Association of <Emphasis Type="Italic">XPA</Emphasis> Polymorphisms Towards Lung Cancer Susceptibility and its Predictive Role in Overall Survival of North Indians

The present study investigated the role of Xeroderma pigmentosum group A (XPA) polymorphism (A23G and G709A) with lung cancer risk and its association with overall survival in North Indians. 370 cases and 370 controls were investigated to evaluate association between XPA polymorphism (A23G and G709A) with lung cancer risk using logistic regression analysis. A follow-up study was also conducted for 291 lung cancer cases illustrating correlation between overall survival in lung cancer patients and XPA variants. GG genotype showed an increased lung cancer risk (p = 0.0007) for A23G polymorphism whereas G709A polymorphism was associated with significant protective effect in heterozygous (AG) subjects (p = 0.001). When stratified according to smoking status an increased risk for lung cancer was observed for GG genotype in A23G polymorphism (p = 0.0002). A poor survival in females carrying variant genotype (GG) was observed (p = 0.001; MST = 4.16 months) for A23G polymorphism. Adenocarcinoma patients with heterozygous genotype showed an increased hazard ratio (p = 0.02) for A23G polymorphism. G709A was associated with a reduced hazard ratio marking a better survival among mutant females (HR 0.17; p = 0.05; MST = 18.63 months). It can be concluded that A23G polymorphism might contribute to increased lung cancer risk in North Indian population emphasizing on poor survival among females. G709A polymorphism might result in protective effect in lung cancer subjects. The present study had a low sample size but it could act as reference for the large sample studies in future.     

Characterization of <Emphasis Type="Italic">Gladiolus</Emphasis> Germplasm Using Morphological,Physiological, and Molecular Markers

Estimation of variability and genetic relationships among breeding materials is one of the important strategies in crop improvement programs. Morphological (plant height, spike length, a number of florets/spike), physiological (chlorophyll content, chlorophyll fluorescence, and rapid light curve parameters) and Directed amplification of minisatellite DNA (DAMD) markers were used to investigate the relationships among 50 Gladiolus cultivars. Cluster analysis based on morphological data, physiological characteristics, molecular markers, and cumulative data discriminated all cultivars into seven, five, seven, and six clusters in the unweighted pair-group method using arithmetic mean (UPGMA) dendrogram, respectively. The results of the principal coordinate analysis (PCoA) also supported UPGMA clustering. Variations among the Gladiolus cultivars at phenotypic level could be due to the changes in physiology, environmental conditions, and genetic variability. DAMD analysis using 10 primers produced 120 polymorphic bands with 80% polymorphism showing polymorphic information content (PIC = 0.28), Marker index (MI = 3.37), Nei’s gene diversity (h = 0.267), and Shannon’s information index (I = 0.407). Plant height showed a positive significant correlation with Spike length and Number of florets/spike (r = 0.729, p < 0.001 and r = 0.448, p = 0.001 respectively). Whereas, Spike length showed positive significant correlation with Number of florets/spike (r = 0.688, p < 0.001) and Chlorophyll content showed positive significant correlation with Electron transport rate (r = 0.863, p < 0.001). Based on significant morphological variations, high physiological performance, high genetic variability, and genetic distances between cultivars, we have been able to identify diverse cultivars of Gladiolus that could be the potential source as breeding material for further genetic improvement in this ornamental crop.     

Congruence and the Biomonitoring of Aquatic Ecosystems: Are Odonate Larvae or Adults the Most Effective for the Evaluation of Impacts

