ABSTRACT
The objective of this exploratory study was to assess the changes on lipidome and metabolome profiling of Longissimus lumborum bull muscle with different ultimate pH (pHu) and aging periods. The bull muscles classified as normal, intermediate, or high pHu were collected from a Brazilian commercial slaughterhouse, cut into steaks, individually vacuum-packaged, and aged for 3 days (3-d) or 21 days (21-d) at 2 °C. Muscle extracts were analyzed for the profiles of both lipids, by mass spectrometry (via direct flow-injection), and metabolites, by nuclear magnetic resonance, with downstream multivariate data analysis. As major results, pairwise comparisons identified C12:0 and C14:0 acylcarnitines as potential biomarkers of the intermediate pHu-muscle, which are related to lipid catabolism for alternative energy metabolism and indicate less protein breakage postmortem. Interestingly, the concentration of arginine at early postmortem aging (3-d) may influence the previously reported improved tenderness in normal and high pHu-muscles. Moreover, upregulation of fumarate, formate, and acetate with increased pHu muscle at 21-d aging indicate more intense tricarboxylic acid cycle, amino acid degradation, and pyruvate oxidation by reactive oxygen species, respectively. These three compounds (fumarate, formate, and acetate) discriminated statistically the muscle with high pHu at 21-d aging. The normal pHu-muscle showed higher concentrations of glycogenolysis and glycolysis metabolites, including glucose, mannose, and pyruvate. Hence, our results enhance knowledge of postmortem biochemical changes of beef within different pHu groups aged up to 21 days, which is essential to understand the mechanisms underpinning bull meat quality changes.
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This study aimed to evaluate the thermal performance and meat quality in broilers reared in positive pressure tunnel ventilation (PP) and negative pressure tunnel ventilation (NP) in production houses. 320 Cobb broilers (40 broilers per house) were used. Pectoralis major muscles from 40 broilers (10 broilers per house) were randomly selected and analysed for L* (lightness), a* (redness), b* (yellowness), pH, drip loss (DL), cooking loss (CL) and shear force (SF). Air temperature and humidity of the transportation and slaughterhouse waiting room were recorded in the last week of rearing. Subsequently, the enthalpy comfort index (ECI) was calculated. Air temperature and ECI were higher (p < 0.05) in positive pressure sheds, whereas relative humidity was higher (p < 0.001) in negative pressure sheds. There was no statistically significant difference between the enthalpy comfort index during transport and lairage (p > 0.005). Meat quality defects (high L*, DL, CL, SF) were found in PP and NP. It was observed that b* was higher in PP, although pH and CL were higher in NP. Differences in pH, b* and CL indicate that broilers from PP had a higher level of heat stress. In conclusion, differences in pH, b*value and cooking loss in breast broilers indicate that birds in PP had a higher level of heat stress. Additional studies investigating pre-slaughter handling methods to minimise injuries and heat stress are recommended in order to improve animal welfare and meat quality.
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This study aimed to evaluate for the first time the temporal dynamic changes in early postmortem proteome of normal and high ultimate pH (pHu) beef samples from the same cattle using a shotgun proteomics approach. Ten selected carcasses classified as normal (pHu < 5.8; n = 5) or high (pHu ≥ 6.2; n = 5) pHu beef from pasture-finished Nellore (Bos taurus indicus) bulls were sampled from Longissimus thoracis muscle at 30 min, 9 h and 44 h postmortem for proteome comparison. The temporal proteomics profiling quantified 863 proteins, from which 251 were differentially abundant (DAPs) between high and normal pHu at 30 min (n = 33), 9 h (n = 181) and 44 h (n = 37). Among the myriad interconnected pathways regulating pH decline during postmortem metabolism, this study revealed the pivotal role of energy metabolism, cellular response to stress, oxidoreductase activity and muscle system process pathways throughout the early postmortem. Twenty-three proteins overlap among postmortem times and may be suggested as candidate biomarkers to the dark-cutting condition development. The study further evidenced for the first time the central role of ribosomal proteins and histones in the first minutes after animal bleeding. Moreover, this study revealed the disparity in the mechanisms underpinning the development of dark-cutting beef condition among postmortem times, emphasizing multiple dynamic changes in the muscle proteome. Therefore, this study revealed important insights regarding the temporal dynamic changes that occur in early postmortem of high and normal muscle pHu beef, proposing specific pathways to determine the biological mechanisms behind dark-cutting determination.
