Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance.

Mitofusin 2 (MFN2) plays critical roles in both mitochondrial fusion and the establishment of mitochondria-endoplasmic reticulum (ER) interactions. Hypothalamic ER stress has emerged as a causative factor for the development of leptin resistance, but the underlying mechanisms are largely unknown. Here, we show that mitochondria-ER contacts in anorexigenic pro-opiomelanocortin (POMC) neurons in the hypothalamus are decreased in diet-induced obesity. POMC-specific ablation of Mfn2 resulted in loss of mitochondria-ER contacts, defective POMC processing, ER stress-induced leptin resistance, hyperphagia, reduced energy expenditure, and obesity. Pharmacological relieve of hypothalamic ER stress reversed these metabolic alterations. Our data establish MFN2 in POMC neurons as an essential regulator of systemic energy balance by fine-tuning the mitochondrial-ER axis homeostasis and function. This previously unrecognized role for MFN2 argues for a crucial involvement in mediating ER stress-induced leptin resistance.

Synthesis of a new 2-prenylated quinoline as potential drug for metabolic syndrome with pan-PPAR activity and anti-inflammatory effects.

We have previously reported the total synthesis and structure-activity relationships (SAR) of 2-prenylated benzopyrans with PPAR agonist activity. Herein, we have described the synthesis and PPAR activity of 2-prenylated benzopyrans and 2-prenylated quinolines. The benzopyran nucleus was generated via enamine-catalyzed Kabbe condensation, and the quinoline nucleus via Friedländer condensation. Results demonstrated that both benzopyran (5a) and quinoline (4b) derivatives bearing a γ,δ-unsaturated ester displayed a pan-PPAR agonism. They were full PPARα agonists, but showed different preferences for PPARγ and PPARß/δ activation. It was noteworthy that quinoline 4b displayed full hPPARα activation (2-fold than WY-14,643), weak PPARß/δ and partial PPARγ activation. In addition, quinoline 4b showed anti-inflammatory effects on macrophages by reducing LPS-induced expression of both MCP-1 and IL-6. Therefore, 4b emerges as a first-in-class promising hit compound for the development of potential therapeutics aimed at treating metabolic syndrome, metabolic dysfunction-associated fatty liver disease (MAFLD), and its associated cardiovascular comorbidities.

The potential of lemon peel powder as an additive in layer quails (Coturnix coturnix Japonica): An experimental study.

The current research intended to examine the impact of dietary lemon peel powder (LPP) on laying quail performance, egg quality criteria, and the antioxidant capacity of the yolk. A total of 120 female Japanese quails (272.6±9.3 g), aged 21 weeks, were allotted to 6 trial groups, each with 5 replicates of 4 quails. Additions of 0, 1, 2, 3, 4, or 5 g/kg of LPP to the basal diet were used to create the treatment groups. Quails were fed ad libitum for 70 days. Neither performance parameters nor egg production was affected by LPP. However, eggshell-breaking strength improved by adding 2 g/kg LPP to the diet, but worsened at 5 g/kg. Moreover, the relative weight of eggshell and yolk L* value decreased with the treatments. Dietary LPP enhanced oxidative stability, reducing malondialdehyde (MDA) and increasing 1,1-diphenyl-2-picrylhydrazyl (DPPH) yolk values. The current study demonstrated that LPP, a safe and easily accessible agricultural by-product, enhanced eggshell quality when it was included in the diet of laying quails at doses of 2 g/kg. In contrast, improvement of yolk antioxidant capacity required increased amounts of LPP (4 g/kg). LPP could be advantageous to animal nutrition as an adequate substitute to reduce waste by-products.

Dietary supplementation with mushroom powder (Agaricus bisporus) on performance, carcass traits, meat quality, and bone biomechanical properties of quail (Coturnix coturnix japonica).