Odonata have been widely used as indicators for the biomonitoring of terrestrial and aquatic habitats due to their sensitivity to environmental impacts. We aimed to determine whether the larval or adult phases of these insects were the best predictors of variation in habitat parameters and the loss of environmental integrity. Specimens were collected during three seasons (dry, rainy, and ebb) from 12 points in the Suiá-missu River basin, at the headwaters of the Xingu River in Mato Grosso, Brazil. The Protest analysis indicated a high degree of congruence between the assemblages of larvae and adults in streams with varying degrees of habitat integrity (R = 0.832, p < 0.001, m ² = 0.307). When the congruence with environmental factors was analyzed, a significant association was found only for the larval phase (R = 0.318, p = 0.03, m ² = 0.888). When the suborders were analyzed separately, congruence was confirmed for anisopteran adults (R = 0.338, p = 0.031, m ² = 0.885) and larvae (R = 0.417, p = 0.003, m ² = 0.826) and for the zygopteran adults (R = 0.345, p = 0.027, m ² = 0.881) and larvae (R = 0.405, p = 0.011, m ² = 0.836). These results indicate that both larvae and adults respond systematically to environmental impacts. We suggest that either life phase can be used for biomonitoring, given their effectiveness for the interpretation of disturbance in terrestrial and aquatic habitats. These findings further reinforce the effectiveness of this insect order for the detection of modifications to the environment, showing that they are good indicators of environmental conditions.     

Association between the blood concentrations of ammonia and carnitine/amino acid of schizophrenic patients treated with valproic acid

Background

Administration of valproic acid (VPA) is complicated with approximately 0.9% of patients developing hyperammonemia, but the pathogenesis of this adverse effect remains to be clarified. The aim of the present study was to search for mechanisms associated with VPA-induced hyperammonemia in the light of changes in serum amino acids concentrations associated with the urea cycle of schizophrenic patients.

Method

Blood samples (10 mL) were obtained from 37 schizophrenic patients receiving VPA for the prevention of violent behaviors in the morning after overnight fast. Blood concentrations of ammonia, VPA, free carnitine, acyl-carnitine, and 40 amino acids including glutamate and citrulline were measured for each patient. Univariate and multivariate regression analyses were performed to identify amino acids or concomitantly administered drugs that were associated with variability in the blood concentrations of ammonia.

Result

The blood ammonia level was positively correlated with the serum glutamate concentration (r = 0.44, p < 0.01) but negatively correlated with glutamine (r = ?0.41, p = 0.01), citrulline (r = ?0.42, p = 0.01), and glycine concentrations (r = ?0.54, p < 0.01). It was also revealed that the concomitant administration of the mood stabilizers (p = 0.04) risperidone (p = 0.03) and blonanserin (p < 0.01) was positively associated with the elevation of the blood ammonia level.

Conclusion

We hypothisized that VPA would elevate the blood ammonia level of schizophrenic patients. The observed changes in serum amino acids are compatible with urea cycle dysfunction, possibly due to reduced carbamoyl-phosphate synthase 1 (CPS1) activity. We conclude that VPA should be prudently prescribed to schizophrenic patients, particularly those receiving mood stabilizers or certain antipsychotics.

     

How are anatomical and hydraulic features of the mangroves <Emphasis Type="Italic">Avicennia marina</Emphasis> and <Emphasis Type="Italic">Rhizophora mucronata</Emphasis> influenced by siltation?

Key message

This article provides significant data in the debate on whether siltation might have a negative impact on the hydraulic functioning of two widespread mangrove tree species Avicennia marina and Rhizophora mucronata.

Abstract

Elevated sediment addition, or siltation, within mangrove ecosystems is considered as being negative for trees and saplings, resulting in stress and higher mortality rates. However, little is known about how siltation influences the hydraulic functioning of mangrove trees. Comparing two mangrove tree species (Avicennia marina Vierh. Forsk. and Rhizophora mucronata Lam.) from low and high-siltation plots led to the detection of anatomical and morphological differences and tendencies. Adaptations to high siltation were found to be either mutual among both species, e.g., significant smaller single leaf area (p _A.marina  = 0.058, F1.38 = 3.8; p _R.mucronata  = 0.005, F1.38 = 8.7; n = 20 × 20) and a tendency towards smaller stomatal areas (p _A.marina  = 0.131, F1.8 = 2.8; p _R.mucronata  = 0.185, F1.8 = 2.1, n = 5 × 60), or species-specific trends for A. marina, such as higher phloem band/growth layer ratios (p = 0.101, F1.8 = 3.4, n = 5 × 3) and stomatal density (p = 0.052, F1.8 = 5.2, n = 5 × 4). All adaptations seemingly contributed to a comparable hydraulic conductivity independent of the degree of siltation. These findings indicate that silted trees level off fluctuations in their hydraulic performance as a survival mechanism to cope with this less favourable environment. Most of the trees’ structural adaptations to cope with siltation are similar to known drought stress-imposed adaptations.

