Decreased Hepatic and Serum Levels of IL-10 Concur with Increased Lobular Inflammation in Morbidly Obese Patients.

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. Accumulating evidence in animal models suggests that loss of interleukin-10 (IL-10) anti-inflammatory actions might contribute to lobular inflammation, considered one of the first steps toward NASH development. However, the role of IL-10 in lobular inflammation remains poorly explored in humans. We examined mRNA and protein levels of IL-10 in liver biopsies and serum samples from morbidly obese patients, investigating the relationship between IL-10 and lobular inflammation degree. Materials and Methods: We prospectively enrolled morbidly obese patients of both sexes, assessing the lobular inflammation grade by the Brunt scoring system to categorize participants into mild (n = 7), moderate (n = 19), or severe (n = 13) lobular inflammation groups. We quantified the hepatic mRNA expression of IL-10 by quantitative polymerase chain reaction and protein IL-10 levels in liver and serum samples by Luminex Assay. We estimated statistical differences by one-way analysis of variance (ANOVA) and Tukey's multiple comparison test. Results: The hepatic expression of IL-10 significantly diminished in patients with severe lobular inflammation compared with the moderate lobular inflammation group (p = 0.01). The hepatic IL-10 protein levels decreased in patients with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.008 and p = 0.0008, respectively). In circulation, IL-10 also significantly decreased in subjects with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.005 and p < 0.0001, respectively). Conclusions: In liver biopsies and serum samples of morbidly obese patients, the protein levels of IL-10 progressively decrease as lobular inflammation increases, supporting the hypothesis that lobular inflammation develops because of the loss of the IL-10-mediated anti-inflammatory counterbalance.

Neolithic expansion and the 17q21.31 inversion in Iberia: an evolutionary approach to H2 haplotype distribution in the Near East and Europe.

The chromosomal region 17q21.31 harbors a 900 kb inversion polymorphism named after the microtubule-associated protein tau (MAPT) gene. Since no recombination occurs, two haplotypes are recognized: a directly oriented variant (H1) and an inverted variant (H2). The H2 haplotype features a distribution pattern with high frequencies in the Near East and Europe, medium levels in South Asia and North Africa, and low levels elsewhere. Studies of this genomic region are relevant owing to its likely association with numerous neurodegenerative diseases. However, the causes underlying the geographic distribution of the haplotype frequencies remain a bone of contention among researchers. With this work, we have intended to outline a plausible hypothesis on the origin of the high European H2 frequencies. To that end, we have analyzed an extensive population database (including three new Iberian populations) to explore potential clinal variations of H2 frequencies. We found a sigmoidal frequency cline with an upward trend from South Asia to Europe. The maximum value was detected in the Basques from Gipuzkoa province (0.494) with the curve's inflection point in the Near East. From our results, we suggest that the most likely scenario for high H2 frequencies in Europe would be a founding event in the Near East during the late Paleolithic or early Neolithic. Subsequently, such H2 overrepresentation would have reached Europe with the arrival of the first Neolithic farmers. The current frequencies and geographic distribution of the 17q21.31 inversion suggest that the founding events mainly affected the H2D subhaplotype.

Effect of nanocellulose polymorphism on electrochemical analytical performance in hybrid nanocomposites with non-oxidized single-walled carbon nanotubes.

Two cellulose nanocrystals/single-walled carbon nanotube (CNC/SW) hybrids, using two cellulose polymorphs, were evaluated as electrochemical transducers: CNC type I (CNC-I/SW) and CNC type II (CNC-II/SW). They were synthesized and fully characterized, and their analytical performance as electrochemical sensors was carefully studied. In comparison with SWCNT-based and screen-printed carbon electrodes, CNC/SW sensors showed superior electroanalytical performance in terms of sensitivity and selectivity, not only in the detection of small metabolites (uric acid, dopamine, and tyrosine) but also in the detection of complex glycoproteins (alpha-1-acid glycoprotein (AGP)). More importantly, CNC-II/SW exhibited 20 times higher sensitivity than CNC-I/SW for AGP determination, yielding a LOD of 7 mg L-1.These results demonstrate the critical role played by nanocellulose polymorphism in the electrochemical performance of CNC/SW hybrid materials, opening new directions in the electrochemical sensing of these complex molecules. In general, these high-active-surface hybrids smartly exploited the preserved non-oxidized SW conductivity with the high aqueous dispersibility of the CNC, avoiding the use of organic solvents or the incorporation of toxic surfactants during their processing, making the CNC/SW hybrids promising nanomaterials for electrochemical detection following greener approaches.

