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Neurocognitive deficits and schizotypal features are elevated in first-degree relatives of schizophrenia patients. However, the co-aggregation of these indicators is not well known. Some studies have found that neurocognitive deficits and schizotypy increase in severity with the density of family history of schizophrenia. Therefore, we studied in affected families a) whether the status of Presumed Carrier (PC) of the genetic risk for schizophrenia is associated with higher levels of neurocognitive deficits and schizotypic features and b) the relationship between schizotypy and neurocognition.
From an ongoing Catalan Multicentric Family Study on Schizophrenia, 70 families were included in this analysis. 90 non-psychotic parents of schizophrenic patients (age 50.7/8.8; education 10.3/4.04; IQ 96.2/14.6) were defined as PC if they had at least one first (apart of offspring) or second degree relative with schizophrenia spectrum disorders (FIGS), resulting in 17 PC and 73 non-PC. Schizotypic features were assessed with the SCID-II and the SPQ-B. Working memory (WM), executive functioning, sustained attention, verbal fluency and logical memory were also assessed.
PC differed significantly from NPC on verbal working memory, even after controlling for IQ (d=0.8). They did not differ on any of the self-reported or interview measures of schizotypy. The negative schizotypic dimension was associated with more WCST-perseverative errors, and low scores in spatial-WM, verbal fluency and immediate/delayed logical memory.
A large association was found between verbal-WM and the familial background of schizophrenia. Only negative features were associated with some neurocognitive functions, supporting the view of multiple independent dimensions or a pleiotropic expression of risk.
The well-established relationship between childhood adversity and psychosis is likely to involve other factors such as genetic variants, which could help to understand why not everyone exposed to adverse events develops psychotic symptoms later in life (Van Winkel, et al. 2008; Simmons et al. 2009).
The present study investigated the influence of childhood abuse and neglect on positive and negative psychosis-like experiences in adulthood and the potential moderating effect of the BDNF-Val66Met polymorphism.
Psychosis-like experiences and childhood adversity were assessed in 533 individuals from the general population.
Childhood abuse showed a strong independent effect on the positive dimension of psychosis-like experiences (B = .16; SE = .05; p = .002). Furthermore, this association was moderated by the BDNF-Val66Met polymorphism (B = .17; SE = .09; p = .004).
Individuals exposed to childhood abuse are more likely to report positive psychosis-like experiences. Met carriers reported more positive psychosis-like experiences when exposed to childhood abuse than did individuals carrying the Val/Val genotype.
Therefore, the observed gene-environment interaction effect may be partially responsible for individual variation in response to childhood abuse.
The extent and causes of covariance between schizotypy and neurocognition is not well-known yet. Certain models conceive their association as necessary for the construct validity of schizotypy, whereas others view them as independently contributing to a multivariate endophenotype. It is also not clear whether those at increased genetic risk for schizophrenia present stronger covariance, reflecting an extra latent source of variance. We analysed their association within relatives of schizophrenia patients defined with FIGS as Presumed Carriers -PC- of the genetic risk for schizophrenia, Presumed Non Carriers -PNC-, and controls.
108 healthy relatives of schizophrenia patients and 72 healthy controls were assessed with the SCID-II and completed the SPQ-B. Neurocognitive assessment: Letter-Number Sequencing (LNS), WCST, CPT-IP, verbal fluency, and logical memory.
Partial correlations adjusting for age and education showed that within PC-relatives self-rated negative schizotypy was associated with lower LNS and CPT-IP; positive schizotypy was associated with CPT-IP, and disorganization with memory and failure to maintain set. Schizoid symptoms had an association with failure to maintain set (though not perseveration) and paranoid symptoms with memory. Within PNC-relatives, negative schizotypy was associated with lower verbal fluency and more perseverative errors. Within controls, positive schizotypy was associated with perseverative errors and both positive and negative dimensions were associated with verbal fluency.
