Association between dental hygiene, gingivitis and overweight or the risk of overweight in primary teeth of 4- and 5-year-old preschoolers in México.

OBJECTIVE: To determine the association between dental hygiene, gingivitis and overweight or the risk of overweight according to body mass index (BMI). METHODS: A cross-sectional study was performed with 1527 preschoolers. The children were divided into 4 groups: (i) absence of visible plaque and normal weight; (ii) absence of visible plaque and risk of overweight or overweight; (iii) presence of visible plaque and normal weight; and (iv) presence of visible plaque and risk of overweight or overweight. The clinical parameters evaluated were as follows: body mass index, degree of urban marginalization, dental caries, the simplified oral hygiene index and gingival status. Bivariate analysis and multivariate binary logistic regression models were used to identify associations between variables. RESULTS: The highest mean of gingivitis (0.28) was observed in the groups with visible plaque with normal weight and with overweight and risk of overweight. The presence of visible plaque and risk of overweight or overweight were positively associated (P = .0001) with the mean of gingivitis (OR = 8.28, 95% CI = 3.30-19.8). The absence of visible plaque and risk of overweight or overweight (P = .0001) were also positively associated with the presence of gingivitis (OR = 2.44, 95% CI = 0.68-8.06). This is after both models were adjusted by gender and degree of marginalization. CONCLUSIONS: The professionals should develop interdisciplinary approaches to (i) propose appropriate interventions to improve oral health in overweight preschoolers; and (ii) propose interventions to decrease the overweight with the possibility of also reducing its association with gingivitis.

High frequency of CYP2D6 ultrarapid metabolizer genotypes in an Ashkenazi Jewish population from Argentina.

A twofold higher frequency of CYP2D6 ultrarapid metabolizers (estimated from genotype: gUMs) was reported among Ashkenazi Jews (AJ) living in New York (USA) than in other North American Caucasians, which might be important to guide the prescription for CYP2D6 substrates in AJ communities around the world. This study was aimed to determine whether the high frequency of CYP2D6 gUMs described in AJ from USA was replicated in AJ from Argentina when compared with other multiethnic admixture Argentines (GA). The frequency of the most common allelic variants and of CYP2D6 gUMs (>2 active genes) and poor metabolizers (0 active genes, gPMs) was also compared among the studied Argentine populations. CYP2D6 genotyping was performed in 173 AJ and 246 GA DNA samples of unrelated donors from the metropolitan area of Buenos Aires. CYP2D6 alleles (*2, *3, *4, *5, *6, *10, *17, *35, *41 and multiple copies), genotypes and functional phenotype frequencies were determined. The frequencies of gUMs and gPMs in AJ from Argentina were 11.5% and 5.2%, respectively, whereas in GA, the frequencies of gUM and gPMs were 6.5% and 4.9%, respectively. Comparisons between AJ and GA showed that gUMs frequencies were twofold higher (P<0.05) in AJ than GA. CYP2D6*35 allele was more frequent in GA than AJ, whereas CYP2D6*41 and *1xN were more frequent in AJ than in GA (P<0.05). This study supports the previously reported high frequency of gUMs on another Ashkenazi population in New York. The present findings also support the interethnic variability of CYP2D6 genetic polymorphism in the overall Argentine population.

Nonsurgical Therapies for Basal Cell Carcinoma: A Review. / Terapias no quirúrgicas para el carcinoma basocelular: revisión.

Basal cell carcinoma (BCC) is the most prevalent malignant tumor in humans and the local destruction of tissue that can result from excision has a significant impact on well-being. Treating BCC is costly for health care systems given the high incidence of this tumor, especially in older patients. Standard treatment involves either resection with histologic assessment of margins or Mohs micrographic surgery. Surgery is sometimes contraindicated, however, due to the presence of significant comorbidity or high cosmetic expectations. For such patients, nonsurgical treatments have become available. These alternatives can offer good local control of disease, preserve function, and achieve excellent cosmetic results.

High frequency of CYP2D6 ultrarapid metabolizers in Spain: controversy about their misclassification in worldwide population studies.

