An investigation for airflow and deposition of PM2.5 contaminated with SAR-CoV-2 virus in healthy and diseased human airway.

This study is motivated by the amplified transmission rates of the SAR-CoV-2 virus in areas with high concentrations of fine particulates (PM2.5) as reported in northern Italy and Mexico. To develop a deeper understanding of the contribution of PM2.5 in the propagation of the SAR-CoV-2 virus in the population, the deposition patterns and efficiencies (DEs) of PM2.5 laced with the virus in healthy and asthmatic airways are studied. Physiologically correct 3-D models for generations 10-12 of the human airways are applied to carry out a numerical analysis of two-phase flow for full breathing cycles. Two concentrations of PM2.5 are applied for the simulation, i.e., 30 µg⋅m-3 and 80 µg⋅m-3 for three breathing statuses, i.e., rest, light exercise, and moderate activity. All the PM2.5 injected into the control volume is assumed to be 100% contaminated with the SAR-CoV-2 virus. Skewed air-flow phenomena at the bifurcations are proportional to the Reynolds number at the inlet, and their intensity in the asthmatic airway exceeded that of the healthy one. Upon exhalation, two peak air-flow vectors from daughter branches combine to form one big vector in the parent generation. Asthmatic airway models has higher deposition efficiencies (DEs) for contaminated PM2.5 as compared to the healthy one. Higher DEs arise in the asthmatic airway model due to complex secondary flows which increase the impaction of contaminated PM2.5 on airways' walls.

Assessment of Antibiotic Levels, Multi-Drug Resistant Bacteria and Genetic Biomarkers in the Waters of the Rio Grande River Between the United States-Mexico Border.

BACKGROUND: The worldwide emergence of multi-drug resistant bacteria has become a health crisis, as fewer or sometimes no antimicrobial agents are effective against these bacteria. The Rio Grande River is the natural boundary between the United States (US) and Mexico. It spans a border region between Texas, New Mexico and Mexico. Underserved populations on the Mexican side use the river for recreational purposes, while on the US side, the river is used for irrigation and as a source of drinking water. OBJECTIVES: The purpose of the present study was to evaluate the concentration of antibiotic residues, to determine the presence of genetic elements conferring antibiotic resistance and to characterize multi-drug resistant bacteria in the waters of the Rio Grande River. METHODS: Water samples were obtained from the Rio Grande River. Deoxyribonucleic acid (DNA) was extracted from both isolated bacteria and directly from the water. Amplification of selected genetic elements was accomplished by polymerase chain reaction. Identification and isolation of bacteria was performed through MicroScan autoSCAN-4. Fecal contamination was assessed by IDEXX Colilert. Antibiotic residues were determined by liquid chromatography and mass spectrometry. RESULTS: Antibiotics were found in 92% of both water and sediment samples. Antibiotic concentrations ranged from 0.38 ng/L - 742.73 ng/L and 0.39 ng/l - 66.3 ng/g dry weight in water and sediment samples, respectively. Genetic elements conferring resistance were recovered from all collection sites. Of the isolated bacteria, 91 (64.08%) were resistant to at least two synergistic antibiotic combinations and 11 (14.79%) were found to be resistant to 20 or more individual antibiotics. Fecal contamination was higher during the months of April and July. CONCLUSIONS: The 26 km segment of the Rio Grande River from Sunland Park NM to El Paso, TX and Juarez, Mexico is an area of concern due to poor water quality. The presence of multidrug resistant bacteria, antibiotics and mobile genetic elements may be a health hazard for the surrounding populations of this binational border region. Policies need to be developed for the appropriate management of the environmental natural resources in this border region. COMPETING INTERESTS: The authors declare no competing financial interests.

Drug target mining and analysis of the Chinese tree shrew for pharmacological testing.

The discovery of new drugs requires the development of improved animal models for drug testing. The Chinese tree shrew is considered to be a realistic candidate model. To assess the potential of the Chinese tree shrew for pharmacological testing, we performed drug target prediction and analysis on genomic and transcriptomic scales. Using our pipeline, 3,482 proteins were predicted to be drug targets. Of these predicted targets, 446 and 1,049 proteins with the highest rank and total scores, respectively, included homologs of targets for cancer chemotherapy, depression, age-related decline and cardiovascular disease. Based on comparative analyses, more than half of drug target proteins identified from the tree shrew genome were shown to be higher similarity to human targets than in the mouse. Target validation also demonstrated that the constitutive expression of the proteinase-activated receptors of tree shrew platelets is similar to that of human platelets but differs from that of mouse platelets. We developed an effective pipeline and search strategy for drug target prediction and the evaluation of model-based target identification for drug testing. This work provides useful information for future studies of the Chinese tree shrew as a source of novel targets for drug discovery research.

