

The authors reported a case of ileal invagination secondary to metastasis of a cutaneous melanoma. This complication is exceptional On the occasion of this observation, the authors point out the jejuno-ileal preferential localization, the difficulties of diagnosis and management of intestinal metastasis of cutaneous malignant melanoma also the poor prognosis of these lesions. The princeps treatment of these metastases is surgical, to compensate for the possible occlusive emergency and permit carcinologic resection. This surgery will be coupled with adjuvant chemotherapy.     

The first case of mastitis in sheep caused by Actinobacillus ureae from Iran

Actinobacillus ureae, previously known as Pasteurella urea, is a commensal bacterium, which rarely causes disease in humans and has not been reported from any animal case in the veterinary literature. In this report, the occurrence of acute mastitis caused by A. ureae in an Iranian Ghezel sheep is described.