Past progress in environmental nanoanalysis and a future trajectory for atomic mass-spectrometry methods.

The development of engineered nanotechnology has necessitated a commensurate maturation of nanoanalysis capabilities. Building off a legacy established by electron microscopy and light-scattering, environmental nanoanalysis has now benefited from ongoing advancements in instrumentation and data analysis, which enable a deeper understanding of nanomaterial properties, behavior, and impacts. Where once environmental nanoparticles and colloids were grouped into broad 'dissolved or particulate' classes that are dependent on a filter size cut-off, now size distributions of submicron particles can be separated and characterized providing a more comprehensive examination of the nanoscale. Inductively coupled plasma-quadrupole mass spectrometry (ICP-QMS), directly coupled to field flow fractionation (FFF-ICP-QMS) or operated in single particle mode (spICP-MS) have spearheaded a revolution in nanoanalysis, enabling research into nanomaterial behavior in environmental and biological systems at expected release concentrations. However, the complexity of the nanoparticle population drives a need to characterize and quantify the multi-element composition of nanoparticles, which has begun to be realized through the application of time-of-flight MS (spICP-TOFMS). Despite its relative infancy, this technique has begun to make significant strides in more fully characterizing particulate systems and expanding our understanding of nanoparticle behavior. Though there is still more work to be done with regards to improving instrumentation and data processing, it is possible we are on the cusp of a new nanoanalysis revolution, capable of broadening our understanding of the size regime between dissolved and bulk particulate compartments of the environment.

Data reduction for spatially resolved reflectance anisotropy spectrometer.

We show that in spatially resolved reflectance anisotropy (RA) spectrometers, off-axis optical rays introduce a spurious signal component that cannot be addressed by optical alignment. Such a component is associated with the difference between the reflectivities s and p of the sample and depends, in a complex manner, on the incidence position of the incident light on the surface of the sample. We report a data-reduction procedure to easily identify and remove spurious RA signals associated with the off-axis optical rays, based on the singular value decomposition analysis of spatially resolved RA spectra. We validated this approach by developing a spatially resolved RA spectrometer based on an 8 × 8 multi-anode photomultiplier (PMT). The PMT allowed the use of phase-sensitive detection techniques to enhance the signal-to-noise ratio, which is essential for the evaluation of the proposed data reduction procedure.

The experience of obstetric nursing students in an innovative maternal care programme in Chiapas, Mexico: a qualitative study.

In Mexico, over the last decade, more non-physician medical professionals have been participating in birth care according to recent federal regulations. So far, very few sites have been able to implement birth care models where midwives and obstetric nurses participate. We describe the experience of a group of intern obstetric nurses participating in a model that provides respectful birth care to rural populations, managed by an international NGO in partnership with the Ministry of Health of Chiapas, Mexico. We conducted a case study including individual interviews and focus group discussions with obstetric nurse interns participating in the Compañeros En Salud programme over four years from 2016 to 2019. We applied targeted content analysis to the qualitative data. There were 28 participants from 4 groups of interns. Informants expressed their opinions in four areas: (a) training as a LEO, (b) training experience at CES, (c) LEO role in health care delivery; and (d) LEOs' perspectives about respectful maternity care. Interns identified gaps in their training including a higher load of theoretical content vs practical experience, as well as little supervision of clinical care in public hospitals. Their adaptation to the health services model has increased over time, and recent classes acknowledge the difficulties that earlier ones had to confront, including the challenging interactions with hospital staff. Interns have incorporated the value of respectful birth care and their role to protect this right in rural populations. Findings could be useful to call for the expansion of the model in public birth centres.

Influence of dissolution on the uptake of bimetallic nanoparticles Au@Ag-NPs in soil organism Eisenia fetida.