Subject(s)
Muscle, Skeletal , Proteome , Red Meat , Animals , Cattle , Red Meat/analysis , Male , Hydrogen-Ion Concentration , Muscle, Skeletal/chemistry , Muscle, Skeletal/metabolism , Muscle Proteins/metabolism , Proteomics/methods , Postmortem ChangesABSTRACT
Objectives: The spread of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) has resulted in increased morbidity, mortality, and health care costs worldwide. To identify the factors associated with ESCrE and CRE colonization within hospitals, we enrolled hospitalized patients at a regional hospital located in Guatemala. Methods: Stool samples were collected from randomly selected patients using a cross-sectional study design (March-September, 2021), and samples were tested for the presence of ESCrE and CRE. Hospital-based and household variables were examined for associations with ESCrE and CRE colonization using lasso regression models, clustered by ward (n = 21). Results: A total of 641 patients were enrolled, of whom complete data sets were available for 593. Colonization with ESCrE (72.3%, n = 429/593) was negatively associated with carbapenem administration (odds ratio [OR] 0.21, 95% confidence interval [CI] 0.11-0.42) and positively associated with ceftriaxone administration (OR 1.61, 95% CI 1.02-2.53), as was reported hospital admission within 30 days of the current hospitalization (OR 2.84, 95% CI 1.19-6.80). Colonization with CRE (34.6%, n = 205 of 593) was associated with carbapenem administration (OR 2.62, 95% CI 1.39-4.97), reported previous hospital admission within 30 days of current hospitalization (OR 2.58, 95% CI 1.17-5.72), hospitalization in wards with more patients (OR 1.05, 95% CI 1.02-1.08), hospitalization for ≥4 days (OR 3.07, 95% CI 1.72-5.46), and intubation (OR 2.51, 95% CI 1.13-5.59). No household-based variables were associated with ESCrE or CRE colonization in hospitalized patients. Conclusion: The hospital-based risk factors identified in this study are similar to what has been reported for risk of health care-associated infections, consistent with colonization being driven by hospital settings rather than community factors. This also suggests that colonization with ESCrE and CRE could be a useful metric to evaluate the efficacy of infection and prevention control programs in clinics and hospitals.
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BACKGROUND: Up to 70% of suspected Lynch syndrome patients harboring MMR deficient tumors lack identifiable germline pathogenic variants in MMR genes, being referred to as Lynch-like syndrome (LLS). Previous studies have reported biallelic somatic MMR inactivation in a variable range of LLS-associated tumors. Moreover, translating tumor testing results into patient management remains controversial. Our aim is to assess the challenges associated with the implementation of tumoral MMR gene testing in routine workflows. METHODS: Here, we present the clinical characterization of 229 LLS patients. MMR gene testing was performed in 39 available tumors, and results were analyzed using two variant allele frequency (VAF) thresholds (≥5% and ≥10%). RESULTS AND DISCUSSION: More biallelic somatic events were identified at VAF ≥ 5% than ≥10% (35.9% vs. 25.6%), although the rate of nonconcordant results regarding immunohistochemical pattern increased (30.8% vs. 20.5%). Interpretation difficulties question the current utility of the identification of MMR somatic hits in the diagnostic algorithm of suspected LS cases.
Subject(s)
Brain Neoplasms , Colorectal Neoplasms, Hereditary Nonpolyposis , Colorectal Neoplasms , Neoplastic Syndromes, Hereditary , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/pathology , Germ-Line Mutation , DNA Mismatch Repair/geneticsABSTRACT
Background: Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS). Methods: We analyzed >22 million variants for 398,238 women. Associations were assessed separately by consortium and meta-analysed. OCAC and CIMBA data were used to develop PGS which were trained on FinnGen data and validated in UKBB and BioBank Japan. Results: Eight novel variants were associated with HGSOC risk. An interesting discovery biologically was finding that TP53 3'-UTR SNP rs78378222 was associated with HGSOC (per T allele relative risk (RR)=1.44, 95%CI:1.28-1.62, P=1.76×10-9). The optimal PGS included 64,518 variants and was associated with an odds ratio of 1.46 (95%CI:1.37-1.54) per standard deviation in the UKBB validation (AUROC curve=0.61, 95%CI:0.59-0.62). Conclusions: This study represents the largest GWAS for HGSOC to date. The results highlight that improvements in imputation reference panels and increased sample sizes can identify HGSOC associated variants that previously went undetected, resulting in improved PGS. The use of updated PGS in cancer risk prediction algorithms will then improve personalized risk prediction for HGSOC.
