On the approximation of interaction effect models by Hadamard powers of the additive genomic relationship.

Whole genome epistasis models with interactions between different loci can be approximated by genomic relationship models based on Hadamard powers of the additive genomic relationship. We illustrate that the quality of this approximation reduces when the degree of interaction d increases. Moreover, considering relationship models defined as weighted sum of interactions of different degree, we investigate the impact of this decreasing quality of approximation of the summands on the approximation of the weighted sum. Our results indicate that these approximations remain on a reliable level, but their quality reduces when the weights of interactions of higher degrees do not decrease quickly.

The activity of IKCa and BKCa channels contributes to insulin-mediated NO synthesis and vascular tone regulation in human umbilical vein.

Insulin regulates the l-arginine/nitric oxide (NO) pathway in human umbilical vein endothelial cells (HUVECs), increasing the plasma membrane expression of the l-arginine transporter hCAT-1 and inducing vasodilation in umbilical and placental veins. Placental vascular relaxation induced by insulin is dependent of large conductance calcium-activated potassium channels (BKCa), but the role of KCa channels on l-arginine transport and NO synthesis is still unknown. The aim of this study was to determine the contribution of KCa channels in both insulin-induced l-arginine transport and NO synthesis, and its relationship with placental vascular relaxation. HUVECs, human placental vein endothelial cells (HPVECs) and placental veins were freshly isolated from umbilical cords and placenta from normal pregnancies. Cells or tissue were incubated in absence or presence of insulin and/or tetraethylammonium, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole, iberiotoxin or NG-nitro-l-arginine methyl ester. l-Arginine uptake, plasma membrane polarity, NO levels, hCAT-1 expression and placenta vascular reactivity were analyzed. The inhibition of intermediate-conductance KCa (IKCa) and BKCa increases l-arginine uptake, which was related with protein abundance of hCAT-1 in HUVECs. IKCa and BKCa activities contribute to NO-synthesis induced by insulin but are not directly involved in insulin-stimulated l-arginine uptake. Long term incubation (8 h) with insulin increases the plasma membrane hyperpolarization and hCAT-1 expression in HUVECs and HPVECs. Insulin-induced relaxation in placental vasculature was reversed by KCa inhibition. The results show that the activity of IKCa and BKCa channels are relevant for both physiological regulations of NO synthesis and vascular tone regulation in the human placenta, acting as a part of negative feedback mechanism for autoregulation of l-arginine transport in HUVECs.

Dynamic biochar effects on nitrogen use efficiency, crop yield and soil nitrous oxide emissions during a tropical wheat-growing season.

The application of biochar to soil combined with synthetic fertilizers has been proposed for enhancing N availability to plants and crop yields while reducing nitrous oxide (N2O) emissions. However, little is known about those interactions for tropical soils. Thus, this study evaluated the effects of sugarcane straw biochar on tropical soil attributes, crop productivity, N2O emissions and N use efficiency. It was conducted a greenhouse pot experiment with wheat cultivation using a15N-labelled source (NH415NO3). The treatments evaluated were: Soil, with N, no biochar; Soil, with N and biochar at rates equivalent to 0.4%, 0.8% and 1.9% (w/w); and a control (soil only). Increasing biochar amendments decreased cumulative N2O emissions by 71% compared to the fertilized, no-biochar soil. Moreover, increasing biochar rates to soil increased available P up to 30% and led to 8-fold higher exchangeable K+ concentrations. Grain yield and shoot biomass increased by 27 and 16%, respectively, with the rate of 1.9% biochar to soil, which also resulted in higher tillering and number of heads compared to fertilized, no-biochar soil. The amount of 15N in grains was 28% higher with 0.8 and 1.9% of biochar compared to no-biochar soil, which correspond to 25% of the total 15N-labelled fertilizer applied to soil. The 15N loss by volatilization did not differ between treatments. Nevertheless, the biochar amended soils produced less N2O than the no-biochar treatment, indicating that biochar amendment to tropical soil led to gaseous N losses in forms other than N2O. The application of biochar to soil improved N utilization and the efficiency with which N is acquired by the plants and converted to grain yield, thereby enhancing crop performance, while simultaneously reducing N2O emissions from N fertilization, thus mitigating GHG emissions to the atmosphere under tropical conditions.

