Toxicity and health effects of ultrafine particles: Towards an understanding of the relative impacts of different transport modes.

Exposure to particulate matter (PM) has been associated with a wide range of adverse health effects, but it is still unclear how particles from various transport modes differ in terms of toxicity and associations with different human health outcomes. This literature review aims to summarize toxicological and epidemiological studies of the effect of ultrafine particles (UFPs), also called nanoparticles (NPs, <100 nm), from different transport modes with a focus on vehicle exhaust (particularly comparing diesel and biodiesel) and non-exhaust as well as particles from shipping (harbor), aviation (airport) and rail (mainly subway/underground). The review includes both particles collected in laboratory tests and the field (intense traffic environments or collected close to harbor, airport, and in subway). In addition, epidemiological studies on UFPs are reviewed with special attention to studies aimed at distinguishing the effects of different transport modes. Results from toxicological studies indicate that both fossil and biodiesel NPs show toxic effects. Several in vivo studies show that inhalation of NPs collected in traffic environments not only impacts the lung, but also triggers cardiovascular effects as well as negative impacts on the brain, although few studies compared NPs from different sources. Few studies were found on aviation (airport) NPs, but the available results suggest similar toxic effects as traffic-related particles. There is still little data related to the toxic effects linked to several sources (shipping, road and tire wear, subway NPs), but in vitro results highlighted the role of metals in the toxicity of subway and brake wear particles. Finally, the epidemiological studies emphasized the current limited knowledge of the health impacts of source-specific UFPs related to different transport modes. This review discusses the necessity of future research for a better understanding of the relative potencies of NPs from different transport modes and their use in health risk assessment.

Insights into DNA-drug interactions in the era of omics.

Despite the rise of sophisticated new targeting strategies in cancer chemotherapy, many classic DNA-binding drugs remain on the front line of the therapy against cancer. Based on examples primarily from the author's laboratory, this article reviews the capabilities of several DNA-binding drugs to alter gene expression. Research is ongoing about the molecular bases of the inhibition of gene expression and how alteration of the cellular transcriptome can commit cancer cells to die. The development of a variety of omic techniques allows us to gain insights into the effect of antitumor drugs. Genome-wide approaches provide unbiased genomic data that can facilitate a deeper understanding of the cellular response to DNA-binding drugs. Moreover, the results of large-scale genomic studies are gathered in publicly available databases that can be used in developing precision medicine in cancer treatment.

Premature, Opportune, and Delayed Weaning in Mechanically Ventilated Patients: A Call for Implementation of Weaning Protocols in Low- and Middle-Income Countries.

OBJECTIVES: Weaning protocols establish readiness-to-wean criteria to determine the opportune moment to conduct a spontaneous breathing trial. Weaning protocols have not been widely adopted or evaluated in ICUs in low- and middle-income countries. We sought to compare clinical outcomes between participants whose weaning trials were retrospectively determined to have been premature, opportune, or delayed based on when they met readiness-to-wean criteria. DESIGN: Prospective, multicenter observational study. SETTING: Five medical ICUs in four public hospitals in Lima, Perú. SUBJECTS: Adults with acute respiratory failure and at least 24 hours of invasive mechanical ventilation (n = 1,657). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We established six readiness-to-wean criteria and retrospectively categorized our sample into three weaning groups: 1) premature: if the weaning trial took place before fulfilling all criteria, 2) opportune: if the weaning trial took place within 24 hours after fulfilling the criteria, and 3) delayed: if the weaning trial took place over 24 hours after fulfilling criteria. We compared 90-day mortality, ventilator-free days, ICU-free days, and hospital-free days between premature, opportune, and delayed weaning groups. In our sample, 761 participants (60.8%) were classified as having a premature weaning trial, 196 underwent opportune weaning (15.7%), and 295 experienced delayed weaning (23.6%). There was no significant difference in 90-day mortality between the groups. Both the premature and delayed weaning groups had poorer clinical outcomes with fewer ventilator-free days (-2.18, p = 0.008) and (-3.49, p < 0.001), ICU-free days (-2.25, p = 0.001) and (-3.72, p < 0.001), and hospital-free days (-2.76, p = 0.044) and (-4.53, p = 0.004), respectively, compared with the opportune weaning group. CONCLUSIONS: Better clinical outcomes occur with opportune weaning compared with premature and delayed weaning. If readiness-to-wean criteria can be applied in resource-limited settings, it may improve ICU outcomes associated with opportune weaning.