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This study aimed to investigate the incorporation of micronized salt (MS) to reduce sodium content in fresh sausages while preserving technological, chemical, textural, and sensory characteristics. Four treatments were prepared: control (C) with 2.0% regular salt; M2.0% with 2.0% micronized salt; M1.5% with 1.5% micronized salt; and M1.0% with 1.0% micronized salt, containing 1004, 1133, 860, and 525 mg of sodium/100 g of product, respectively. To characterize the samples, analyses of sodium content, cooking loss, relative myoglobin content, and instrumental color were carried out. The sensory analysis was performed using the Temporal-Check-All-That-Apply (TCATA) method. Half of the micronized salt treatment was mixed with the fat during the processing of the fresh sausages. It was possible to achieve a 50% reduction in sodium (M1.0%) in the fresh sausages without negative effects on most technological, chemical, and textural parameters, which did not differ from the control treatment (C). Conversely, "chewiness" decreased in M2.0% compared to the control (C) due to mixing micronized salt with the fat. The sodium reduction did not impact the temporal sensory profile and overall liking. Therefore, using micronized salt in fresh sausages reduces sodium content without affecting sensory traits and product stability.
ABSTRACT
The quality of beef, defined by key attributes such as the intrinsic sensory qualities texture, flavour, and juiciness, is shaped by various intrinsic and extrinsic factors. This study conducted a detailed examination of Nellore beef, focusing on two categories based on ultimate pH (pHu) levels: intermediate (pHu ≥ 5.8) and normal (pHu < 5.6) beef. A comprehensive approach was taken, involving twenty trained assessors who applied the Optimised Descriptive Profile (ODP) method to evaluate grilled striploin steak samples. In parallel, consumer preferences were measured through a hedonic test and a Check-all-that-apply (CATA) task, involving 135 participants. The ODP results revealed that the intermediate pHu samples were juicier (P < 0.05) compared to the normal pHu group. The CATA analysis highlighted differences in both intermediate and normal pHu beef, especially in juiciness, a crucial factor for consumer satisfaction. Notably, variations in deoxymyoglobin content linked to ageing were observed, with higher levels at the 3rd day compared to the 28th day, especially in the intermediate pHu samples (P < 0.05). Moreover, colour-related aspects such as L*, b*, chroma (C*), and oxymyoglobin were significantly influenced (P < 0.05) by both the pHu category and ageing time. Regarding consumer acceptance, the study found no significant difference in perception between the intermediate and normal pHu groups (P > 0.05). These findings revealed the complex interactions between pHu levels, sensory characteristics, and consumer preferences in beef quality, offering valuable insights for both the industry and research community.
Subject(s)
Flavoring Agents , Taste , Animals , Humans , Cattle , Food , Hydrogen-Ion ConcentrationABSTRACT
Bos taurus indicus bulls are very susceptible to pre-slaughter stress, which directly impacts the decline in muscle pH, leading to darker meat. The aim was to investigate the effect of succinate and atmosphere on the color stability of Nellore (Bos taurus indicus) Longissimus lumborum steaks classified by ultimate pH (pHu): normal pHu (5.40 ≤ pHu ≤ 5.79) and high pHu (pHu ≥ 5.80). The experimental treatment systems were: (i) vacuum packaging without succinate injection, (ii) HiOx-MAP (80 % O2 + 20 % CO2), and (iii) HiOx-MAP (80 % O2 + 20 % CO2) enhanced with sodium succinate injection (pH 5.4). Steaks from all treatment systems were stored at 4 °C for 14 days and tested for instrumental color, myoglobin content, oxygen consumption (OC), metmyoglobin-reducing activity (MRA), lipid oxidation, and microbiological analysis. High and normal pHu vacuum-packaged steaks exhibited greater color stability due to higher MRA. High and normal pHu steaks packaged with HiOx-MAP or HiOx-MAP enhanced with succinate showed improved color due to lower deoxymyoglobin content (%DMb) and OC up to the eighth day of storage. Still, succinate injection promoted increased (P < 0.05) lipid oxidation in normal pHu steaks and reduced MRA after 14 days. These findings emphasize the intricate interplay between pHu and packaging systems on Bos taurus indicus meat quality. Further research in this area could contribute to a better understanding of meat color abnormalities and provide insights into potential meat preservation and enhancement strategies.