Tau (MAPT) haplotypes in Jordan: new evidence on the Middle East as a melting-pot predating Neolithic migration.

Frequencies of H1 and H2 haplotypes of the microtubule-associated protein tau (MAPT) gene were examined in two Jordanian samples. The criterion for haplotype assignment was the presence/absence of the intronic 238-bp deletion, located between exons 9 and 10 of the MAPT genomic region. We further compiled MAPT haplotype frequencies in Middle Eastern, South Asian, and European populations to widen the scope of analyses. Jordan MAPT*H2 haplotype frequencies peaked among worldwide samples analysed to date, with the Jordan general population featuring the top value (0.386). AMOVA tests results indicated spatial genetic structuring, as they unveiled significant differences in H2 frequencies between South Asia and Europe, with a hypothetical contact zone in the Middle East. The southeastern region of the Middle East shares low H2 frequencies with South Asia, while the northwestern area shows high H2 frequencies, similar to and even higher than observed in Europe. We suggest that high H2 frequencies could have originated at the beginning of the Neolithic in the western region of the Middle East, most likely through genetic drift episodes associated with founding events. Subsequently, the arrival of Neolithic farmers boosted the H2 haplotype spreading throughout Europe.

Afghanistan: conduits of human migrations identified using AmpFlSTR markers.

This study describes autosomal STR profiles of the populations of South and North Afghanistan. A total of 188 unrelated individuals residing north (n = 42) and south (n = 146) of the Hindu Kush Range within the territory of Afghanistan were examined against the background of 54 geographically targeted reference populations from Eurasia and North East Africa. The main objective of this study was to investigate longitudinal gene flow across the Hindu Kush Range and Eurasia. Genetic differentiation tests between North and South Afghanistan generated insignificant genetic differences for all loci. Multidimensional scaling (MDS) plots based on Fst distances and Neighbor-Joining (N-J) analysis indicated genetic affinities between the Afghani groups and Indian/Near East/West Asian populations. Admixture and Structure analyses demonstrate a gradient of genetic continuity within a major east to west cline that includes North and South Afghanistan as intermediate populations. Overall, although Afghanistan is surrounded by a number of natural barriers, instead of an isolated territory, it has been a genetically porous region providing a migrational nexus to the rest of Eurasia.

Paternal heritage in Jujuy province (Northwest Argentina): Evidence for sex-biased gene flow and genetic drift effects.

OBJECTIVES: This study aimed to explore the diversity of paternal lineages in Jujuy province (Argentina) by analyzing Y chromosome markers. Furthermore, we examined among-population genetic variability based both on paternally (NRY haplotypes) and maternally (mtDNA haplogroups) inherited markers. We sought to evaluate the impact of sex-biased gene flow on genetic background in Jujuy, and contribute data on the microevolutionary forces acting in this zone. METHODS: DNA from 149 males from five Jujuy regions were analyzed for 12 non-recombining Y (NRY) markers. Genetic heterogeneity among Jujuy regions was evaluated through population differentiation tests. To identify potential genetic boundaries in Jujuy, analysis of molecular variance (AMOVA) and the Monmonier's algorithm implemented in the Barrier v2.2 software were employed. RESULTS: A clear divergence between Jujuy highlands and lowlands for NRY haplotypes was found. A marked discrepancy between genetic structuring for paternal lineages and the lack of geographical pattern for mitogenomes was confirmed by all statistical analyses. CONCLUSIONS: Genetic structuring of paternal lineages is most likely caused by admixture processes that have occurred since colonial times in the Jujuy lowlands. Immigrants were predominantly male that settled in the lower altitude zones, due to the steep orography of the region. Input of allochthonous male lineages because of gene flow toward the lowlands would have increased diversity of NRY markers, thus compensating for drift effects. Likewise, limited input of allochthonous mitogenomes would have promoted genetic drift, a key factor in the shaping of diversity of maternal lineages across Jujuy subpopulations, irrespective of altitude.