     

Serum Trace Elements and Electrolytes Are Associated with Fasting Plasma Glucose and HbA<Subscript>1c</Subscript> in Postmenopausal Women with Type 2 Diabetes Mellitus

The primary aim of the research was to assess the level of trace elements and electrolytes in serum of postmenopausal diabetic women. Sixty-four postmenopausal women with type 2 diabetes mellitus (DM2) and 64 age- and body mass index-matched controls were examined. Serum trace elements were assessed using inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS). Fasting plasma glucose (FPG) and glycated hemoglobin (HbA_1c) levels were evaluated using Randox kits. The obtained data demonstrate that DM2 patients were characterized by 42 and 34 % higher FPG and HbA_1c levels, respectively (p < 0.001). The level of Cu and Se in diabetic postmenopausal women was increased by 10 and 15 % in comparison to the respective control values (p = 0.002 and <0.001). Serum Mn, Zn, and Ni concentrations were lower than the control ones by 32 % (p = 0.003), 8 % (p = 0.003), and 23 % (p = 0.046), respectively. FPG and HbA_1c levels directly correlated with serum Se (p < 0.001) and Cu (p = 0.014 and p = 0.028) concentrations and inversely related to Zn (p < 0.001) and Tl (p = 0.023 and p = 0.029) levels. Multiple regression analysis demonstrated a significant association between serum Zn and Se and FPG and HbA_1c levels. It is proposed that Zn and Se play an important role in DM2 pathogenesis. Further studies are required to assess the intimate mechanisms of the observed differences.     

Association between <Emphasis Type="Italic">cagA</Emphasis>, <Emphasis Type="Italic">vacAi</Emphasis>, and <Emphasis Type="Italic">dupA</Emphasis> genes of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> and gastroduodenal pathologies in Chilean patients

In addition to the already known cagA gene, novel genetic markers have been associated with Helicobacter pylori (H. pylori) virulence: the dupA and vacAi genes. These genes might play an important role as specific markers to determine the clinical outcome of the disease, especially the vacAi gene, which has been expected to be a good marker of severe pathologies like gastric adenocarcinoma. In the present study, the association of cagA, dupA, and vacAi genes with gastroduodenal pathologies in Chilean patients was studied. One hundred and thirty-two patients positive for H. pylori were divided into two groups—non-severe and severe gastric pathologies—and investigated for the presence of cagA, dupA, and vacAi H. pylori virulence genes by PCR. The cagA gene was detected in 20/132 patients (15.2%), the vacAi1 gene was detected in 54/132 patients (40.9%), the vacAi2 gene was detected in 26/132 patients (19.7%), and the dupA gene was detected in 50/132 (37.9%) patients. Logistic regression model analysis showed that the vacAi1 isoform gene in the infected strains and the severity of the diseases outcome were highly associated, causing severe gastric damage that may lead to gastric cancer (p < 0.0001; OR = 8.75; 95% CI 3.54–21.64). Conversely, cagA (p = 0.3507; OR = 1.62; 95% CI 0.59–4.45) and vacAi2 (p = 0.0114; OR = 3.09; 95% CI 1.26–7.60) genes were not associated with damage, while the dupA gene was associated significantly with non-severe clinical outcome (p = 0.0032; OR = 0.25; 95% CI 0.09–0.65). In addition, dupA gene exerts protection against severe gastric pathologies induced by vacAi1 by delaying the outcome of the disease by approximately 20 years.     