Subject(s)
Food Packaging , Succinic Acid , Cattle , Male , Animals , Carbon Dioxide , Meat/analysis , Metmyoglobin , Succinates , Hydrogen-Ion Concentration , LipidsABSTRACT
Despite the relatively high occurrence of bovine meat with intermediate to high ultimate pH (pHu), there is a lack of studies focused on the effects of long-term conventional air-blasting freezing storage on quality parameters of commercial beefs of Zebu Nellore (Bos indicus) with varying pHu ranges. The objective of this work was to evaluate the influence of pHu ranges [normal (≤5.79), intermediate (5.80 to 6.19), and high (≥6.20)] and long-term frozen storage on quality parameters of aged Longissimus dorsi beefs of Zebu Nellore (Bos indicus). The aging conditions were set at 2 °C for 14 days, while the freezing conditions were set at - 20 °C, and samples were collected after 3, 6, 9, and 12 months of storage. The results indicated that the pHu influenced meat quality parameters, as well as the chemical forms of myoglobin, which changed throughout the frozen storage, leading to a brighter red color, especially for the normal pHu beef samples, likely due to increased oxymyoglobin content. Frozen storage improved tenderness, with high pHu beef samples being the more tender after 12 months, potentially due to lower protein oxidation, as measured by the carbonyl content. Increased drip loss was observed over freezing time, with a concomitant decrease in protein solubility, especially for myofibrillar and sarcoplasmic proteins, which differed among the pHu ranges. These findings are valuable for determining freezing time as a preservation strategy to maintain beef quality within different pHu ranges.
Subject(s)
Meat , Paraspinal Muscles , Animals , Cattle , Freezing , Solubility , Hydrogen-Ion ConcentrationABSTRACT
The reaction of three [FeII(TSC)2] complexes, where TSC is a pyridine-substituted thiosemicarbazone of the HDpT or HBpT families, with H2O2 in acetonitrile solution does not result in the accumulation of the corresponding [FeIII(TSC)2]+ complexes. Instead, a mixture of diamagnetic low-spin FeII species is generated. According to the MS spectra, those species result from the sequential addition of up to five oxygen atoms to the complex. This capability for the addition of oxygen atoms suggested that oxygen atom transfer to external substrates may be possible, and these TSC complexes were tested in the oxidation of thioanisole and styrene with H2O2. As hypothesized, the complexes are active in both the oxidation of thioanisole to its sulfoxide and styrene to benzaldehyde, with time scales indicating the participation of the species containing added oxygen atoms. Interestingly, the free thiosemicarbazone ligands and the [Zn(Dp44mT)2] complex also catalyse the selective sulfoxidation of thioanisole, but they are ineffective in catalysing styrene oxidation to benzaldehyde. These findings open up new directions for the development of thiosemicarbazone-based metal catalysts for oxidation processes.
ABSTRACT
tRNAs are typically transcribed with extended 5' and 3' ends that must be removed before they attain their active form. One of the first steps of tRNA processing in nearly every organism is the removal of the 5' leader sequence by ribonuclease P (RNase P). Here, we investigate a recently discovered class of RNase P enzymes, Homologs of Aquifex RNase P (HARPs). In contrast to other RNase Ps, HARPs consist only of a metallonuclease domain and lack the canonical substrate recognition domain essential in other classes of proteinaceous RNase P. We determined the cryo-EM structure of Aquifex aeolicus HARP (Aq880) and two crystal structures of Hydrogenobacter thermophilus HARP (Hth1307) to reveal that both enzymes form large ring-like assemblies: a dodecamer in Aq880 and a tetradecamer in Hth1307. In both oligomers, the enzyme active site is 42 Å away from a positively charged helical region, as seen in other protein-only RNase P enzymes, which likely serves to recognize and bind the elbow region of the pre-tRNA substrate. In addition, we use native mass spectrometry to confirm and characterize the previously unreported tetradecamer state. Notably, we find that multiple oligomeric states of Hth1307 are able to cleave pre-tRNAs. Furthermore, our single-turnover kinetic studies indicate that Hth1307 cleaves pre-tRNAs from multiple species with a preference for native substrates. These data provide a closer look at the nuanced similarities and differences in tRNA processing across disparate classes of RNase P.