This study was performed to determine the effect of mushroom powder (MP) (Agaricus bisporus) supplementation on growing Japanese quail (Coturnix coturnix japonica). A total of 300 unsexed 1-day-old Japanese quails with similar body weights (8.38 ± 0.2 g) were randomly assigned to five treatment groups with six replications. Additions of 0, 0.25, 0.50, 0.75, or 1.00% of MP to the basal diet were used to develop the treatment groups. Quails were fed ad libitum for 42 days. At the end of the experiment, 12 quails from each experimental unit were euthanised to determine performance, carcass traits, meat quality, and bone biochemical properties. Results showed that all dietary MP did not negatively affect any performance parameters (P > 0.05), while by the third week of life, there was an increase (P < 0.05) in body weight and body weight gain in the quails of the 0.75% MP group compared to the control group. Nevertheless, these differences disappeared at the end of the trial (P > 0.05). No differences were observed (P > 0.05) for any of the studied carcass traits, except for the pancreas weight which decreased (P < 0.05) with the addition of high MP (1.00%). Regarding meat quality, all color parameters were affected on the fifth day of sampling (P < 0.05) but not on the first day (P > 0.05). It was detected that the breast of the quails in group 0.75% MP had the highest L* value and the lowest a* value. While the breast of the 1.00% MP group had the highest b value and the lowest pH value. Dietary MP enhanced oxidative stability, reducing malondialdehyde (MDA) value in the breast compared to the control at both sampling points (P < 0.01), being more noted on the fifth day of sampling. Bone biomechanical properties (in terms of shear force or shear stress) were improved (P < 0.01) with the dietary addition of MP at 0.75% compared to the control. It can be suggested that MP is a secure ingredient in animal feed without negatively affecting performance parameters, carcass traits, or meat quality. Therefore, including an interval of 0.50-0.75% of MP in the diet of growing quails could be a suitable strategy to improve certain parameters such as the meat's oxidative stability and the bone's biomechanical parameters. Moreover, the efficacy of MP on performance development would be greater during the first weeks of the quails' life due to their intestinal conditions at this stage.

Anti-inflammatory effects and improved metabolic derangements in ob/ob mice by a newly synthesized prenylated benzopyran with pan-PPAR activity.

BACKGROUND AND PURPOSE: Selective peroxisome proliferator-activated receptors (PPARs) are widely used to treat metabolic complications; however, the limited effect of PPARα agonists on glucose metabolism and the adverse effects associated with selective PPARγ activators have stimulated the development of novel pan-PPAR agonists to treat metabolic disorders. Here, we synthesized a new prenylated benzopyran (BP-2) and evaluated its PPAR-activating properties, anti-inflammatory effects and impact on metabolic derangements. EXPERIMENTAL APPROACH: BP-2 was used in transactivation assays to evaluate its agonism to PPARα, PPARß/δ and PPARγ. A parallel-plate flow chamber was employed to investigate its effect on TNFα-induced leukocyte-endothelium interactions. Flow cytometry and immunofluorescence were used to determine its effects on the expression of endothelial cell adhesion molecules (CAMs) and chemokines and p38-MAPK/NF-κB activation. PPARs/RXRα interactions were determined using a gene silencing approach. Analysis of its impact on metabolic abnormalities and inflammation was performed in ob/ob mice. KEY RESULTS: BP-2 displayed strong PPARα activity, with moderate and weak activity against PPARß/δ and PPARγ, respectively. In vitro, BP-2 reduced TNFα-induced endothelial ICAM-1, VCAM-1 and fractalkine/CX3CL1 expression, suppressed mononuclear cell arrest via PPARß/δ-RXRα interactions and decreased p38-MAPK/NF-κB activation. In vivo, BP-2 improved the circulating levels of glucose and triglycerides in ob/ob mice, suppressed T-lymphocyte/macrophage infiltration and proinflammatory markers in the liver and white adipose tissue, but increased the expression of the M2-like macrophage marker CD206. CONCLUSION AND IMPLICATIONS: BP-2 emerges as a novel pan-PPAR lead candidate to normalize glycemia/triglyceridemia and minimize inflammation in metabolic disorders, likely preventing the development of further cardiovascular complications.

The use of purple carrot powder in the diet of laying quails improved some egg quality characteristics, including antioxidant capacity.