Sperm midpiece apoptotic markers: impact on fertilizing potential in in vitro fertilization and intracytoplasmic sperm injection

The aim of this study was to investigate the relationship between apoptotic markers present in human spermatozoa, namely phosphatidylserine translocation (PST) from the inner to the outer layer of the cytomembrane and the active form of caspase-3 (c3) versus the fertilizing potential of male gametes in conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) models. A total of 116 male patients treated with their partners for infertility underwent basic semen analysis and an assessment of the presence of PST and the active c3 in sperm using flow cytometry. Forty patients underwent IVF, group A, while 76 patients underwent ICSI, group B. The fertilizing potential of the gametes was measured as the percentage of oocytes with pronuclei present after either procedure. PST and active c3 were identified in vital gametes, mainly in the midpiece area. Concentration, motility, morphology, and viability of spermatozoa strongly negatively correlated with both markers. In group A, a negative correlation between both markers and the success rate of conventional IVF was observed (r = ?0.4, p = 0.04 for PST; r = ?0.4, p = 0.02 for active c3, respectively). In group B, the success rate of ICSI did not correlate with either marker (r = ?0.2, p = 0.85 for PST and r = 0.1, p = 0.51 for active c3). The two apoptotic markers localized in the sperm midpiece area may affect their function not only by decreasing basic andrologic parameters but also by reducing the probability of conception. Therefore, analysis of PST and active c3 in the sperm of patients undergoing infertility treatment should be recommended.     

Tumour infiltrating lymphocytes correlate with improved survival in patients with oesophageal adenocarcinoma

Background

Oesophageal adenocarcinoma (OAC) is increasingly common in the west, and survival remains poor at 10–15 % at 5 years. Immune responses are increasingly implicated as a determining factor of tumour progression. The ability of lymphocytes to recognise tumour antigens provides a mechanism for a host immune attack against cancer providing a potential treatment strategy.

Materials and Methods

Tumour infiltrating lymphocytes (TILs: CD3+, CD4+, CD8+ and FOXp3+) were assessed by immunohistochemistry using tissue microarrays in a contemporary and homogeneous cohort of OAC patients (n = 128) undergoing curative treatment.

Results

Multivariate analysis identified three independent prognostic factors for improved cancer-specific survival (CSS): increased CD8+ TILs (p = 0.003), completeness of resection (p < 0.0001) and lower pathological N stage (p < 0.0001). Independent prognostic factors for favourable disease-free survival included surgery-only treatment (p = 0.015), completeness of resection (p = 0.001), increased CD8+ TILs (p < 0.0001) and reduced pathological N stage (p < 0.0001). Higher levels of TILs in the pathological specimen were associated with significant pathological response to neoadjuvant chemotherapy (NAC). On multivariate analysis increased levels of CD4+ (p = 0.017) and CD8+ TILs (p = 0.005) were associated with significant local tumour regression and lymph node downstaging, respectively.

Discussion

Our results establish an association of TILs and survival in OAC, as seen in other solid tumours, and identify particular TIL subsets that are present at higher levels in patients who responded to NAC compared to non-responders. These findings highlight potential therapeutic strategies in EAC based on utilising the host immunological response and highlight the immune responses biomarker potential.

     

Maternal obesity is associated with gut microbial metabolic potential in offspring during infancy

Children born to obese mothers are at increased risk for obesity, but the mechanisms behind this association are not fully understood. Our study aimed to investigate differences in the functions encoded by the microbiome of infants at 18 months of age when the transition from early infant-feeding to solid family foods is established. To investigate the impact of maternal prepregnancy body mass index on infants’ gut microbiome, faecal samples from infants born to normoweight (n = 21) and obese mothers (n = 18) were analysed by 16S rRNA gene sequencing and a functional-inference-based microbiome analysis. Our results indicated that Firmicutes was significantly enriched in infants born to normoweight mothers whereas Bacteroidetes was significantly enriched in infants born to obese women. In both microbiomes, the greatest number of genes (>50%) that were assigned a function encoded for proteins involved in “metabolism” among tier 1 KEGG Orthology (KO) categories. At lower KO functional categories, the microbiome of infants born to normoweight mothers was characterized by a significant enrichment in the abundances of “pentose phosphate pathway” (p = 0.037), “lysine biosynthesis” (p = 0.043), “glycerolipid metabolism” (p = 0.042), and “C5-branched dibasic acid metabolism” (p = 0.045). Notably, the microbiome of infants born to obese mothers was significantly enriched in “streptomycin biosynthesis” (p = 0.047), “sulphur metabolism” (p = 0.041), “taurine and hypotaurine metabolism” (p = 0.036), and “lipopolysaccharide biosynthesis” (p = 0.043). In summary, our study showed that maternal prepregnancy obesity may imprint a selective gut microbial composition during late infancy with distinct functional performances.     