Human umbilical vein endothelium-derived exosomes play a role in foetoplacental endothelial dysfunction in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) characterizes by foetoplacental endothelial dysfunction. Human umbilical vein endothelial cells (HUVECs) from women with GDM show increased L-arginine transport via the human cationic amino acid transporter 1 (hCAT-1). Moreover, expression of endothelial nitric oxide synthase (eNOS) and nitric oxide synthesis are increased. Exosomes are increased in maternal plasma from GDM. We evaluated the role of foetoplacental endothelial exosomes on endothelial dysfunction in GDM. Exosomes were isolated from HUVECs from normal (ExN) and GDM (ExGDM) pregnancies. HUVECs were exposed (8h) to ExN or ExGDM and used for wound recovery assay (up to 8h), L-arginine transport, hCAT-1 and eNOS expression and activity, reactive oxygen species (ROS) generation, and 44 and 42kDa mitogen activated protein kinases (p44/42mapk) and protein kinase B/Akt (Akt) activation. Wound recovery was slower in GDM compared with normal pregnancies and was recovered by ExN. However, ExGDM delayed wound recovery in cells from normal pregnancies. GDM-increased L-arginine transport, hCAT-1 and eNOS expression and activity, and p44/42mapk activation were blocked by ExN, but ExGDM increased these parameters and ROS generation, and reduced eNOS phosphorylation at threonine495 in cells from normal pregnancies. Inhibition of p44/42mapk, but not Akt reversed GDM-increased L-arginine uptake. In conclusion foetoplacental endothelial-released exosomes play a role in the maintenance of a GDM phenotype in HUVECs. It is suggested that ExN and ExGDM cargo are different with differential effects in cells from normal or GDM pregnancies. This phenomenon could contribute to the understanding of mechanisms behind foetoplacental endothelial dysfunction in GDM pregnancies.

Intracellular acidification reduces l-arginine transport via system y+L but not via system y+/CATs and nitric oxide synthase activity in human umbilical vein endothelial cells.

l-Arginine is taken up via the cationic amino acid transporters (system y+/CATs) and system y+L in human umbilical vein endothelial cells (HUVECs). l-Arginine is the substrate for endothelial NO synthase (eNOS) which is activated by intracellular alkalization, but nothing is known regarding modulation of system y+/CATs and system y+L activity, and eNOS activity by the pHi in HUVECs. We studied whether an acidic pHi modulates l-arginine transport and eNOS activity in HUVECs. Cells loaded with a pH-sensitive probe were subjected to 0.1-20 mmol/L NH4Cl pulse assay to generate pHi 7.13-6.55. Before pHi started to recover, l-arginine transport (0-20 or 0-1000 µmol/L, 10 s, 37 °C) in the absence or presence of 200 µmol/L N-ethylmaleimide (NEM) (system y+/CATs inhibitor) or 2 mmol/L l-leucine (systemy+L substrate) was measured. Protein abundance for eNOS and serine1177 or threonine495 phosphorylated eNOS was determined. The results show that intracellular acidification reduced system y+L but not system y+/CATs mediated l-arginine maximal transport capacity due to reduced maximal velocity. Acidic pHi reduced NO synthesis and eNOS serine1177 phosphorylation. Thus, system y+L activity is downregulated by an acidic pHi, a phenomenon that may result in reduced NO synthesis in HUVECs.

