Genetic parameters for milk yield and reproductive traits in Honduran Holstein cattle.

The aim of this study was to estimate the (co)variance components and genetic parameters for milk yield adjusted to 305d (MY305), calving-to-conception interval (CCI), number of services per conception (NSC) and calving interval (CI) of Honduran Holstein cows, by fitting a bivariate animal model using Maximum Restricted Likelihood procedures. Model included the fixed effects of calving number, the contemporary calving group (farm-season-year of calving and the cow age as covariate). The estimated means and standard deviations for MY, CCI, NSC and CI were, 5098.60 ± 1564.32 kg, 168.27 ± 104.71 days, 2.46 ± 1.69 services, and 448.73 ± 109.16 days, respectively; and their estimated heritabilities were 0.21 ± 0.05, 0.03 ± 0.028, 0.02 ± 0.024 and 0.06 ± 0.04, respectively. The genetic correlations between MY305 and CCI, NSC and CI were positive and antagonist, with values of 0.64 ± 0.52, 0.99 ± 0.56, and 0.32 ± 0.24 respectively. Even though moderate to low heritability was estimated for MY305, systematic selection for milk yield, with a reduction in reproductive efficiency, if considered as the only selection criterion is important to be considered. By including reproductive traits and considering permanent environment effects into the breeding program, might yield a slow, but constant and permanent improvement over time.

Effects of Exercise Intervention for the Management of Delirium in Hospitalized Older Adults: A Randomized Clinical Trial.

OBJECTIVE: Delirium is a serious neuropsychiatric syndrome frequently occurring in hospitalized older adults, for which pharmacological treatments have shown limited effectiveness. Multicomponent physical exercise programs have demonstrated functional benefits; however, the impact of exercise on the course of delirium remains unexplored. The aim of this study was to investigate the effect of an individualized, multicomponent exercise intervention on the evolution of delirium and patient outcomes. DESIGN: A single-center, single-blind randomized controlled trial. SETTING AND PARTICIPANTS: Medical inpatients with delirium in an acute geriatric unit of a tertiary public hospital. METHODS: Thirty-six patients (mean age 87 years) were recruited and randomized into 2 groups. The control group received usual care and the intervention group received individualized physical exercise (1 daily session) for 3 consecutive days. Primary endpoints were the duration and severity of delirium (4-AT, Memorial Delirium Assessment Scale) and change in functional status [Barthel Index, Short Physical Performance Battery, Hierarchical Assessment of Balance and Mobility (HABAM), and handgrip strength]. Secondary endpoints included length of stay, falls, and health outcomes at 1- and 3-month follow-up. RESULTS: The intervention group showed more functional improvement at discharge (HABAM, P = .015) and follow-up (Barthel, P = .041; Lawton P = .027). Less cognitive decline was observed at 1 and 3 months (Informant Questionnaire on Cognitive Decline in the Elderly, P = .017). Exercise seemed to reduce delirium duration by 1 day and contribute to delirium resolution at discharge, although findings did not reach statistical significance. No exercise-related adverse events occurred. CONCLUSION AND IMPLICATIONS: Findings suggest that individualized exercise in acutely hospitalized older patients with delirium is safe, may improve delirium course and help preserve post-hospitalization function and cognition.

The Effect of HMGB1 and HMGB2 on Transcriptional Regulation Differs in Neuroendocrine and Adenocarcinoma Models of Prostate Cancer.

Human high-mobility group-B (HMGB) proteins regulate gene expression in prostate cancer (PCa), a leading cause of oncological death in men. Their role in aggressive PCa cancers, which do not respond to hormonal treatment, was analyzed. The effects of HMGB1 and HMGB2 silencing upon the expression of genes previously related to PCa were studied in the PCa cell line PC-3 (selected as a small cell neuroendocrine carcinoma, SCNC, PCa model not responding to hormonal treatment). A total of 72% of genes analyzed, using pre-designed primer panels, were affected. HMGB1 behaved mostly as a repressor, but HMGB2 as an activator. Changes in SERPINE1, CDK1, ZWINT, and FN1 expression were validated using qRT-PCR after HMGB1 silencing or overexpression in PC-3 and LNCaP (selected as an adenocarcinoma model of PCa responding to hormonal treatment) cell lines. Similarly, the regulatory role of HMGB2 upon SERPINE1, ZWINT, FN1, IGFPB3, and TYMS expression was validated, finding differences between cell lines. The correlation between the expression of HMGB1, HMGB2, and their targets was analyzed in PCa patient samples and also in PCa subgroups, classified as neuroendocrine positive or negative, in public databases. These results allow a better understanding of the role of HMGB proteins in PCa and contribute to find specific biomarkers for aggressive PCa.

Association of postoperative delirium with serum and cerebrospinal fluid proteomic profiles: a prospective cohort study in older hip fracture patients.