Takotsubo cardiomyopathy: serious early complications and two-year mortality – a 101 case study

Background

Takotsubo cardiomyopathy (TTC) is characterised by transient contractility disturbances of the apex of the left ventricle.

Methods

We enrolled 101 patients from the northern-eastern part of Poland in the years 2008–2012 who were hospitalised for TCC. The control group consisted of female patients diagnosed with anterior myocardial infarction with ST-segment elevation (anterior STEMI) (n = 101).

Results

89?% of the study group were women. Patients with TTC had diabetes (12.6?% vs 29.7?%; p = 0.002) and hyperlipidaemia (36.8?% vs 64.4?%; p = 0.0001) significantly less frequently, and better kidney function assessed by estimated glomerular filtration rate versus patients with anterior STEMI (74.52?% vs 64.30?%; p = 0.004). In the TTC group there were more patients with chronic obstructive pulmonary disease (11.6?% vs 1.0?%; p = 0.002) and thyroid disturbances, especially hyperthyroidism (23.4?% vs 11.0?%; p = 0.021). In patients with TTC sudden cardiac arrest, pulmonary oedema and cardiogenic shock were observed less frequently than in the control group (14.7?% vs 30.7?%; p = 0.0078). Hospitalisations in TTC patients were less frequently complicated by pneumonia (20.0?% vs 35.6?%; p = 0.0148) and urinary infection (4.2?% vs 21.8?%; p = 0.0003). Cardiac rupture occurred in 3 patients with TTC and in 1 with anterior STEMI. In-hospital mortality was significantly lower in the group with TTC. Also, mortality at 30 days, 3 months, 1 year and 2.5 years was significantly lower in patients with TTC than in patients with MI (p = 0.035; p = 0.0226; p = 0.0075; p = 0.009).

Conclusions

Previously considered to be a benign syndrome, TTC should be reconsidered as a clinical condition at risk for serious complications such as cardiac arrest, cardiogenic shock, pulmonary oedema and cardiac rupture leading to death and causing substantial early hazard. The prognosis in TTC is significantly better than in patients with anterior STEMI.

     

Clinical and Microbiological Investigation of Fungemia from Four Hospitals in China

In this study, fungemia cases from four tertiary hospitals located in Shanghai and Anhui province in China from March 2012 to December 2013 were enrolled to investigate clinical features, species distribution, antifungal susceptibility and strain relatedness. During the study period, 137 non-duplicate cases and their corresponding isolates were collected. Six different genera of fungi were identified, of which Candida spp. were the most common (126/137, 91.97 %), with C. albicans predominating (48/137, 35.03 %). The non-Candida fungi rate reached 8.03 % (11/137), and Pichia spp. was the most common (5/137, 3.65 %). Compared with C. albicans, non-C. albicans fungi-associated fungemia was more likely in younger (p = 0.004) and male patients (χ ² = 6.2618, p = 0.0123) and patients from ICUs (χ ² = 6.3783, p = 0.0116). Overall, the susceptible/WT rates of common Candida spp. to fluconazole, itraconazole, voriconazole, flucytosine, amphotericin B and caspofungin were 74.63, 92.31, 93.16, 96.58, 100 and 95.69 %, respectively. C. tropicalis and C. guilliermondii had a low susceptibility to fluconazole: 79.95 and 77.78 %, respectively. No isolates were resistant/WT to caspofungin, but C. parapsilosis and C. guilliermondii had high MIC₉₀ values; 1 and 2 mg/L, respectively. In terms of genotyping, MLST was taken for C. glabrata and C. tropicalis, while microsatellite marker analysis was used for C. albicans and C. parapsilosis. C. glabrata was predominantly clone ST7, accounting for 75 %, while the other isolates showed genetic diversity. Considering the increased proportion of non-C. albicans fungi and the presence of endemic clones of C. glabrata, it is essential to undertake additional surveillance of fungemia.     