Mean Airway Pressure As a Predictor of 90-Day Mortality in Mechanically Ventilated Patients.

OBJECTIVES: To determine the association between mean airway pressure and 90-day mortality in patients with acute respiratory failure requiring mechanical ventilation and to compare the predictive ability of mean airway pressure compared with inspiratory plateau pressure and driving pressure. DESIGN: Prospective observational cohort. SETTING: Five ICUs in Lima, Peru. SUBJECTS: Adults requiring invasive mechanical ventilation via endotracheal tube for acute respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of potentially eligible participants (n = 1,500), 65 (4%) were missing baseline mean airway pressure, while 352 (23.5%) were missing baseline plateau pressure and driving pressure. Ultimately, 1,429 participants were included in the analysis with an average age of 59 ± 19 years, 45% female, and a mean PaO2/FIO2 ratio of 248 ± 147 mm Hg at baseline. Overall, 90-day mortality was 50.4%. Median baseline mean airway pressure was 13 cm H2O (interquartile range, 10-16 cm H2O) in participants who died compared to a median mean airway pressure of 12 cm H2O (interquartile range, 10-14 cm H2O) in participants who survived greater than 90 days (p < 0.001). Mean airway pressure was independently associated with 90-day mortality (odds ratio, 1.38 for difference comparing the 75th to the 25th percentile for mean airway pressure; 95% CI, 1.10-1.74) after adjusting for age, sex, baseline Acute Physiology and Chronic Health Evaluation III, baseline PaO2/FIO2 (modeled with restricted cubic spline), baseline positive end-expiratory pressure, baseline tidal volume, and hospital site. In predicting 90-day mortality, baseline mean airway pressure demonstrated similar discriminative ability (adjusted area under the curve = 0.69) and calibration characteristics as baseline plateau pressure and driving pressure. CONCLUSIONS: In a multicenter prospective cohort, baseline mean airway pressure was independently associated with 90-day mortality in mechanically ventilated participants and predicts mortality similarly to plateau pressure and driving pressure. Because mean airway pressure is readily available on all mechanically ventilated patients and all ventilator modes, it is a potentially more useful predictor of mortality in acute respiratory failure.

Sedation practices and clinical outcomes in mechanically ventilated patients in a prospective multicenter cohort.

OBJECTIVES: We sought to study the association between sedation status, medications (benzodiazepines, opioids, and antipsychotics), and clinical outcomes in a resource-limited setting. DESIGN: A longitudinal study of critically ill participants on mechanical ventilation. SETTING: Five intensive care units (ICUs) in four public hospitals in Lima, Peru. PATIENTS: One thousand six hundred fifty-seven critically ill participants were assessed daily for sedation status during 28 days and vital status by day 90. RESULTS: After excluding data of participants without a Richmond Agitation Sedation Scale score and without sedation, we followed 1338 (81%) participants longitudinally for 18,645 ICU days. Deep sedation was present in 98% of participants at some point of the study and in 12,942 ICU days. Deep sedation was associated with higher mortality (interquartile odds ratio (OR) = 5.42, 4.23-6.95; p < 0.001) and a significant decrease in ventilator (- 7.27; p < 0.001), ICU (- 4.38; p < 0.001), and hospital (- 7.00; p < 0.001) free days. Agitation was also associated with higher mortality (OR = 39.9, 6.53-243, p < 0.001). The most commonly used sedatives were opioids and benzodiazepines (9259 and 8453 patient days respectively), and the latter were associated with a 41% higher mortality in participants with a higher cumulative dose (75th vs 25th percentile, interquartile OR = 1.41, 1.12-1.77; p < 0.01). The overall cumulative dose of benzodiazepines and opioids was high, 774.5 mg and 16.8 g, respectively, by day 7 and by day 28; these doses approximately doubled. Haloperidol was only used in 3% of ICU days; however, the use of it was associated with a 70% lower mortality (interquartile OR = 0.3, 0.22-0.44, p < 0.001). CONCLUSIONS: Deep sedation, agitation, and cumulative dose of benzodiazepines were all independently associated with higher 90-day mortality. Additionally, deep sedation was associated with less ventilator-, ICU-, and hospital-free days. In contrast, haloperidol was associated with lower mortality in our study.

