Adverse effects of fetal exposure of electronic-cigarettes and high-fat diet on male neonatal hearts.

Epidemiological studies have shown an increased risk of cardiovascular diseases in children born to mothers who smoked during pregnancy. The cardiovascular risk in the offspring associated with in utero nicotine exposure is further exaggerated by maternal obesity. The consumption of electronic cigarettes (e-cigarettes) is alarmingly increasing among adolescents and young adults without the knowledge of their harmful health effects. There has also been a substantial increase in e-cigarette use by women of reproductive age. This study investigates the detrimental effects of gestational exposure of e-cigarette and a high-fat diet (HFD) on neonatal hearts. Time-mated pregnant mice were fed a HFD and exposed to saline or e-cigarette aerosol with 2.4% nicotine from embryonic day 4 (E4) to E20. We demonstrated that in utero exposure of e-cigarettes and HFD from E4 to E20 triggers cardiomyocyte (CM) apoptosis in the offspring at postnatal day1 (PND1), PND3, and PND14. Induction of CM apoptosis following gestational exposure of e-cigarettes and HFD was associated with inactivation of AMP-activated protein kinase (AMPK), increased cardiac oxidative stress coupled with perturbation of cardiac BAX/BCL-2 ratio and activation of caspase 3 at PND 14. Electron microscopy further revealed that left ventricles of pups at PND14 after e-cigarette exposure exhibited apoptotic nuclei, convoluted nuclear membranes, myofibrillar derangement, and enlarged mitochondria occasionally showing signs of crystolysis, indicative of cardiomyopathy and cardiac dysfunction. Our results show profound adverse effects of prenatal exposure of e-cigarette plus HFD in neonatal hearts that may lead to long-term adverse cardiac consequences in the adult.

A mouse model for chronic intermittent electronic cigarette exposure exhibits nicotine pharmacokinetics resembling human vapers.

Electronic cigarettes (E-cig) use is increasing rapidly, particularly among youths. Animal models for E-cig exposure with pharmacokinetics resembling human E-cig users are lacking. We developed an E-cig aerosol exposure system for rodents and a chronic intermittent delivery method that simulates E-cig users who vape episodically during wakefulness and abstain during sleep. Mice were exposed to E-cig in a programmed schedule at very low, low, medium, or high doses defined by duration of each puff, number of puffs per delivery episode and frequency of episodes in the dark phase of a 12/12-h circadian cycle for 9 consecutive days. The plasma nicotine/cotinine levels and their time courses were determined using LC/MS-MS. We assessed the body weight, food intake and locomotor activity of Apolipoprotein E null (ApoE-/-) mice exposed to chronic intermittent E-cig aerosol. Plasma nicotine and cotinine levels were positively correlated with exposure doses. Nicotine and cotinine levels showed a circadian variation as they increased with time up to the maximum nicotine level of 21.8 ±â€¯7.1 ng/mL during the daily intermittent E-cig exposure in the 12-h dark phase and then declined during the light phase when there was no E-cig delivery. Chronic E-cig exposure to ApoE-/- mice decreased body weight, food intake and increased locomotion. Our rodent E-cig exposure system and chronic intermittent exposure method yield clinically relevant nicotine pharmacokinetics associated with behavioral and metabolic changes. The methodologies are essential tools for in vivo studies of the health impacts of E-cig exposure on CNS, cardiovascular, pulmonary, hepatic systems, metabolism and carcinogenesis.

Assessment of adulthood in the living Spanish population based on ossification of the medial clavicle epiphysis using ultrasound methods.

It is a fact that in recent years requests have greatly increased to obtain estimates of the legal age of undocumented individuals alleged to be minors who have been forced to enter different European Community countries for socioeconomic reasons or due to war. Spain is one of the countries most affected by this illegal immigration because of its proximity to North Africa. Therefore, it has become necessary to develop new standards which help provide a response to the demands of the justice administration. In recent years, the Superior Justice Court has rejected several pieces of expert evidence on the grounds that the age intervals therein were not sufficiently reliable and that the radiographic techniques used to determine age were invasive, potentially causing harm to the alleged minor. These sentences have caused interest in this field of work to increase within the scientific community. As a result, in order to improve age predictions and, above all, reduce minors' exposure to radiation, this study was created for completion on the Spanish population, using the ultrasound scan as a diagnostic technique. Used as a study sample were the ultrasound images of the proximal sternal epiphysis of the clavicle among 221 individuals of both sexes, of ages ranging from 5 to 30 years. All of the images were classified into 4 stages of fusion, in accordance with the development of metaphyseal closure proposed by Schulz et al. in 2008. The results show differences among the 4 proposed groups for each of the stages of fusion, with the results found in Stage II being especially important because, for both sexes, they would imply that the patient studied has reached an age of over 18 years, which is the legal age of adulthood in Spain, as established by the Spanish Constitution of 1978. Though further research is still recommended, these results, coupled with the use of ultrasound as a non-invasive diagnostic technique, could help solve some of the problems currently arising in justice courts.