The goal of the current experiment was to investigate the effect of dietary concentrations of purple carrot powder (PCP) on performance, egg production, egg quality, and the antioxidant capacity of the yolk in laying quails. A total of one hundred and fifty 22-week-old Japanese laying quails were allotted to 5 dietary treatments each with 6 replicates of 5 quails. Quails were allocated to five dietary treatments (0, 0.1, 0.2, 0.3, and 0.4%) with PCP addition at an increasing level from 0 to 4000 mg/kg diet respectively, which were fed ad-libitum throughout the duration of the experiment. No differences were detected between dietary treatments for any of the performance parameters or egg production. Eggshell weight and eggshell thickness (P < 0.05) were linearly affected by PCP dietary, reaching maximum levels at 0.4% of PCP supplementation, while the percentage of damaged egg and egg-breaking strength remained similar for all experimental groups (P < 0.05). Quails receiving PCP diets showed a yellowness (b*) (P < 0.05) egg yolk color than those fed the control diet, without affecting the rest of the color parameters and egg internal quality. Increasing PCP levels in diets reduced linearly yolk TBARS (P < 0.01) and increased linearly DPPH (P < 0.01). The addition of PCP, a safe and readily available agricultural by-product, as a component of the diet of laying quail was effective without adversely affecting quail production. Moreover, the inclusion of PCP in the diet might benefit laying quails' eggs by improving some quality traits and enhancing the yolk's antioxidant capacity, which could improve their shelf-life and acceptability.

Reuse of vegetable wastes in animal feed: the influence of red beet powder supplementation on performance, egg quality, and antioxidant capacity of layer quails.

The survey was carried out to establish the impact of red beet powder (RBP) on performance parameters and egg quality in laying quails. One twenty hundred (120) female laying quails aged 22 weeks were randomly assigned into five groups of 4 females each, and six replicates. Treatments diets were formed by adding 0, 0.2, 0.4, 0.6, and 0.8% RBP to the basal diet. The dietary inclusion of RBP did not affect performance parameters and egg production (P > 0.05) except feed conversion ratio, which was quadratically affected (P < 0.05). The feed conversion ratio was improved in the 0.4% group with concerning control. The inclusion of RBP did not modify the yolk color (L*, a*, b*) or egg quality (P > 0.05). However, the yolk index showed the highest value (P < 0.05) in quails fed 0.2% RBP. Free radical scavenging capacity (DPPH) of the yolk decreased (P < 0.05) when RBP levels increased above 0.6%. In contrast, the 0.6% RBP group had the highest level of thiobarbituric acid reactive substances (TBARS). Data from the present study provide valuable information to include RBP as an ingredient without affecting performance and egg production. It is an interesting option within the framework of the circular economy and of reusing vegetable products to use this ingredient in animal feed.

Synthesis and biological studies of "Polycerasoidol" and "trans-δ-Tocotrienolic acid" derivatives as PPARα and/or PPARγ agonists.

2-Prenylated benzopyrans represent a class of natural and synthetic compounds showing a wide range of significant activities. Polycerasoidol is a natural prenylated benzopyran isolated from the stem bark of Polyalthia cerasoides (Annonaceae) that exhibits dual PPARα/γ agonism and an anti-inflammatory effect by inhibiting mononuclear leukocyte adhesion to the dysfunctional endothelium. Herein, we report the synthesis of three new series of prenylated benzopyrans containing one (series 1), two (series 2, "polycerasoidol" analogs) and three (series 3, "trans-δ-tocotrienolic acid" analogs) isoprenoid units in the hydrocarbon side chain at the 2-position of the chroman-6-ol (6-hydroxy-dihydrobenzopyran) scaffold. Isoprenoid moieties were introduced through a Grignard reaction sequence, followed by Johnson-Claisen rearrangement and subsequent Wittig olefination. hPPAR transactivation activity and the structure activity relationships (SAR) of eleven novel synthesized 2-prenylated benzopyrans were explored. PPAR transactivation activity demonstrated that the seven-carbon side chain analogs (series 1) displayed selectivity for hPPARα, while the nine-carbon side chain analogs (polycerasoidol analogs, series 2) did so for hPPARγ. The side chain elongation to 11 or 13 carbons (series 3) resulted in weak dual PPARα/γ activation. Therefore, 2-prenylated benzopyrans of seven- and nine-carbon side chain (polycerasoidol analogs) are good lead compounds for developing useful candidates to prevent cardiovascular diseases associated with metabolic disorders.