Insulin therapy and its consequences for the mother, foetus, and newborn in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a disease characterised by glucose intolerance and first diagnosed in pregnancy. This condition relates to an anomalous placental environment and aberrant placental vascular function. GDM-associated hyperglycaemia changes the placenta structure leading to abnormal development and functionality of this vital organ. Aiming to avoid the GDM-hyperglycaemia and its deleterious consequences in the mother, the foetus and newborn, women with GDM are firstly treated with a controlled diet therapy; however, some of the women fail to reach the recommended glycaemia values and therefore they are passed to the second line of treatment, i.e., insulin therapy. The several protocols available in the literature regarding insulin therapy are variable and not a clear consensus is yet reached. Insulin therapy restores maternal glycaemia, but this beneficial effect is not reflected in the foetus and newborn metabolism, suggesting that other factors than d-glucose may be involved in the pathophysiology of GDM. Worryingly, insulin therapy may cause alterations in the placenta and umbilical vessels as well as the foetus and newborn additional to those seen in pregnant women with GDM treated with diet. In this review, we summarised the variable information regarding indications and protocols for administration of the insulin therapy and the possible outcomes on the function and structure of the foetoplacental unit and the neonate parameters from women with GDM.

Tetrahydrobiopterin Role in human umbilical vein endothelial dysfunction in maternal supraphysiological hypercholesterolemia.

Maternal physiological hypercholesterolemia (MPH) allows a proper foetal development; however, maternal supraphysiological hypercholesterolemia (MSPH) associates with foetal endothelial dysfunction and early development of atherosclerosis. MSPH courses with reduced endothelium-dependent dilation of the human umbilical vein due to reduced endothelial nitric oxide synthase activity compared with MPH. Whether MSPH modifies the availability of the nitric oxide synthase cofactor tetrahydrobiopterin is unknown. We investigated whether MSPH-associated lower umbilical vein vascular reactivity results from reduced bioavailability of tetrahydrobiopterin. Total cholesterol <7.2mmol/L was considered as maternal physiological hypercholesterolemia (n=72 women) and ≥7.2mmol/L as MSPH (n=35 women). Umbilical veins rings were used for vascular reactivity assays (wire myography), and primary cultures of human umbilical vein endothelial cells (HUVECs) to measure nitric oxide synthase, GTP cyclohydrolase 1, and dihydrofolate reductase expression and activity, as well as tetrahydrobiopterin content. MSPH reduced the umbilical vein rings relaxation caused by calcitonine gene-related peptide, a phenomenon partially improved by incubation with sepiapterin. HUVECs from MSPH showed lower nitric oxide synthase activity (l-citrulline synthesis from l-arginine) without changes in its protein abundance, as well as reduced tetrahydrobiopterin level compared with MPH, a phenomenon reversed by incubation with sepiapterin. Expression and activity of GTP cyclohydrolase 1 was lower in MSPH, without changes in dihydrofolate reductase expression. MSPH is a pathophysiological condition reducing human umbilical vein reactivity due to lower bioavailability of tetrahydrobiopterin leading to lower NOS activity in the human umbilical vein endothelium.

Maternal insulin therapy does not restore foetoplacental endothelial dysfunction in gestational diabetes mellitus.

Pregnant women diagnosed with gestational diabetes mellitus subjected to diet (GDMd) that do not reach normal glycaemia are passed to insulin therapy (GDMi). GDMd associates with increased human cationic amino acid transporter 1 (hCAT-1)-mediated transport of L-arginine and nitric oxide synthase (NOS) activity in foetoplacental vasculature, a phenomenon reversed by exogenous insulin. Whether insulin therapy results in reversal of the GDMd effect on the foetoplacental vasculature is unknown. We assayed whether insulin therapy normalizes GDMd-associated foetoplacental endothelial dysfunction. Primary cultures of human umbilical vein endothelial cells (HUVECs) from GDMi pregnancies were used to assay L-arginine transport kinetics, NOS activity, p44/42mapk and protein kinase B/Akt activation, and umbilical vein rings reactivity. HUVECs from GDMi or GDMd show increased hCAT-1 expression and maximal transport capacity, NOS activity, and eNOS, and p44/42mapk, but not Akt activator phosphorylation. Dilation in response to insulin or calcitonin-gene related peptide was impaired in umbilical vein rings from GDMi and GDMd pregnancies. Incubation of HUVECs in vitro with insulin (1 nmol/L) restored hCAT-1 and eNOS expression and activity, and eNOS and p44/42mapk activator phosphorylation. Thus, maternal insulin therapy does not seem to reverse GDMd-associated alterations in human foetoplacental vasculature.