Sex and age at death estimation from the sternal end of the fourth rib. Does Íscan's method really work?

The fourth rib has been used commonly in order to estimate age at death and even sex in skeletal remains but many often, Iscan's estimates do not adjust to the real age of the individual. Population specific references for sex and age-at-death estimation from the sternal end of the fourth rib are presented for a contemporary Mexican sample. A total of 504 ribs with known sex and age from a morgue sample were studied (444 males, 60 females, 17 to 92 years old). The height and breadth of the sternal end of the rib were sexually dimorphic (p = .000), and allowed a correct sex assignment in 73.3% to 84% of the cases from univariate and multivariate discriminant functions. With regard to age-at-death estimation, the morphological changes summarized by the phases of the sternal end of the fourth rib are correlated with known age in this sample (Spearman's Rho, p = .000). However, the original age intervals tend to underestimate age at death and inaccuracy increases with phase scored in males. Descriptive statistics for rib phase are provided for males and females, and new age-at-death estimates based on transition analysis and Bayesian statistics are provided for the male sample. The test of universally applied methods and the development of population specific references is an important task for forensic anthropology around the world.

Cellular shear stiffness reflects progression of arsenic-induced transformation during G1.

Cancer cells consistently exhibit decreased stiffness; however, the onset and progression of this change have not been characterized. To study the development of cell stiffness changes, we evaluated the shear stiffness of populations of cells during transformation to a carcinogenic state. Bronchial epithelial cells were exposed to sodium arsenite to initiate early stages of transformation. Exposed cells were cultured in soft agar to further transformation and select for clonal populations exhibiting anchorage-independent growth. Shear stiffness of various cell populations in G1 was assessed using a novel non-invasive assay that applies shear stress with fluid flow and evaluates nanoscale deformation using quantitative phase imaging (QPI). Arsenic-treated cells exhibited reduced stiffness relative to control cells, while arsenic clonal lines, selected by growth in soft agar, were found to have reduced stiffness relative to control clonal lines, which were cultured in soft agar but did not receive arsenic treatment. The relative standard deviation (RSD) of the stiffness of Arsenic clones was reduced compared with control clones, as well as to the arsenic-exposed cell population. Cell stiffness at the population level exhibits potential to be a novel and sensitive framework for identifying the development of cancerous cells.

Neurovascular study of the trigeminal nerve at 3 t MRI.

This study aimed to show a novel visualization method to investigate neurovascular compression of the trigeminal nerve (TN) using a volume-rendering fusion imaging technique of 3D fast imaging employing steady-state acquisition (3D FIESTA) and coregistered 3D time of flight MR angiography (3D TOF MRA) sequences, which we called "neurovascular study of the trigeminal nerve". We prospectively studied 30 patients with unilateral trigeminal neuralgia (TN) and 50 subjects without symptoms of TN (control group), on a 3 Tesla scanner. All patients were assessed using 3D FIESTA and 3D TOF MRA sequences centered on the pons, as well as a standard brain protocol including axial T1, T2, FLAIR and GRE sequences to exclude other pathologies that could cause TN. Post-contrast T1-weighted sequences were also performed. All cases showing arterial imprinting on the trigeminal nerve (n = 11) were identified on the ipsilateral side of the pain. No significant relationship was found between the presence of an artery in contact with the trigeminal nerve and TN. Eight cases were found showing arterial contact on the ipsilateral side of the pain and five cases of arterial contact on the contralateral side. The fusion imaging technique of 3D FIESTA and 3D TOF MRA sequences, combining the high anatomical detail provided by the 3D FIESTA sequence with the 3D TOF MRA sequence and its capacity to depict arterial structures, results in a tool that enables quick and efficient visualization and assessment of the relationship between the trigeminal nerve and the neighboring vascular structures.