A key aspect in the safety testing of metal nanoparticles (NPs) is the measurement of their dissolution and of the true particle uptake in organisms. Here, based on the tendency of Ag-NP to dissolve and Au-NP to be inert in the environment, we exposed the earthworm Eisenia fetida to Au core-Ag shell NPs (Au@Ag-NPs, Ag-NPs with a Au core) and to both single and combined exposures of non-coated Au-NPs, Ag-NPs, Ag+ and Au+ ions in natural soil. Our hypothesis was that the Ag shell would partially or completely dissolve from the Au@Ag-NPs and that the Au core would thereby behave as a tracer of particulate uptake. Au and Ag concentrations were quantified in all the soils, in soil extract and in organisms by inductively coupled plasma mass spectrometry (ICP-MS). The earthworm exposed to Au@Ag-NPs, and to all the combinations of Ag and Au, were analyzed by single particle inductively coupled plasma time-of-flight mass spectrometry (spICP-TOFMS) to allow the quantification of the metals that were truly part of a bimetallic particle. Results showed that only 5% of the total metal amounts in the earthworm were in the bimetallic particulate form and that the Ag shell increased in thickness, suggesting that biotransformation processes took place at the surface of the NPs. Additionally, the co-exposure to both metal ions led to a different uptake pattern compared to the single metal exposures. The study unequivocally confirmed that dissolution is the primary mechanism driving the uptake of (dissolving) metal NPs in earthworms. Therefore, the assessment of the uptake of metal nanoparticles is conservatively covered by the assessment of the uptake of their ionic counterpart.

Cell-free DNA analysis in current cancer clinical trials: a review.

Cell-free DNA (cfDNA) analysis represents a promising method for the diagnosis, treatment selection and clinical follow-up of cancer patients. Although its general methodological feasibility and usefulness has been demonstrated, several issues related to standardisation and technical validation must be addressed for its routine clinical application in cancer. In this regard, most cfDNA clinical applications are still limited to clinical trials, proving its value in several settings. In this paper, we review the current clinical trials involving cfDNA/ctDNA analysis and highlight those where it has been useful for patient stratification, treatment follow-up or development of novel approaches for early diagnosis. Our query included clinical trials, including the terms 'cfDNA', 'ctDNA', 'liquid biopsy' AND 'cancer OR neoplasm' in the FDA and EMA public databases. We identified 1370 clinical trials (FDA = 1129, EMA = 241) involving liquid-biopsy analysis in cancer. These clinical trials show promising results for the early detection of cancer and confirm cfDNA as a tool for real-time monitoring of acquired therapy resistance, accurate disease-progression surveillance and improvement of treatment, situations that result in a better quality of life and extended overall survival for cancer patients.

Relation of body composition indexes to cardiovascular disease risk factors in young adults / Relación de índices de composición corporal con factores de riesgo de enfermedad cardiovascular en adultos jóvenes

BACKGROUND: To evaluate the relationship of body composition indexes with altered metabolic analytical parameters that show higher risk of cardiovascular disease in young adults. MATERIAL AND METHODS: A cross-sectional study. Sample of 1351 young adults, different body composition parameters were obtained such as Waist Circumference (WC), Hip Circumference (HC), Body Mass Index (BMI), Body Fat% (BF%), Waist-to-height Ratio (WHtR), and Waist-Hip Ratio (WHR), conicity index (C-Index), body surface area (BSA), abdominal volume index (AVI) and deep abdominal adipose-tissue (AT). Areas under receiver operating characteristic curves (AUCs) and odds ratios for the parameters were analyzed and their optimal cut-offs. Separately a MANOVA was applied to altered metabolic analytical parameters and two body composition indexes (BMI and BSA) and their interaction. RESULTS: BMI correlate significantly with metabolic analytical parameters (FPG r = 0.08, TCh r = 0.14, TGL r = 0.23, HDL-C r = -0.23, LDL-C r = 0.2, UA r = 0.22, All P < 0.01), BSA correlate with all (All P < 0.001) except FPG. BMI and BSA correlate significantly with all metabolic analytical parameters (All P < 0.001). The BMI individually predicts the changes of the six metabolic analytical parameters as a set [Wilk's Lambda = 0.89, F(18,1570) = 3.4, P < 0.0001], but not BSA [Wilk's Lambda = 0.98, F(6,555) = 1.4, P = 0.18], the interaction between these two indexes (BMI and BSA altered in the same individual) significantly predicts changes of the six metabolic analytical parameters of cardiovascular disease risk [Wilk's Lambda = 0.97, F(6,555) = 2.3, P = 0.03]. CONCLUSIONS: BMI and BSA correlate with cardiovascular disease risk factor. They are superior to WC, WHtR, WHR, BF%, C-index, AVI and AT

