Effects of medium voltage electrical stimulation on initial pH decline and quality parameters during ageing and frozen storage of Nellore beef.

This study aimed to evaluate the influence of medium voltage electrical stimulation (ES) at three different intensities, 200 V (Treatment 200 V, T200), 300 V (Treatment 200 V, T300), and 400 V (Treatment 400 V, T400) on the initial pH decline in post mortem muscle and the quality parameters on M. longissimus thoracis - Nellore beef, both throughout the ageing process and during frozen storage. The colour, cooking loss, and shear force parameters for samples of aged beef were determined. Additional parameters, like thaw loss, pH, and lipid oxidation were also analyzed for the frozen storage. The shear force and cooking loss decreased and colour parameters increased in Nellore beef ES compared with CON on ageing time (14 days). At frozen storage, quality parameters like pH, a*, and b* were reduced over time, and no negative effect on lipid oxidation was found. Electrical stimulation at 200 V demonstrated effectiveness for decreasing shear force to Nellore beef (M. longissimus thoracis) during frozen storage. The application of medium voltage electrical stimulation can contribute to improved quality and tenderness in Nellore beef, both during ageing and frozen storage conditions.

[Cancer and the Kidney: A Deadly Embrace].

A deadly embrace occurs between cancer and chronic kidney disease. The estimation of kidney function in cancer patients is of utmost interest due to its direct impact on chemotherapy dosing, selection, and eligibility for chemotherapeutics. Overestimating kidney function (determined as estimated glomerular filtration rate -eGFR) can lead to overdosing and drug toxicity, while underestimating kidney function can prevent patients from receiving novel therapies. Notably, the current measures of eGFR are not validated in transplanted patients yet. The field of onconephrology ranges from nephrotoxicity of existing and novel therapeutics, paraproteinemias, and cancer-associated electrolyte imbalance, fluid and acid-base disturbances, the effects of the destruction of cancer cells, and acute and/or chronic kidney injuries. Recently, the therapeutic armamentarium has been enriched with new agents that interfere with specific proteins involved in oncogenesis. These are the so-called target therapies, which although acquired as "targeted" therapies do not have absolute specificity and selectivity and tend to inhibit multiple targets, often involving the kidney. Renal biopsy may be critical in managing these adverse effects. Moreover, primary hematological and oncological disorders can have significant kidney implications in the form of glomerular or nonglomerular diseases presenting with proteinuria, hematuria, hypertension, and kidney function decline, specifically including cast nephropathy or systemic light chain amyloidosis, and paraneoplastic glomerulopathies that occur as a result of occult malignancy, such as Membranous Nephropathy and Minimal Change disease.

A Descriptive Study of Repeated Hospitalizations and Survival of Patients with Metastatic Melanoma in the Northern Italian Region during 2004-2019.

BACKGROUND: Survival rates for metastatic melanoma (MM) patients have improved in recent years, leading to major expenses and health resource use. We conducted a non-concurrent prospective study to describe the burden of hospitalization in a real-world setting for patients with MM. METHODS: Patients were tracked throughout all hospital stays in 2004-2019 by means of hospital discharges. The number of hospitalizations, the rehospitalization rate, the average time spent in the hospital and the time span between consecutive admissions were evaluated. Relative survival was also calculated. RESULTS: Overall, 1570 patients were identified at the first stay (56.5% in 2004-2011 and 43.7% in 2012-2019). A total of 8583 admissions were retrieved. The overall rehospitalization rate was 1.78 per patient/year (95%CI = 1.68-1.89); it increased significantly with the period of first stay (1.51, 95%CI = 1.40-1.64 in 2004-2011 and 2.11, 95%CI = 1.94-2.29 thereafter). The median time span between hospitalizations was lower for patients hospitalized after 2011 (16 vs. 26 months). An improvement in survival for males was highlighted. CONCLUSIONS: The hospitalization rate of patients with MM was higher in the last years of the study. Compared with a shorter length of stay, patients were admitted to hospitals with a higher frequency. Knowledge of the burden of MM is essential for planning the allocation of healthcare resources.

X-ray polarization evidence for a 200-year-old flare of Sgr A.