Clinical Burden of Inpatient Wound Care in Internal Medicine Units During the First Wave of COVID-19 Outbreak.

OBJECTIVE: To explore the clinical burden and epidemiologic profile of hospitalized patients with wounds during the first wave of COVID-19. METHODS: A retrospective and observational study was conducted to analyze the inpatient episodes of wound care in the University Hospital of Salamanca (Spain) during the initial COVID-19 crisis from March 1, 2020, to June 1, 2020. Data were collected from nursing care reports and clinical discharge reports. Included patients were 18 years or older, had a hospital length of stay of 1 day or longer, and were hospitalized in an internal medicine unit. Surgical and traumatic wounds and pediatric patients were excluded. RESULTS: A total of 116 patients and 216 wounds were included. The overall wound prevalence was 7.6%, and incidence was 3.5% in the internal medicine units. Pressure injuries (PIs) were the most common wound type, and patients with COVID-19 had significantly higher PI risk (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.1-4.0; P = .042). Significant differences in PI staging were noted: 83.2% of wounds in patients with COVID-19 were stages I-II versus 67.8% in patients without COVID-19; the probability of stage III-IV PIs among patients without COVID-19 was doubled (OR, 2.3; 95% CI, 1.2-4.5; P = .009). The probability of acute wounds tripled in patients with COVID-19 (OR, 3.7; 95% CI, 2.1-6.6; P < .001). Patients with COVID-19 also had longer mean hospital stays and higher ICU admission rates. No case fatality rate differences were observed. CONCLUSIONS: In this context of clinical practice, protocolized assessment and implementation of preventive measures must be ensured among older adult populations, patients with associated comorbidities, and ICU patients.

Tungstate promotes ß-cell survival in Irs2-/- mice.

Pancreatic ß-cells play a central role in type 2 diabetes (T2D) development, which is characterized by the progressive decline of the functional ß-cell mass that is associated mainly with increased ß-cell apoptosis. Thus, understanding how to enhance survival of ß-cells is key for the management of T2D. The insulin receptor substrate-2 (IRS-2) protein is pivotal in mediating the insulin/IGF signaling pathway in ß-cells. In fact, IRS-2 is critically required for ß-cell compensation in conditions of increased insulin demand and for ß-cell survival. Tungstate is a powerful antidiabetic agent that has been shown to promote ß-cell recovery in toxin-induced diabetic rodent models. In this study, we investigated whether tungstate could prevent the onset of diabetes in a scenario of dysregulated insulin/IGF signaling and massive ß-cell death. To this end, we treated mice deficient in IRS2 (Irs2(-/-)), which exhibit severe ß-cell loss, with tungstate for 3 wk. Tungstate normalized glucose tolerance in Irs2(-/-) mice in correlation with increased ß-cell mass, increased ß-cell replication, and a striking threefold reduction in ß-cell apoptosis. Islets from treated Irs2(-/-) exhibited increased phosphorylated Erk1/2. Interestingly, tungstate repressed apoptosis-related genes in Irs2(-/-) islets in vitro, and ERK1/2 blockade abolished some of these effects. Gene expression profiling showed evidence of a broad impact of tungstate on cell death pathways in islets from Irs2(-/-) mice, consistent with reduced apoptotic rates. Our results support the finding that ß-cell death can be arrested in the absence of IRS2 and that therapies aimed at reversing ß-cell mass decline are potential strategies to prevent the progression to T2D.

Benzopyran hydrazones with dual PPARα/γ or PPARα/δ agonism and an anti-inflammatory effect on human THP-1 macrophages.