OBJETIVO: Evaluar la relación de los índices de composición corporal con los parámetros analíticos metabólicos alterados que muestran mayor riesgo de enfermedad cardiovascular en adultos jóvenes. MATERIAL Y MÉTODOS: Estudio transversal. Muestra de 1.351 adultos jóvenes, se obtuvieron diferentes parámetros de composición corporal: circunferencia de cintura (WC), circunferencia de cadera (HC), índice de masa corporal (IMC), % de grasa corporal (BF%), índice cintura-altura (WHtR) e índice cintura-cadera (WHR), índice de conicidad (C-index), superficie corporal (BSA), índice de volumen abdominal (AVI) y tejido adiposo abdominal profundo (AT). Se analizaron áreas bajo la curva y razones de momios de los parámetros y sus puntos de corte óptimos. Se aplicó un MANOVA por separado a los parámetros analíticos metabólicos alterados y 2 índices de composición corporal (IMC y BSA) y su interacción. RESULTADOS: El IMC se correlacionó con los parámetros analíticos metabólicos (FPG r = 0,08, TCh r = 0,14, TGL r = 0,23, HDL-C r = -0,23, LDL-C r = 0,2, UA r = 0,22; todos p < 0,01), BSA correlacionó con todos (p < 0,001) menos con FPG. El IMC, por sí solo, predice los cambios en los 6 parámetros analíticos metabólicos del riesgo de enfermedad cardiovascular en conjunto (Wilk's Lambda = 0,89, F [18,1570] = 3,4; p < 0,0001), pero no la BSA (Wilk's Lambda = 0,98, F [6,555]=1,4; p = 0,18), la interacción entre estos 2 índices (IMC y BSA alterados en el mismo individuo) predice significativamente los cambios de los 6 componentes metabólicos (Wilk's Lambda = 0,97, F [6,555] = 2,3; p = 0,03). CONCLUSIONES: El IMC y la BSA están relacionados con los factores de riesgo de enfermedad cardiovascular. Son superiores a WC, WHtR, WHR, BF%, C-index, AVI y AT

Relation of body composition indexes to cardiovascular disease risk factors in young adults.

BACKGROUND: To evaluate the relationship of body composition indexes with altered metabolic analytical parameters that show higher risk of cardiovascular disease in young adults. MATERIAL AND METHODS: A cross-sectional study. Sample of 1351 young adults, different body composition parameters were obtained such as Waist Circumference (WC), Hip Circumference (HC), Body Mass Index (BMI), Body Fat% (BF%), Waist-to-height Ratio (WHtR), and Waist-Hip Ratio (WHR), conicity index (C-Index), body surface area (BSA), abdominal volume index (AVI) and deep abdominal adipose-tissue (AT). Areas under receiver operating characteristic curves (AUCs) and odds ratios for the parameters were analyzed and their optimal cut-offs. Separately a MANOVA was applied to altered metabolic analytical parameters and two body composition indexes (BMI and BSA) and their interaction. RESULTS: BMI correlate significantly with metabolic analytical parameters (FPG r=0.08, TCh r=0.14, TGL r=0.23, HDL-C r=-0.23, LDL-C r=0.2, UA r=0.22, All P<0.01), BSA correlate with all (All P<0.001) except FPG. BMI and BSA correlate significantly with all metabolic analytical parameters (All P<0.001). The BMI individually predicts the changes of the six metabolic analytical parameters as a set [Wilk's λ=0.89, F(18,1570)=3.4, P<0.0001], but not BSA [Wilk's λ=0.98, F(6,555)=1.4, P=0.18], the interaction between these two indexes (BMI and BSA altered in the same individual) significantly predicts changes of the six metabolic analytical parameters of cardiovascular disease risk [Wilk's λ=0.97, F(6,555)=2.3, P=0.03]. CONCLUSIONS: BMI and BSA correlate with cardiovascular disease risk factor. They are superior to WC, WHtR, WHR, BF%, C-index, AVI and AT.

The RIPASA score for the diagnosis of acute appendicitis: A comparison with the modified Alvarado score. / Escala RIPASA para el diagnóstico de apendicitis aguda: comparación con la escala de Alvarado modificada.