Postoperative delirium (POD) is a common neuropsychiatric complication in geriatric inpatients after hip fracture surgery and its occurrence is associated with poor outcomes. The purpose of this study was to investigate the relationship between preoperative biomarkers in serum and cerebrospinal fluid (CSF) and the development of POD in older hip fracture patients, exploring the possibility of integrating objective methods into future predictive models of delirium. Sixty hip fracture patients were recruited. Blood and CSF samples were collected at the time of spinal anesthesia when none of the subjects had delirium. Patients were assessed daily using the 4AT scale, and based on these results, they were divided into POD and non-POD groups. The Olink® platform was used to analyze 45 cytokines. Twenty-one patients (35%) developed POD. In the subsample of 30 patients on whom proteomic analyses were performed, a proteomic profile was associated with the incidence of POD. Chemokine (C-X-C motif) ligand 9 (CXCL9) had the strongest correlation between serum and CSF samples in patients with POD (rho = 0.663; p < 0.05). Although several cytokines in serum and CSF were associated with POD after hip fracture surgery in older adults, there was a significant association with lower preoperative levels of CXCL9 in CSF and serum. Despite the small sample size, this study provides preliminary evidence of the potential role of molecular biomarkers in POD, which may provide a basis for the development of new delirium predictive models.

Design rules for efficient endosomal escape.

The inefficient translocation of proteins across biological membranes limits their application as therapeutic compounds and research tools. In most cases, translocation involves two steps: uptake into the endocytic pathway and endosomal escape. Certain charged or amphiphilic molecules promote protein uptake but few enable efficient endosomal escape. One exception is ZF5.3, a mini-protein that exploits natural endosomal maturation machinery to translocate across endosomal membranes. Although certain ZF5.3-protein conjugates are delivered efficiently into the cytosol or nucleus, overall delivery efficiency varies widely with no obvious design rules. Here we evaluate the role of protein size and thermal stability in the ability to efficiently escape endosomes when attached to ZF5.3. Using fluorescence correlation spectroscopy, a single-molecule technique that provides a precise measure of intra-cytosolic protein concentration, we demonstrate that delivery efficiency depends on both size and the ease with which a protein unfolds. Regardless of size and pI, low-Tm cargos of ZF5.3 (including intrinsically disordered domains) bias its endosomal escape route toward a high-efficiency pathway that requires the homotypic fusion and protein sorting (HOPS) complex. Small protein domains are delivered with moderate efficiency through the same HOPS portal even if the Tm is high. These findings imply a novel protein- and/or lipid-dependent pathway out of endosomes that is exploited by ZF5.3 and provide clear guidance for the selection or design of optimally deliverable therapeutic cargo.

Effect of Pelagic Sargassum on In Vitro Dry Matter and Organic Matter Degradation, Gas Production, and Protozoa Population.

This study determined the effect of pelagic Sargassum on in vitro dry matter and organic matter degradation, total gas production (TGP), and protozoa population. The treatments were different levels of Sargassum inclusion on a basal substrate (Stargrass hay; Cynodon nlemfuensis) as follows: T0 (control treatment based on Stargrass hay), T10 (90% Stargrass hay + 10% Sargassum), T20 (80% Stargrass hay + 20% Sargassum), and T30 (70% Stargrass hay + 30% Sargassum). Ruminal fermentation kinetics and protozoa population were determined during 72 h of in vitro incubations. Compared to control, dry matter degradability at 48 and 72 h and organic matter degradability at 24 and 48 h were higher in Sargassum treatments. TGP was lower with T20 at 48 h. The total population of protozoa and the concentration of Entodinium spp. were lower at T20 at 48 h and T30 at 72 h. Cl, S, Ca, K, and Zn (103, 5.97, 88.73, 285.70 g/kg, and 15,900 mg/kg) were high in Sargassum, reaching twice or even nine times higher than the contents in Stargrass (11.37, 1.60, 43.53, 87.73 g/kg, and 866.67 mg/kg). Overall, up to 30% pelagic Sargassum could be included in hay-based substrates from tropical grasses without negative effects on in vitro dry matter and organic matter degradability.

A noninvasive method for whole-genome skin methylome profiling.

BACKGROUND: Ageing, disease and malignant transformation of the skin are associated with changes in DNA methylation. So far, mostly invasive methodologies such as biopsies have been applied in collecting DNA methylation signatures. Tape stripping offers a noninvasive option for skin diagnostics. It enables the easy but robust capture of biologic material in large numbers of participants without the need for specialized medical personnel. OBJECTIVES: To design and validate a methodology for noninvasive skin sample collection using tape stripping for subsequent DNA -methylation analysis. METHODS: A total of 175 participants were recruited and provided tape-stripping samples from a sun-exposed area; 92 provided matched tape-stripping samples from a sun-protected area, and an additional 5 provided matched skin-shave biopsies from the same area. Using -enzymatic conversion and whole-genome Illumina sequencing, we generated genome-wide DNA methylation profiles that were used to evaluate the feasibility of noninvasive data acquisition, to compare with established sampling approaches and to investigate biomarker identification for age and ultraviolet (UV) exposure. RESULTS: We found that tape-stripping samples showed strong concordance in their global DNA methylation landscapes to those of conventional invasive biopsies. Moreover, we showed sample reproducibility and consistent global methylation profiles in skin tape-stripping samples collected from different areas of the body. Using matched samples from sun-protected and sun-exposed areas of the body we were able to validate the capacity of our method to capture the effects of environmental changes and ageing in a cohort covering various ages, ethnicities and skin types. We found DNA methylation changes on the skin resulting from UV exposure and identified significant age-related hypermethylation of CpG islands, with a pronounced peak effect at 50-55 years of age, including methylation changes in well-described markers of ageing. CONCLUSIONS: These data demonstrate the feasibility of using tape stripping combined with whole-genome sequencing as a noninvasive approach to measuring DNA methylation changes in the skin. In addition, they outline a viable experimental framework for the use of skin tape stripping, particularly when it is performed in large cohorts of patients to identify biomarkers of skin ageing, UV damage and, possibly, to track treatment response to therapeutic interventions.