The centre of the Milky Way Galaxy hosts a black hole with a solar mass of about 4 million (Sagittarius A* (Sgr A)) that is very quiescent at present with a luminosity many orders of magnitude below those of active galactic nuclei1. Reflection of X-rays from Sgr A* by dense gas in the Galactic Centre region offers a means to study its past flaring activity on timescales of hundreds and thousands of years2. The shape of the X-ray continuum and the strong fluorescent iron line observed from giant molecular clouds in the vicinity of Sgr A* are consistent with the reflection scenario3-5. If this interpretation is correct, the reflected continuum emission should be polarized6. Here we report observations of polarized X-ray emission in the direction of the molecular clouds in the Galactic Centre using the Imaging X-ray Polarimetry Explorer. We measure a polarization degree of 31% ± 11%, and a polarization angle of -48° ± 11°. The polarization angle is consistent with Sgr A* being the primary source of the emission, and the polarization degree implies that some 200 years ago, the X-ray luminosity of Sgr A* was briefly comparable to that of a Seyfert galaxy.

Prognostic Role of Soluble and Extracellular Vesicle-Associated PD-L1, B7-H3 and B7-H4 in Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors.

The treatment of non-small cell lung cancer (NSCLC) has changed dramatically with the advent of immune checkpoint inhibitors (ICIs). Despite encouraging results, their efficacy remains limited to a subgroup of patients. Circulating immune checkpoints in soluble (s) form and associated with extracellular vesicles (EVs) represent promising markers, especially in ICI-based therapeutic settings. We evaluated the prognostic role of PD-L1 and of two B7 family members (B7-H3, B7-H4), both soluble and EV-associated, in a cohort of advanced NSCLC patients treated with first- (n = 56) or second-line (n = 126) ICIs. In treatment-naïve patients, high baseline concentrations of sPD-L1 (>24.2 pg/mL) were linked to worse survival, whereas high levels of sB7-H3 (>0.5 ng/mL) and sB7-H4 (>63.9 pg/mL) were associated with better outcomes. EV characterization confirmed the presence of EVs positive for PD-L1 and B7-H3, while only a small portion of EVs expressed B7-H4. The comparison between biomarker levels at the baseline and in the first radiological assessment under ICI-based treatment showed a significant decrease in EV-PD-L1 and an increase in EV-B7H3 in patients in the disease response to ICIs. Our study shows that sPD-L1, sB7-H3 and sB7-H4 levels are emerging prognostic markers in patients with advanced NSCLC treated with ICIs and suggests potential EV involvement in the disease response to ICIs.

Cascading disasters: The impact of hurricane Maria and Covid-19 on post-disaster Puerto Rican migrants' adaptation and integration in Florida.

Based on data from 103 surveys of Puerto Rican migrants living in Florida and 54 in-depth interviews with a subgroup of them, we examine how Puerto Ricans who left the archipelago after Hurricane Maria have navigated settlement in their new homes. In this article, we observed and classified our participants' descriptions of how they managed opportunities and challenges regarding education, employment, and social relations, the traditional benchmarks for the assessment of societal integration. We also observed how our participants described Covid-19's interaction with these benchmarks. We found that our participants have experienced a series of cascading disasters since 2017-namely, Hurricane Maria, the earthquakes that affected Puerto Rico starting in late 2019, the humanitarian crises that followed both disasters, and now the global pandemic. These disasters, compounded with migration, have resulted in a process of adaptation to Florida in which social and labor-market integration and the ability to nurture social ties have been significantly diminished.

Basándonos en los datos de 103 encuestas con migrantes puertorriqueños residentes en Florida y cincuenta y cuatro entrevistas a fondo con un subgrupo de estas personas, examinamos cómo los puertorriqueños que abandonaron el archipiélago después del huracán María han lidiado con la adaptación a sus nuevos hogares. En este artículo observamos y clasificamos las descripciones de los participantes: cómo manejaron las oportunidades y los retos relacionados con la educación, el empleo y las relaciones sociales, que son los puntos de referencia tradicionales para evaluar la integración social. Observamos también cómo los participantes describían la interacción de la pandemia de COVID-19 con estos puntos de referencia. Encontramos que estas personas han experimentado una serie de desastres en cascada desde 2017, específicamente el huracán María, los terremotos que comenzaron a afectar a Puerto Rico a finales de 2019, las crisis humanitarias que siguieron a ambos desastres y ahora la pandemia global. Estos desastres, agravados por la migración, han tenido como resultado un proceso de adaptación a la Florida en el cual ha disminuido significativamente la integración social y laboral y la capacidad de nutrir los vínculos sociales.