Risk factors for the development of acute respiratory distress syndrome in mechanically ventilated adults in Peru: a multicenter observational study.

BACKGROUND: Clinical and epidemiological differences between acute respiratory distress syndrome (ARDS) that presents at the initiation of mechanical ventilation [MV] (ARDS at MV onset) and that which develops during the course of MV (ARDS after MV onset) are not well understood. We conducted an observational study in five Peruvian ICUs to characterize differences between ARDS at MV onset and after MV onset and identify risk factors for the development of ARDS after MV onset. METHODS: We consecutively enrolled critically ill patients with acute respiratory failure requiring at least 24 h of mechanical ventilation and followed them prospectively during the first 28 days and compared baseline characteristics and clinical outcomes by ARDS status. RESULTS: We enrolled 1657 participants on MV (mean age 60.0 years, 55% males) of whom 334 (20.2%) had ARDS at MV onset and 180 (10.9%) developed ARDS after MV onset. Average tidal volume at the initiation of MV was 8.7 mL/kg of predicted body weight (PBW) for participants with ARDS at MV onset, 8.6 mL/kg PBW for those who developed ARDS after MV onset, and 8.5 mL/kg PBW for those who never developed ARDS (p = 0.23). Overall, 90-day mortality was 56% and 55% for ARDS after MV onset and ARDS at MV onset, respectively, as compared to 46% among those who never developed ARDS (p < 0.01). Adults with ARDS had a higher body mass index (BMI) than those without ARDS (27.3 vs 26.5 kg/m2, p < 0.01). Higher peak pressure (adjusted interquartile OR = 1.51, 95% CI 1.21-1.88), higher mean airway pressure (adjusted interquartile OR = 1.41, 95% CI 1.13-1.76), and higher positive end-expiratory pressure (adjusted interquartile OR = 1.29, 95% CI 1.10-1.50) at MV onset were associated with a higher odds of developing ARDS after MV onset. CONCLUSIONS: In this study of mechanically ventilated patients, 31% of study participants had ARDS at some point during their ICU stay. Optimal lung-protective ventilation was not used in a majority of patients. Patients with ARDS after MV onset had a similar 90-day mortality as those with ARDS at MV onset. Higher airway pressures at MV onset, higher PEEP, and higher BMI were associated with the development of ARDS after MV onset.

Spatial analysis of reported new cases and local risk of leprosy in hyper-endemic situation in Northeastern Brazil.

OBJECTIVE: To analyse the spatial distribution of the incidence of leprosy and identify areas at risk for occurrences of hyper-endemic disease in Northeastern Brazil. METHODS: Ecological study using municipalities as the analysis unit. Data on new cases of leprosy came from the Health Hazard Notification System (SINAN). This study focused on Pernambuco and covered the years 2005 to 2014. Indicators for monitoring were calculated per 100 000 inhabitants. The local empirical Bayes method was used to minimise rate variance, and spatial autocorrelation maps were used for spatial pattern analysis (box maps and Moran maps). RESULTS: A total of 28 895 new cases were registered in the study period. The average incidence was 21.88/100 000; the global Moran's I index was 0.36 (P < 0.01), thus indicating the existence of spatial dependence; and the Moran map identified 20 municipalities with high priority for attention. The average incidence rate among individuals under 15 years of age was 8.78/100 000; the global Moran's I index showed the presence of positive spatial autocorrelation (0.43; P < 0.01), and the Moran map showed a main cluster of 15 hyper-endemic municipalities. The average rate of grade 2 physical disability at the time of diagnosis was 1.12/100 000; the global Moran index presented a positive spatial association (0.17; P < 0.01); and the Moran map located clusters of municipalities (high-high) in three mesoregions. CONCLUSION: Application of different spatial analysis methods made it possible to locate areas that would not have been identified by epidemiological indicators alone.