Impact of neutrophil-to-lymphocyte ratio on periprocedural myocardial infarction in patients undergoing non-urgent percutaneous coronary revascularisation

Background

Pro-thrombotic conditions importantly influence myocardial perfusion and procedural results after percutaneous coronary intervention (PCI). The neutrophil-to-lymphocyte ratio (NLR) has emerged as a predictor of cardiovascular events and of long-term prognosis, especially in ST-elevation myocardial infarction patients undergoing primary PCI. The aim of our study was to evaluate the role of NLR on periprocedural myocardial infarction (MI) in patients undergoing non-urgent PCI.

Methods

In a consecutive cohort of 1542 patients undergoing PCI, myonecrosis biomarkers were determined at 6, 12, 24 and 48 hours post-procedure. Patients were divided into quintiles according to NLR values. Periprocedural myonecrosis was defined as a troponin I increase of 3 times the upper limit of normal or as 50?% of an elevated baseline value, whereas periprocedural MI was defined as a CK-MB increase of 3 times the upper limit of normal or 50?% of baseline.

Results

Higher NLR was related to age, established risk factors and cardiovascular history. NLR was associated with severe coronary artery disease (p = 0.009), tighter stenosis (p < 0.001), coronary calcifications (p = 0.005), intracoronary thrombus or thrombectomy use (p < 0.001), TIMI flow pre- and post-PCI (p < 0.001), and inversely to restenosis (p = 0.04) and use of a drug-eluting stent (p = 0.001). NLR did not influence the occurrence of myonecrosis (p = 0.75; adjusted OR (95?% CI) = 0.99 (0.63–1.54), p = 0.96), but was associated with a higher occurrence of periprocedural MI, even after correction for baseline differences (p = 0.03; adjusted OR (95?% CI) = 1.33 (1.02–2.3), p = 0.02), with NLR ≥ 3 best predicting the risk of periprocedural MI at the receiver operating characteristic curve analysis.

Conclusion

In patients undergoing non-urgent PCI, a higher NLR increases the risk of periprocedural MI, especially for values ≥ 3.

     

Milk and Dairy Products Intake Is Associated with Low Levels of Lead (Pb) in Workers highly Exposed to the Metal

Lead (Pb) is a toxic metal, frequently associated with occupational exposure, due to its widespread use in industry and several studies have shown high Pb levels in workers occupationally exposed to the metal. The aim of this study was to evaluate the influence of milk and dairy products (MDP) on Pb levels in blood (B-Pb), plasma (P-Pb), and urine (U-Pb), in workers from automotive battery industries in Brazil. The study included 237 male workers; information concerning diet and lifestyle were gathered through a questionnaire, and B-Pb, P-Pb, and U-Pb were determined by ICP-MS. Mean B-Pb, P-Pb, and U-Pb were 21 ± 12, 0.62 ± 0.73 μg/dL, and 39 ± 47 μg/g creatinine, respectively. Forty three percent of participants declared consuming ≤3 portions/week of MDP (classified as low-MDP intake), while 57% of individuals had >3portions/week of MDP (high-MDP intake). B-Pb and P-Pb were correlated with working time (r _s  = 0.21; r _s  = 0.20; p < 0.010). Multivariable linear regressions showed a significant influence of MDP intake on B-Pb (β = ?0.10; p = 0.012) and P-Pb (β = ?0.16; p < 0.010), while no significance was seen on U-Pb. Our results suggest that MDP consumption may modulate Pb levels in individuals highly exposed to the metal; these findings may be due to the Pb-Ca interactions, since the adverse effects of Pb are partially based on its interference with Ca metabolism and proper Ca supplementation may help to reduce the adverse health effects induced by Pb exposure.     