Peroxisome proliferator-activated receptors (PPARs) play a major role in regulating inflammatory processes, and dual or pan-PPAR agonists with PPARγ partial activation have been recognised to be useful to manage both metabolic syndrome and metabolic dysfunction-associated fatty liver disease (MAFLD). Previous works have demonstrated the capacity of 2-prenylated benzopyrans as PPAR ligands. Herein, we have replaced the isoprenoid bond by hydrazone, a highly attractive functional group in medicinal chemistry. In an attempt to discover novel and safety PPAR activators, we efficiently prepared benzopyran hydrazone/hydrazine derivatives containing benzothiazole (series 1) or 5-chloro-3-(trifluoromethyl)-2-pyridine moiety (series 2) with a 3- or 7-carbon side chain at the 2-position of the benzopyran nucleus. Benzopyran hydrazones 4 and 5 showed dual hPPARα/γ agonism, while hydrazone 14 exerted dual hPPARα/δ agonism. These three hydrazones greatly attenuated inflammatory markers such as IL-6 and MCP-1 on the THP-1 macrophages via NF-κB activation. Therefore, we have discovered novel hits (4, 5 and 14), containing a hydrazone framework with dual PPARα/γ or PPARα/δ partial agonism, depending on the length of the side chain. Benzopyran hydrazones emerge as potential lead compounds which could be useful for treating metabolic diseases.

Effect of dietary fat on proximal composition, sensorial analysis and shelf life of a traditional Spanish cooked pork product "Lomo de Sajonia" from Iberian pork.

This study aims to evaluate the effect of different dietary fat sources on the quality of a Spanish-cooked meat product Lomo de Sajonia (LSA) and its shelf-life. Forty loins were selected from Iberian pigs fed four dietary treatments containing pork fat (G-1), Greedy-Grass Olive® (GGO) (enriched oleic-acid oil) (G-2), G-2 and high oleic sunflower (G-3), and G-3 plus a mixture of commercial organic acids (Bioll®) (G-4). Loins were manufactured to obtain LSA, and the quality and sensorial attributes were assessed. The shelf life was established according to microbial count and sensorial analysis, which was packed in a modified atmosphere and stored under retail conditions. All meat quality parameters of LSA remained stable in all groups, except fat content and overall liking, which showed the highest values for G-2 LSA. Regarding the shelf life, sensorial attributes remained acceptable in all groups during storage time, while a delay in microbial growth was recorded for the LSA of G-3. According to the results, including GGO in Iberian pig diets could enhance LSA traits, possibly linked to increased assimilation compared with conventional fat sources. However, adding organic acids to the diet did not have the expected effect on improving the shelf life of the LSA.

Comparative Effects of Including Inorganic, Organic, and Hydroxy Zinc Sources on Growth Development, Egg Quality, Mineral Excretion, and Bone Health of Laying Quails.

The purpose of this study was to determine the effects of the dietary addition of zinc (Zn) in the form of sulphate (Zn-S), glycine (Zn-G), and hydroxychloride (Zn-H) on quail performance, eggshell quality, antioxidant status, mineral excretion, biomechanical properties and mineralization of bone. A total of 75 female quails (10-weeks-old) were randomly distributed into 3 groups with 5 replications, each with 5 female quails. Treatment groups were set up by adding Zn-S and Zn-H as the inorganic form and Zn-G as the organic form of zinc to the corn-soybean basal diet (34.14 mg/kg Zn) to obtain 50 mg/kg Zn and the feeding experiment lasted for 12 weeks. Performance parameters and egg production were not impaired by the Zn source (P > 0.05). The inclusion of Zn-S in the diet produced a reduction in eggshell thickness, while an improvement in yolk antioxidant capacity (measured as MDA concentration) was detected compared to the other Zn sources (P < 0.05). Shear strength and cortical bone area increased (P < 0.05) with Zn-G supplementation, however, the mineral concentration of the tibia was higher (P < 0.01) in those quails who had received Zn-H. Lower levels of mineral excretion were observed in both types of supplementations compared to Zn-S. Therefore, it can be stated that Zn-G or Zn-H supplementation in the diet of laying quails could be an interesting strategy to reduce mineral excretion and improve bone mineralization without affecting performance compared to Zn-S. However, further studies are needed to determine the differences between Zn-G and Zn-H.

Downregulation of Sfrp5 promotes beta cell proliferation during obesity in the rat.