INTRODUCTION AND OBJECTIVES: Acute appendicitis is the first cause of surgical emergencies. It is still a difficult diagnosis to make, especially in young persons, the elderly, and in reproductive-age women, in whom a series of inflammatory conditions can have signs and symptoms similar to those of acute appendicitis. Different scoring systems have been created to increase diagnostic accuracy, and they are inexpensive, noninvasive, and easy to use and reproduce. The modified Alvarado score is probably the most widely used and accepted in emergency services worldwide. On the other hand, the RIPASA score was formulated in 2010 and has greater sensitivity and specificity. There are very few studies conducted in Mexico that compare the different scoring systems for appendicitis. The aim of our article was to compare the modified Alvarado score and the RIPASA score in the diagnosis of patients with abdominal pain and suspected acute appendicitis. MATERIAL AND METHODS: An observational, analytic, and prolective study was conducted within the time frame of July 2002 and February 2014 at the Hospital Universitario de Puebla. The questionnaires used for the evaluation process were applied to the patients suspected of having appendicitis. RESULTS: The RIPASA score with 8.5 as the optimal cutoff value: ROC curve (area .595), sensitivity (93.3%), specificity (8.3%), PPV (91.8%), NPV (10.1%). Modified Alvarado score with 6 as the optimal cutoff value: ROC curve (area .719), sensitivity (75%), specificity (41.6%), PPV (93.7%), NPV (12.5%). CONCLUSIONS: The RIPASA score showed no advantages over the modified Alvarado score when applied to patients presenting with suspected acute appendicitis.

Corrigendum: A multiply-add engine with monolithically integrated 3D memristor crossbar/CMOS hybrid circuit.

This corrects the article DOI: 10.1038/srep42429.

Genome-wide association analysis of body conformation traits in Mexican Holstein cattle using a mix of sampled and imputed SNP genotypes.

In arid and semi-arid zones, animal health and production are closely correlated with body conformation traits. These selected traits, in turn, allow livestock to adapt unfavorable soil and environmental conditions. The primary objective of this study was to perform a genome-wide association analysis for a set of sampled and imputed SNPs with 16 conformation traits in a population of Holstein cows from a desert area of Northwestern Mexico. Imputation from 6K to 50K SNPs was performed as a low-cost optimization strategy. Results show eight SNPs associated with two conformation traits. The Udder Depth trait resulted in seven associated SNPs from chromosome 10, that related to Marbling Score, Milk Yield, Fat Yield, Protein Yield, and Protein Percentage Quantitative Trait Loci (QTLs). The Body Depth trait resulted in one associated SNP from chromosome 2, although no QTL relation was found. The discovery of genes associated with conformation traits may be indicative of the adaptive selection pressures the Holstein breed has undergone in response to the extreme weather conditions found in the northwestern areas of Mexico. Results of this study indicate that traits such as stature and body depth may be used as indicators of cows' potential genetic merits for milk, fat, and protein production.

A multiply-add engine with monolithically integrated 3D memristor crossbar/CMOS hybrid circuit.

Silicon (Si) based complementary metal-oxide semiconductor (CMOS) technology has been the driving force of the information-technology revolution. However, scaling of CMOS technology as per Moore's law has reached a serious bottleneck. Among the emerging technologies memristive devices can be promising for both memory as well as computing applications. Hybrid CMOS/memristor circuits with CMOL (CMOS + "Molecular") architecture have been proposed to combine the extremely high density of the memristive devices with the robustness of CMOS technology, leading to terabit-scale memory and extremely efficient computing paradigm. In this work, we demonstrate a hybrid 3D CMOL circuit with 2 layers of memristive crossbars monolithically integrated on a pre-fabricated CMOS substrate. The integrated crossbars can be fully operated through the underlying CMOS circuitry. The memristive devices in both layers exhibit analog switching behavior with controlled tunability and stable multi-level operation. We perform dot-product operations with the 2D and 3D memristive crossbars to demonstrate the applicability of such 3D CMOL hybrid circuits as a multiply-add engine. To the best of our knowledge this is the first demonstration of a functional 3D CMOL hybrid circuit.

Frequency of the Val1016Ile mutation on the kdr gene in Aedes aegypti (Diptera: Culicidae) in south Brazil.

Recently, the number of Aedes aegypti foci has increased in west of Santa Catarina, south Brazil, which has increased concern regarding mosquito-borne disease outbreaks such as dengue fever, Zika virus, and chikungunya. Therefore, it is important to monitor genetic resistance to insecticides through "knockdown resistance". Homozygosity (Ile/Ile) at position 1016 in the coding region of a voltage-dependent sodium channel gene (Nav) may induce resistance to pyrethroid insecticides. We evaluated the frequency of these alleles in A. aegypti in west Santa Catarina. In total, 349 specimens were obtained from the microregions of Joaçaba (31), Concórdia (35), Chapecó (154), and São Miguel do Oeste (129). We found that 109 individuals (31.0%) were homozygous for Val/Val, 102 (29.0%) were heterozygous for Val/Ile, and 138 (40.0%) were homozygous for Ile/Ile. The allele frequencies were similar for Val (0.455) and Ile (0.545). Joaçaba and Concórdia had the highest mutant allele frequencies (0.825 and 0.685, respectively). Therefore, these populations should be monitored for increases in pyrethroid resistance. The São Miguel do Oeste and Chapecó populations had similar frequencies of Val and Ile and were not in Hardy-Weinberg equilibrium, suggesting that a selection pressure or other evolutionary force has occurred. In conclusion, the observed frequency of Ile/Ile homozygous individuals in the region studied requires attention, because the implementation of controls using pyrethroid may increase the frequency of the mutant allele through the selection of resistant populations.