Factors affecting the natural decay of hepatitis B surface antigen in children with chronic hepatitis B virus infection during long-term follow-up.

OBJECTIVE: To investigate the factors predicting spontaneous clearance of hepatitis B surface antigen (HBsAg) in a long-term, prospectively followed cohort from childhood into adult life. STUDY DESIGN: Children with chronic hepatitis B virus (HBV) infection without treatment were followed longitudinally every 6 months. At each visit, liver profiles and HBV markers were assessed. Hepatitis B vaccination history and the maternal HBV markers also were studied. RESULTS: A total of 349 children (205 male) were followed for 20.6 ± 4.4 years with initial ages of 8.4 ± 3.9 years; 42 (12.0%) cleared HBsAg spontaneously. The HBsAg titers decayed with age, with an average annual clearance rate of 0.58%. Children had a lower annual HBsAg decay rate if their mothers are HBsAg carriers (P < .001). Hepatitis B e antigen-seroconversion is a favorable predictor for spontaneous HBsAg clearance (P = .04). Those with HBsAg titer ≤1000 IU/mL at enrollment during childhood have a higher rate of HBsAg clearance (hazard ratio = 5.23; P < .001). Using HBsAg titer ≤1000 IU/mL to predict HBsAg clearance, the sensitivity is 38.1%, specificity is 90.6%, positive predictive value is 35.6%, and negative predictive value is 91.4%. CONCLUSIONS: During long-term follow-up, spontaneous HBsAg clearance is most likely to occur in a patient born to a non-HBsAg-carrier mother, is a hepatitis B e antigen-seroconverter, and had an initial HBsAg level ≤1000 IU/mL.

Temporal-spatial analysis of U.S.-Mexico border environmental fine and coarse PM air sample extract activity in human bronchial epithelial cells.

Particulate matter less than 10 microm (PM10) has been shown to be associated with aggravation of asthma and respiratory and cardiopulmonary morbidity. There is also great interest in the potential health effects of PM2.5. Particulate matter (PM) varies in composition both spatially and temporally depending on the source, location and seasonal condition. El Paso County which lies in the Paso del Norte airshed is a unique location to study ambient air pollution due to three major points: the geological land formation, the relatively large population and the various sources of PM. In this study, dichotomous filters were collected from various sites in El Paso County every 7 days for a period of 1 year. The sampling sites were both distant and near border crossings, which are near heavily populated areas with high traffic volume. Fine (PM2.5) and Coarse (PM10-2.5) PM filter samples were extracted using dichloromethane and were assessed for biologic activity and polycyclic aromatic (PAH) content. Three sets of marker genes human BEAS2B bronchial epithelial cells were utilized to assess the effects of airborne PAHs on biologic activities associated with specific biological pathways associated with airway diseases. These pathways included in inflammatory cytokine production (IL-6, IL-8), oxidative stress (HMOX-1, NQO-1, ALDH3A1, AKR1C1), and aryl hydrocarbon receptor (AhR)-dependent signaling (CYP1A1). Results demonstrated interesting temporal and spatial patterns of gene induction for all pathways, particularly those associated with oxidative stress, and significant differences in the PAHs detected in the PM10-2.5 and PM2.5 fractions. Temporally, the greatest effects on gene induction were observed in winter months, which appeared to correlate with inversions that are common in the air basin. Spatially, the greatest gene expression increases were seen in extracts collected from the central most areas of El Paso which are also closest to highways and border crossings.

Soil-borne polycyclic aromatic hydrocarbons in El Paso, Texas: analysis of a potential problem in the United States/Mexico border region.

Ultrasonic extraction followed by Stir Bar Sorptive Extraction (SBSE) and thermal desorption inline coupled with Gas Chromatography and Mass Spectrometry (TD/GC/MS) was used to perform a comprehensive determination of soil-borne polycyclic aromatic hydrocarbons (PAHs) in El Paso, Texas. The method provided good sensitivity and faster processing time for the analysis. The total PAHs in El Paso soil ranged from 0.1 to 2225.5 microg kg(-1). Although the majority of PAH concentrations did not exceed the soil screening levels regulated by the United States Environmental Protection Agency, the existence of PAHs in this ecosystem is ubiquitous. Naphthalene were found in 100% of the soil samples; while the heavy PAHs (five- and six-ring) were not often detected and mostly remained in closer proximity to industrial areas and major traffic points. The results ruled out the possibility of petroleum refining as the significant source of local soil-borne PAH contamination, but they suggested that the PAHs found in El Paso soil were closely linked to human activities and possible other industrial processes.