The CYP17-MspA1 rs743572 polymorphism is not associated with gender dysphoria

Gender dysphoria is commonly thought to arise from discrepant cerebral and genital sexual differentiation. Increasing evidence supports the idea of genetic vulnerability. The purpose of this paper was to investigate whether the polymorphism CYP17-MspA1 rs743572 is associated with gender dysphoria. Fragments that included the rs743572 polymorphism were PCR amplified and digested with MspA1 in 317 MtFs, 223 FtMs, 358 control men and 264 control women. The allele/genotype frequencies were compared between groups, with the 1000 Genomes Data Base and with international literature. Allele and genotype frequencies did not differ significantly between the FtM and female control groups (χ² = 0.631; p = 0.43 and χ² = 2.767; p = 0.25), or between the MtF and male control groups (χ² = 0.105; p = 0.74 and χ² = 0.789; p = 0.67). A2 frequency was higher in the FtM (0.43) than the female control group (0.41), male control group (0.40), or MtF group (0.39), but this difference did not reach statistical significance. Genotype frequencies did not differ significantly between groups (p = 0.66), between genotypes (p = 0.4) or between sexes (p = 0.66). Our data contradict previous findings about the CYP17-MspA1 rs743572 polymorphism and gender dysphoria and concur with the 1000 Genomes Data Base, which shows that the allele frequencies vary between countries and ethnicities but not between sexes. Our data do not support a hypothetical involvement of the rs743572 polymorphism in the genetic basis of gender dysphoria.     

Factors Influencing Non-<Emphasis Type="Italic">albicans</Emphasis> Candidemia: A Case–Case–Control Study

The study identified factors predisposing to non-albicans candidemia with special interest to prior antimicrobial treatment. A retrospective, case–case–control study was performed at the University Hospital of Heraklion, Greece, from November 2007 through September 2011 including adult patients. The study had three groups. The first included 58 patients with non-albicans candidemia, the second 48 with C. albicans candidemia, while the third (control) 104 without candidemia. Each of the two candidemia groups was compared with the control using multivariate logistic regression model. The mean (SD) age of the non-albicans, the albicans and the control patients was 67 (12), 67 (18) and 59 (19) years, respectively. The most common non-albicans Candida spp. isolated were C. parapsilosis in 19 patients (33%), C. glabrata in 17 (29%) and C. tropicalis in 15 (26%). Independent risk factors for non-albicans candidemia were prior treatment with quinolones (p < 0.001), b-lactam-b-lactamase inhibitors (p = 0.011) and presence of central venous catheter (p = 0.05), while for C. albicans candidemia were prior treatment with quinolones (p < 0.001), carbapenems (p = 0.003) along with cardiac disease (p < 0.001). Neither duration of hospitalization nor in-hospital mortality [41% for the non-albicans vs 29% for C. albicans group (p = 0.192)] was significantly different between the two candidemia groups. The study reveals the role of antimicrobial exposure as a risk factor for candidemia caused by different species. Prior treatment with b-lactam-b-lactamase inhibitors was associated with non-albicans, while with carbapenems with C. albicans candidemia. Prior use of quinolones was associated with candidemia in general.     

Genetic Differentiation of Colombian Populations of <Emphasis Type="Italic">Anopheles darlingi</Emphasis> Root (Diptera: Culicidae)

