Search

There is an increased interest for novel biomarkers in order to improve the diagnostic accuracy for deep vein thrombosis (DVT). Moreover, the link between inflammation and venous thromboembolism has attracted increasing research interests. The present study aimed to evaluate the role of the platelet‑to‑lymphocyte ratio (PLR), neutrophil‑to‑lymphocyte ratio (NLR) and monocyte‑to‑high‑density lipoprotein cholesterol ratio (MHR) as biomarkers for acute DVT. For this purpose, 300 consecutive patients who were hospitalized were considered; 33 patients out of the 300 were admitted for acute DVT of the lower limbs. The PLR, NLR and MHR, as well as the acute phase inflammation markers (leukocytes, neutrophils, C‑reactive protein and fibrinogen) were measured. The patients with DVT exhibited significantly higher levels of PLR, NLR and MHR compared to those without DVT (P<0.001). Simple binary linear regression analysis (without confounding factors) between the NLR, PLR and MHR highest quartile and DVT revealed an odds ratio of 3.149 (P=0.01) for PLR, and an odds ratio of 4.191 (P=0.001) for MHR. Following the correction for the main confounding factors, PLR maintained a significant association with DVT (odds ratio, 3.379; P=0.007) and MHR maintained a stronger significant association with DVT (odds ratio, 4.378; P=0.001). It was thus hypothesized that the assessment of PLR and MHR, but not of NLR may help clinicians to improve the laboratory evaluation in elderly hospitalized patients with suspected DVT.

Little attention has been paid to the biological role of arginine and its dietary supplementation in broilers under heat stress (HS) conditions. Therefore, the main aim of this study was to assess the response of broilers to arginine supplementation and cyclic HS, with a focus on liver, pectoral muscle, and blood metabolic profiles and the cecal microbiota. Day-old male Ross 308 broilers ( n = 240) were placed in 2 rooms with 12 pens each for a 44-day trial. Pens were assigned to one of two groups (6 pens/group/room): the control group (CON) was given a basal diet in mash form and the treated group (ARG) was fed CON diet supplemented with crystalline L -arginine. The total arginine:lysine ratio of CON diet ranged between 1.02 and 1.07, while that of ARG diet was 1.20. One room was constantly kept at thermoneutral (TN) conditions, while the birds in the other room were kept at TN conditions until D34 and subjected to cyclic HS from D35 onwards (∼34°C; 9:00 A.M.-6:00 P.M.). Blood, liver, Pectoralis major muscle, and cecal content were taken from 2 birds per pen (12 birds/group/room) for metabolomics and microbiota analysis. Growth performance data were also collected on a pen basis. Arginine supplementation failed to reduce the adverse effects of HS on growth performance. Supplemented birds showed increased levels of arginine and creatine in plasma, liver, and P. major and methionine in liver, and reduced levels of glutamine in plasma, liver, and P. major . HS altered bioenergetic processes (increased levels of AMP and reduced levels of fumarate, succinate, and UDP), protein metabolism (increased protein breakdown to supply the liver with amino acids for energy production), and promoted the accumulation of antioxidant and protective molecules (histidine-containing dipeptides, beta-alanine, and choline), especially in P. major . Arginine supplementation may have partially counterbalanced the effects of HS on energy homeostasis by increasing creatine levels and attenuating the increase in AMP levels, particularly in P. major . It also significantly reduced cecal observed diversity, while HS increased alpha diversity indices and affected beta diversity. Results of taxonomic analysis at the phylum and family level are also provided., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Brugaletta, Laghi, Zampiga, Oliveri, Indio, Piscitelli, Pignata, Petracci, De Cesare and Sirri.)