Evaluation of Human Attachment by Larval Amblyomma maculatum (Acari: Ixodidae).

The tick, Amblyomma maculatum Koch (Gulf Coast tick), has recently been shown to be an important disease vector of both medical and veterinary concern. Although much is known about the behavior and ecology of adults, little is known of the immatures. Larval feeding on humans has never been demonstrated (and thus, there are no collection records from humans). In this experiment, 10 larval A. maculatum, Amblyomma americanum (L.) (a positive control), and Dermacentor variabilis (Say) (a negative control), were applied to both forearms of 10 human volunteers (five male, five female). Ticks were placed in plastic caps and secured to skin with medical-grade adhesive tape, and volunteers remained sedentary during the experiment. After 15 min, caps were removed, and attachment was determined using fine-tipped forceps. Any A. maculatum that were attached were then removed and subsequently examined microscopically to verify identification. In total, 34 ticks attached to the subjects, including 11 A. maculatum (5.5%), 23 A. americanum (11.5%), and no D. variabilis. Amblyomma maculatum attached to six volunteers, and no apparent association between gender and attachment rate was noted. No skin lesions developed in the human volunteers bit by A. maculatum. This is the first report of larval A. maculatum attaching to humans, and is significant in that Rickettsia parkeri, a human pathogen vectored by this species, has recently been reported to be transmitted transovarially. If A. maculatum are infected as larvae, they could potentially transmit R. parkeri to people.

Autophagy modulates the effects of bis-anthracycline WP631 on p53-deficient prostate cancer cells.

Treatment of p53-deficient PC-3 human prostate carcinoma cells with nanomolar concentrations of bis-anthracycline WP631 induced changes in gene expression, which resulted in G2/M cell cycle arrest, autophagy and cell death. The presence of 2-deoxy-D-glucose (2-DG), which induces metabolic stress and autophagy, enhanced the antiproliferative effects of WP631. Changes induced by WP631, 2-DG, or co-treatments with both compounds, in the expression of a variety of genes involved in autophagy and apoptosis were quantified by real-time PCR. They were consistent with a raise in autophagy followed by cell death. Some cells dying from G2/M phase showed features of necrosis like early changes in membrane permeability, while others were dying by apoptosis that occurred in presence of little caspase-3 activity. Our results indicate that WP631 is not only an antiproliferative agent acting on gene transcription, but it can also induce autophagy regardless of the presence of other pro-autophagy stimuli. The development of autophagy seemed to improve the cytotoxicity of WP631 in PC-3 cells. Our results indicate that autophagy would enhance the activity of DNA-binding drugs like WP631 that are potent inhibitors of gene transcription.

Transcriptomic and proteomic analyses reveal key innate immune signatures in the host response to the gastrointestinal pathogen Campylobacter concisus.

Pathogenic species within the genus Campylobacter are responsible for a considerable burden on global health. Campylobacter concisus is an emergent pathogen that plays a role in acute and chronic gastrointestinal disease. Despite ongoing research on Campylobacter virulence mechanisms, little is known regarding the immunological profile of the host response to Campylobacter infection. In this study, we describe a comprehensive global profile of innate immune responses to C. concisus infection in differentiated THP-1 macrophages infected with an adherent and invasive strain of C. concisus. Using RNA sequencing (RNA-seq), quantitative PCR (qPCR), mass spectrometry, and confocal microscopy, we observed differential expression of pattern recognition receptors and robust upregulation of DNA- and RNA-sensing molecules. In particular, we observed IFI16 inflammasome assembly in C. concisus-infected macrophages. Global profiling of the transcriptome revealed the significant regulation of a total of 8,343 transcripts upon infection with C. concisus, which included the activation of key inflammatory pathways involving CREB1, NF-κB, STAT, and interferon regulatory factor signaling. Thirteen microRNAs and 333 noncoding RNAs were significantly regulated upon infection, including MIR221, which has been associated with colorectal carcinogenesis. This study represents a major advance in our understanding of host recognition and innate immune responses to infection by C. concisus.

Mithramycin and its analogs: Molecular features and antitumor action.