Tau haplotypes support the Asian ancestry of the Roma population settled in the Basque Country.

We examined tau haplotype frequencies in two different ethnical groups from the Basque Country (BC): Roma people and residents of European ancestry (general population). In addition, we analyzed the spatial distribution of tau haplotypes in Eurasian populations to explore the genetic affinities of the Romani groups living in Europe in a broader scope. The 17q21.31 genomic region was characterized through the genotyping of two diagnostic single nucleotide polymorphisms, SNPs (rs10514879 and rs199451), which allow the identification of H1 and H2 haplotypes. A significant heterozygous deficit was detected in the Romani for rs10514879. The H2 haplotype frequency proved to be more than twice in the BC general population (0.283) than in the Roma people (0.127). In contrast, H2 frequency proved to be very similar between Basque and Hungarian Romani, and similar to the H2 frequencies found in northwestern India and Pakistan as well. Several statistical analyses unveiled genetic structuring for the MAPT diversity, mirrored in a significant association between geography and genetic distances, with an upward trend of H2 haplotype frequencies from Asia to Europe. Yet, Roma samples did not fit into this general spatial patterning because of their discrepancy between geographical position and H2 frequency. Despite the long spatial coexistence in the Basque region between the residents of European ancestry and the Roma, the latter have preserved their Asian genetic ancestry. Bearing in mind the lack of geographical barriers between both ethnical groups, these findings support the notion that sociocultural mores might promote assortative matings in human populations.

Synthesis of New 5-Aryl-benzo[f][1,7]naphthyridines via a Cascade Process (Ugi-3CR/Intramolecular Aza-Diels-Alder Cycloaddition)/Aromatization.

A series of eight new 5-aryl-benzo[f][1,7]naphthyridines were synthesized in 17 to 64% overall yields via an improved MW-assisted cascade-like one pot process (Ugi⁻three component reaction/intramolecular aza-Diels-Alder cycloaddition) coupled to an aromatization process from tri-functional dienophile-containing ester-anilines, substituted benzaldehydes and the chain-ring tautomerizable 2-isocyano-1-morpholino-3-phenylpropan-1-one as starting reagents, under mild conditions. The doubly activated dienophile and the aza-diene functionalities of the eight new Ugi-adducts were exploited to perform an in situ aza-Diels-Alder cycloaddition/aromatization (dehydration/oxidation) process, toward the complex polysubstituted 5-aryl-polyheterocycles, which could be taken as starting point for further SAR studies because the benzo[f][1,7]naphthyridine is the core of various bioactive products. It is relevant to emphasize that the synthesis or isolation of benzo[f][1,7]naphthyridines containing a substituted aromatic ring in the C-5 position, has not been published before.

Norms for 10,491 Spanish words for five discrete emotions: Happiness, disgust, anger, fear, and sadness.

The discrete emotion theory proposes that affective experiences can be reduced to a limited set of universal "basic" emotions, most commonly identified as happiness, sadness, anger, fear, and disgust. Here we present norms for 10,491 Spanish words for those five discrete emotions collected from a total of 2,010 native speakers, making it the largest set of norms for discrete emotions in any language to date. When used in conjunction with the norms from Hinojosa, Martínez-García et al. (Behavior Research Methods, 48, 272-284, 2016) and Ferré, Guasch, Martínez-García, Fraga, & Hinojosa (Behavior Research Methods, 49, 1082-1094, 2017), researchers now have access to ratings of discrete emotions for 13,633 Spanish words. Our norms show a high degree of inter-rater reliability and correlate highly with those from Ferré et al. (2017). Our exploration of the relationship between the five discrete emotions and relevant lexical and emotional variables confirmed findings of previous studies conducted with smaller datasets. The availability of such large set of norms will greatly facilitate the study of emotion, language and related fields. The norms are available as supplementary materials to this article.

Long-Term Outcome of Patients With Chronic Thromboembolic Pulmonary Hypertension: Results From an International Prospective Registry.