Results indicate a wider array of covariation between relatives with presumed higher genetic liability. A consistent pattern of associations between psychotic-like dimensions and the brain functions tapped by neurocognitive tests did not emerge across groups.
Effective and safe prescription of individualized opioid-doses for opioid-dependent is a complicated task for the clinician, due inter-individual differences in dosage requirements and narrow therapeutic range.
Mu-opioid receptor gene (OPRM1) plays a key role in addiction. A118G-rs1799971 polymorphism in OPRM1 is probably the most promising biomarker of better response in opioid-dependents.
Gene polymorphisms in CYP450-isoenzymes (CYP3A5, CYP3A4, CYP2D6, CYP2B6, CYP1A2, CYP2C9 and CYP2C19) also significantly influence pharmacokinetics and effects of opioids and concomitant treatments.
Objectives and aims
Association of heroin-dose requirements to OPRM1-rs1799971, CYP3A4-rs2740574 and CYP3A5- rs776746 gene polymorphisms in patients from a Heroin Prescription Program (PPH) in Andalusia.
Series of cases: 15 patients with opioid-addiction. Collection of heroin-doses/patient administered for a year. Genotyping of A118G, CYP3A4 and CYP3A5 polymorphisms was performed by Polymerase Chain Reaction and Restriction Fragment Length Polymorphism.
Eleven patients were AA homozygous (11/15;73.33%) and four heterozygous AG (4/15;26.67%) for A118G-OPRM1; median doses: 179.57[157.85,225.49] and 271.38[145.11,288.88]mg/day respectively were no statistically different (p=0.240). Four subjects presented doses>250mg/day, showing an association of AG-OPRM1 genotype with higher doses, OR:30.00(CI95%:1.41,638.15);p=0.033.
Fourteen patients were homozygous AA and GG for CYP3A4 and CYP3A5 respectively (14/15;93.33%), and one patient was heterozygous AG(1/15;6.66%) for both isoenzymes and presented a high dose(280 mg/day).
Higher heroin-doses (>250mg/day) were associated to AG genotype for OPRM1-A118G, despite the great variability in the dose prescription avoided to find an association between OPRM1 genotype and the specific administered dose.
Pharmacogenetic analysis, focused on OPRM1-A118G, may be a useful tool to adjust the pharmacotherapeutic dose in each case.
Opioid addiction is a serious health/social problem, associated with high morbidity and mortality.Several gene polymorphisms on the mu-opioid receptor gene(OPRM1), which plays an important role in reward system, have been related to opioid dependence (A118G, C17T, C2044A). A118G is the most studied and probably the most promising biomarker of better response in these patients, despite discrepancies has been manifested even in studies conducted on the same ethnicity.
Objectives and aims
Description of A118G, C17T and C2044A allele frequencies in an opioid-dependent population. Evaluation of the association of A118G gene polymorphism with opioid dependence.
Case group: 16 patients with opioid addiction, included in a Heroin Prescription Program in Andalusia, based on the protocolized individual prescription of diacetylmorphine. Control group: 32 non opioid-dependent subjects.Genotyping of A118G, C17T and C2044A was performed by Polymerase Chain Reaction and Restriction Fragment Length Polymorphism.
Case group: 12 patients were AA homozygous (12/16;75%) and 4 patients were heterozygous AG (4/12;25%) for A118G. All patients were homozygous CC for C17T and C2044A (16/16;100%). The distribution of the genotype frequencies of OPRM1 gene polymorphisms in the case series were not statistically different from those reported for European populations in HapMap for A118G (p=0.6418) and the GENO PANEL for C17T. Control group:19 patients were AA homozygous(19/32; 59.4%) and 13 patients were heterozygous AG (13/32;40.6%) for A118G. This polymorphism was not associated to opioid addiction (p=0.3503).
Distribution of genotype frequencies in opioid dependants corresponded to specific frequencies from European population for A118G and C17T polymorphisms. OPRM1 gene polymorphisms were not associated to opioid addiction in this population.