Descriptive Epidemiology of Hospitalization of Patients with a Rare Tumor in an Italian Region.

OBJECTIVES: Rare tumors (RT) collectively account for one quarter of all malignancies in Italy. The low frequency and the large heterogeneity in natural history and outcome of individual diseases, together with a scarcity of epidemiological information make them a challenge for clinical practice, as well as for public healthcare organizations. We conducted a retrospective study to quantify the burden of hospitalization in a real-word setting in patients diagnosed with these diseases in an Italian region. METHODS: RT patients were tracked along all hospital stays from 2000 to 2019 using hospital discharge records. Frequency of hospitalizations, average time spent in hospital and median timespan between consecutive admissions were considered. Re-hospitalization rates were analyzed through a multivariable negative binomial regression analysis to adjust for confounding and allowing for over-dispersion in count data. RESULTS: As a whole, 57,329 patients were identified at first stay for all studied tumors. A total of 183,959 admissions were retrieved, along a median of 3 hospitalizations per patient. Median timespan between hospitalizations shortened in the course of the study years (12.5 months in 2000-2004 to 5.4 months in 2015-2019). The overall re-hospitalization rate increased from 0.92 per patient/year (95% CI = 0.81-1.04) in 2000-2004 to 2.17 (95% CI = 1.90-2.47) in 2015-2019. CONCLUSIONS: Overall, the hospitalization rate of patients with a RT increased in the twenty years since the 2000 and particularly doubled starting from 2015. A higher burden of hospitalizations was found for tumors of the central nervous system, thoracic cavity, digestive tract and sarcomas. To the best of our knowledge this is the first paper related to access to Italian healthcare facilities of patients with these tumors.

Vela pulsar wind nebula X-rays are polarized to near the synchrotron limit.

Pulsar wind nebulae are formed when outflows of relativistic electrons and positrons hit the surrounding supernova remnant or interstellar medium at a shock front. The Vela pulsar wind nebula is powered by a young pulsar (B0833-45, aged 11,000 years)1 and located inside an extended structure called Vela X, which is itself inside the supernova remnant2. Previous X-ray observations revealed two prominent arcs that are bisected by a jet and counter jet3,4. Radio maps have shown high linear polarization of 60% in the outer regions of the nebula5. Here we report an X-ray observation of the inner part of the nebula, where polarization can exceed 60% at the leading edge-approaching the theoretical limit of what can be produced by synchrotron emission. We infer that, in contrast with the case of the supernova remnant, the electrons in the pulsar wind nebula are accelerated with little or no turbulence in a highly uniform magnetic field.

Polarized x-rays from a magnetar.

Magnetars are neutron stars with ultrastrong magnetic fields, which can be observed in x-rays. Polarization measurements could provide information on their magnetic fields and surface properties. We observed polarized x-rays from the magnetar 4U 0142+61 using the Imaging X-ray Polarimetry Explorer and found a linear polarization degree of 13.5 ± 0.8% averaged over the 2- to 8-kilo-electron volt band. The polarization changes with energy: The degree is 15.0 ± 1.0% at 2 to 4 kilo-electron volts, drops below the instrumental sensitivity ~4 to 5 kilo-electron volts, and rises to 35.2 ± 7.1% at 5.5 to 8 kilo-electron volts. The polarization angle also changes by 90° at ~4 to 5 kilo-electron volts. These results are consistent with a model in which thermal radiation from the magnetar surface is reprocessed by scattering off charged particles in the magnetosphere.

Proteome basis for the biological variations in color and tenderness of longissimus thoracis muscle from beef cattle differing in growth rate and feeding regime.