BACKGROUND: Chronic thromboembolic pulmonary hypertension, a rare complication of acute pulmonary embolism, is characterized by fibrothrombotic obstructions of large pulmonary arteries combined with small-vessel arteriopathy. It can be cured by pulmonary endarterectomy, and can be clinically improved by medical therapy in inoperable patients. A European registry was set up in 27 centers to evaluate long-term outcome and outcome correlates in 2 distinct populations of operated and not-operated patients who have chronic thromboembolic pulmonary hypertension. METHODS AND RESULTS: A total of 679 patients newly diagnosed with chronic thromboembolic pulmonary hypertension were prospectively included over a 24-month period. Estimated survival at 1, 2, and 3 years was 93% (95% confidence interval [CI], 90-95), 91% (95% CI, 87-93), and 89% (95% CI, 86-92) in operated patients (n=404), and only 88% (95% CI, 83-91), 79% (95% CI, 74-83), and 70% (95% CI, 64-76) in not-operated patients (n=275). In both operated and not-operated patients, pulmonary arterial hypertension-targeted therapy did not affect survival estimates significantly. Mortality was associated with New York Heart Association functional class IV (hazard ratio [HR], 4.16; 95% CI, 1.49-11.62; P=0.0065 and HR, 4.76; 95% CI, 1.76-12.88; P=0.0021), increased right atrial pressure (HR, 1.34; 95% CI, 0.95-1.90; P=0.0992 and HR, 1.50; 95% CI, 1.20-1.88; P=0.0004), and a history of cancer (HR, 3.02; 95% CI, 1.36-6.69; P=0.0065 and HR, 2.15; 95% CI, 1.18-3.94; P=0.0129) in operated and not-operated patients, respectively. Additional correlates of mortality were bridging therapy with pulmonary arterial hypertension-targeted drugs, postoperative pulmonary hypertension, surgical complications, and additional cardiac procedures in operated patients, and comorbidities such as coronary disease, left heart failure, and chronic obstructive pulmonary disease in not-operated patients. CONCLUSIONS: The long-term prognosis of operated patients currently is excellent and better than the outcome of not-operated patients.

Characterization of scientific studies usually cited as evidence of adverse effects of GM food/feed.

GM crops are the most studied crops in history. Approximately 5% of the safety studies on them show adverse effects that are a cause for concern and tend to be featured in media reports. Although these reports are based on just a handful of GM events, they are used to cast doubt on all GM crops. Furthermore, they tend to come from just a few laboratories and are published in less important journals. Importantly, a close examination of these reports invariably shows methodological flaws that invalidate any conclusions of adverse effects. Twenty years after commercial cultivation of GM crops began, a bona fide report of an adverse health effect due to a commercialized modification in a crop has yet to be reported.

Riociguat in patients with chronic thromboembolic pulmonary hypertension: results from an early access study.

BACKGROUND: Following positive results from the Phase III CHEST-1 study in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), the Phase IIIb CTEPH early access study (EAS) was designed to assess the safety and tolerability of riociguat in real-world clinical practice, as well as to provide patients with early access to riociguat before launch. Riociguat is approved for the treatment of inoperable and persistent/recurrent CTEPH. METHODS: We performed an open-label, uncontrolled, single-arm, early access study in which 300 adult patients with inoperable or persistent/recurrent CTEPH received riociguat adjusted from 1 mg three times daily (tid) to a maximum of 2.5 mg tid. Patients switching from unsatisfactory prior pulmonary arterial hypertension (PAH)-targeted therapy (n = 84) underwent a washout period of at least 3 days before initiating riociguat. The primary aim was to assess the safety and tolerability of riociguat, with World Health Organization functional class and 6-min walking distance (6MWD) as exploratory efficacy endpoints. RESULTS: In total, 262 patients (87%) completed study treatment and entered the safety follow-up (median treatment duration 47 weeks). Adverse events were reported in 273 patients (91%). The most frequently reported serious adverse events were syncope (6%), right ventricular failure (3%), and pneumonia (2%). There were five deaths, none of which was considered related to study medication. The safety and tolerability of riociguat was similar in patients switched from other PAH-targeted therapies and those who were treatment naïve. In patients with data available, mean ± standard deviation 6MWD had increased by 33 ± 42 m at Week 12 with no clinically relevant differences between the switched and treatment-naïve subgroups. CONCLUSIONS: Riociguat was well tolerated in patients with CTEPH who were treatment naïve, and in those who were switched from other PAH-targeted therapies. No new safety signals were observed. TRIAL REGISTRATION: ClinicalTrials.org NCT01784562 . Registered February 4, 2013.