Childhood obesity is considered one of the most serious public health problems of the 21st century. Obesity-associated inflammation could be one of the mechanisms that triggers insulin resistance that could drive systemic alterations such as metabolic disorder. Recently, circulating levels of S100A4 has been associated with insulin resistance and subcutaneuous white adipose tissue inflammation independently of body mass index (BMI) in a cohort of obese adults. Nonetheless, the link between S100A4 and insulin resistance in children is still not known yet. Thus, the aim of the study was to determine if S100A4 plasma levels were associated with insulin resistance status in a cohort of prepuberal children.
Material and methods:
In this case-control multicentre study, 250 prepuberal children took part and were stratified in six groups according to sex, obesity stage and insulin resistance status. Blood samples were withdrawn in resting conditions after an overnight fasting. Anthropometric measurements and a routine biochemical analyses were performed. Homeostasis model assessment for insulin resistance index (HOMA-IR) was calculated using fasting plasma glucose and insulin values. S100A4 plasma levels were determined by ELISA CSBEL02032HU (Cusabio Biotech, Wuhan, China).
A lineal multiple regresión (α = 0.05) identified a significative association between S100A4 plasma levels and HOMA-IR in the cohort; each HOMA-IR increasing unit correlated with an increase of 0.008mg/dL in S100A4 plasma levels. (SE = 0.003 and p = 0.02). Moreover, we also observed a positive significative association between S100A4 plasma levels and glucose blood levels (p = 0.005) and BMI (p = 0.008). Inter-group comparations analyses revealed significative differences between normal-weight and insulino-resistant obese boys (p = 0.024). The same result was obtained between normal-weight and insulino-resistant obese girls (p = 0.04), finding a higher S100A4 concentration in insulino- resistant children. As expected, plasma S100A4 levels were also higher in obese children versus normal-weight children (p = 0.02).
These data could be clinical relevant due to the possible potential of S100A4 protein as a new circulating biomarker of resistance insulin in a cohort of prepuberal children. These results are supported by other studies in obese adults and adolescents. In conclusion, these results suggest that S100A4 is associated with obesity and insulin resistance in prepuberal children. However, more studies are needed to study the implication and mechanism of this protein in the development of insulin resistance.
Childhood obesity is associated with multiple cardio-metabolic abnormalities. A sensitive hypothesis underlying these alterations is oxidative stress, shown to be present in obesity, often accompanied by a diminished antioxidant defense. Specifically, plasma vitamin concentrations have been observed to be associated with obesity in adults and children. However, their association with cardio-metabolic alterations in children is less clear.
Materials and Methods
985 children (49.2% males, 71.7% prepubertal, 71.9% excess weight) were recruited in a case-control study of obesity in three Spanish hospitals. Pubertal status was assessed and anthropometry (weight, height), systolic and diastolic blood pressure (SBP, DBP) and serum glucose, insulin, triacylglycerols (TAG) and high-density lipoprotein cholesterol (HDL-C) were measured. Plasma concentrations of tocopherols and carotenes were determined with HPLC-MS and referred to TAG. Children were classified as MU if showing one or more of these criteria: SBP or DBP ≥ 90th percentile (age, sex, height), serum TAG > 90th percentile (age, sex), HDL-C < 10th percentile (age, sex), glucose ≥ 100 mg/dL or elevated HOMA-IR (≥ 2.5 prepubertal, ≥ 3.38 pubertal males, ≥ 3.905 pubertal females). Non-fulfillment was indicative of MH status. General linear models adjusted for sex, age, recruitment center and BMI were used to evaluate differences in vitamins between MH and MU children.