Background: Arginine is an essential amino acid for chickens and feeding diets with arginine beyond the recommended levels has been shown to influence the growth performance of broiler chickens in a positive way. Nonetheless, further research is required to understand how arginine supplementation above the widely adopted dosages affects metabolism and intestinal health of broilers. Therefore, this study was designed to assess the effects of arginine supplementation (i.e., total arginine to total lysine ratio of 1.20 instead of 1.06-1.08 recommended by the breeding company) on growth performance of broiler chickens and to explore its impacts on the hepatic and blood metabolic profiles, as well as on the intestinal microbiota. For this purpose, 630 one-day-old male Ross 308 broiler chicks were assigned to 2 treatments (7 replicates each) fed a control diet or a crystalline L-arginine-supplemented diet for 49 d., Results: Compared to control birds, those supplemented with arginine performed significantly better exhibiting greater final body weight at D49 (3778 vs. 3937 g; P < 0.001), higher growth rate (76.15 vs. 79.46 g of body weight gained daily; P < 0.001), and lower cumulative feed conversion ratio (1.808 vs. 1.732; P < 0.05). Plasma concentrations of arginine, betaine, histidine, and creatine were greater in supplemented birds than in their control counterparts, as were those of creatine, leucine and other essential amino acids at the hepatic level. In contrast, leucine concentration was lower in the caecal content of supplemented birds. Reduced alpha diversity and relative abundance of Firmicutes and Proteobacteria (specifically Escherichia coli), as well as increased abundance of Bacteroidetes and Lactobacillus salivarius were found in the caecal content of supplemented birds., Conclusions: The improvement in growth performance corroborates the advantages of supplementing arginine in broiler nutrition. It can be hypothesized that the performance enhancement found in this study is associated with the increased availability of arginine, betaine, histidine, and creatine in plasma and the liver, as well as to the ability of extra dietary arginine to potentially ameliorate intestinal conditions and microbiota of supplemented birds. However, the latter promising property, along with other research questions raised by this study, deserve further investigations., (© 2023. The Author(s).)

With the growing global demand for animal protein and rising temperatures caused by climate change, heat stress (HS) is one of the main emerging environmental challenges for the poultry industry. Commercially-reared birds are particularly sensitive to hot temperatures, so adopting production systems that mitigate the adverse effects of HS on bird performance is essential and requires a holistic approach. Feeding and nutrition can play important roles in limiting the heat load on birds; therefore, this review aims to describe the effects of HS on feed intake (FI) and nutrient digestibility and to highlight feeding strategies and nutritional solutions to potentially mitigate some of the deleterious effects of HS on broiler chickens. The reduction of FI is one of the main behavioral changes induced by hot temperatures as birds attempt to limit heat production associated with the digestion, absorption, and metabolism of nutrients. Although the intensity and length of the heat period influences the type and magnitude of responses, reduced FI explains most of the performance degradation observed in HS broilers, while reduced nutrient digestibility appears to only explain a small proportion of impaired feed efficiency following HS. Targeted feeding strategies, including feed restriction and withdrawal, dual feeding, and wet feeding, have showed some promising results under hot temperatures, but these can be difficult to implement in intensive rearing systems. Concerning diet composition, feeding increased nutrient and energy diets can potentially compensate for decreased FI during HS. Indeed, high energy and high crude protein diets have both been shown to improve bird performance under HS conditions. Specifically, positive results may be obtained with increased added fat concentrations since lipids have a lower thermogenic effect compared to proteins and carbohydrates. Moreover, increased supplementation of some essential amino acids can help support increased amino acid requirements for maintenance functions caused by HS. Further research to better characterize and advance these nutritional strategies will help establish economically viable solutions to enhance productivity, health, welfare, and meat quality of broilers facing HS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Teyssier, Brugaletta, Sirri, Dridi and Rochell.)

Heat stress (HS) compromises the yield and quality of poultry products and endangers the sustainability of the poultry industry. Despite being homeothermic, chickens, especially fast-growing broiler lines, are particularly sensitive to HS due to the phylogenetic absence of sweat glands, along with the artificial selection-caused increase in metabolic rates and limited development of cardiovascular and respiratory systems. Clinical signs and consequences of HS are multifaceted and include alterations in behavior (e.g., lethargy, decreased feed intake, and panting), metabolism (e.g., catabolic state, fat accumulation, and reduced skeletal muscle accretion), general homeostasis (e.g., alkalosis, hormonal imbalance, immunodeficiency, inflammation, and oxidative stress), and gastrointestinal tract function (e.g., digestive and absorptive disorders, enteritis, paracellular barrier failure, and dysbiosis). Poultry scientists and companies have made great efforts to develop effective solutions to counteract the detrimental effects of HS on health and performance of chickens. Feeding and nutrition have been shown to play a key role in combating HS in chicken husbandry. Nutritional strategies that enhance protein and energy utilization as well as dietary interventions intended to restore intestinal eubiosis are of increasing interest because of the marked effects of HS on feed intake, nutrient metabolism, and gut health. Hence, the present review series, divided into Part I and Part II, seeks to synthesize information on the effects of HS on physiology, gut health, and performance of chickens, with emphasis on potential solutions adopted in broiler chicken nutrition to alleviate these effects. Part I provides introductory knowledge on HS physiology to make good use of the nutritional themes covered by Part II., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Brugaletta, Teyssier, Rochell, Dridi and Sirri.)