Sodium/proton exchanger isoform 1 regulates intracellular pH and cell proliferation in human ovarian cancer.

Cancer cells generate protons (H+) that are extruded to the extracellular medium mainly via the Na+/H+ exchanger 1 (NHE1), which regulates intracellular pH (pHi) and cell proliferation. In primary cultures of human ascites-derived ovarian cancer cells (haOC) we assayed whether NHE1 was required for pHi modulation and cell proliferation. Human ovary expresses NHE1, which is higher in haOC and A2780 (ovarian cancer cells) compared with HOSE cells (normal ovarian cells). Basal pHi and pHi recovery (following a NH4Cl pulse) was higher in haOC and A2780, compared with HOSE cells. Zoniporide (NHE1 inhibitor) caused intracellular acidification and pHi recovery was independent of intracellular buffer capacity, but reduced in NHE1 knockdown A2780 cells. Zoniporide reduced the maximal proliferation capacity, cell number, thymidine incorporation, and ki67 (marker of proliferation) fluorescence in haOC cells. SLC9A1 (for NHE1) amplification associated with lower overall patient survival. In conclusion, NHE1 is expressed in human ovarian cancer where it has a pro-proliferative role. Increased NHE1 expression and activity constitute an unfavourable prognostic factor in these patients.

Nitric oxide and pH modulation in gynaecological cancer.

Nitric oxide plays several roles in cellular physiology, including control of the vascular tone and defence against pathogen infection. Neuronal, inducible and endothelial nitric oxide synthase (NOS) isoforms synthesize nitric oxide. Cells generate acid and base equivalents, whose physiological intracellular concentrations are kept due to membrane transport systems, including Na+ /H+ exchangers and Na+ /HCO3- transporters, thus maintaining a physiological pH at the intracellular (~7.0) and extracellular (~7.4) medium. In several pathologies, including cancer, cells are exposed to an extracellular acidic microenvironment, and the role for these membrane transport mechanisms in this phenomenon is likely. As altered NOS expression and activity is seen in cancer cells and because this gas promotes a glycolytic phenotype leading to extracellular acidosis in gynaecological cancer cells, a pro-inflammatory microenvironment increasing inducible NOS expression in this cell type is feasible. However, whether abnormal control of intracellular and extracellular pH by cancer cells regards with their ability to synthesize or respond to nitric oxide is unknown. We, here, discuss a potential link between pH alterations, pH controlling membrane transport systems and NOS function. We propose a potential association between inducible NOS induction and Na+ /H+ exchanger expression and activity in human ovary cancer. A potentiation between nitric oxide generation and the maintenance of a low extracellular pH (i.e. acidic) is proposed to establish a sequence of events in ovarian cancer cells, thus preserving a pro-proliferative acidic tumour extracellular microenvironment. We suggest that pharmacological therapeutic targeting of Na+ /H+ exchangers and inducible NOS may have benefits in human epithelial ovarian cancer.

Insulin requires A1 adenosine receptors expression to reverse gestational diabetes-increased L-arginine transport in human umbilical vein endothelium.