The proteome basis for the biological variations in color and tenderness of longissimus thoracis muscle from ½ Angus (Bos taurus taurus) × ½ Nellore (Bos taurus indicus) crossbred steers was evaluated in a completely randomized experimental design consisting of four treatments (n = 9 per treatment): 1) feedlot finished, high growth rate (FH); 2) feedlot finished, low growth rate (FL); 3) pasture finished, high growth rate (PH); and 4) pasture finished, low growth rate (PL). The following comparisons were made to evaluate the effects of finishing systems and growth rates on muscle proteome: 1) FH × PL; 2) FL × PH; 3) FH × FL; and 4) PH × PL. Sixteen protein spots were differentially abundant among these comparisons (P ≤ 0.05), which were distinguished in two major clusters, energy metabolism- and muscle structure-related proteins that impacted glycolysis, carbon metabolism, amino acid biosynthesis and muscle contraction pathways (FDR ≤ 0.05). For FH × PL comparison, triosephosphate isomerase (TPI), phosphoglucomutase-1 (PGM1) and phosphoglycerate kinase 1 (PGK1) were overabundant in FH beef whereas troponin T (TNNT3), α-actin (ACTA1) and myosin regulatory light chain 2 (MYLPF) were overabundant in PL beef. For the FL × PH comparison, PGM1, phosphoglycerate mutase 2 (PGAM2) and annexin 2 (ANXA2) were overabundant in PH beef. For the FH × FL comparison, AMP deaminase (AMPD1) and serum albumin (ALB) were overabundant in FH beef whereas glycogen phosphorylase (PYGM) was overabundant in FL beef. For the PH × PL comparison, myoglobin (MB) was overabundant in PH beef whereas PYGM and MYLPF were overabundant in PL beef. In non-aged beef, L* was positively correlated with PGM1 (r = 0.54) while tenderness was negatively correlated with PGAM2 (r = -0.74) and ANXA2 (r = -0.60). In 7-d aged beef, color attributes (L*, a* and b*) were positively correlated with PGM1 (r = 0.67, 0.64 and 0.64, respectively) while tenderness was negatively correlated with TNNT3 (r = -0.57), PGK1 (r = -0.52) and MYLPF (r = -0.66). Therefore, finishing systems and growth rate affected the muscle proteome profile, which was related to beef color and tenderness. Additionally, these results suggest potential biomarkers for beef color (PGM1 and PGAM2) and tenderness (ANXA2, MYLPF, PGK1 and TNNT3).

Ultra-hyper-fractionated radiotherapy for high-grade gliomas.

High-grade gliomas (HGGs; WHO grades III and IV) are invariably lethal brain tumors. Low-dose hyper-radiosensitivity (HRS) of HGG is a well-established phenomenon in vitro. However, possibly linked to the unavailability of accurate animal models of the diseases, this therapeutic effect could not be consistently translated to the animal setting, thus impairing its subsequent clinical development. The purpose of this study was to develop radiotherapeutic (RT) schedules permitting to significantly improve the overall survival of faithful animal models of HGG that have been recently made available. We used primary glioma initiating cell (GIC)-driven orthotopic animal models that accurately recapitulate the heterogeneity and growth patterns of the patients' tumors, to investigate the therapeutic effects of low radiation doses toward HGG. With the same total dose, RT fractions ≤0.5 Gy twice per week [ultra-hyper-fractionation (ultra-hyper-FRT)] started at early stages of tumor progression (a condition that in the clinical setting often occurs at the end of the guidelines treatment) improved the effectiveness of RT and the animal survival in comparison to standard fractions. For the same cumulative dose, the use of fractions ≤0.5 Gy may permit to escape one or more tumor resistance mechanisms thus increasing the effectiveness of RT and the overall animal survival. These findings suggest investigating in the clinical setting the therapeutic effect of an ultra-hyper-FRT schedule promptly extending the conventional RT component of the current guideline ("Stupp") therapeutic protocol.

Effect of different selenium sources and concentrations on glutathione peroxidase activity and cholesterol metabolism of beef cattle.