Background and Aims: Remdesivir (GS-5734), an inhibitor of the viral RNA-dependent, RNA polymerase was early identified as a promising therapeutic candidate against COVID-19. Our aim was to evaluate the impact of several metabolic parameters on Remdesivir effectiveness among hospitalized COVID-19 patients., Methods and Results: We conducted an observational study on patients with SARS-CoV-2-related pneumonia admitted between May 2020 and September 2021 to the COVID-19 Units of Internal Medicine, Pneumology and Intensive Care of Garibaldi Hospital, Catania, Italy, and treated with Remdesivir. The "Ordinal Scale For Clinical Improvement" was used to assess patients' clinical improvement within 28 days of hospitalization. Short-term mortality rate was also evaluated. A total of 142 patients with SARS-CoV-2-related pneumonia were studied. The prevalence of obesity (20.7% vs. 41.9%, p = 0.03), the average BMI (27.1 ± 4.4 vs. 31.1 ± 6.1, p < 0.01) and the mean LDL-C levels (78 ± 19 mg/dl vs. 103 ± 18 mg/dl, p = 0.03) were significantly lower in early-improved (EI) compared to not-improved (NI) individuals. Obesity was negatively associated to clinical improvement after Remdesivir (OR 0.48, 95%CI 0.17-0.97, p = 0.04). Both obesity (OR 2.82, 95% CI 1.05-7.71, p = 0.04) and dyslipidemia (OR 2.78, 95%CI 1.17-7.16, p = 0.03) were significantly related to patients' mortality. Dyslipidemic subjects experienced a slower clinical improvement than non-dyslipidemic ones (Long-Rank p = 0.04)., Conclusion: Our study showed that unfavorable metabolic conditions such as obesity and dyslipidemia could predict a worse clinical response to Remdesivir as well as the mortality in hospitalized COVID-19 patients. Further prospective and larger-scale studies are needed to confirm these preliminary findings., Competing Interests: Declaration of competing interest All the authors declare no conflict of interest in connection with submitted material., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Heat stress (HS) is devastating to poultry production sustainability due its detrimental effects on performance, welfare, meat quality, and profitability. One of the most known negative effects of HS is feed intake depression, which is more pronounced in modern high-performing broilers compared to their ancestor unselected birds, yet the underlying molecular mechanisms are not fully defined. The present study aimed, therefore, to determine the hypothalamic expression of a newly involved pathway, hypoxia/oxygen homeostasis, in heat-stressed broiler-based research lines and jungle fowl. Three populations of broilers (slow growing ACRB developed in 1956, moderate growing 95RB from broilers available in 1995, and modern fast growing MRB from 2015) and unselected Jungle fowl birds were exposed to cyclic heat stress (36°C, 9 h/day for 4 weeks) in a 2 × 4 factorial experimental design. Total RNAs and proteins were extracted from the hypothalamic tissues and the expression of target genes and proteins was determined by real-time quantitative PCR and Western blot, respectively. It has been previously shown that HS increased core body temperature and decreased feed intake in 95RB and MRB, but not in ACRB or JF. HS exposure did not affect the hypothalamic expression of HIF complex, however there was a line effect for HIF-1α ( P = 0.02) with higher expression in JF under heat stress. HS significantly up regulated the hypothalamic expression of hemoglobin subunits (HBA1, HBBR, HBE, HBZ), and HJV in ACRB, HBA1 and HJV in 95RB and MRB, and HJV in JF, but it down regulated FPN1 in JF. Additionally, HS altered the hypothalamic expression of oxygen homeostasis- up and down-stream signaling cascades. Phospho-AMPK Thr172 was activated by HS in JF hypothalamus, but it decreased in that of the broiler-based research lines. Under thermoneutral conditions, p-AMPK Thr172 was higher in broiler-based research lines compared to JF. Ribosomal protein S6K1, however, was significantly upregulated in 95RB and MRB under both environmental conditions. HS significantly upregulated the hypothalamic expression of NF-κB2 in MRB, RelB, and TNFα in ACRB, abut it down regulated RelA in 95RB. The regulation of HSPs by HS seems to be family- and line-dependent. HS upregulated the hypothalamic expression of HSP60 in ACRB and 95RB, down regulated HSP90 in JF only, and decreased HSP70 in all studied lines. Taken together, this is the first report showing that HS modulated the hypothalamic expression of hypoxia- and oxygen homeostasis-associated genes as well as their up- and down-stream mediators in chickens, and suggests that hypoxia, thermotolerance, and feed intake are interconnected, which merit further in-depth investigations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Brugaletta, Greene, Ramser, Maynard, Tabler, Sirri, Anthony, Orlowski and Dridi.)