Neuroendoscopic treatment for hydrocephalus associated to midline arachnoid cysts in a series of nine pediatric patients.

BACKGROUND: Arachnoid cysts are extra-axial cerebrospinal fluid (CSF) collections surrounded by a membrane. Occasionally, hydrocephalus is associated due to a change in CSF circulatory dynamics. Neuroendoscopic treatment has been recommended for patients who develop symptoms resulting from the cyst location. METHODS: We retrospectively evaluate the results in our series of 9 patients with hydrocephalus associated to midline arachnoid cysts treated endoscopically. Success was rated on a scale of five degrees of neuroendoscopical success. RESULTS: We performed endoscopic third ventriculostomy (ETV) in three cases; ETV was associated to ventriculocystostomy (VC) in three cases; ETV, VC and septostomy (SPT) were performed in one patient; neuroendoscopic Monro foraminoplasty (NEFPMO) plus SPT were associated in one case; last patient was performed ETV, VC and cystocysternostomy (CC). For first procedures, 6 patients completed permanent Success (grade I). In one case success was transitory (grade II) and required a second procedure (ETV). In one patient VC success and ETV failure implied partial success (grade III). One patient's early failure (grade V) required a second procedure (ETV + NEFPMO). Success in second procedures was grade I in both patients. Follow-up period was over 12 months and altogether success was grade I in 8/9 patients and grade III in 1/9 patients. Shunt independency went over 88%. CONCLUSIONS: Endoscopy allows a solution avoiding the implantation of cerebrospinal fluid shunt devices. When possible, we likely approach both, hydrocephalus and arachnoid cyst, with different endoscopic maneuvers in a single procedure. It is important to expand the usage of success classifications for combined procedures.

Norms of valence and arousal for 14,031 Spanish words.

Most current models of research on emotion recognize valence (how pleasant a stimulus is) and arousal (the level of activation or intensity that a stimulus elicits) as important components in the classification of affective experiences (Barrett, 1998; Kuppens, Tuerlinckx, Russell, & Barrett, 2012). Here we present a set of norms for valence and arousal for a very large set of Spanish words, including items from a variety of frequencies, semantic categories, and parts of speech, including a subset of conjugated verbs. In this regard, we found that there were significant but very small differences between the ratings for conjugations of the same verb, validating the practice of applying the ratings for infinitives to all derived forms of the verb. Our norms show a high degree of reliability and are strongly correlated with those of Redondo, Fraga, Padrón, and Comesaña's (2007) Spanish version of the influential Affective Norms for English Words (Bradley & Lang, 1999), as well as those from Warriner, Kuperman, and Brysbaert (2013), the largest available set of emotional norms for English words. Additionally, we included measures of word prevalence-that is, the percentage of participants that knew a particular word-for each variable (Keuleers, Stevens, Mandera, & Brysbaert, 2015). Our large set of norms in Spanish not only will facilitate the creation of stimuli and the analysis of texts in that language, but also will be useful for cross-language comparisons and research on emotional aspects of bilingualism. The norms can be downloaded and available as a supplementary materials to this article.

Outcrossing potential between 11 important genetically modified crops and the Chilean vascular flora.