Influence of protein nutrition and virginiamycin supplementation on feedlot growth performance and digestive function of calf-fed Holstein steers.

Two experiments were conducted to examine the influence of protein and virginiamycin (VM) supplementation on feedlot growth performance, digestion, and metabolizable AA (MAA) supply of calf-fed Holstein steers. Growth performance and dietary energetics were evaluated in 120 Holstein steers (127 ± 9 kg). During the initial 112-d feeding period, a steam-flaked corn-based diet was balanced to meet either 100% (MAB) or 87% (UREA) of MAA requirements. Diets were supplemented with or without 22.5 mg/kg VM in a 2 × 2 factorial arrangement. Subsequently (d 112 to 308), all steers received the UREA diet with or without VM. During the initial 112-d, MAB increased ADG, G:F, and dietary NE ( < 0.01). Thereafter, when all steers received the UREA diet, ADG, G:F, and dietary NE were not different ( > 0.10) across initial supplementation treatments. Overall (d 1 to 308), MAB did not affect ADG ( > 0.10) but enhanced G:F efficiency ( = 0.03) and dietary NE ( = 0.05). During the initial 112-d period and through the remainder of the experiment, VM increased G:F ( < 0.01) and dietary NE ( < 0.01). Four Holstein steers (146 ± 4 kg) with cannulas in the rumen and proximal duodenum were used in a 4 × 4 Latin square design to evaluate initial 112-d treatment effects on digestive function. There were no treatment effects ( > 0.10) on ruminal digestion of OM, NDF, starch, microbial efficiency, or total tract digestion of OM and NDF. The MAB increased indispensable AA flow to the small intestine ( < 0.01) and total tract digestion of N ( < 0.01) and starch ( = 0.04). Observed AA supply to small intestine was in agreement with expected supply ( = 0.96). Virginiamycin decreased ( = 0.04) nonammonia N flow to the small intestine and did not affect ( > 0.10) total tract N digestion. Extrapolating from AA supplies in the metabolism study, MAB satisfied indispensable AA requirements during the initial 112-d period, whereas the UREA diet met 73.5% and 79.2% of methionine and lysine requirements, respectively. During the subsequent periods (d 112 to 308) indispensable AA supplies exceeded theoretical requirements. We conclude that enhancements in energy utilization when diets are balanced to meet MAA requirements of calf-fed Holstein steers during the initial 112-d feedlot period remain appreciable throughout time on feed. Virginiamycin enhanced efficiency of energy utilization throughout the feedlot growing-finishing period.

Influence of Wheat Straw Pelletizing and Inclusion Rate in Dry Rolled or Steam-flaked Corn-based Finishing Diets on Characteristics of Digestion for Feedlot Cattle.