AIMS/HYPOTHESIS: During obesity, the increment in beta cell mass in response to the rising demand for insulin is essential to maintain normal glucose homeostasis. However, the precise cellular and molecular mechanisms involved in beta cell mass plasticity remain poorly understood. The Wnt signalling pathway has been suggested as one possible modulator of beta cell proliferation, which represents the principal process involved in beta cell mass expansion. Here, we sought to determine the mechanisms involved in beta cell mass proliferation using diet-induced obese rats. METHODS: Wistar rats aged 8 weeks old were fed a standard or cafeteria diet. Global transcriptomic analysis of pancreatic rat islets was performed using microarray analysis. Genetic loss-of-function approaches were performed in dispersed primary rat islets and the beta cell line INS1E. Gene expression was measured by real-time PCR, protein levels by immunoblot analysis, proliferation rates by ELISA and apoptosis by flow cytometry. RESULTS: Sfrp5, coding for secreted frizzled-related protein 5, is downregulated in the pancreatic islets of cafeteria-diet-fed rats as well as in the pancreatic islets of human obese patients. We demonstrate that silencing Sfrp5 increases beta cell proliferation, which correlates with activation of Wnt signalling and enhanced levels of proliferation markers. In addition, we show that expression of Sfrp5 in beta cells is modulated by IGF binding protein 3 (IGFBP3) secreted from visceral adipose tissue. CONCLUSIONS/INTERPRETATION: Together, these findings reveal an important role for SFRP5 and Wnt signalling in the regulation of beta cell proliferation in obesity.

Improving Fatty Acid Profile in Native Breed Pigs Using Dietary Strategies: A Review.

Meat from native-bred animals is growing in popularity worldwide due to consumers' perception of its higher quality than meat from industrial farms. The improvement in indigenous pork has been related to increased intramuscular and unsaturated fat and a reduced saturated fat content resulting in a healthy product with enhanced sensorial attributes. This manuscript aims to provide an overview offering useful information about the fat content and the fatty acid profile of different autochthonous pork. Fat content and fatty acid profile are greater in native than in industrial pig breeds, even though certain factors, such as genetics, nutrition, farming system, age, or slaughter weight, may influence these variations. Among that, studies on dietary strategies to improve these parameters have been evaluated. According to the results obtained, many natural ingredients could have a positive effect on the lipid profile when added to indigenous pigs' diets. This fact may promote autochthonous pork intake. Nevertheless, there is a wide range of potential natural ingredients to be added to the indigenous pig diet that needs to be evaluated.

Synthesis of 2-aminopropyl benzopyran derivatives as potential agents against triple-negative breast cancer.

Synthesis of three series of 2-aminopropyl derivatives containing a benzopyran nucleus was performed to evaluate their performance against triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-436) and normal breast epithelial cells (MCF10A). For the three series, the cytotoxic activity was as follows: N-methylated derivatives (tertiary amines) 5b, 6b, and 7b > secondary amine benzopyrans 5, 6, and 7 > quaternary amine salts 5c, 6c, and 7c > free phenolic derivatives 5a, 6a, and 7a. The structure-activity relationship showed the importance of the presence of an amine group and a p-fluorobenzyloxy substituent in the chromanol ring (IC50 values from 1.5 µM to 58.4 µM). In addition, 5a, 5b, 6a, and 7b displayed slight selectivity towards tumor cells. Compounds 5, 5a, 5b, 6, 6a, 6c, 7, and 7b showed apoptotic/necrotic effects due to, at least in part, an increase in reactive oxygen species generation, whereas 5b, 5c, 6b, 7a, and 7c caused cell cycle arrest in the G1 phase. Further cell-based mechanistic studies revealed that 5a, 6a, and 7b, which were the most promising compounds, downregulated the expression of Bcl-2, while 5b downregulated the expression of cyclins CCND1 and CCND2. Therefore, 2-aminopropyl benzopyran derivatives emerge as new hits and potential leads for developing useful agents against breast cancer.

Does the addition of choline and/or betaine to diets reduce the methionine requirements of laying quails? Assessment of performance and egg antioxidant capacity.