The antitumor antibiotic mithramycin A (MTA) binds to G/C-rich DNA sequences in the presence of dications. MTA inhibits transcription regulated by the Sp1 transcription factor, often enhanced during tumor development. It shows antitumor activity, but its clinical use was discontinued due to toxic side effects. However, recent observations have led to its use being reconsidered. The MTA biosynthetic pathways have been modified to produce mithramycin analogs (mithralogs) that encompass lower toxicity and improved pharmacological activity. Some mithralogs reduce gene expression in human ovarian and prostate tumors, among other types of cancer. They down-regulate gene expression in various cellular processes, including Sp1-responsive genes that control tumor development. Moreover, MTA and several mithralogs, such as EC-8042 (DIG-MSK) and EC-8105, effectively treat Ewing sarcoma by inhibiting transcription controlled by the oncogenic EWS-FLI1 transcription factor.

Linking the use of reclaimed water to indicators of crop stress by metabolomic and transcriptomic analyses. A tool to compare water irrigation quality.

The occurrence of contaminants of emerging concern (CECs) or heavy metals in reclaimed water used for agricultural irrigation may affect crop morphology and physiology. Here, we analyzed lettuce (Lactuca sativa) grown in outdoor lysimeters and irrigated with either tap water, used as a control, or reclaimed water: CAS-reclaimed water, an effluent from a conventional activated sludge system (CAS) followed by chlorination and sand filtration, or MBR-reclaimed water, an effluent from a membrane biological reactor (MBR). Chemical analyses identified seven CECs in the reclaimed waters, but only two of them were detected in lettuce (carbamazepine and azithromycin). Metabolomic and transcriptomic analyses revealed that irrigation with reclaimed water increased the concentrations of several crop metabolites (5-oxoproline, leucine, isoleucine, and fumarate) and of transcripts codifying for the plant stress-related genes Heat-Shock Protein 70 (HSP70) and Manganese Superoxide Dismutase (MnSOD). In both cases, MBR-water elicited the strongest response in lettuce, perhaps related to its comparatively high sodium adsorption ratio (4.5), rather than to its content in CECs or heavy metals. Our study indicates that crop metabolomic and transcriptomic profiles depend on the composition of irrigating water and that they could be used for testing the impact of water quality in agriculture.

Toxicity of airborne nanoparticles: Facts and challenges.

Air pollution is one of the most severe environmental healthhazards, and airborne nanoparticles (diameter <100 nm) are considered particularly hazardous to human health. They are produced by various sources such as internal combustion engines, wood and biomass burning, and fuel and natural gas combustion, and their origin, among other parameters, determines their intrinsic toxicity for reasons that are not yet fully understood. Many constituents of the nanoparticles are considered toxic or at least hazardous, including polycyclic aromatic hydrocarbons (PAHs) and heavy metal compounds, in addition to gaseous pollutants present in the aerosol fraction, such as NOx, SO2, and ozone. All these compounds can cause oxidative stress, mitochondrial damage, inflammation in the lungs and other tissues, and cellular organelles. Epidemiological investigations concluded that airborne pollution may affect the respiratory, cardiovascular, and nervous systems. Moreover, particulate matter has been linked to an increased risk of lung cancer, a carcinogenic effect not related to DNA damage, but to the cellular inflammatory response to the pollutants, in which the release of cytokines promotes the proliferation of pre-existing mutated cancer cells. The mechanisms behind toxicity can be investigated experimentally using cell cultures or animal models. Methods for gathering particulate matter have been explored, but standardized protocols are needed to ensure that the samples accurately represent chemical mixtures in the environment. Toxic constituents of nanoparticles can be studied in animal and cellular models, but designing realistic exposure settings is challenging. The air-liquid interface (ALI) system directly exposes cells, mimicking particle inhalation into the lungs. Continuous research and monitoring of nanoparticles and other airborne pollutants is essential for understanding their effects and developing active strategies to mitigate their risks to human and environmental health.

Efficient removal of toxicity associated to wastewater treatment plant effluents by enhanced Soil Aquifer Treatment.