Eight Holstein steers (216±48 kg body weight) fitted with ruminal and duodenal cannulas were used to evaluate effects of wheat straw processing (ground vs pelleted) at two straw inclusion rates (7% and 14%; dry matter basis) in dry rolled or steam-flaked corn-based finishing diets on characteristics of digestion. The experimental design was a split plot consisting of two simultaneous 4×4 Latin squares. Increasing straw level reduced ruminal (p<0.01) and total tract (p = 0.03) organic matter (OM) digestion. As expected, increasing wheat straw level from 7% to 14% decreased (p<0.05) ruminal and total tract digestion of OM. Digestion of neutral detergent fiber (NDF) and starch, per se, were not affected (p>0.10) by wheat straw level. Likewise, straw level did not influence ruminal acetate and propionate molar proportions or estimated methane production (p>0.10). Pelleting straw did not affect (p≥0.48) ruminal digestion of OM, NDF, and starch, or microbial efficiency. Ruminal feed N digestion was greater (7.4%; p = 0.02) for ground than for pelleted wheat straw diets. Although ruminal starch digestion was not affected by straw processing, post-ruminal (p<0.01), and total-tract starch (p = 0.05) digestion were greater for ground than for pelleted wheat straw diets, resulting in a tendency for increased post-ruminal (p = 0.06) and total tract (p = 0.07) OM digestion. Pelleting wheat straw decreased (p<0.01) ruminal pH, although ruminal volatile fatty acids (VFA) concentration and estimated methane were not affected (p≥0.27). Ruminal digestion of OM and starch, and post-ruminal and total tract digestion of OM, starch and N were greater (p<0.01) for steam-flaked than for dry rolled corn-based diets. Ruminal NDF digestion was greater (p = 0.02) for dry rolled than for steam-flaked corn, although total tract NDF digestion was unaffected (p = 0.94). Ruminal microbial efficiency and ruminal degradation of feed N were not affected (p>0.14) by corn processing. However, microbial N flow to the small intestine and ruminal N efficiency (non-ammonia N flow to the small intestine/N intake) were greater (p<0.01) for steam-flaked than for dry rolled corn-based diets. Ruminal pH and total VFA concentration were not affected (p≥ 0.16) by corn processing method. Compared with dry rolled corn, steam-flaked corn-based diets resulted in decreased acetate:propionate molar ratio (p = 0.02). It is concluded that at 7% or 14% straw inclusion rate, changes in physical characteristics of wheat straw brought about by pelleting negatively impact OM digestion of both steam-flaked and dry-rolled corn-based finishing diets. This effect is due to decreased post-ruminal starch digestion. Replacement of ground straw with pelleted straw also may decrease ruminal pH.

Evaluation of isoquinoline alkaloid supplementation levels on ruminal fermentation, characteristics of digestion, and microbial protein synthesis in steers fed a high-energy diet.

Four Holstein steers with ruminal and duodenal cannulas were used in a 4 × 4 Latin square design to examine the effect of daily intake of 0, 2, 4 or 6 g/steer of standardized plant extract containing a mixture of quaternary benzophenanthridine alkaloids and protopine alkaloids (QBA+PA) on the characteristics of ruminal fermentation and characteristics of digestion. The basal diet consisted of a steam-flaked corn-based finishing diet that contained 62% corn and 12% sudangrass hay and the rest of diet was composed of mainly dried distillers grains, molasses, fat, and minerals. The source of QBA+PA used was Sangrovit-RS (Phytobiotics Futterzusatzstoffe GmbH, Eltville, Germany) and supplementation levels of 2, 4, and 6 g Sangrovit-RS∙steer∙d, which represented a net daily ingestion of approximately 6, 12, and 18 mg of QBA+PA compounds, respectively. Inclusion of QBA+PA linearly increased ( = 0.04) flow to the duodenum of nonammonia N and linearly decreased ( < 0.01) duodenal flows of ammonia N. Ruminal microbial efficiency (duodenal microbial N; g/kg OM fermented in the rumen) and protein efficiency (duodenal nonammonia N; g/g N intake) were increased ( < 0.05) as the level of QBA+PA increased. There were no effects of QBA+PA supplementation on ruminal, postruminal, and total tract digestion of OM, starch, and NDF, but postruminal and total tract digestion of N increased ( < 0.01) as the level of QBA+PA increased. Digestible energy of the diet tended to increase (linear affect, = 0.09) with QBA+PA supplementation. Ruminal pH and total VFA molar concentrations were not different between treatments. Ruminal NH-N concentration linearly decreased ( = 0.02) with QBA+PA supplementation. Ruminal molar proportion of acetate increased ( = 0.04) as the supplementation level of QBA+PA increased. It is concluded that QBA+PA supplementation enhances efficiency of N utilization in feedlot steers fed a steam-flaked corn-based finishing diet. This effect was due, in part, to enhanced ruminal microbial efficiency, decreased ruminal degradation of dietary nonammonia N, and enhanced postruminal N digestion.

The effect of obesity and tobacco smoke exposure on inflammatory mediators and matrix metalloproteinases in rat model.