The objective of this study was to investigate the effects of different Se sources and concentrations on glutathione forms and cholesterol metabolism in beef cattle. Sixty-three Nellore bulls (412 ± 19 kg body weight (BW); 24 mo old) were randomly assigned to a completely randomized design in a 2 × 3 + 1 factorial arrangement (63 pens; one animal/pen) with two Se sources (sodium selenite, ING and Se-yeast, ORG), three concentrations (0.3, 0.9, and 2.7 mg supplemental Se/kg dry matter (DM)), and control treatment (without Se supplementation) fed for 90 d. Blood samples were collected on day 0, 28, 56, and 84. Muscle and liver samples were collected at harvest. Hepatic GSSG (P = 0.004), GSH/GSSG ratio (P = 0.030), and GSH-Px (P = 0.004) were affected by Se source × concentration interaction. Oxidized glutathione was higher in the ORG group vs. ING at concentration 2.7 mg supplemental Se/kg DM, but at 0.3 mg supplemental Se/kg DM the ING group was higher than ORG. The liver GSH-Px activity was higher in the ORG group vs. ING at concentration 0.9 and 2.7 mg supplemental Se/kg DM. The GSH/GSSG ratio was the highest in animals fed 0.3 mg supplemental Se/kg DM of ORG. Selenium liver concentration increased linearly with the supplemental Se concentration in the diet (y = 0.0583 + 0.4254x, R2 = 0.92, P < 0.0001), regardless of source. Total meat cholesterol was greater (P < 0.001) in CON (control) vs. SUP (supplemented, regardless source) group. The muscle GSH-Px activity was higher (P < 0.001) in SUP vs. CON and increased (P < 0.004) with increasing supplemental Se concentrations. There was an increase on very low-density lipoprotein (VLDL), glucose, and triglycerides in ORG vs. ING (P ≤ 0.035). In general, serum Se was higher (P < 0.001) in SUP vs. CON and increased with increasing supplemental Se concentration. Lastly, the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) concentration was lower (P = 0.002) in SUP (0.39 ng/mL) vs. CON (0.55 ng/mL). Selenium supplementation with different sources and concentrations has the potential to affect cholesterol metabolism by affecting GSH/GSSG ratio, GSH-Px, and the HMGCR.

Dietary Habits and Risk of Esophagitis and Barrett's Esophagus: A Multicenter Italian Case-Control Study.

BACKGROUND: Barrett's esophagus (BE) and esophagitis share potentially modifiable risk factors such as obesity, smoking, and alcohol. The role of diet on BE and esophagitis is still debated. AIMS: The objective of this study was to examine the association between some dietary habits and the risk of BE and esophagitis in Italy. METHODS: A multicenter case-control study involving 1285 individuals was carried out in 12 areas. Patients with a new diagnosis of BE (320) or esophagitis (359) and a group of endoscopic controls (606) were included. Information on personal history and dietary habits was collected using a structured questionnaire. RESULTS: No clear monotonic significant dose-response relationship was found for most of the considered food items. Nevertheless, the most extreme consumption category of red meat, cold cuts, dairy products, and fried foods showed esophagitis risk excesses varying from 19 to 49%. A higher fat rich diet seemed to increase risk by 49% for BE and 94% for esophagitis. A downward tendency in esophagitis (- 27%) and BE risk (- 20%) was found associated with higher frequency of fresh fruit intake. In addition, a statistically significant twofold increased risk for both BE and esophagitis was found for subjects eating late evening snacks more than once every three days in comparison with the lowest intake category (no consumption). CONCLUSIONS: BE and esophagitis patients appeared to be more likely than controls to follow a diet rich in fats and poor in fruit and vegetables. Late evening snacks were found to be associated with both disorders.

Welfare traits of Bos indicus cattle castrated immunologically and fed beta-adrenergic agonists.

OBJECTIVE: This work was carried out to evaluate the effects of zilpaterol hydrochloride (ZH) and ractopamine hydrochloride (RH) combined with immunocastration on the welfare traits of feedlot Nellore cattle. METHODS: Ninety-six Nellore males (average body weight [BW] = 409±50 kg; average 20 mo of age) were divided into two groups according to BW; half of the animals in each group received two doses of an immunocastration (ImC) vaccine in a 30 day interval, and the other half did not receive the vaccine (NoC). Afterward, the animals were housed and fed a common diet for 70 days. Then, they were split into three groups and fed one of the following diets for 30 additional days: control (CO) diet, with no ß-AA; ZH diet, containing 80 mg/d ZH; and RH diet, containing 300 mg/d RH. Welfare traits were assessed by monitoring body surface temperature using infrared thermography (IRT) and plasma cortisol and temperament measurements. RESULTS: There was no interaction between sexual condition and diet for any trait. The ImC and NoC groups did not differ in rectal and ocular temperatures. The ImC animals had higher flight speeds (p = 0.022) and tended to have higher cortisol levels (p = 0.059) than the NoC animals. Animals fed ZH and RH did not differ in cortisol levels, respiratory rate, rectal temperature, temperature measured by IRT, or temperament behaviour. CONCLUSION: The ImC animals showed a less stable temperament during handling practices than NoC, whereas ZH and RH supplementation had no adverse effects on animal welfare.