Sex-specific patterns and deregulation of endocrine pathways in the gene expression profiles of Bangladeshi adults exposed to arsenic contaminated drinking water.

Arsenic contamination of drinking water occurs globally and is associated with numerous diseases including skin, lung and bladder cancers, and cardiovascular disease. Recent research indicates that arsenic may be an endocrine disruptor. This study was conducted to evaluate the nature of gene expression changes among males and females exposed to arsenic contaminated water in Bangladesh at high and low doses. Twenty-nine (55% male) Bangladeshi adults with water arsenic exposure ranging from 50 to 1000 µg/L were selected from the Folic Acid Creatinine Trial. RNA was extracted from peripheral blood mononuclear cells for gene expression profiling using Affymetrix 1.0 ST arrays. Differentially expressed genes were assessed between high and low exposure groups for males and females separately and findings were validated using quantitative real-time PCR. There were 534 and 645 differentially expressed genes (p<0.05) in the peripheral blood mononuclear cells of males and females, respectively, when high and low water arsenic exposure groups were compared. Only 43 genes overlapped between the two sexes, with 29 changing in opposite directions. Despite the difference in gene sets both males and females exhibited common biological changes including deregulation of 17ß-hydroxysteroid dehydrogenase enzymes, deregulation of genes downstream of Sp1 (specificity protein 1) transcription factor, and prediction of estrogen receptor alpha as a key hub in cardiovascular networks. Arsenic-exposed adults exhibit sex-specific gene expression profiles that implicate involvement of the endocrine system. Due to arsenic's possible role as an endocrine disruptor, exposure thresholds for arsenic may require different parameters for males and females.

Short communication: Traits unique to genus Homo within primates at the cervical spine (C2-C7).

From a comparative study of 222 human and 261 nonhuman primates complete cervical spines, two bony variants associated to the course of the vertebral artery are proposed as unique to genus Homo within primates. First, the opening of the foramen transversarium at C2, a trait present at low frequency in humans (3 to 5.6%). Second, the presence of a bipartite foramen transversarium in the cervical segment C3-C6, a trait that can be observed fully formed in human fetal skeletons, with a clear frequency pattern along the cervical spine (C3>C4>C5>C6

Sodium metavanadate exhibits carcinogenic tendencies in vitro in immortalized human bronchial epithelial cells.

Pentavalent vanadium compounds induce intracellular changes in vitro that are consistent with those of other carcinogenic substances. While there is no clear evidence that vanadium compounds cause cancer in humans, vanadium pentoxide causes lung cancer in rodents after long-term inhalation exposures and in turn IARC has categorized it as a group 2B possible human carcinogen. The goal of this study was to investigate the carcinogenicity of NaVO3 in the human immortalized bronchial epithelial cell line, Beas-2B. Cells were treated with 10 µM NaVO3 for 5 weeks, with or without recovery time, followed by gene expression microarray analysis. In a separate experiment, cells were exposed to 1-10 µM NaVO3 for 4 weeks and then grown in soft agar to test for anchorage-independent growth. A dose-dependent increase in the number of colonies was observed. In scratch tests, NaVO3-transformed clones could repair a wound faster than controls. In a gene expression microarray analysis of soft agar clones there were 2010 differentially expressed genes (DEG) (adjusted p-value ≤ 0.05) in NaVO3-transformed clones relative to control clones. DEG from this experiment were compared with the DEG of 5 week NaVO3 exposure with or without recovery, all with adjusted p-values < 0.05, and 469 genes were altered in the same direction for transformed clones, 5 week NaVO3-treated cells, and the recovered cells. The data from this study imply that chronic exposure to NaVO3 causes changes that are consistent with cellular transformation including anchorage-independent growth, enhanced migration ability, and gene expression changes that were likely epigenetically inherited.

Nutritionally mediated oxidative stress and inflammation.