Prepubertal and pubertal children with excess weight showed lower tocopherols (Pre: 0.133 ± 0.061 vs 0.165 ± 0.065, P < 0.001; Pub: 0.120 ± 0.057 vs 0.163 ± 0.066, P < 0.001) and carotenes (Pre: 15.63 ± 13.72 vs 30.31 ± 26.04, P < 0.001; Pub: 12.34 ± 9.86 vs 22.98 ± 19.25, P < 0.001) plasma concentrations than normal-weight children. MU prepubertal and pubertal children showed lower tocopherols (Pre: 0.120 ± 0.056 vs 0.165 ± 0.064, P < 0.001; Pub: 0.111 ± 0.051 vs 0.154 ± 0.066, P < 0.001) and carotenes (Pre: 14.07 ± 12.61 vs 25.97 ± 21.94, P < 0.001; Pub: 10.90 ± 8.54 vs 19.03 ± 14.58, P < 0.001) plasma concentrations than MH children, independently of BMI. Individual MU components analyses showed similar associations between tocopherols and carotenes and insulin resistance, low HDL-C values and hypertriglyceridemia in prepubertal children; and between tocopherols and carotenes and elevated SBP, hyperglycemia and hypertriglyceridemia in pubertal children.
Our findings agree with previous studies that showed decreased plasma concentrations of tocopherols and carotenes in children with obesity. However, we observe further implications of low circulating concentrations of non-enzymatic antioxidants in terms of their negative association with cardio-metabolic alterations such as insulin resistance and dyslipidemia in prepubertal and pubertal children, independently of BMI. These results must be considered when designing prevention and treatment strategies of obesity and its complications.
Insulin resistance (IR) is the major driver for the development of obesity-associated metabolic and cardiovascular complications. It is well known that IR increase physiologically during puberty; hence, pubertal maturation might favour this metabolic risk in obese children. Recently, a study carried out in adult women with obesity has identified a new adipokine, known as S100A4, strongly associated with IR and inflammation in adipose tissue. On the contrary, little is known about the implication of S100A4 in the development of such metabolic disturbances during the onset and course of pubertal development.
Materials and methods:
A longitudinal study was conducted on 53 Spanish girls distributed in six experimental conditions according to their obesity and IR status (before (T0) and after (T1) the onset of puberty). Anthropometric and biochemical parameters were evaluated in all samples and time points. Classification of pubertal stage was made according to the Tanner scale. S100A4 protein levels were quantified by ELISA CSB-EL02032HU in plasma samples (Cusabio Biotech, Wuhan, China). The statistical analysis of the results was carried out with the “nlme” package in R v3.4.4, using a mixed-effects linear model with random intercept and slope.
At a significance level of alpha = 0.05, a linear mixed-effects model reported a significant association (P = 0.03) between the interaction term “time*experimental group” and S100A4 levels. Post-hoc pairwise comparisons between experimental groups revealed a strong association between a worsening/improvement of the IR status and the increase/decrease of S100A4 levels (yielding significant results for 5 of the 15 comparisons (P = 0.008, P = 0.04, P = 0.02, P = 0.04 and P = 0.02)). Furthermore, a multiple linear regression model reported a positive correlation between the increase in S100A4 levels and the increase in HOMA values during the course of puberty (B = 6.03, SE = 2.66 and P = 0.028).
The S100A4 protein is strongly associated with the development of IR in girls with childhood obesity and this association is accentuated during pubertal development. Increase in S100A4 levels could be one of the molecular mechanisms by which pubertal maturation favour an increased metabolic risk in children with obesity.
Considering the impact of coastal dynamics on the radiocarbon (14C) marine reservoir effect (MRE), upwelling has the potential of enhancing marine influence, usually 14C depleted. Freshwater input can contribute either to increased reservoir offsets, when dead carbon from rock weathering is available, but also towards an atmospheric 14C signal, when the presence of terrestrial organic matter from catchment prevails. An overview of the MRE studies based on shellmounds on the coast of Rio de Janeiro reveals a pattern of negative local corrections for Saquarema and Rio das Ostras but positive values for Cabo Frio island, suggesting the presence of cold upwelling waters in Cabo Frio at 1.6–1.2 cal kBP. New results for a shellmound on the Ilha Grande island, in the western portion of the Rio de Janeiro coast, revealed a negative value at about 3 ka. We discuss distribution of MRE values and temporal variability in the region and their relation to ocean dynamics, continental input and the choice of marine organisms used for ∆R determination. A comparison of local reservoir offsets for the Saquarema region obtained from fish otolith and mollusk shells revealed similar ΔR distributions, showing that both materials can be equally used.