The potential impact of genetically modified (GM) crops on biodiversity is one of the main concerns in an environmental risk assessment (ERA). The likelihood of outcrossing and pollen-mediated gene flow from GM crops and non-GM crops are explained by the same principles and depend primarily on the biology of the species. We conducted a national-scale study of the likelihood of outcrossing between 11 GM crops and vascular plants in Chile by use of a systematized database that included cultivated, introduced and native plant species in Chile. The database included geographical distributions and key biological and agronomical characteristics for 3505 introduced, 4993 native and 257 cultivated (of which 11 were native and 246 were introduced) plant species. Out of the considered GM crops (cotton, soya bean, maize, grape, wheat, rice, sugar beet, alfalfa, canola, tomato and potato), only potato and tomato presented native relatives (66 species total). Introduced relative species showed that three GM groups were formed having: a) up to one introduced relative (cotton and soya bean), b) up to two (rice, grape, maize and wheat) and c) from two to seven (sugar beet, alfalfa, canola, tomato and potato). In particular, GM crops presenting introduced noncultivated relative species were canola (1 relative species), alfalfa (up to 4), rice (1), tomato (up to 2) and potato (up to 2). The outcrossing potential between species [OP; scaled from 'very low' (1) to 'very high' (5)] was developed, showing medium OPs (3) for GM-native relative interactions when they occurred, low (2) for GMs and introduced noncultivated and high (4) for the grape-Vitis vinifera GM-introduced cultivated interaction. This analytical tool might be useful for future ERA for unconfined GM crop release in Chile.

Binuclear Lanthanide-Radical Complexes Featuring Two Centers with Different Magnetic and Luminescence Properties.

Binuclear complexes with general formula [Ln2(hfac)6(H2O)2(dppnTEMPO)] (LnIII = Gd, Tb, and Dy) have been obtained using the paramagnetic ligand 1-piperidinyl-4-[(diphenylphosphinyl)amino]-2,2,6,6-tetramethyl (dppnTEMPO) as a bridge. One of the lanthanide ions is ferromagnetically coupled with the TEMPO moiety. Two of the complexes (Dy and Tb) show slow relaxation of the magnetization, and the non-magneto-equivalence of the two LnIII ions was clearly observed. The ab initio CASSCF calculations were employed to confirm this behavior, as well as to rationalize the Ln-Rad interaction. The simulations of the magnetic properties were allowed by the insights given by the calculations. The inequivalence of the TbIII ions was also proved by emission spectroscopy.

STR Markers Unveil Microgeographic Differentiation over the Steep Mountainous Landscape of Jujuy Province, Northwest Argentina.

This study explores potential signals of microdifferentiation in the gene pool of three high-altitude populations from Jujuy province in northwest Argentina using highly polymorphic markers. These human communities are characterized by extreme living conditions and very low population densities owing to considerable height above sea level and steep orography. A set of autosomal short tandem repeats (STRs) located at chromosome 6 (6p21.3) was typed in samples from Quebrada Baja (∼2,500 m), Quebrada Alta (∼3,300 m), and Puna (> 3,500 m). Genetic diversity was estimated through the observed and expected heterozygosities and the haplotype diversity. Analyses of the molecular variance (AMOVAs) and population differentiation tests based on allele and haplotype frequencies were performed to assess genetic heterogeneity among subgroups. No deviation from Hardy-Weinberg equilibrium was detected in any subpopulation, yet significant departures were detected in the analysis considering the whole area (D6S2792 and D6S105 loci). Overall, genetic diversity showed a decreasing trend as the altitude increased. Thus, allele and haplotype frequencies showed the most significant differences between Puna and Quebrada Baja, the populations sited at the edges of the altitude range. The trend toward reduction of heterozygosity with altitude is compatible with historical patterns of colonization, interregional migration trends, population density, and genetic admixture. The main consequence of the complex mountainous landscape of Jujuy would be an imbalance in the interplay of gene flow and genetic drift, favoring the latter. The combined effect of restricted gene flow and intense genetic drift would have promoted local genetic differentiation between the Jujuy highland subpopulations, leading to spatial patterning of the allele frequencies not entirely attributable to geographic distance. Our findings corroborate the effectiveness of STRs to identify microevolutionary changes.

Influence of Dopaminergic System Genetic Variation and Lifestyle Factors on Excessive Alcohol Consumption.