There are many sources of nutritionally mediated oxidative stress that trigger inflammatory cascades along short and long time frames. These events are primarily mediated via NF κ B. On the short-term scale postprandial inflammation is characterized by an increase in circulating levels of IL-6 and TNF- α and is mirrored on the long-term by proinflammatory gene expression changes in the adipocytes and peripheral blood mononuclear cells (PBMCs) of obese individuals. Specifically the upregulation of CCL2/MCP-1, CCL3/MIP-1 α , CCL4/MIP-1 ß , CXCL2/MIP-2 α , and CXCL3/MIP-2 ß is noted because these changes have been observed in both adipocytes and PBMC of obese humans. In comparing numerous human intervention studies it is clear that pro-inflammatory and anti-inflammatory consumption choices mediate gene expression in humans adipocytes and peripheral blood mononuclear cells. Arachidonic acid and saturated fatty acids (SFAs) both demonstrate an ability to increase pro-inflammatory IL-8 along with numerous other inflammatory factors including IL-6, TNF α , IL-1 ß , and CXCL1 for arachidonic acid and IGB2 and CTSS for SFA. Antioxidant rich foods including olive oil, fruits, and vegetables all demonstrate an ability to lower levels of IL-6 in PBMCs. Thus, dietary choices play a complex role in the mediation of unavoidable oxidative stress and can serve to exacerbate or dampen the level of inflammation.

Gene expression profiles in peripheral blood mononuclear cells of Chinese nickel refinery workers with high exposures to nickel and control subjects.

BACKGROUND: Occupational exposure to nickel (Ni) is associated with an increased risk of lung and nasal cancers. Ni compounds exhibit weak mutagenic activity, alter the cell's epigenetic homeostasis, and activate signaling pathways. However, changes in gene expression associated with Ni exposure have only been investigated in vitro. This study was conducted in a Chinese population to determine whether occupational exposure to Ni was associated with differential gene expression profiles in the peripheral blood mononuclear cells (PBMC) of Ni-refinery workers when compared with referents. METHODS: Eight Ni-refinery workers and ten referents were selected. PBMC RNA was extracted and gene expression profiling was conducted using Affymetrix exon arrays. Differentially expressed genes (DEG) between both groups were identified in a global analysis. RESULTS: There were a total of 2,756 DEGs in the Ni-refinery workers relative to the referents [false discovery rate (FDR) adjusted P < 0.05] with 770 upregulated genes and 1,986 downregulated genes. DNA repair and epigenetic genes were significantly overrepresented (P < 0.0002) among the DEGs. Of 31 DNA repair genes, 29 were repressed in the Ni-refinery workers and 2 were overexpressed. Of the 16 epigenetic genes, 12 were repressed in the Ni-refinery workers and 4 were overexpressed. CONCLUSIONS: The results of this study indicate that occupational exposure to Ni is associated with alterations in gene expression profiles in PBMCs of subjects. IMPACT: Gene expression may be useful in identifying patterns of deregulation that precede clinical identification of Ni-induced cancers.

Gene expression profiling and pathway analysis of human bronchial epithelial cells exposed to airborne particulate matter collected from Saudi Arabia.

Epidemiological studies have established a positive correlation between human mortality and increased concentration of airborne particulate matters (PM). However, the mechanisms underlying PM related human diseases, as well as the molecules and pathways mediating the cellular response to PM, are not fully understood. This study aims to investigate the global gene expression changes in human cells exposed to PM(10) and to identify genes and pathways that may contribute to PM related adverse health effects. Human bronchial epithelial cells were exposed to PM(10) collected from Saudi Arabia for 1 or 4 days, and whole transcript expression was profiled using the GeneChip human gene 1.0 ST array. A total of 140 and 230 genes were identified that significantly changed more than 1.5 fold after PM(10) exposure for 1 or 4 days, respectively. Ingenuity Pathway Analysis revealed that different exposure durations triggered distinct pathways. Genes involved in NRF2-mediated response to oxidative stress were up-regulated after 1 day exposure. In contrast, cells exposed for 4 days exhibited significant changes in genes related to cholesterol and lipid synthesis pathways. These observed changes in cellular oxidative stress and lipid synthesis might contribute to PM related respiratory and cardiovascular disease.

Gene expression changes in human lung cells exposed to arsenic, chromium, nickel or vanadium indicate the first steps in cancer.

The complex process of carcinogenesis begins with transformation of a single cell to favor aberrant traits such as loss of contact inhibition and unregulated proliferation - features found in every cancer. Despite cancer's widespread prevalence, the early events that initiate cancer remain elusive, and without knowledge of these events cancer prevention is difficult. Here we show that exposure to As, Cr, Ni, or vanadium (V) promotes changes in gene expression that occur in conjunction with aberrant growth. We exposed immortalized human bronchial epithelial cells to one of four metals/metalloid for four to eight weeks and selected transformed clonal populations based upon anchorage independent growth of single cells in soft agar. We detected a metal-specific footprint of cancer-related gene expression that was consistent across multiple transformed clones. These gene expression changes persisted in the absence of the progenitor metal for numerous cell divisions. Our results show that even a brief exposure to a carcinogenic metal may cause many changes in gene expression in the exposed cells, and that from these many changes, the specific change(s) that each metal causes that initiate cancer likely arise.