Anopheles darlingi Root is a primary vector of malaria in the neotropic region, a species not just highly anthropophilic but very efficient in transmitting Plasmodium species and considered the most important vector in the Amazon region. The main goal of this study was to determine the genetic structure of the A. darlingi populations using microsatellites (STR) in western and eastern regions of Colombia. DNA extraction was done with the cited protocol of band using the Genomic Prep? cell and tissue isolation commercial kits. We used the STR reported by Conn et al (Mol Ecol Notes 1: 223-225, 2001). The analysis with STR proved there was a high genetic diversity and significant alterations of the Hardy-Weinberg equilibrium. The greatest genetic diversity was recorded in Mitu (Vaupes) (Na = 14, Ho = 0.520). The lowest was in Pueblo Nuevo (Cordoba) (Na = 12, Ho = 0.457). The eastern region and the Mitu (Vaupes) populations presented the highest number of primer alleles (Ap = 30; Ap = 13; Ap = 9), with variations between 0.010 and 0.097. The AMOVA revealed that the whole population underwent moderate genetic differentiation (F _ST = 0.063, p < 0.05). The same differentiation was noticed (0.06 < F _ST > 0.06, p < 0.05) with five of the six populations included in this job, and there was a low differentiation in the Las Margaritas (Santander) area (F _ST = 0.02s3, p < 0.05). Our results suggest a slight positive correlation, which does not show a statistical significance between the geographic and genetic distances, probably suggesting that the moderate genetic differentiation found between pairs of populations does not need to be explained for the hypothesis of separation by distance.     

Epigenetic and genetic variation in <Emphasis Type="Italic">GATA5</Emphasis> is associated with gastric disease risk

Gastric cancer incidence varies considerably among populations, even those with comparable rates of Helicobacter pylori infection. To test the hypothesis that genetic variation plays a role in gastric disease, we assessed the relationship between genotypes and gastric histopathology in a Colombian study population, using a genotyping array of immune-related single nucleotide polymorphisms (SNPs). Two synonymous SNPs (rs6061243 and rs6587239) were associated with progression of premalignant gastric lesions in a dominant-effects model after correction for multiple comparisons (p = 2.63E?07 and p = 7.97E?07, respectively); effect sizes were β = ?0.863 and β = ?0.815, respectively, where β is an estimate of effect on histopathology scores, which ranged from 1 (normal) to 5 (dysplasia). In our replication cohort, a second Colombian population, both SNPs were associated with histopathology when additively modeled (β = ?0.256, 95 % CI = ?0.47, ?0.039; and β = ?0.239, 95 % CI = ?0.45, ?0.024), and rs6587239 was significantly associated in a dominant-effects model (β = ?0.330, 95 % CI = ?0.66, 0.00). Because promoter methylation of GATA5 has previously been associated with gastric cancer, we also tested for the association of methylation status with more advanced histopathology scores in our samples and found a significant relationship (p = 0.001). A multivariate regression model revealed that the effects of both the promoter methylation and the exonic SNPs in GATA5 were independent. A SNP-by-methylation interaction term was also significant. This interaction between GATA5 variants and GATA5 promoter methylation indicates that the association of either factor with gastric disease progression is modified by the other.     

Changes in the lung bacteriome in relation to antipseudomonal therapy in children with cystic fibrosis

The lung in cystic fibrosis (CF) is home to numerous pathogens that shorten the lives of patients. The aim of the present study was to assess changes in the lung bacteriome following antibiotic therapy targeting Pseudomonas aeruginosa in children with CF. The study included nine children (9–18 years) with CF who were treated for their chronic or intermittent positivity for Pseudomonas aeruginosa. The bacteriomes were determined in 16 pairs of sputa collected at the beginning and at the end of a course of intravenous antibiotic therapy via deep sequencing of the variable region 4 of the 16S rRNA gene, and the total bacterial load and selected specific pathogens were assessed using quantitative real-time PCR. The effect of antipseudomonal antibiotics was observable as a profound decrease in the total 16S rDNA load (p = 0.001) as well as in a broad range of individual taxa including Staphylococcus aureus (p = 0.03) and several members of the Streptococcus mitis group (S. oralis, S. mitis, and S. infantis) (p = 0.003). Improvements in forced expiratory volume (FEV₁) were associated with an increase in Granulicatella sp. (p = 0.004), whereas a negative association was noted between the total bacterial load and white blood cell count (p = 0.007). In conclusion, the data show how microbial communities differ in reaction to antipseudomonal treatment, suggesting that certain rare species may be associated with clinical parameters. Our work also demonstrates the utility of absolute quantification of bacterial load in addition to the 16S rDNA profiling.