Preliminary study on the characterization of Longissimus lumborum dark cutting meat in Angus × Nellore crossbreed cattle using NMR-based metabolomics.

The aim of this preliminary study was to evaluate meat quality properties, muscle metabolite profile and metabolic pathways associated with the occurrence of dark cutting meat in Angus x Nellore crossbreed cattle. After 14 days' ageing, dark cutting meat presented a higher pH, lower cooking loss and colour parameters, and greater tenderness compared with normal meat. Dark cutting meat had a higher ATP level and lower concentrations of glucose-6-phosphate, lactate, glucose, serine, threonine, creatine phosphate, inosine, leucine, methionine, succinate and glucose-1-phosphate compared to normal meat. In dark cutting samples, the ultimate pH was positively correlated with carnitine and negatively correlated with glucose-6-phosphate. However, in normal meat, the ultimate pH presented a positive correlation with arginine, leucine, methionine, proline, threonine, tyrosine and valine. Pathway analysis showed that differentiation of the groups was linked to energetic pathways such as starch and sucrose metabolism, the pentose phosphate pathway, amino sugar, nucleotide sugar metabolism, and glycolysis or gluconeogenesis. In conclusion, the occurrence of dark cutting meat has a notable impact on meat quality attributes and concentrations of post-mortem glycolytic metabolites, appears to be correlated with mitochondrial activity and affects energetic metabolic pathways.

Effects of Feeding Increasing Levels of Yerba Mate on Lamb Meat Quality and Antioxidant Activity.

The present study investigated the inclusion of yerba mate extract (YME) in the lamb's diet on meat quality traits, antioxidant activity, and shelf-life. Thirty-six lambs were distributed according to a block design with the following groups: control group without YME (0%) and three treatment groups with 1, 2, and 4% YME inclusion in the dry matter. The animals were fed these diets for 53 days. Samples were collected from the Longissimusthoracis (LT) muscle to analyze antioxidant activity and meat quality. Samples were placed on a counter display simulating a retail environment for 0, 3, and 6 days at 4 ± 2 °C. All data were analyzed using a MIXED model with orthogonal contrasts. Inclusion of 1 and 4% YME in the diet changed the yellow (b*) and the chroma (C*) of the meat (p ≤ 0.05). The pH, colour, thiobarbituric acid reactive substances, and carbonyl values were influenced by the retail display time for all the evaluated treatments (p ≤ 0.03). However, neither diet nor the retail display time influenced the oxidation of proteins or the antioxidant enzyme activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione activity (GSH) in meat. Therefore, the inclusion of 4% YME showed positive results in the yellow and colour stability parameters of the meat without increasing the lipid peroxidation values or altering the normal meat quality parameters in lambs.

Effect of Macleaya cordata and Magnolia officinalis plant extracts on oxidative stress control in lambs fed a high-concentrate diet.

OBJECTIVE: The objective of this experiment was to compare conventional antioxidants and plant extracts for oxidative stress control in lambs fed a high-concentrate diet. METHODS: Forty-eight male Dorper×Santa Ines lambs with an initial weight of 20±1.49 kg and 60 days of age, were used to evaluate the effects of feeding a combination of Macleaya cordata and Magnolia officinalis plant extracts (0 vs 320 mg/kg dry matter [DM]) in combination with selenium+vitamin E (0 vs 100 IU/kg DM of vitamin E and 0.1 mg/kg DM of selenium) in a completely randomized block design in a 2×2 factorial arrangement. The animals were housed in individual pens and received a high-concentrate diet consisting of 80% whole corn and 20% protein pellet for 60 days. The animals were weighed at the beginning of the experiment and every 14 days for performance monitoring. Three blood samplings were performed during the experimental period for the evaluation of oxidative and protein parameters. RESULTS: The treatments with vitamin E and selenium as additives had a positive influence on final weight, daily weight gain, carcass weight, and selenium content in longissimus muscle (p = 0.01). Plant extracts tended to improve final weight (p = 0.064) and daily weight gain (p = 0.059), showing similar effect as selenium and vitamin E. There was no effect of treatment on blood proteins, indicating that the animals were healthy throughout the experiment. CONCLUSION: The use of plant extracts had a similar effect as the addition of selenium and vitamin E, with dietary inclusion of additives resulting in better performance of lambs but both supplements did not have strong influence on oxidative stress.