Subject(s)
RNA, Bacterial , Ribonuclease P , Ribonuclease P/metabolism , RNA, Bacterial/metabolism , Kinetics , Nucleic Acid Conformation , RNA, Transfer/metabolism , Bacteria/metabolism , RNA Precursors/metabolismABSTRACT
This study estimates the shelf life of vacuum packed beef meat (three muscles: striploin (longissimus thoracis et lumborum, LTL), tenderloin (psoas major, PM) and outside chuck (trapezius thoracis, TT)) at refrigeration temperatures (0 °C-10 °C) based on modelling the growth of two relevant groups of spoilage microorganisms: lactic acid bacteria (LAB) and Enterobacteriaceae. The growth models were developed combining a two-step and a one-step approach. The primary modelling was used to identify the parameters affecting the growth kinetics, guiding the definition of secondary growth models. For LAB, the secondary model included the effect of temperature and initial pH on the specific growth rate. On the other hand, the model for Enterobacteriaceae incorporated the effect of temperature on the specific growth rate and the lag phase; as well as the effect of the initial pH on the specific growth rate, the lag phase and the initial microbial count. We did not observe any significant effect of the type of muscle on the growth kinetics. Once the equations were defined, the models were fitted to the complete dataset using a one-step approach. Model validation was carried out by cross-validation, mitigating the impact of an arbitrary division between training and validation sets. The models were used to estimate the shelf life of the product, based on the maximum admissible microbial concentration (7 log CFU/g for LAB, 5 log CFU/g for Enterobacteriaceae). Although LAB was the dominant microbiota, in several cases, both LAB and Enterobacteriaceae reached the critical concentration practically at the same time. Furthermore, in some scenarios, the end of shelf life would be determined by Enterobacteriaceae, pointing at the potential importance of non-dominant microorganisms for product spoilage. These results can aid in the implementation of effective control measures in the meat processing industry.
Subject(s)
Enterobacteriaceae , Food Microbiology , Animals , Cattle , Vacuum , Uncertainty , Colony Count, Microbial , Temperature , Meat/microbiology , Food Packaging/methods , Food Preservation/methodsABSTRACT
BACKGROUND: We estimated the prevalence of colonization with extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) from a hospital and associated communities in western Guatemala. METHODS: Randomly selected infants, children, and adults (<1, 1-17, and ≥18 years, respectively) were enrolled from the hospital (n = 641) during the coronavirus disease 2019 (COVID-19) pandemic, March to September 2021. Community participants were enrolled using a 3-stage cluster design between November 2019 and March 2020 (phase 1, n = 381) and between July 2020 and May 2021 (phase 2, with COVID-19 pandemic restrictions, n = 538). Stool samples were streaked onto selective chromogenic agar, and a Vitek 2 instrument was used to verify ESCrE or CRE classification. Prevalence estimates were weighted to account for sampling design. RESULTS: The prevalence of colonization with ESCrE and CRE was higher among hospital patients compared to community participants (ESCrE: 67% vs 46%, P < .01; CRE: 37% vs 1%, P < .01). Hospital ESCrE colonization was higher for adults (72%) compared with children (65%) and infants (60%) (P < .05). Colonization was higher for adults (50%) than children (40%) in the community (P < .05). There was no difference in ESCrE colonization between phase 1 and 2 (45% and 47%, respectively, P > .05), although reported use of antibiotics among households declined (23% and 7%, respectively, P < .001). CONCLUSIONS: While hospitals remain foci for ESCrE and CRE colonization, consistent with the need for infection control programs, community prevalence of ESCrE in this study was high, potentially adding to colonization pressure and transmission in healthcare settings. Better understanding of transmission dynamics and age-related factors is needed.