Gestational diabetes mellitus (GDM) associates with increased L-arginine transport and extracellular concentration of adenosine in human umbilical vein endothelial cells (HUVECs). In this study we aim to determine whether insulin reverses GDM-increased L-arginine transport requiring adenosine receptors expression in HUVECs. Primary cultured HUVECs from full-term normal (n = 38) and diet-treated GDM (n = 38) pregnancies were used. Insulin effect was assayed on human cationic amino acid transporter 1 (hCAT1) expression (protein, mRNA, SLC7A1 promoter activity) and activity (initial rates of L-arginine transport) in the absence or presence of adenosine receptors agonists or antagonists. A1 adenosine receptors (A1AR) and A2AAR expression (Western blot, quantitative PCR) was determined. Experiments were done in cells expressing or siRNA-suppressed expression of A1AR or A2AAR. HUVECs from GDM exhibit higher maximal transport capacity (maximal velocity (V max)/apparent Michaelis Menten constant (K m), V max/K m), which is blocked by insulin by reducing the V max to values in cells from normal pregnancies. Insulin also reversed the GDM-associated increase in hCAT-1 protein abundance and mRNA expression, and SLC7A1 promoter activity for the fragment -606 bp from the transcription start point. Insulin effects required A1AR, but not A2AAR expression and activity in this cell type. In the absence of insulin, GDM-increased hCAT-1 expression and activity required A2AAR expression and activity. HUVECs from GDM pregnancies exhibit a differential requirement of A1AR or A2AAR depending on the level of insulin, a phenomenon that represent a condition where adenosine or analogues of this nucleoside could be acting as helpers of insulin biological effects in GDM.

[Access to cholecystectomy among patients attended at primary family health centers]. / Acceso a colecistectomía en un programa de tamizaje ecográfico de colelitiasis en centros de medicina familiar.

BACKGROUND: Cholelithiasis (CL) represents a major health burden in Chile, with rates of cholecystectomy (CCT) of ~40.000 per year. The explicit health care guaranties (GES) program includes prioritized CCT for CL carriers between 35 and 49 years of age. AIM: To assess the access and opportunity of CCT in a screening program of CL in Family Medicine Centers, according to the age of the patients. MATERIAL AND METHODS: A systematic ultrasound screening program of CL was developed in Family Medicine Centers ANCORA-UC between March 2009 and March 2013 during which 1.450 individuals were assessed, (80% women) and 281 were identified as having CL (19.4%). After a minimum follow up interval of six months, patients with CL were contacted and surveyed by phone. They were categorized as being beneficiaries of the GES program (those aged between 35 to 49 years) or not (those aged < 35 o > 49 years). RESULTS: Two hundred thirteen patients were contacted (76%), 81 beneficiaries of the program and 132 non-beneficiaries. The attending physician indicated CCT to 191 patients (89.6%). During a mean follow-up time of 641 days/person, 100 patients had CCT, 11% of which were emergency interventions due to complications. A greater proportion of program beneficiaries than non-beneficiaries had an elective CCT (74 and 21% respectively). The waiting interval for elective CCT was longer in non-beneficiaries compared with beneficiaries (340 ± 247 and 229 ± 201 days respectively). Only 46% of the elective CCT in GES patients were done within deadlines determined by the program (≤ 150 days). CONCLUSIONS: The age of patients at the moment of CL diagnosis conditions the access and opportunity to CCT. Beneficiaries of the explicit health care guaranties program have higher rates of cholecystectomy with less waiting time.

A Bayesian optimization R package for multitrait parental selection.

Selecting and mating parents in conventional phenotypic and genomic selection are crucial. Plant breeding programs aim to improve the economic value of crops, considering multiple traits simultaneously. When traits are negatively correlated and/or when there are missing records in some traits, selection becomes more complex. To address this problem, we propose a multitrait selection approach using the Multitrait Parental Selection (MPS) R package-an efficient tool for genetic improvement, precision breeding, and conservation genetics. The package employs Bayesian optimization algorithms and three loss functions (Kullback-Leibler, Energy Score, and Multivariate Asymmetric Loss) to identify parental candidates with desirable traits. The software's functionality includes three main functions-EvalMPS, FastMPS, and ApproxMPS-catering to different data availability scenarios. Through the presented application examples, the MPS R package proves effective in multitrait genomic selection, enabling breeders to make informed decisions and achieve strong performance across multiple traits.

Irritant contact dermatitis due to ammonium bifluoride in two infant twins.

Ammonium bifluoride is one of the most corrosive acids that may produce severe chemical burns when in contact with skin. This hazardous chemical is widely used in household products. We report two pediatric cases of irritant contact dermatitis after exposure to a rust remover, which contained ammonium bifluoride.