Kang and Liu [‘On supersolvability of factorized finite groups’, Bull. Math. Sci.3 (2013), 205–210] investigate the structure of finite groups that are products of two supersoluble groups. The goal of this note is to give a correct proof of their main theorem.
Among other zooarchaeological remains, terrestrial snails’ shells from the Thaumastus and Megalobulimus genera are found in some Brazilian shellmounds, presenting a potential substitute for charcoal in radiocarbon dating analyses, as reliable representatives of the atmospheric carbon isotopic ratio. In this paper, we present statistically similar results of both charcoal and land snails samples from the same archaeological contexts in three settlements on the coast of Rio de Janeiro. The Manitiba I shellmound results range from 4.2 to 3.7 ka cal BP (95.4%), contemporary with the Saquarema shellmound, occupied during the period from 4.3 to 3.6 ka cal BP (95.4%). For the Usiminas shellmound, two groups of samples revealed different periods of time for two occupational layers from 2.3 to 2.1 ka cal BP (95.4%) and from 1.6 and 1.3 ka cal BP (95.4%). A model constraining each group of samples to within a single phase has a general agreement of 97% with only two outliers out of 22 dates, yielding minimum individual agreement of 74% and 7% posterior outlier probability for Saquarema shells. These are good examples of sites in which the occupation chronology can be successfully obtained by the radiocarbon dating of land snails.
The aim of the study was to determine whether routine probiotic supplementation (RPS) with Lactobacillus rhamnosus GG (LGG) or Lactobacillus acidophilus +Lactobacillus bifidum is associated with reduced risk of necrotising enterocolitis (NEC)≥Stage II in preterm neonates born at ≤32 weeks’ gestation. We conducted a retrospective cohort study on the effect of probiotic supplementation in very low birth weight infants in our neonatal unit by comparing two periods: before and after supplementation. The incidence of NEC≥Stage II, late-onset sepsis and all-cause mortality was compared for an equal period ‘before’ (Period I) and ‘after’ (Period II) RPS with LGG or L. acidophillus+L. bifidum. Multivariate logistic regression analysis was conducted to adjust for relevant confounders. The study population was composed of 261 neonates (Period I v. II: 134 v. 127) with comparable gestation duration and birth weights. In <32 weeks, we observed a significant reduction in NEC≥Stage II (11·3 v. 4·8 %), late-onset sepsis (16 v. 10·5 %) and mortality (19·4 v. 2·3 %). The benefits in neonates aged ≤27 weeks did not reach statistical significance. RPS with LGG or L. acidophillus+L. bifidum is associated with a reduced risk of NEC≥Stage II, late-onset sepsis and mortality in preterm neonates born at ≤32 weeks’ gestation.
The regional component (∆R) of the marine reservoir effect (MRE), which is crucial for the accurate calibration of radiocarbon ages of marine-influenced samples, was determined for the Cuban northwestern coast. Fifteen different locations were studied by 14C dating of pre-bomb known-age marine shells specimens of bivalves and gastropods from the Felipe Poey Museum collection. Accelerator mass spectrometry (AMS) 14C measurements were performed at the Radiocarbon Laboratory of the Universidade Federal Fluminense (LAC-UFF) and mean ΔR values were estimated. The distribution of results indicates ∆R values from −46±38 to 140±52 14C yr and a possible pattern related to the position along the coast and ocean dynamics. We present both mean values for each region and a general ∆R of 28±13 14C yr for the northwestern coast of Cuba.