Subject(s)
Anti-Bacterial Agents , COVID-19 , Adult , Child , Humans , Infant , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteria , Carbapenems , Drug Resistance, Microbial , Guatemala/epidemiology , Hospitals , Pandemics , Child, Preschool , AdolescentABSTRACT
NO2 is one of the main greenhouse gases, which is mainly generated by the combustion of fossil fuels. In addition to its contribution to global warming, this gas is also directly dangerous to humans. The present work reports the structural and gas sensing properties of the CaCu3Ti4O12 compound prepared by the sol-gel technique. Rietveld refinement confirmed the formation of the pseudo-cubic CaCu3Ti4O12 compound, with less than 4 wt% of the secondary phases. The microstructural and elemental composition analysis were carried out using scanning electron microscopy and X-ray energy dispersive spectroscopy, respectively, while the elemental oxidation states of the samples were determined by X-ray photoelectron spectroscopy. The gas sensing response of the samples was performed for different concentrations of NO2, H2, CO, C2H2 and C2H4 at temperatures between 100 and 300 °C. The materials exhibited selectivity for NO2, showing a greater sensor signal at 250 °C, which was correlated with the highest concentration of nitrite and nitrate species on the CCTO surface using DRIFT spectroscopy.
ABSTRACT
BACKGROUND: Several laboratory techniques for anti double-stranded (ds) DNA detection in systemic lupus erythematosus (SLE) are available, with variable diagnostic performance. We aimed to evaluate anti-dsDNA's diagnostic performance by indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (EIA). METHODS: We conducted a single-center retrospective (2015 to 2020) study. Patients with anti-dsDNA tests by IIF and EIA were included. We evaluated the indications, applications, concordance, positive predictive value (PPV) of anti-dsDNA to confirm SLE diagnosis or flares, and associations of disease manifestations with positivity with each technique. RESULTS: A total of 1368 reports of anti-dsDNA tests by IIF and EIA and the corresponding medical records of the patients were analyzed. The main indication for anti-dsDNA testing was to help in the diagnosis of SLE in 890 (65%) of the samples, and the main application after obtaining the results was SLE exclusion in 782 (57.2%) cases. The combination with the highest frequency was the negativity result by both techniques in 801 (58.5%) cases (Cohen kappa 0.57). Both methods were positive in 300 patients with SLE (Cohen kappa 0.42). The PPVs of anti-dsDNA tests to confirm diagnosis/flare was 79.64% (95% CI, 75.35-83.35) by EIA, 78.75% (95% CI, 74.27-82.62) by IIF, and 82% (95% CI, 77.26-85.93) when both were positive. CONCLUSIONS: Anti-dsDNA detection by IIF and EIA are complementary and may indicate different clinical patterns in patients with SLE. The detection of anti-dsDNA antibodies by both techniques has a higher PPV than either separately for confirming SLE diagnosis or flares. These results highlight the need for evaluating both methods in clinical practice.
Subject(s)
Antibodies, Antinuclear , Lupus Erythematosus, Systemic , Humans , Enzyme-Linked Immunosorbent Assay/standards , Fluorescent Antibody Technique, Indirect/standards , Lupus Erythematosus, Systemic/diagnosis , Retrospective Studies , Antibodies, Antinuclear/analysis , Male , Female , Young Adult , Adult , Middle Aged , Predictive Value of Tests , Regression AnalysisABSTRACT
Efficiency of expanded genomic profiling (EGP) programmes in terms of final inclusion of patients in genomically matched therapies is still unknown. Fit patients with advanced and refractory colorectal cancer (CRC) were selected for an EGP programme. Next-generation sequencing (NGS) analysis from formalin-fixed paraffin-embedded tumour samples was performed. The purpose was to describe the prevalence of genomic alterations defined by the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT), as well as the percentage of patients finally included in genomically guided clinical trials. In total, 187 patients were recruited. Mutational profile was obtained in 177 patients (10 patients were failure due to insufficient tumour sample), copy number alterations in 41 patients and fusions in 31 patients. ESCAT-defined alterations were detected in 28.8% of the intention-to-analyse population. BRAF V600E was clustered in ESCAT I, with a prevalence of 3.7%, KRAS G12C and ERBB2 amplification were clustered in ESCAT II, whose prevalence was 4.2% and 1.6%, respectively. Most alterations were classified in ESCAT III (mutations in ERBB2, PIK3CA or FGFR genes and MET amplification) and IV (mutations in BRAF non-V600E, ERBB3, FBXW7, NOTCH, RNF43), with a single prevalence under 5%, except for PIK3CA mutation (9%). The final rate of inclusion into genomically guided clinical trials was 2.7%, including therapies targeting BRAF V600E or RNF43 mutations in two patients each, and ERBB2 mutation in one patient. In conclusion, EGP programmes in patients with advanced CRC are feasible and identify a subset of patients with potentially druggable genomic alterations. However, further efforts must be made to increase the rate of patients treated with genomically guided therapies.