Diagnóstico prenatal ecográfico de nefroma mesoblástico congénito / Sonographic prenatal diagnosis of congenital mesoblastic nephroma

El nefroma mesoblástico congénito es la neoplasia renal primaria más común vista en el primer mes de vida. Intraútero aparece como una gran masa vascular sólida. Frecuentemente se manifiesta con polihidramnios. Es benigno y la nefrectomía postnatal es curativa. Describimos el caso de una paciente que cursa una gestación de 29 semanas y discutimos los hallazgos en las imágenes abdominales fetales

Diagnóstico prenatal ecográfico de nefroma mesoblástico congénito / Sonographic prenatal diagnosis of congenital mesoblastic nephroma

El nefroma mesoblástico congénito es la neoplasia renal primaria más común vista en el primer mes de vida. Intraútero aparece como una gran masa vascular sólida. Frecuentemente se manifiesta con polihidramnios. Es benigno y la nefrectomía postnatal es curativa. Describimos el caso de una paciente que cursa una gestación de 29 semanas y discutimos los hallazgos en las imágenes abdominales fetales (AU)

Diagnóstico prenatal ecográfico de nefroma mesoblástico congénito / Sonographic prenatal diagnosis of congenital mesoblastic nephroma

El nefroma mesoblástico congénito es la neoplasia renal primaria más común vista en el primer mes de vida. Intraútero aparece como una gran masa vascular sólida. Frecuentemente se manifiesta con polihidramnios. Es benigno y la nefrectomía postnatal es curativa. Describimos el caso de una paciente que cursa una gestación de 29 semanas y discutimos los hallazgos en las imágenes abdominales fetales (AU)

Elucidating the mechanisms of nickel compound uptake: a review of particulate and nano-nickel endocytosis and toxicity.

Nickel (Ni) is a worldwide pollutant and contaminant that humans are exposed to through various avenues resulting in multiple toxic responses - most alarming is its clear carcinogenic nature. A variety of particulate Ni compounds persist in the environment and can be distinguished by characteristics such as solubility, structure, and surface charge. These characteristics influence cellular uptake and toxicity. Some particulate forms of Ni are carcinogenic and are directly and rapidly endocytized by cells. A series of studies conducted in the 1980s observed this process, and we have reanalyzed the results of these studies to help elucidate the molecular mechanism of particulate Ni uptake. Originally the process of uptake observed was described as phagocytosis, however in the context of recent research we hypothesize that the process is macropinocytosis and/or clathrin mediated endocytosis. Primary considerations in determining the route of uptake here include calcium dependence, particle size, and inhibition through temperature and pharmacological approaches. Particle characteristics that influenced uptake include size, charge, surface characteristics, and structure. This discussion is relevant in the context of nanoparticle studies and the emerging interest in nano-nickel (nano-Ni), where toxicity assessments require a clear understanding of the parameters of particulate uptake and where establishment of such parameters is often obscured through inconsistencies across experimental systems. In this regard, this review aims to carefully document one system (particulate nickel compound uptake) and characterize its properties.

Evaluación de oxidación bacteriana de sulfuros con Acidithiobacillus ferrooxidans mediante pruebas de / Evaluating Acidithiobacillus ferrooxidans bacterial oxidation of sulphur compounds using FTIR and X-ray diffraction assays

Una cepa bacteriana nativa con capacidad de oxidar hierro ferroso y compuestos del azufre fue aislada a partir de efluentes y material de la mina de oro La Maruja, en el municipio de Marmato (Caldas), la cual fue identificada bioquímicamente como Acidithiobacillus ferrooxidans. Esta cepa fue evaluada en su capacidad de oxidar concentrados de sulfuros metálicos a dos diferentes concentraciones de pulpa y dos tamaños de partícula. Después de 15 días de biooxidación de los sulfuros se observó que, efectivamente, la bacteria mostró acción catalizadora sobre el proce-so de disolución del mineral.