Contrasting genome-wide distribution of 8-hydroxyguanine and acrolein-modified adenine during oxidative stress-induced renal carcinogenesis

Oxidative stress is a persistent threat to the genome and is associated with major causes of human mortality, including cancer, atherosclerosis, and aging. Here we established a method to generate libraries of genomic DNA fragments containing oxidatively modified bases by using specific monoclonal antibodies to immunoprecipitate enzyme-digested genome DNA. We applied this technique to two different base modifications, 8-hydroxyguanine and 1,N6-propanoadenine (acrotein-Ade), in a ferric nitrilotriacetate-induced murine renal carcinogenesis model. Renal cortical genomic DNA derived from 10- to 12-week-old male C57BL/6 mice, of untreated control or 6 hours after intraperitoneal injection of 3 mg iron/kg ferric nitrilotriacetate, was enzyme digested, immunoprecipitated, cloned, and mapped to each chromosome. The results revealed that distribution of the two modified bases was not random but differed in terms of chromosomes, gene size, and expression, which could be partially explained by chromosomal territory. In the wild-type mice, low GC content areas were more likely to harbor the two modified bases. Knockout of OGG1, a repair enzyme for genomic 8-hydroxyguanine, increased the amounts of acrolein-Ade as determined by quantitative polymerase chain reaction analyses. This versatile technique would introduce a novel research area as a high-throughput screening method for critical genomic loci under oxidative stress.

Analysis of the structural determinants for RNA binding of the human protein AUF1/hnRNP D.

The protein AUF1/hnRNP D was one of the first factors identified that binds to the AU-rich region of certain mRNAs and mediates their fast degradation. Here we describe experiments to address the structural determinants for the binding of AUF1 to the RNA by combining comparative molecular modeling with gel shift assays. From our model of the RNA binding region of AUF1 we predicted that it interacts with RNA predominantly through stacking interactions that do not provide base-specific recognition. Only two RNA positions bound by AUF1 show base preferences: one for pyrimidine bases and the second for a conserved adenine residue. Gel shift assays with a panel of RNA oligonucleotides largely confirmed these model-based binding determinants. An alignment with proteins of the hnRNP family demonstrated that the amino acids involved in the stacking interactions are conserved whereas those that confer a base-specific recognition in AUF1 are variable.

Comparison of different crystal forms of 3-dehydroquinase from Salmonella typhi and its implication for the enzyme activity.

The type I 3-dehydroquinate dehydratase (DHQase) which catalyses the reversible dehydration of 3-dehydroquinic acid to 3-dehydroshikimic acid is involved in the shikimate pathway for the biosynthesis of aromatic compounds. The shikimate pathway is absent in mammals, which makes structural information about DHQase vital for the rational design of antimicrobial drugs and herbicides. The crystallographic structure of the type I DHQase from Salmonella typhi has now been determined for the native form at 1.78 A resolution (R = 19.9%; R(free) = 24.7%). The structure of the modified enzyme to which the product has been covalently bound has also been determined but in a different crystal form (2.1 A resolution; R = 17.7%; R(free) = 24.5%). An analysis of the three available crystal forms has provided information about the physiological dimer interface. The enzyme relies upon the closure of a lid-like loop to complete its active site. As the lid-loop tends to stay in the closed position, dimerization appears to play a role in biasing the arrangement of the loop towards its open position, thus facilitating substrate access.

Estudo do comportamento das taxas de mortalidade fetal, perinatal e neonatal em um hospital universitário: II. Inter-relaçöes de causa básica de morte, obtida em necrópsia com o peso ao nascer e a idade no óbito

O objetivo deste trabalho foi estudar as inter-relaçöes do peso ao nascer da idade no óbito e das causas de óbito fetais e neonatais pro necrópsias no HCFMRPUSP no período de 1973 a 1982. Relacionando-se os três parâmetros acima nota-se que: nas mortes fetais a causa indeterminada teve distribuiçäo semelhante nas três faixas de peso e as mortes por causa obstétrica aumentam proporcionalmente com o peso ao nascer. O contrário acontece com a doença hipertensiva materna. A morte por prematuridade nos óbitos neonatais säo mais freqüentes nas crianças com baixo peso e nas de causa obstétrica é o inverso. As mortes por prematuridade e por causa obstétrica ocorrem com maiores freqüências no 1§ dia de vida. A morte por infecçäo ocorre mais freqüentemente no período neonatal tardio. As crianças mais leves e as mais pesadas morrem em maiores proporçöes no 1§ dia de vida