AIMS: To examine the role of genetic and environmental factors in the pathogenesis of alcohol dependence in a Spanish cohort of women and men. METHODS: We analyzed the relationship between 56 genetic variants in 7 genes associated with the dopaminergic reward pathway and excessive alcohol consumption. The study sample (N = 1533, of which 746 were women) consisted of 653 heavy consumers and 880 very low consumers from the Spanish subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Single nucleotide polymorphisms (SNPs) were genotyped using a customized array. Lifestyle variables were also examined to assess associations between genetic and environmental factors. RESULTS: No statistically significant differences were found between cases and controls for the allele frequencies in five genes: TH, SLC18A2, DRD1, DRD3 and COMT. Conversely, some alleles of the 12 SNPs from the DRD2 locus and the 5 from the MAOA locus showed significant associations with excessive alcohol consumption. Namely, rs10891556 (DRD2) proved to be the only SNP positively correlated with excessive alcohol consumption in both sexes. DRD2 rs1800497 and rs877138 were significantly associated in men, whereas DRD2 rs17601612 and rs4936271 and MAOA rs5906898 were associated with excessive alcohol consumption in women. A correspondence analysis provided an overall lifestyle profile of excessive drinkers, who were predominantly men who smoked, had large intakes of meat, small intakes of fruit and vegetables, whose jobs did not require high education levels and who engaged in little physical activity. CONCLUSIONS: It has shown the influence of dopaminergic pathway in the genetics of alcohol dependence with differences between men and women and providing a lifestyle profile of excessive drinkers.

The number of circulating monocytes as biomarkers of the clinical response to methotrexate in untreated patients with rheumatoid arthritis.

BACKGROUND: The aim of this work was to analyze the number and distribution of circulating monocytes, and of their CD14(+high)CD16(-), CD14(+high)CD16(+) and CD14(+low)CD16(+) subset cells, in treatment-naive patients with rheumatoid arthritis (RA), and to determine their value in predicting the clinical response to methotrexate (MTX) treatment. METHODS: This prospective work investigated the number of circulating monocytes, and the numbers of CD14(+high)CD16(-), CD14(+high)CD16(+) and CD14(+low)CD16(+) subset cells, in 52 untreated patients with RA before MTX treatment, and at 3 and 6 months into treatment, using flow cytometry. RESULTS: The absolute number of circulating monocytes, and the numbers of CD14(+high)CD16(-), CD14(+high)CD16(+) and CD14(+low)CD16(+) subset cells, were significantly higher in MTX non-responders than in responders and healthy controls before starting and throughout treatment. Responders showed normal numbers of monocytes, and of their subset cells, over the study period. The pre-treatment absolute number of circulating monocytes, and the numbers of CD14(+high)CD16(-) and CD14(+high)CD16(+) subset cells, were found to be predictive of the clinical response to MTX, with a sensitivity and specificity of >70% and >88%, respectively. CONCLUSIONS: Treatment-naive patients with RA showed an anomalous distribution of circulating monocyte subsets, and an anomalous number of cells in each subset. A higher pre-treatment number of circulating monocytes, and higher numbers of CD14(+high)CD16(-) and CD14(+high)CD16(+) subset cells, predict a reduced clinical response to MTX in untreated patients with RA.

Sousse: extreme genetic heterogeneity in North Africa.

The male genetic landscape of the territory currently known as Tunisia is hampered by the scarcity of data, especially from cosmopolitan areas such as the coastal city of Sousse. In order to alleviate this lacuna, 220 males from Sousse were examined, for the first time, for more than 50 Y-chromosome single-nucleotide polymorphisms (Y-SNPs) markers and compared with 3099 individuals from key geographically targeted locations in North Africa, Europe and the Near East. The paternal lineages observed belong to a common set of Y haplogroups previously described in North Africa. In addition to the prominent autochthonous North African E-M81 haplogroup which is exclusively represented by its subclade E-M183 (44.55% of Y-chromosomes), a number of Near Eastern Neolithic lineages including E-M78, J-M267 and J-M172 account for 39% of the Y-chromosomes detected. Principal component analysis based on haplogroup frequencies, multidimensional scaling based on Rst genetic distances and analyses of molecular variance using both Y-chromosome short tandem repeat haplotypes and Y-SNP haplogroup data revealed that the Tunisian and North African groups, as a whole, are intra- and inter-specific diverse with Sousse being highly heterogeneous.