Obesity is characterized by hypertrophy of adipose tissue and chronic obstructive pulmonary disease (COPD) by lung damage; both diseases are associated with systemic low-grade inflammation. There are no animal models combining obesity and COPD; therefore, these diseases were induced simultaneously in rats to analyze their effects on the expression of inflammatory mediators and enzymes involved in lung tissue remodeling. Obesity was induced with sucrose (30%) for 4 months concomitant with tobacco smoke exposure (20 cigarettes/day, 5 days/wk) for the last 2 months. Were evaluated: body weight, abdominal fat, dyslipidemia, glucose tolerance test (GTT), histology, inflammatory mediators with qPCR and enzyme-linked immunosorbent assay, matrix metalloproteinases (MMP-2), MMP-9, MMP-12, TIMP-1 and TIMP-2 through qRT-PCR, and MMP-2 and MMP-9 by gelatin zymography. The rats on a sucrose diet exhibited increased body weight, abdominal fat, triglycerides, GTT, and plasma levels of insulin, adiponectin, leptin, resistin, IL-6, IL-1ß, tumor necrosis factor-α (TNF-α) and IFN-γ, upregulated lung IL-6, IL-1ß, TNF-α and IFN-γ, showing hyperplastic bronchial and alveolar epithelium. The animals exposed to sucrose and tobacco smoke exhibited decreased body weight, abdominal fat and plasma levels of leptin, resistin, IL-1ß and IFN-γ, reducing inflammation but showing emphysematous lesions. Expression of gelatinases and MMP-12 augmented in the rats exposed to tobacco smoke alone or combined with sucrose. Zymography showed prominent gelatinases activity in all the experimental groups. These results suggest that simultaneous exposure to sucrose and tobacco smoke decreases inflammation but results in emphysematous lesions similar to those observed with tobacco smoke exposure, suggesting that obesity does not confer any protective effect against lung damage.

Genotypic testing on HIV-1 DNA as a tool to assess HIV-1 co-receptor usage in clinical practice: results from the DIVA study group.

PURPOSE: We have developed a sequencing assay for determining the usage of the genotypic HIV-1 co-receptor using peripheral blood mononuclear cell (PBMC) DNA in virologically suppressed HIV-1 infected patients. Our specific aims were to (1) evaluate the efficiency of V3 sequences in B versus non-B subtypes, (2) compare the efficiency of V3 sequences and tropism prediction using whole blood and PBMCs for DNA extraction, (3) compare the efficiency of V3 sequences and tropism prediction using a single versus a triplicate round of amplification. RESULTS: The overall rate of successful V3 sequences ranged from 100 % in samples with >3,000 copies HIV-1 DNA/10(6) PBMCs to 60 % in samples with <100 copies total HIV-1 DNA /10(6) PBMCs. Analysis of 143 paired PBMCs and whole-blood samples showed successful V3 sequences rates of 77.6 % for PBMCs and 83.9 % for whole blood. These rates are in agreement with the tropism prediction obtained using the geno2pheno co-receptor algorithm, namely, 92.1 % with a false-positive rate (FPR) of 10 or 20 % and of 96.5 % with an FPR of 5.75 %. The agreement between tropism prediction values using single versus triplicate amplification was 98.2 % (56/57) of patients using an FPR of 20 % and 92.9 % (53/57) using an FPR of 10 or 5.75 %. For 63.0 % (36/57) of patients, the FPR obtained via the single amplification procedure was superimposable to all three FPRs obtained by triplicate amplification. CONCLUSIONS: Our results show the feasibility and consistency of genotypic testing on HIV-1 DNA tropism, supporting its possible use for selecting patients with suppressed plasma HIV-1 RNA as candidates for CCR5-antagonist treatment. The high agreement between tropism prediction by single and triple amplification does not support the use of triplicate amplification in clinical practice.

Oxidative stress and lung injury induced by short-term exposure to wood smoke in guinea pigs.

Oxidative stress and lung injury induced by short-term exposure to wood smoke were evaluated in guinea pigs through cell profile, bronchoalveolar lavage (BAL), conventional histology and immunohistochemistry (4-hydroxynonenal, 3-nitrotyrosine, Mn-superoxide dismutase, heme oxygenase-1); malondialdehyde and 4-hydroxynonenal concentration, Mn-superoxide dismutase, glutathione reductase, glutathione peroxidase, and catalase activities in plasma, lung and BAL. Total cells increased in BAL, and the percentage of macrophages, neutrophils and lymphocytes augmented (72-96 h). Histopathological examination of lung tissues showed mild thickening of membranous bronchiole walls, infiltration of foamy macrophages and polymorphonuclear leukocytes in bronchial, bronchiolar and intraalveolar spaces. Goblet cell hyperplasia was also observed in bronchial and bronchiolar epithelia. Plasma malondialdehyde concentration was increased at all times, while 4-hydroxynonenal was increased only in plasma and BAL after 24 h. Plasma glutathione reductase activity increased at 24 and 72 h, BAL glutathione peroxidase activity decreased at 72 and 96 h, whereas catalase activity increased in plasma at 72 h, and decreased in BAL at 24 h. Immunostaining intensity to 4-hydroxynonenal, 3-nitrotyrosine, Mn-superoxide dismutase and heme oxygenase-1 was enhanced mainly in macrophages, bronchial/bronchiolar epithelial cells and type II pneumocytes after 72-96 h of wood smoke exposure. Overall, short-term exposure to wood smoke induces alterations in oxidative/antioxidant state in lung and airway injury, similar to those observed in humans with domestic exposure.