The purpose of the present study was to assess the performance, quality of eggs internally and externally, and antioxidant capacity of yolks in laying quails with the administration of choline and betaine to diets containing reduced methionine levels. A total of 150 Japanese laying quails (Coturnix coturnix japonica) at the 10-wk age were randomly assigned to 6 experimental groups, each consisting of 5 replicates and 5 birds for 10 wk. The treatment diets were designed by adding the following substances: 0.45% methionine (C), 0.30% methionine (LM), 0.30% methionine + 0.15% choline (LMC), 0.30% methionine + 0.20% betaine (LMB), 0.30% methionine + 0.075% choline + 0.10% betaine (LMCB1), 0.30% methionine + 0.15% choline + 0.20% betaine (LMCB2). The treatments did not affect performance, egg production, or egg internal quality (P > 0.05). No significant effect was determined on the damaged egg rate (P > 0.05), but the egg-breaking strength, eggshell thickness, and eggshell relative weight decreased in the LMCB2 group (P < 0.05). Regarding lipid peroxidation, treatments did not affect the yolk 2,2 diphenyl-1-picrylhydrazyl value (P > 0.05), although the lowest thiobarbituric acid reactive substances value was observed in the LMB compared to the control group (P < 0.05). It may be summarized that methionine can be decreased to levels of 0.30% for laying quail diets with no negative effect on performance, egg production, or egg internal quality, whereas the combination of methionine (0.30%) and betaine (0.2%) could improve antioxidant stability of eggs over the 10-wk experimental period. These findings provide useful information to the traditional recommendations on the requirements of laying quail. However, further studies are needed to test whether these effects persist throughout extended study periods.

Is the Increase in Record of Skin Wounds in Hospitalized Patients in Internal Medicine Units a Side Effect of the COVID-19 Pandemic?

Wound care is an important public health challenge that is present in all areas of the healthcare system, whether in hospitals, long term care institutions or in the community. We aimed to quantify the number of skin wounds reported after and during the COVID-19 pandemic. This descriptive longitudinal retrospective study compared of wound records in patients hospitalized in the internal medicine service during the first year of the COVID-19 pandemic (from 1 March 2020, to 28 February 2021) and previous-year to the outbreak (from 1 January 2019, to 31 December 2019). A sample of 1979 episodes was collected corresponding to 932 inpatients, 434 from the pre-pandemic year and 498 from the first year of COVID-19 pandemic; 147 inpatients were diagnosed with SARS-CoV-2 infection (3.2%). The percentage of wound episodes in the first year of the COVID-19 pandemic was higher than the pre-pandemic year, 17.9% (1092/6090) versus 15% (887/5906), with a significant increase in the months with the highest incidence of COVID cases. This study shows an increase in the burden of wound care during the COVID-19 pandemic, and it could be attributable to the increase in the number of patients hospitalized for SARS-CoV-2 infection in internal medicine units.

A Novel External Auditory Canal Squamous Cell Carcinoma Cell Line Sensitive to CDK4/6 Inhibition.

OBJECTIVE: To characterize cell line CAE606 derived from a squamous cell carcinoma (SCC) of the external auditory canal (EAC) and to show its usefulness as a model for testing candidate therapeutic agents. STUDY DESIGN: Preclinical translational research. SETTING: Biomedical research institute. METHODS: The cell line was initiated from a moderately differentiated T2N0M0 EAC SCC. We studied its histologic and genetic features as well as growth and invasion parameters. Sensitivity to cell CDK4/6 cell cycle inhibitor palbociclib was analyzed. RESULTS: CAE606 cells expressed heavy molecular weight cytokeratin, p63, and vimentin. The population doubling time was 25.8 hours, and the cells showed fast collective cell migration in a wound-healing assay. Short tandem repeat analysis confirmed it to be derived from the primary tumor of the patient. Next-generation sequencing revealed alterations in cell cycle regulation genes, including inactivating mutations in CDKN2A and TP53 and high-level amplification of CCND1 and EGFR. CAE606 showed a strong decrease of phospo-Rb expression upon exposure to the CDK4/6 inhibitor palbociclib, causing significant growth inhibition with an IC50 of 0.46 µM. CONCLUSION: This is the first report of a stable EAC SCC cell line. Its genetic features make it a useful tool for preclinical testing of new therapeutic agents for EAC SCC, particularly those targeting cell cycle regulation in combination with radio- and chemotherapy or other specific signaling pathway inhibitors.

A technical improvement in retropharyngeal carotid reconstruction.

The carotid-carotid bypass via a retropharyngeal tunnel enables treating proximal occlusions. With reference to two clinical cases, we present a technique that consists of transposition of one of the carotid arteries to contralateral position, avoiding simultaneous clamping of both carotids.