A high frequency (7-10%) of CYP2D6 ultrarapid metabolizers estimated from the genotype (gUMs) has been claimed to exist among Spaniards and Southern Europeans. However, methodological aspects such as the inclusion of individuals carrying non-active multiplied alleles as gUMs may have led to an overestimation. Thus, this study aimed to analyze the gUM frequency (considering only those carrying more than two active genes) in 805 Spanish healthy volunteers studied for CYP2D6*2, *3, *4, *5, *6, *10, *17, *35, *41, and multiplications. Second, all worldwide studies reporting gUM frequencies were reviewed in order to evaluate potential misclassifications. The gUM frequency in this Spanish population was 5.34%, but increased to 8.3% if all individuals with CYP2D6 multiplications were classified as gUMs without considering the activity of the multiplied alleles. Moreover, among all reviewed worldwide studies only 55.6% precisely determined whether the multiplied alleles were active. Present results suggest that the evaluation of CYP2D6 ultrarapid metabolism should be standarized, and that the frequency of gUMs should be reconsidered in Spaniards and globally.

Interethnic variation of CYP2C19 alleles, 'predicted' phenotypes and 'measured' metabolic phenotypes across world populations.

The present study evaluates the worldwide frequency distribution of CYP2C19 alleles and CYP2C19 metabolic phenotypes ('predicted' from genotypes and 'measured' with a probe drug) among healthy volunteers from different ethnic groups and geographic regions, as well as the relationship between the 'predicted' and 'measured' CYP2C19 metabolic phenotypes. A total of 52 181 healthy volunteers were studied within 138 selected original research papers. CYP2C19*17 was 42- and 24-fold more frequent in Mediterranean-South Europeans and Middle Easterns than in East Asians (P<0.001, in both cases). Contrarily, CYP2C19*2 and CYP2C19*3 alleles were more frequent in East Asians (30.26% and 6.89%, respectively), and even a twofold higher frequency of these alleles was found in Native populations from Oceania (61.30% and 14.42%, respectively; P<0.001, in all cases), which may be a consequence of genetic drift process in the Pacific Islands. Regarding CYP2C19 metabolic phenotype, poor metabolizers (PMs) were more frequent among Asians than in Europeans, contrarily to the phenomenon reported for CYP2D6. A correlation has been found between the frequencies of CYP2C19 poor metabolism 'predicted' from CYP2C19 genotypes (gPMs) and the poor metabolic phenotype 'measured' with a probe drug (mPMs) when subjects are either classified by ethnicity (r=0.94, P<0.001) or geographic region (r=0.99, P=0.002). Nevertheless, further research is needed in African and Asian populations, which are under-represented, and additional CYP2C19 variants and the 'measured' phenotype should be studied.

[Asynchronous twin births. Case report and obstetric management review]. / Parto gemelar asincrónico. Presentación de un caso y revisión del tratamiento obstétrico.

BACKGROUND: The incidence of multiple pregnancy has increased in the last years. These pregnancies are associated with more obstetric complications regarding single pregnancies, one of the most important is prematurity. In extremely rare cases premature delivery of one fetus may occur, being retained in the uterine cavity the second fetus until birth later, producing the so-called delayed delivery of twins. CASE REPORT: We report the case of a double twin pregnancy with delayed delivery of the second fetus after birth of the first one within 22.6 weeks of gestation and the second one birth at at 24 weeks of gestation, eight days later after the first one. A review of cases published in the literature is performed and the obstetric management of delayed delivery discussed.

A combined high CYP2D6-CYP2C19 metabolic capacity is associated with the severity of suicide attempt as measured by objective circumstances.