Heat stress (HS) is devastating to poultry production sustainability worldwide. In addition to its adverse effects on growth, welfare, meat quality, and mortality, HS alters the gut integrity, leading to dysbiosis and leaky gut syndrome; however, the underlying mechanisms are not fully defined. Here, we used a high-throughput mass spectrometric metabolomics approach to probe the metabolite profile in the duodenum of modern broilers exposed to acute (AHS, 2 h) or chronic cyclic (CHS, 8 h/day for 2 weeks) HS in comparison with thermoneutral (TN) and pair-fed birds. Ultra high performance liquid chromatography coupled with high resolution mass spectrometry (UHPLC-HRMS) identified a total of 178 known metabolites. The trajectory analysis of the principal component analysis (PCA) score plots (both 2D and 3D maps) showed clear separation between TN and each treated group, indicating a unique duodenal metabolite profile in HS birds. Within the HS groups, partial least squares discriminant analysis (PLS-DA) displayed different clusters when comparing metabolite profiles from AHS and CHS birds, suggesting that the metabolite signatures were also dependent on HS duration. To gain biologically related molecule networks, the above identified duodenal metabolites were mapped into the Ingenuity Pathway Analysis (IPA) knowledge-base and analyzed to outline the most enriched biological functions. Several common and specific top canonical pathways were generated. Specifically, the adenosine nucleotide degradation and dopamine degradation pathways were specific for the AHS group; however, the UDP-D-xylose and UDP-D-glucuronate biosynthesis pathways were generated only for the CHS group. The top diseases enriched by the IPA core analysis for the DA metabolites, including cancer, organismal (GI) injury, hematological, cardiovascular, developmental, hereditary, and neurological disorders, were group-specific. The top altered molecular and cellular functions were amino acid metabolism, molecular transport, small molecule biochemistry, protein synthesis, cell death and survival, and DNA damage and repair. The IPA-causal network predicted that the upstream regulators (carnitine palmitoyltransferase 1B, CPT1B; histone deacetylase 11, HDAC11; carbonic anhydrase 9, CA9; interleukin 37, IL37; glycine N-methyl transferase, GNMT; GATA4) and the downstream mediators (mitogen-activated protein kinases, MAPKs; superoxide dismutase, SOD) were altered in the HS groups. Taken together, these data showed that, independently of feed intake depression, HS induced significant changes in the duodenal metabolite profile in a duration-dependent manner and identified a potential duodenal signature for HS.

A novel dietary muramidase has been shown to have positive effects on broiler chickens. However, very little is known about its mechanisms of action. The present multi-omics investigation sought to address this knowledge gap. A total of 2,340 day-old male broilers were assigned to 3 groups (12 replicates each) fed, from 0 to 42 d, a basal diet (control group-CON) or the basal diet supplemented with muramidase at 25,000 (low-dose group-MUL) or 45,000 LSU(F)/kg feed (high-dose group-MUH). MUH significantly outperformed CON in terms of cumulative feed intake (4,798 vs 4,705 g), body weight (2,906 vs 2,775 g), and feed conversion ratio (1.686 vs 1.729), while MUL exhibited intermediate performance. At caecal level, MUH showed the lowest alpha diversity, a significantly different beta diversity, a reduction in Firmicutes, and a rise in Bacteroidetes, especially compared with MUL. MUH also exhibited a considerable decrease in Clostridiaceae and an overrepresentation of Bacteroidaceae and Lactobacillaceae. At blood level, MUH had lower hypoxanthine-probably due to its drop at caecal level-histidine, and uracil, while greater pyruvate, 2-oxoglutarate, and glucose. This study sheds light on the mode of action of this muramidase and lays the groundwork for future investigations on its effects on the intestinal ecosystem and systemic metabolism of broiler chickens., (© 2022. The Author(s).)