The regeneration of wastewater has been recognized as an effective strategy to counter water scarcity. Nonetheless, Wastewater Treatment Plant (WWTP) effluents still contain a wide range of contaminants of emerging concern (CECs) even after water depuration. Filtration through Soil Aquifer Treatment (SAT) systems has proven efficient for CECs removal although the attenuation of their associated biological effects still remains poorly understood. To evaluate this, three pilot SAT systems were monitored, two of them enhanced with different reactive barriers. SATs were fed with secondary effluents during two consecutive campaigns. Fifteen water samples were collected from the WWTP effluent, below the barriers and 15 m into the aquifer. The potential attenuation of effluent-associated biological effects by SATs was evaluated through toxicogenomic bioassays using zebrafish eleutheroembryos and human hepatic cells. Transcriptomic analyses revealed a wide range of toxic activities exerted by the WWTP effluents that were reduced by more than 70% by SAT. Similar results were observed when HepG2 hepatic cells were tested for cytotoxic and dioxin-like responses. Toxicity reduction appeared partially determined by the barrier composition and/or SAT managing and correlated with CECs removal. SAT appears as a promising approach to efficiently reduce effluent-associated toxicity contributing to environmental and human health preservation.

Using spatial analysis to identify areas vulnerable to infant mortality.

OBJECTIVE: To analyze the spatial distribution of infant mortality and identify clusters with high risk of death in the first year of life. METHODS: The Thiessen (Voronoi) polygon method was used to analyze spatial distribution of the infant mortality rate, calculated by municipality. The triennium 2006 - 2008 was used as a reference to estimate the average infant mortality rate, and the first analysis of the spatial distribution of the rate was performed to test for first-order spatial stationarity. The spatial pattern was then analyzed using Moran's index and G-statistic (α = 5%). RESULTS: The surface projections on trends showed that infant mortality is not constant in space. The Moran index (0.34, P < 0.01) and G-statistic (0.03, P < 0.01) confirmed a spatial autocorrelation between infant mortality and clusters when the Thiessen polygon method was used. CONCLUSIONS: The Voronoi polygons proved accurate for spatial analysis of infant mortality and were predictive of clusters with high risk of death in the first year of life.

Changes in gene expression induced by Sp1 knockdown differ from those caused by challenging Sp1 binding to gene promoters.

C/G-rich DNA regions, which include those recognized by the Sp1 transcription factor in several gene promoters, also encompass potential binding sites for the DNA-intercalating anthracyclines doxorubicin and WP631. We explored the differences between changes in gene expression caused by the ability of these drugs to compete with Sp1 for binding to DNA and those produced by Sp1 knockdown. By quantitative RT-PCR of around 100 genes, most of them involved in control of cell cycle progression, we found that the treatment of human MDA-MB231 breast carcinoma cells with bis-anthracycline WP631 for 24 h produced a profile of gene down-regulation markedly different from the profile caused by doxorubicin treatment or by stable Sp1 knockdown. These observations are rationalized by considering a near-specific effect of WP631 on Sp1 interaction with several gene promoters, thus representing potential therapeutic targets for WP631, in contrast to a less specific effect of reducing the availability of Sp1 through RNA interference. Genes down-regulated upon each treatment were mapped to their molecular and biological functions, which documented the down-regulation, among other things, of genes involved in mRNA transcription regulation, granting us insights into the effects of challenging the transactivation of gene expression by Sp1.

Pathogenic potential of Campylobacter ureolyticus.

The recent detection and isolation of the aflagellate Campylobacter ureolyticus (previously known as Bacteroides ureolyticus) from intestinal biopsy specimens and fecal samples of children with newly diagnosed Crohn's disease led us to investigate the pathogenic potential of this bacterium. Adherence and gentamicin protection assays were employed to quantify the levels of adherence to and invasion into host cells. C. ureolyticus UNSWCD was able to adhere to the Caco-2 intestinal epithelial cell line with a value of 5.341% ± 0.74% but was not able to invade the Caco-2 cells. The addition of two proinflammatory cytokines, tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ), to the cell line did not affect attachment or invasion, with attachment levels being 4.156% ± 0.61% (P = 0.270) for TNF-α and 6.472% ± 0.61% (P = 0.235) for IFN-γ. Scanning electron microscopy visually confirmed attachment and revealed that C. ureolyticus UNSWCD colonizes and adheres to intestinal cells, inducing cellular damage and microvillus degradation. Purification and identification of the C. ureolyticus UNSWCD secretome detected a total of 111 proteins, from which 29 were bioinformatically predicted to be secretory proteins. Functional classification revealed three putative virulence and colonization factors: the surface antigen CjaA, an outer membrane fibronectin binding protein, and an S-layer RTX toxin. These results suggest that C. ureolyticus has the potential to be a pathogen of the gastrointestinal tract.