A total of 16 pure-bred Iberian (IB) sows, all of them suckling six piglets, were used, eight of them in each of the two consecutive trials (1 and 2). Daily milk yield and composition were determined weekly over a 34-day lactation period. Within each litter, one piglet at birth and four piglets on day 35 of life were slaughtered. Milk intake per piglet tended to be greater in trial 2 (832 v. 893 g/day; P=0.066), but piglets grew at 168±3.3 g/day, irrespective of the trial. In the IB sow milk, the linoleic (LA) : linolenic (LNA) acid ratio averaged 14.6 and 15.2 in trial 1 and trial 2, respectively. A fivefold increase in piglet body fat content was observed over lactation (P<0.001). Most of this fat (81.4%) was present in the carcass. After 34 days of lactation, whole-body relative content of palmitic, palmitoleic, stearic and oleic acids were very close to those in the milk consumed, suggesting direct deposition. Daily deposition of LA derivatives and of LNA and its derivatives was found to be extremely low (<0.02 g, on average). Moreover, some of the arachidonic acid (ARA) in tissues of the IB piglet at birth disappeared throughout the lactating period. An overall fractional deposition for total fatty acids (FA) was 0.409. Fractional oxidation (disappearance) rates were 0.939 and 0.926 for n-6 and n-3 polyunsaturated FA. The overall rate of disappearance for the major non-essential FA (myristic, palmitic, palmitoleic, stearic and oleic acids), estimated as 1−the overall fractional deposition rate, was 0.546. It is concluded that the high degree of FA unsaturation, high oxidation rate of LA and LNA, and poor synthesis of ARA from LA and of docosahexaenoic acid from LNA found in the suckling piglet might increase the energy cost of whole-body fat accretion, a contributor to the observed low efficiency of use of milk energy for growth.
The main objective of this research was to utilize pollen monitoring methodology to predict olive yields in three Mediterranean olive cultivation areas (Spain, Italy and Tunisia) and their relationships with the olive oil price dynamics. Moreover, olive yield and olive oil production compared with olive oil price trends in the last two decades was evaluated. The statistical analyses confirmed that biological parameters such as the pollen emission, the pollen season start (Pss), the full flowering (Ff) date or the pollen season length (Psl) showed positive correlation values with productive parameters, especially the Pollen Index (Pi). However, the difficulty to define clear relationships with oil price for optimizing the marketing strategies can be due to the olive sector European policy and to the complex international olive oil market situation. The occurrence of unharvested trees was increased and the reduction in agricultural operations as well as non-harvesting could become more widespread above all in traditional extensive systems.
Piglet body composition at weaning could be a determinant for pig’s viability and may be influenced by factors such as the nutritional management followed during suckling. An experiment was conducted to study whether intermittent suckling (IS) affects body composition at weaning and nutrient and energy retention during a 34-day lactation period in Iberian piglets. Litters were subjected to conventional suckling (CS) or IS (n=10 litters of six piglets per treatment) in two trials. All piglets had ad libitum access to creep feed from day 15 onwards. In IS, piglets were progressively separated from the sow for 6, 8 and 10 h daily during the last week of lactation, whereas in CS piglets had continuous access to their dams. Creep feed intake in litters and BW development of individual piglets were measured throughout the 34-day lactation. Within each litter, both at birth and at weaning (day 35), one piglet was used to assess nutrient retention and body composition by the comparative slaughter approach. During days 29 to 35 of the experiment, daily creep feed intake was greater in IS piglets (IS 124, CS 67 g/piglet, P=0.040), and average daily gain differed significantly between groups (IS 190, CS 150 g/day, P=0.010). BW at weaning was higher in the IS than in the CS piglets (IS 8.19, CS 7.48 kg, P=0.011). Empty-body fat and energy content at weaning were higher in the IS compared with CS litters, as well as fat content in the carcass (P=0.04). The IS treatment did not affect empty-body protein deposition, but significantly increased daily retention of fat, energy, ash and calcium, compared with CS litters (P<0.05). Thus, IS in Iberian piglets seems to enhance feed intake, growth rate and retention of some body components, which may contribute to a higher body fat content at weaning and facilitate the weaning process.