Inhibition of metastasis by HEXIM1 through effects on cell invasion and angiogenesis.

We report on the role of hexamethylene-bis-acetamide-inducible protein 1 (HEXIM1) as an inhibitor of metastasis. HEXIM1 expression is decreased in human metastatic breast cancers when compared with matched primary breast tumors. Similarly we observed decreased expression of HEXIM1 in lung metastasis when compared with primary mammary tumors in a mouse model of metastatic breast cancer, the polyoma middle T antigen (PyMT) transgenic mouse. Re-expression of HEXIM1 (through transgene expression or localized delivery of a small molecule inducer of HEXIM1 expression, hexamethylene-bis-acetamide) in PyMT mice resulted in inhibition of metastasis to the lung. Our present studies indicate that HEXIM1 downregulation of HIF(-)1α protein allows not only for inhibition of vascular endothelial growth factor-regulated angiogenesis, but also for inhibition of compensatory pro-angiogenic pathways and recruitment of bone marrow-derived cells (BMDCs). Another novel finding is that HEXIM1 inhibits cell migration and invasion that can be partly attributed to decreased membrane localization of the 67 kDa laminin receptor, 67LR, and inhibition of the functional interaction of 67LR with laminin. Thus, HEXIM1 re-expression in breast cancer has therapeutic advantages by simultaneously targeting more than one pathway involved in angiogenesis and metastasis. Our results also support the potential for HEXIM1 to indirectly act on multiple cell types to suppress metastatic cancer.

Influence of Ionophore Supplementation on Growth Performance, Dietary Energetics and Carcass Characteristics in Finishing Cattle during Period of Heat Stress.

Forty-eight crossbred heifers (378.1±18 kg) were used in a 56-d feeding trial (four pens per treatment in a randomised complete block design) to evaluate the influence of ionophore supplementation on growth performance, dietary energetics and carcass characteristics in finishing cattle during a period of heat stress. Heifers were fed a diet based on steam-flaked corn (2.22 Mcal NEm/kg) with and without an ionophore. Treatments were: i) control, no ionophore; ii) 30 mg/kg monensin sodium (RUM30); iii) 20 mg/kg lasalocid sodium (BOV20), and iv) 30 mg/kg lasalocid sodium (BOV30). Both dry matter intake (DMI) and climatic variables were measured daily and the temperature humidity index (THI) was estimated. The maximum THI during the study averaged 93, while the minimum was 70 (THI average = 79.2±2.3). Compared to controls, monensin supplementation did not influence average daily gain, the estimated NE value of the diet, or observed-to-expected DMI, but tended (p = 0.07) to increase (4.8%) gain to feed. Compared to controls, the group fed BOV30 increased (p≤0.03) daily gain (11.8%), gain to feed (8.3%), net energy of the diet (5%), and observed-to-expected DMI (5.2%). Daily weight gain was greater (7.6%, p = 0.05) for heifers fed BOV30 than for heifers fed MON30. Otherwise, differences between the two treatments in DMI, gain to feed, and dietary NE were not statistically significant (p>0.11). Plotting weekly intakes versus THI, observed intake of controls was greater (p<0.05) at THI values ≤77 than ionophore groups. When THI values were greater than 79, DMI of control and MON30 were not different (p = 0.42), although less than that of groups fed lasalocid (p = 0.04). Variation in energy intake was lower (p>0.05) in the ionophores group (CV = 1.7%) than in the control group (CV = 4.5%). Inclusion of ionophores in the diet resulted in relatively minor changes in carcass characteristics. It is concluded that ionophore supplementation did not exacerbate the decline of DM intake in heat-stressed cattle fed a high-energy finishing diet; on the contrary, it stabilised feed intake and favoured feed efficiency. Ionophore supplementation reduced estimated maintenance coefficients around 10% in finishing cattle during a period of heat stress. This effect was greatest for heifers supplemented with 30 mg lasalocid/kg of diet.