Genetic analyses of tropical maize lines under artificial infestation of fall armyworm and foliar diseases under optimum conditions.

Development and deployment of high-yielding maize varieties with native resistance to Fall armyworm (FAW), turcicum leaf blight (TLB), and gray leaf spot (GLS) infestation is critical for addressing the food insecurity in sub-Saharan Africa. The objectives of this study were to determine the inheritance of resistance for FAW, identity hybrids which in addition to FAW resistance, also show resistance to TLB and GLS, and investigate the usefulness of models based on general combining ability (GCA) and SNP markers in predicting the performance of new untested hybrids. Half-diallel mating scheme was used to generate 105 F1 hybrids from 15 parents and another 55 F1 hybrids from 11 parents. These were evaluated in two experiments, each with commercial checks in multiple locations under FAW artificial infestation and optimum management in Kenya. Under artificial FAW infestation, significant mean squares among hybrids and hybrids x environment were observed for most traits in both experiments, including at least one of the three assessments carried out for foliar damage caused by FAW. Interaction of GCA x environment and specific combining ability (SCA) x environment interactions were significant for all traits under FAW infestation and optimal conditions. Moderate to high heritability estimates were observed for GY under both management conditions. Correlation between GY and two of the three scorings (one and three weeks after infestation) for foliar damage caused by FAW were negative (-0.27 and -0.38) and significant. Positive and significant correlation (0.84) was observed between FAW-inflicted ear damage and the percentage of rotten ears. We identified many superior-performing hybrids compared to the best commercial checks for both GY and FAW resistance associated traits. Inbred lines CML312, CML567, CML488, DTPYC9-F46-1-2-1-2, CKDHL164288, CKDHL166062, and CLRCY039 had significant and positive GCA for GY (positive) and FAW resistance-associated traits (negative). CML567 was a parent in four of the top ten hybrids under optimum and FAW conditions. Both additive and non-additive gene action were important in the inheritance of FAW resistance. Both GCA and marker-based models showed high correlation with field performance, but marker-based models exhibited considerably higher correlation. The best performing hybrids identified in this study could be used as potential single cross testers in the development of three-way FAW resistance hybrids. Overall, our results provide insights that help breeders to design effective breeding strategies to develop FAW resistant hybrids that are high yielding under FAW and optimum conditions.

Platelets and endothelial dysfunction in gestational diabetes mellitus.

The prevalence of gestational diabetes mellitus (GDM) has increased in recent years, along with the higher prevalence of obesity in women of reproductive age. GDM is a pathology associated with vascular dysfunction in the fetoplacental unit. GDM-associated endothelial dysfunction alters the transfer of nutrients to the foetus affecting newborns and pregnant women. Various mechanisms for this vascular dysfunction have been proposed, of which the most studied are metabolic alterations of the vascular endothelium. However, different cell types are involved in GDM-associated endothelial dysfunction, including platelets. Platelets are small, enucleated cell fragments that actively take part in blood haemostasis and thrombus formation. Thus, they play crucial roles in pathologies coursing with endothelial dysfunction, such as atherosclerosis, cardiovascular diseases, and diabetes mellitus. Nevertheless, platelet function in GDM is understudied. Several reports show a potential relationship between platelet volume and mass with GDM; however, platelet roles and signaling mechanisms in GDM-associated endothelial dysfunction are unclear. This review summarizes the reported findings and proposes a link among altered amount, volume, mass, reactivity, and function of platelets and placenta development, resulting in fetoplacental vascular dysfunction in GDM.

Bayesian modelling of phosphorus content in wheat grain using hyperspectral reflectance data.