To evaluate the association between waist-to-height ratio (WHtR) and specific biomarkers of inflammation, CVD risk and endothelial dysfunction in prepubertal obese children.
Prospective, multicentre case–control study matched by age and sex.
Children were recruited between May 2007 and May 2010 from primary-care centres and schools in three cities in Spain (Cordoba, Santiago de Compostela and Zaragoza).
Four hundred and forty-six (223 normal weight and 223 obese) Caucasian prepubertal children aged 6–12 years.
WHtR was higher in the obese than in the normal-weight children. Blood pressure, waist circumference, weight, height, insulin, plasma lipids, leptin, resistin, abnormal neutrophil and monocyte counts, C-reactive protein, IL-6, IL-8, TNF-α, myeloperoxidase, soluble intercellular adhesion molecule-1, selectin and plasminogen activator inhibitor-1 levels were higher in the obese than in the normal-weight group. Adiponectin and HDL-cholesterol were lower and glucose and metalloproteinase-9 showed no differences. Resistin, TNF-α and active plasminogen activator inhibitor-1 were associated with WHtR, a sensitive indicator of central obesity.
Our results lead to the hypothesis that changes in biomarker levels of insulin resistance, inflammation and CVD risk before puberty might induce metabolic consequences of obesity in obese children before reaching adulthood.
Since the beginning of the Holocene, hunter-gatherers have occupied the central-south Brazilian coast, as it was a very productive estuarine environment. Living as fishers and mollusk gatherers, they built prehistoric shellmounds, known as sambaqui, up to 30 m high, which can still be found today from the Espírito Santo (21°S) to Rio Grande do Sul (32°S) states, constituting an important testimony of paleodiversity and Brazilian prehistory. The chronology of the Sambaqui da Tarioba, situated in Rio das Ostras, Rio de Janeiro, is discussed herein. Selected well-preserved shells of Iphigenia brasiliana and charcoal from fireplaces in sequential layers were used for radiocarbon dating analysis. Based on a statistical model developed using OxCal software, the results indicate that the settlement occupation begun most probably around 3800 cal BP and lasted for up to 5 centuries.
Changes in paraoxonase 1 (PON1) activities have been observed in a variety of diseases involving oxidative stress, such as CVD. However, its role in obesity has not been fully established. In the present study, we aimed (1) to genotype sixteen PON1 SNP, (2) to measure serum PON1 activities and (3) to correlate these findings with the incidence of childhood obesity and related traits. We conducted a case–control study of 189 normal-weight and 179 obese prepubertal children, and we measured four different PON1 activities: lactonase; paraoxonase; arylesterase; diazoxonase. Although none of these activities was significantly different between the obese and normal-weight children, lactonase activity was found to be positively correlated with HDL-cholesterol and ApoA1 levels and negatively correlated with myeloperoxidase and fatty acid-binding protein 4 levels. Among the sixteen genotyped PON1 SNP, only the intronic SNP rs854566 exhibited a significant association with obesity (OR 0·61, 95 % CI 0·41, 0·91; P= 0·016). This genetic variant was also associated with increased diazoxonase, lactonase and arylesterase activities and decreased paraoxonase activity. Other genetic variants exhibited different association patterns with serum activities based on their location within the PON1 gene, and SNP that were located within the promoter were strongly associated with lactonase, arylesterase and diazoxonase activities. The functional variant Q192R exhibited the greatest effect on paraoxonase activity (P= 5·88 × 10− 42). In conclusion, SNP rs854566 was negatively associated with childhood obesity and with increased serum PON1 activities in prepubertal children. We determined that lactonase is a reliable indicator of PON1 activities and should be included in future studies of PON1 function.