Heat stress (HS) has been increasingly jeopardizing the sustainability of the poultry production. Moreover, modern high-performing chickens are far less able to withstand HS than their predecessors due to higher growth rate and metabolic rates. Performance losses caused by HS are mainly ascribed to decreases in feed consumption. Since feed intake is tightly controlled by the hypothalamic centers of hunger and satiety, we sought to determine the effect of chronic cyclic HS on the expression of feeding-related hypothalamic neuropeptides (FRHN) in unselected chickens (i.e., the ancestor junglefowl-JF) and three broiler lines from diverse stages of genetic selection (i.e., the slow growing ACRB, the moderate growing 95RN, and the fast growing MRB). From 29 to 56 days, birds ( n = 150 birds for each population) were subjected to either thermoneutral (TN, 25°C) or cyclic heat stress (HS, 36°C, 0900-1,800 h) conditions. Molecular data were analyzed by two-way ANOVA with interaction between the main factors, namely environmental temperature and line. The expression of major FHRN, like neuropeptide Y, agouti-related peptide, proopiomelanocortin, and cocaine and amphetamine regulated transcript remained unchanged. However, melanocortin receptor 1 exhibited a line-dependent decreasing trend from JF to MRB under both TN and HS ( p = 0.09), adiponectin expression showed a distinct trend toward significance with 95RB exhibiting the highest mRNA level irrespective of the environmental temperature ( p = 0.08), and JF had a greater mRNA abundance of visfatin than ACRB under TN ( p < 0.05). The hypothalamic integration of circadian information, acclimation to long-lasting HS exposure, stable hypothalamic pathways unaffected by evolution and genetic selection, focus on mRNA abundances, and use of the entire hypothalamus masking gene expression in specific hypothalamic nuclei are all possible explanations for the lack of variations observed in this study. In conclusion, this is the first assessment of the impacts of heat stress on feeding-related hypothalamic neuropeptides of chicken, with a valuable and informative comparison between the ancestor junglefowl and three differently performing broiler lines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Brugaletta, Greene, Tabler, Orlowski, Sirri and Dridi.)

Solid evidence underlines the pivotal role played by inflammation regarding atherosclerosis. Peripheral artery disease (PAD) is one of atherosclerotic cardiovascular diseases (CVDs), it is highly frequently diagnosed in older individuals. In the present study we carried out an investigation on the association between platelet‑to‑lymphocytes ratio (PLR), neutrophil‑to‑lymphocyte ratio (NLR), monocyte‑to‑HDL cholesterol ratio (MHR) with PAD as favourable markers. We identified 300 subjects aged over 70 years, without any concomitant CVDs. The PLR, NLR and MHR were assessed from peripheral venous blood routinely drawn in the ward during hospitalization. Patients were divided in groups according to ankle brachial index (ABI) value (>0.9; 0.9‑0.99; 1‑1.4; >1.4). Higher PLR (P=0.007), NLR (P=0.0001) and MHR (P=0.0001) were associated with <0.9 ABI. Patients with a >1.4 ABI showed NLR values higher compared to >0.9l ABI (P<0.01). Univariate linear regression analysis demonstrated the direct correlation between increase in PLR (P=0.0023)and MHR (P<0.0001) with the decrease in ABI value. In multivariate linear regression analysis including main cardiovascular risk factors we found that PLR, NLR and MHR were independently associated with lower ABI (P=0.0011). Results show and suggest that the elevated PLR, NLR and MHR are related to PAD evaluated with ABI measurement. PLR and MHR seem to be more reliable markers than NLR in PAD. NLR seems to be more related to incompressibility of arterial wall. It is hypothesized that these three indexes may play a role as simple and repetitive markers of PAD.

This research investigated the effects of different synbiotic administration programs on broiler productive performance and foot pad dermatitis (FPD). Molecular insights on caecal microbiota and plasma metabolomics were also performed. - A total of 1000 one-day-old male chicks were grouped by the synbiotic treatment. The synbiotic was either sprayed as gel droplets onto newly hatched chicks at the hatchery (100 g/10,000 birds) or supplemented in-feed during the entire rearing period (1000, 500, and 250 g/ton according to feeding phase), or both. Only the treatments' combination produced significant results in comparison with the control group (untreated), improving feed conversion ratio from 14 to 29 d and in the overall period of the trial (1.570 vs. 1.509 and 1.643 vs. 1.596, respectively; p < 0.05) while lowering FPD occurrence at slaughter (17% vs. 5%; p < 0.05). These findings can be related to significant variations of caecal microbiota, like higher Firmicutes to Bacteroidetes ratio (with favorable implications for host's energy-harvesting potential from the diet) and more beneficial microbial consortium presumably sustaining eubiosis. Overall, these results indicate that administering synbiotics through gel droplets at the hatchery combined to in-feed supplementation for the whole growing cycle positively affects broiler feed efficiency and welfare.