BACKGROUND: As a result of the technological progress, the use of sensors for crop survey has substantially increased, generating valuable information for modelling agricultural data. Plant spectroscopy jointly with statistical modeling can potentially help to assess certain chemical components of interest present in plants, which may be laborious and expensive to obtain by direct measurements. In this research, the phosphorus content in wheat grain is modeled using reflectance information measured by a hyperspectral sensor at different wavelengths. A Bayesian procedure for selecting variables was used to identify the set of the most important spectral bands. Additionally, three different models were evaluated: the first model assumes that the observations are independent, the other two models assume that the observations are spatially correlated: one of the proposed models, assumes spatial dependence using a Conditionally Autoregressive Model (CAR), and the other through an exponential correlogram. The goodness of fit of the models was evaluated by means of the Deviance Information Criterion, and the predictive power is evaluated using cross validation. RESULTS: We have found that CAR was the model that best fits and predicts the data. Additionally, the selection variable procedure in the CAR model reveals which wavelengths in the range of 500-690 nm are the most important. Comparing the vegetative indices with the CAR model, it was observed that the average correlation of the CAR model exceeded that of the vegetative indices by 23.26%, - 1.2% and 22.78% for the year 2010, 2011 and 2012 respectively; therefore, the use of the proposed methodology outperformed the vegetative indices in prediction. CONCLUSIONS: The proposal to predict the phosphorus content in wheat grain using Bayesian approach, reflect with the results as a good alternative.

Consequences of the exposome to gestational diabetes mellitus.

The exposome is the cumulative measure of environmental influences and associated biological responses throughout the lifespan, including those from the environment, diet, behaviour, and endogenous processes. The exposome concept and the 2030 Agenda for the Sustainable Development Goals (SDGs) from the United Nations are the basis for understanding the aetiology and consequences of non-communicable diseases, including gestational diabetes mellitus (GDM). Pregnancy may be developed in an environment with adverse factors part of the immediate internal medium for fetus development and the external medium to which the pregnant woman is exposed. The placenta is the interface between maternal and fetal compartments and acts as a protective barrier or easing agent to transfer exposome from mother to fetus. Under and over-nutrition in utero, exposure to adverse environmental pollutants such as heavy metals, endocrine-disrupting chemicals, pesticides, drugs, pharmaceuticals, lifestyle, air pollutants, and tobacco smoke plays a determinant role in the development of GDM. This phenomenon is worsened by metabolic stress postnatally, such as obesity which increases the risk of GDM and other diseases. Clinical risk factors for GDM development include its aetiology. It is proposed that knowledge-based interventions to change the potential interdependent ecto-exposome and endo-exposome could avoid the occurrence and consequences of GDM.

"Cauliflower ear" in a teenager: a possible sign of child abuse.

"Cauliflower ear" is a perichondritis of the auricular pavilion, usually caused by infection or repeated trauma. In children, this entity is considered infrequent. We present the case of a 10-year-old girl living in a child care institution with "cauliflower ear" that was interpreted as a possible sign of child abuse.

Characterization of Rapana thomasiana as an indicator of environmental quality of the Black Sea coast of Bulgaria.

The aim of this investigation was to determine the contents of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), minerals, trace elements and bioactivity in the gastropod Rapana thomasiana, which can be used as an environmental bioindicator organism. The chemical differences between Rapana thomasiana from polluted (RapaPol) and non-polluted (RapaNPol) sites of the Black Sea coast in Bulgarian were investigated. Chromatography and high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS) were used for evaluation of PAHs, PCBs, minerals and trace elements. Methanol extracts from RapaPol and RapaNPol (to a lesser degree) contained relatively high amounts of free phenolics (2.50 +/- 0.3 and 1.57 +/- 0.18 mg GAE/g DW, respectively) and exhibited the following respective levels of antioxidant activities determined by two radical-scavenging assays (microMTE/g DW): 1.8 +/- 0.2 and 0.98 +/- 0.08 by 1-diphenyl-2-picrylhydrazyl method (DPPH); 1.74 +/- 0.17 and 1.04 +/- 0.12 by cupric reducing antioxidant capacity (CUPRAC). The total amounts of elements, PAHs and PCBs were higher in RapaPol than in RapaNPol. The obtained indices of Rapana thomasiana can serve as a bioindicator of the environmental ecological quality.