This study examined, for the first time, whether a high CYP2D6-CYP2C19 metabolic capacity combination increases the likelihood of suicidal intent severity in a large study cohort. Survivors of a suicide attempt (n=587; 86.8% women) were genotyped for CYP2C19 (*2, *17) and CYP2D6 (*3, *4, *4xN, *5, *6, *10, wtxN) genetic variation and evaluated with the Beck Suicide Intent Scale (SIS). Patients with a high CYP2D6-CYP2C19 metabolic capacity showed an increased risk for a severe suicide attempt (P<0.01) as measured by the SIS-objective circumstance subscale (odds ratio (OR)=1.37; 95% confidence interval (CI)=1.05-1.78; P=0.02) after adjusting for confounders (gender, age, level of studies, marital status, mental disorders, tobacco use, family history of suicide, personal history of attempts and violence of the attempt). Importantly, the risk was greater in those without a family history of suicide (OR=1.82; CI=1.19-2.77; P=0.002). Further research is warranted to evaluate whether the observed relationship is mediated by the role of CYP2D6 and CYP2C19 involvement in the endogenous physiology or drug metabolism or both.

High frequency and founder effect of the CYP3A4*20 loss-of-function allele in the Spanish population classifies CYP3A4 as a polymorphic enzyme.

Cytochrome P450 3A4 (CYP3A4) is a key drug-metabolizing enzyme. Loss-of-function variants have been reported as rare events, and the first demonstration of a CYP3A4 protein lacking functional activity is caused by CYP3A4*20 allele. Here we characterized the world distribution and origin of CYP3A4*20 mutation. CYP3A4*20 was determined in more than 4000 individuals representing different populations, and haplotype analysis was performed using CYP3A polymorphisms and microsatellite markers. CYP3A4*20 allele was present in 1.2% of the Spanish population (up to 3.8% in specific regions), and all CYP3A4*20 carriers had a common haplotype. This is compatible with a Spanish founder effect and classifies CYP3A4 as a polymorphic enzyme. This constitutes the first description of a CYP3A4 loss-of-function variant with high frequency in a population. CYP3A4*20 results together with the key role of CYP3A4 in drug metabolism support screening for rare CYP3A4 functional alleles among subjects with adverse drug events in certain populations.

Reported foodborne outbreaks due to fresh produce in the United States and European Union: trends and causes.

The consumption of fruit and vegetables continues to rise in the United States and European Union due to healthy lifestyle recommendations. Meanwhile, the rate of foodborne illness caused by the consumption of these products remains high in both regions, representing a significant public health and financial issue. This study addresses the occurrence of reported foodborne outbreaks associated with fresh fruits and vegetables consumption in the United States and European Union during the period 2004-2012, where data are available. Special attention is paid to those pathogens responsible for these outbreaks, the mechanisms of contamination, and the fresh produce vehicles involved. Norovirus is shown to be responsible for most of the produce-related outbreaks, followed by Salmonella. Norovirus is mainly linked with the consumption of salad in the United States and of berries in the European Union, as demonstrated by the Multiple Correspondence Analysis (MCA). Salmonella was the leading cause of multistate produce outbreaks in the United States and was the pathogen involved in the majority of sprouts-associated outbreaks. As is reflected in the MCA, the pattern of fresh produce outbreaks differed in the United States and European Union by the type of microorganism and the food vehicle involved.

Usefulness of the European Epidemic Intelligence Information System in the management of an outbreak of listeriosis, Belgium, 2011.

A cluster of time-linked cases and the identification of a clonal strain suggest the occurrence of an outbreak of listeriosis in Belgium in 2011, presumably due to the consumption of hard cheese made with pasteurised milk and produced by a Belgium manufacturer. The outbreak clone was identified as Listeria monocytogenes serovar 1/2a, sensitive to arsenic and cadmium and of multilocus sequence typing MLST-type 37. Food investigation of this outbreak was facilitated by the European Epidemic Intelligence Information System and data exchanged between French and Belgium listeriosis surveillance systems.

Shigellosis outbreak linked to canteen-food consumption in a public institution: a matched case-control study.

On 13 November 2009, the authorities of Flemish Brabant, Belgium, received an alert concerning a potential outbreak of Shigella sonnei at a public institution. A study was conducted to assess the extent, discover the source and to implement further measures. We performed a matched case-control study to test an association between shigellosis and canteen-food consumption. Water samples and food handlers' faecal samples were tested. The reference laboratory characterized the retrospectively collected Shigella specimens. We found 52 cases distributed over space (25/35 departments) and time (2 months). We found a matched odds ratio of 3·84 (95% confidence interval 1·02-14·44) for canteen-food consumption. A food handler had travelled to Morocco shortly before detection of the first laboratory-confirmed case. Water samples and food handlers' faecal samples tested negative for Shigella. Confirmed cases presented PFGE profiles, highly similar to archived isolates from Morocco. Foodborne transmission associated with the canteen was strongly suspected.