Perspectives on the Use of Toxicogenomics to Assess Environmental Risk.

Environmental toxicogenomics aims to collect, analyze and interpret data on changes in gene expression and protein activity resulting from exposure to toxic substances using high-performance omics technologies. Molecular profiling methods such as genomics, transcriptomics, proteomics, metabolomics, and bioinformatics techniques, permit the simultaneous analysis of a multitude of gene variants in an organism exposed to toxic agents to search for genes prone to damage, detect patterns and mechanisms of toxicity, and identify specific gene expression profiles that can provide biomarkers of exposure and risk. Compared to previous approaches to measuring molecular changes caused by toxicants, toxicogenomic technologies can improve environmental risk assessment while reducing animal studies. We discuss the prospects and limitations of converting omic datasets into valuable information, focusing on assessing the risks of mixed toxic substances to the environment and human health.

Bacillus subtilis Inoculation Improves Nutrient Uptake and Physiological Activity in Sugarcane under Drought Stress.

Sugarcane (Saccharum spp.) is one of the most important crops in the world. Throughout the sugarcane's growth stages, periods of drought are common, causing detrimental effects on plant growth. Therefore, the search for strategies for minimizing the impact of drought on sugarcane development is of great interest. Plant growth-promoting bacteria hold the potential for improving tolerance to drought in agricultural systems. Thus, the present study aimed to evaluate whether inoculation with Bacillus subtilis can reduce the negative effects of drought on the nutritional, physiological, and morphological characteristics of sugarcane plants. For this, sugarcane was cultivated in a greenhouse, under controlled conditions of water and temperature, with the aid of four treatments: without and with inoculation of B. subtilis, in normal conditions of water availability, and in conditions of water restriction (2 × 2 factorial), with four replications. In treatments with inoculation, the pre-emerged seedlings were immersed in a B. subtilis solution and transplanted into experimental pots. Our results showed that inoculation with B. subtilis improved plant nutrition and chlorophyll concentrations. As a result, the gas exchange parameters (especially net photosynthetic rate and water use efficiency) were also improved, even under drought conditions. In addition, stress parameters (antioxidant metabolism activity) were reduced in inoculated plants. The sum of these beneficial effects resulted in increased root growth, tillering, stalk weight, and higher sucrose concentration in the stalks.

Spatial analysis and privation index to identify urban areas with a high risk of lymphatic filariasis.

OBJECTIVE: To evaluate composite living conditions as indicators of urban areas with a higher risk of filariasis transmission. METHODS: This was an ecological study in the municipality of Jaboatão dos Guararapes, in Brazil. The analysis units were census tracts. The study was divided into three phases. First, data gathered during an epidemiological investigation were analysed. Secondly, living condition indicators were drawn up and the relationship between these indicators and microfilaremia prevalence rates was analysed. Thirdly, positive cases were georeferenced with a view to identifying spatial concentration using kernel intensity estimates. Two composite living condition indicators were calculated: a socio-environmental risk index (in the form of scores) and a social deprivation index (through principal-component factor analysis). RESULTS: Of 23,673 individuals examined, 1.4% had microfilaremia. According to the two indicators, greater prevalence was found in the high-risk strata, and this association was confirmed by the kernel intensity estimates. CONCLUSIONS: Classification of census tracts into risk strata showed the relevance of socio-economic factors and environmental conditions in identifying priority areas in urban spaces for interventions by the surveillance services and in planning filariasis control. Spatial analysis also proved to be an important tool for building up a territorially based surveillance system. These indicators, used in association with spatial analysis, are an instrument to be used by the Global Programme to Eliminate Lymphatic Filariasis.