Subject(s)
Colorectal Neoplasms , Proto-Oncogene Proteins B-raf , Humans , Proto-Oncogene Proteins B-raf/genetics , Colorectal Neoplasms/genetics , Mutation/genetics , Genomics , High-Throughput Nucleotide SequencingABSTRACT
This study aimed to improve the color and oxidative stabilities of dark Nellore bull steaks with greater-than-normal ultimate pH (pHu) by the injection (8% raw wet weight basis) of a solution with L-lactate (2.5%), phosphate (0.3%) and rosemary extract (0.06%), with further packaging in high oxygen atmosphere (HiOx MAP). Longissimus lumborum muscles from pasture-fed Nellore bulls were divided into three pHu ranges: normal (<5.80), intermediate (5.81-6.19), and high (≥6.2). Muscles were then halved, with sections were randomly assigned to non-enhanced (C, n = 6/pHu range) or injected (E, n = 6/pHu range) groups, at 72 h postmortem. Each section was cut into 2 cm-slices, which were HiOx-packed and then stored for 5 days (dark) and displayed for 9 days (fluorescent lighting) at 2 °C. Higher pHu steaks exhibited greater a*, b*, h*, C* and surface oxymyoglobin and lower surface deoxymyoglobin and oxygen consumption compared to those of normal pHu between days 0 and 5 (p < 0.05). Over the time, normal-pHu muscles showed oxidative protection (lower TBARS and greater metmyoglobin reducing ability values, p < 0.05) in enhanced-steaks. Therefore, enhancement and HiOx MAP seem to produce greater-than-normal pHu Nellore bull steaks with a preferable color and quality, even after display time.
ABSTRACT
This study evaluated the combination of high-power ultrasound (HPU), micronized salt (MS), and low KCl levels as a strategy to produce reduced sodium Bologna-type sausages. Samples with 50% NaCl reduction were produced with regular salt (RS) or MS and 0.5% KCl. The sausages were sonicated for 0 or 27 min in an ultrasonic bath (25 kHz, 60% amplitude, normal mode, 20 °C) immediately after filling. The sodium reformulation strategy was effective in compensating for the defects in the emulsion stability and texture profile caused by the NaCl reduction. Besides, the combination of HPU, MS, and KCl did not cause major impacts on the evolution of pH, Eh, and TBARS values of the sausages during storage (21 days at 4 °C). The use of MS and KCl also allowed a reduction by 50% of the NaCl content (< 42% Na; Na/K ratio: 1.2 to 1.3) of the samples without affecting the salty taste, which was enhanced by the HPU treatment.
Subject(s)
Meat Products , Sodium Chloride , Sodium Chloride/chemistry , Consumer Behavior , Meat Products/analysis , Sodium Chloride, Dietary , Sodium , TasteABSTRACT
Two oxoiron(IV) isomers (R 2a and R 2b) of general formula [FeIV (O)(R PyNMe3 )(CH3 CN)]2+ are obtained by reaction of their iron(II) precursor with NBu4 IO4 . The two isomers differ in the position of the oxo ligand, cis and trans to the pyridine donor. The mechanism of isomerization between R 2a and R 2b has been determined by kinetic and computational analyses uncovering an unprecedented path for interconversion of geometrical oxoiron(IV) isomers. The activity of the two oxoiron(IV) isomers in hydrogen atom transfer (HAT) reactions shows that R 2a reacts one order of magnitude faster than R 2b, which is explained by a repulsive noncovalent interaction between the ligand and the substrate in R 2b. Interestingly, the electronic properties of the R substituent in the ligand pyridine ring do not have a significant effect on reaction rates. Overall, the intrinsic structural aspects of each isomer define their relative HAT reactivity, overcoming changes in electronic properties of the ligand.