Melatonin is synthesised by yeast during alcoholic fermentation in wines.

Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone produced in the pineal gland. Its biological properties are related to the circadian rhythm. Recently, the European Food Safety Authority (EFSA) accepted the health claim related to melatonin and the alleviation of subjective feelings of jet lag. This molecule has been detected in some foods. In this work, 13 grape varieties were studied; 7 monovarietal wines were produced in an experimental winery under strictly controlled conditions and were sampled in different steps. The grape varieties used to make the wines were: Cabernet Sauvignon, Merlot, Syrah, Tempranillo, Tintilla de Rota, Palomino Fino and Alpha red. Liquid chromatography tandem mass spectrometry (LC-MS/MS) unequivocally confirmed the presence of melatonin in wines. The main contribution of this paper is the results that clearly show that melatonin is synthesised during the winemaking process, specifically after the alcoholic fermentation. Indeed, melatonin is absent in grapes and musts and is formed during alcoholic fermentation.

Evidence of melatonin synthesis and release by mast cells. Possible modulatory role on inflammation.

Mast cells take part of armamentarium immunologic for host defense against parasitic and bacterial infections. They are derived from bone marrow progenitors and can be activated by immunological and chemical stimuli in order to get its degranulation. The activation of mast cells generates a signalling cascade leaded to the rapid release of vasoactives and pro-inflammatory mediators. Melatonin (N-acetyl-5-methoxytryptamine) is a molecule with antioxidant, cytoprotective and immunomodulatory actions. It was initially known to be produced exclusively in the pineal gland but melatonin synthesis has been found in different sites of the organism, and a major source of extrapineal melatonin is the immune system. The aim of the present study was to prove if the rat mast cell line (RBL-2H3) synthesizes and releases melatonin, also to explain its possible mechanism of action. We report that both resting and stimulated mast cells synthesize and release melatonin. We also report that the necessary machinery to synthesize melatonin is present in mast cells and that these cells showed the presence of MT1 and MT2 melatonin membrane receptors. Those results indicated that the melatonin would be able to exert a regulatory effect on inflammatory reactions mediated by mast cells.

Cluster of hepatitis A cases among travellers returning from Egypt, Belgium, September through November 2008.

Following a European alert by France, we detected a hepatitis A cluster in Belgian travellers returning from Egypt. Our investigation supports the hypothesis of a common source outbreak, linked to Nile river cruises. The outbreak also suggests the need to consider an intensification of the vaccination policy for travellers to hepatitis A endemic countries.

Development of genomic resources for Citrus clementina: characterization of three deep-coverage BAC libraries and analysis of 46,000 BAC end sequences.

BACKGROUND: Citrus species constitute one of the major tree fruit crops of the subtropical regions with great economic importance. However, their peculiar reproductive characteristics, low genetic diversity and the long-term nature of tree breeding mostly impair citrus variety improvement. In woody plants, genomic science holds promise of improvements and in the Citrus genera the development of genomic tools may be crucial for further crop improvements. In this work we report the characterization of three BAC libraries from Clementine (Citrus clementina), one of the most relevant citrus fresh fruit market cultivars, and the analyses of 46.000 BAC end sequences. Clementine is a diploid plant with an estimated haploid genome size of 367 Mb and 2n = 18 chromosomes, which makes feasible the use of genomics tools to boost genetic improvement. RESULTS: Three genomic BAC libraries of Citrus clementina were constructed through EcoRI, MboI and HindIII digestions and 56,000 clones, representing an estimated genomic coverage of 19.5 haploid genome-equivalents, were picked. BAC end sequencing (BES) of 28,000 clones produced 28.1 Mb of genomic sequence that allowed the identification of the repetitive fraction (12.5% of the genome) and estimation of gene content (31,000 genes) of this species. BES analyses identified 3,800 SSRs and 6,617 putative SNPs. Comparative genomic studies showed that citrus gene homology and microsyntheny with Populus trichocarpa was rather higher than with Arabidopsis thaliana, a species phylogenetically closer to citrus. CONCLUSION: In this work, we report the characterization of three BAC libraries from C. clementina, and a new set of genomic resources that may be useful for isolation of genes underlying economically important traits, physical mapping and eventually crop improvement in Citrus species. In addition, BAC end sequencing has provided a first insight on the basic structure and organization of the citrus genome and has yielded valuable molecular markers for genetic mapping and cloning of genes of agricultural interest. Paired end sequences also may be very helpful for whole-genome sequencing programs.