Prognostic Relevance of Circulating Tumor Cells and Circulating Cell-Free DNA Association in Metastatic Non-Small Cell Lung Cancer Treated with Nivolumab.

: The treatment of advanced non-small cell lung cancer (NSCLC) has been revolutionized by immune checkpoint inhibitors (ICIs). The identification of prognostic and predictive factors in ICIs-treated patients is presently challenging. Circulating tumor cells (CTCs) and cell-free DNA (cfDNA) were evaluated in 89 previously treated NSCLC patients receiving nivolumab. Blood samples were collected before therapy and at the first and second radiological response assessments. CTCs were isolated by a filtration-based method. cfDNA was extracted from plasma and estimated by quantitative PCR. Patients with baseline CTC number and cfDNA below their median values (2 and 836.5 ng from 3 mL of blood and plasma, respectively) survived significantly longer than those with higher values (p = 0.05 and p = 0.04, respectively). The two biomarkers were then used separately and jointly as time-dependent covariates in a regression model confirming their prognostic role. Additionally, a four-fold risk of death for the subgroup presenting both circulating biomarkers above the median values was observed (p < 0.001). No significant differences were found between circulating biomarkers and best response. However, progressing patients with concomitant lower CTCs and cfDNA performed clinically well (p = 0.007), suggesting that jointed CTCs and cfDNA might help discriminate a low-risk population which might benefit from continuing ICIs beyond progression.

Liver proteomics unravel the metabolic pathways related to Feed Efficiency in beef cattle.

Improving nutrient utilization efficiency is essential for livestock, given the current scenario of increasing demand for animal protein and sustainable resource use. In this context, understanding the biology of feed efficiency (FE) in beef cattle allows the development of markers for identification and selection of best animals for animal production. Thus, 98 young Nellore bulls were evaluated for FE and at the end of the experiment liver samples from six High Feed Efficient (HFE) and six Low Feed Efficient (LFE) animals were collected for protein extraction, digestion and analysis by HPLC-MS/MS. Data were analyzed for differential abundant proteins (DAPs), protein networks, and functional enrichment. Serum endotoxin was also quantified. We found 42 DAPs and 3 protein networks significantly related to FE. The main pathways associated with FE were: microbial metabolism; biosynthesis of fatty acids, amino acids and vitamins; glycolysis/gluconeogenesis; xenobiotic metabolism and; antigen processing and presentation. Serum endotoxins were significantly higher in LFE animals supporting the results. Therefore, the findings presented here confirmed the altered hepatic metabolism and pronounced hepatic inflammation in LFE animals supporting that the increased bacterial load is at least in part responsible for the hepatic lesions and inflammation in LFE animals.

Label-free quantitative proteomic analysis reveals muscle contraction and metabolism proteins linked to ultimate pH in bovine skeletal muscle.

The purpose of this research was to investigate the causes and consequences of pHu variations in beef cattle. A group of 176 Nellore beef cattle was evaluated and classified into two different pHu groups: High (≥6.0, N = 17) and Normal (<5.8, N = 159). Plasma concentrations of cortisol and adrenocorticotropic hormone, lactate and glycogen muscular content, meat color, shear force and Longissimus thoracis muscle proteomic profile were evaluated and compared between pHu groups. Muscle glycogen content, meat color and shear force statistically differed between pHu groups. Label-free quantitative proteomic analysis revealed ten differentially abundant proteins between pHu groups, involved in metabolic processes and muscle contraction, which also were significantly correlated with pHu. Thirty-six and 31 proteins were exclusively present in Normal and High pHu group, respectively, which were related to TCA cycle, cortisol production, calcium regulation, and antioxidant function. The MYH7, UGP2, H2AFJ and VDAC3 were identified as potential indicators of pHu variations. CALM and NNT appeared to be interesting proteins to understand the metabolic pathways behind pHu. Data are available via ProteomeXchange with identifier PXD009320.