Cytokine IL-1 beta but not IL-1 alpha promoter polymorphism is associated with Alzheimer disease in a population from the Canary Islands, Spain.

AIMS: Previous studies have reported the presence of low-grade inflammation in Alzheimer disease (AD). Based on these data, our work attempts to investigate the effects of some promoter polymorphisms of pro-inflammatory cytokines [interleukin (IL)-1 alpha and IL-1 beta] on AD. PATIENTS AND METHODS: A PCR-RFLP technique was used to analyze the promoter polymorphisms of both IL-1 alpha (-889 C/T) and IL-1 beta (-511 C/T) and the APOE genotype from the DNA samples of 282 patients (according to NINCDS-ADRDA criteria) and 312 control subjects. RESULTS: (i) The risk of developing AD in our population was associated with the IL-1 beta (-511 C/T) promoter polymorphism; (ii) such risk was independent of the risk factor allele in the APOE gene (APOE4); and (iii) the IL-1 alpha promoter polymorphism (-889 C/T) was not associated with the disease. CONCLUSION: In our population, IL-1 beta promoter polymorphism (-511 C/T) is an independent risk factor for AD.

Targeting of acetylcholinesterase to lipid rafts of muscle.

Despite the great progress made in setting the basis for the molecular diversity of acetylcholinesterase (AChE), an explanation for the existence of two types of amphiphilic subunits, with and without glicosylphosphatidylinositol (GPI) (Types I and II), has not been provided yet. In searching whether, as for the deficiency of dystrophin, that of merosin (laminin-alpha2 chain) alters the number of caveolae in muscle, a high increase in caveolin-3 (Cav3) was observed in the Triton X-100-resistant membranes (TRM) isolated from muscle of merosin-deficient dystrophic mice (Lama2dy). The rise in Cav3 was accompanied by that of non-caveolar lipid rafts, as showed by the greater ecto-5'-nucleotidase (eNT) activity, a marker of non-caveolar rafts, in TRM of dystrophic muscle. The observation of AChE activity in TRM, the increased levels of rafts and raft-bound AChE activity in merosin-deficient muscle and the presence of phospholipase C-sensitive AChE dimers in TRM supported targeting of glypiated AChE to rafts. This issue and the involvement of TRM in conveying nicotinic receptors to the neuromuscular junction and particular muscarinic receptors to cardiac sarcolemma strongly support a role for lipid rafts in targeting ACh receptors and glypiated AChE. Their nearby location in the surface membrane may provide cells with a fine tuning for regulating cholinergic responses.

The level of aryl acylamidase activity displayed by human butyrylcholinesterase depends on its molecular distribution.

Butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) display both esterase and aryl acylamidase (AAA) activities. Their AAA activity can be measured using o-nitroacetanilide (ONA). In human samples depleted of acetylcholinesterase, we noticed that the ratio of amidase to esterase activities varied depending on the source, despite both activities being due to BuChE. Searching for an explanation, we compared the activities of BuChE molecular forms in samples of human colon, kidney and serum, and observed that BuChE monomers (G(1)) hydrolyzed o-nitroacetanilide much faster than tetramers (G(4)). This fact suggested that association might cause differences in the AAA site between single and polymerized subunits. This and other post-translational modifications in BuChE subunits probably determine their level of AAA activity. The higher amidase activity of monomers could justify the presence of single BuChE subunits in cells as a way to preserve the AAA activity of BuChE, which could be lost by oligomerization.