Identification of lncRNAs Deregulated in Epithelial Ovarian Cancer Based on a Gene Expression Profiling Meta-Analysis.

Epithelial ovarian cancer (EOC) is one of the deadliest gynecological cancers worldwide, mainly because of its initially asymptomatic nature and consequently late diagnosis. Long non-coding RNAs (lncRNA) are non-coding transcripts of more than 200 nucleotides, whose deregulation is involved in pathologies such as EOC, and are therefore envisaged as future biomarkers. We present a meta-analysis of available gene expression profiling (microarray and RNA sequencing) studies from EOC patients to identify lncRNA genes with diagnostic and prognostic value. In this meta-analysis, we include 46 independent cohorts, along with available expression profiling data from EOC cell lines. Differential expression analyses were conducted to identify those lncRNAs that are deregulated in (i) EOC versus healthy ovary tissue, (ii) unfavorable versus more favorable prognosis, (iii) metastatic versus primary tumors, (iv) chemoresistant versus chemosensitive EOC, and (v) correlation to specific histological subtypes of EOC. From the results of this meta-analysis, we established a panel of lncRNAs that are highly correlated with EOC. The panel includes several lncRNAs that are already known and even functionally characterized in EOC, but also lncRNAs that have not been previously correlated with this cancer, and which are discussed in relation to their putative role in EOC and their potential use as clinically relevant tools.

Using plant-based compounds as preservatives for meat products: A review.

The susceptibility of meat and meat products (MP) to oxidation and microbial deterioration poses a risk to the nutritional quality, safety, and shelf life of the product. This analysis provides a brief overview of how bioactive compounds (BC) impact meat and MP preservation, and how they can be utilized for preservation purposes. The use of BC, particularly plant-based antioxidants, can reduce the rate of auto-oxidation and microbial growth, thereby extending the shelf life of MP. These BC include polyphenols, flavonoids, tannins, terpenes, alkaloids, saponins, and coumarins, which have antioxidant and antimicrobial properties. Bioactive compounds can act as preservatives and improve the sensory and physicochemical properties of MP when added under appropriate conditions and concentrations. However, the inappropriate extraction, concentration, or addition of BC can also lead to undesired effects. Nonetheless, BC have not been associated with chronic-degenerative diseases and are considered safe for human consumption. MP auto-oxidation leads to the generation of reactive oxygen species, biogenic amines, malonaldehyde (MDA), and metmyoglobin oxidation products, which are detrimental to human health. The addition of BC at a concentration ranging from 0.025 to 2.5% (w/w in powdered or v/w in oil or liquid extracts) can act as a preservative, improving color, texture, and shelf life. The combination of BC with other techniques, such as encapsulation and the use of intelligent films, can further extend the shelf life of MP. In the future, it will be necessary to examine the phytochemical profile of plants that have been used in traditional medicine and cooking for generations to determine their feasibility in MP preservation.

Biomarkers of delirium risk in older adults: a systematic review and meta-analysis.

Delirium is a neuropsychiatric syndrome associated with increased morbidity and mortality in older patients. The aim of this study was to review predictive biomarkers of delirium in older patients to gain insights into the pathophysiology of this syndrome and provide guidance for future studies. Two authors independently and systematically searched MEDLINE, Embase, Cochrane Library, Web of Science and Scopus databases up to August 2021. A total of 32 studies were included. Only 6 studies were eligible for the meta-analysis, pooled results showed a significant increase in some serum biomarkers (C-reactive protein [CRP], tumour necrosis factor alpha [TNF-α] and interleukin-6 [IL-6]) among patients with delirium (odds ratio = 1.88, 95% CI 1.01 to 1.637; I2 = 76.75%). Although current evidence does not favour the use of any particular biomarker, serum CRP, TNF-α, and IL-6 were the most consistent biomarkers of delirium in older patients.

Thanksgiving to Yeast, the HMGB Proteins History from Yeast to Cancer.

Yeasts have been a part of human life since ancient times in the fermentation of many natural products used for food. In addition, in the 20th century, they became powerful tools to elucidate the functions of eukaryotic cells as soon as the techniques of molecular biology developed. Our molecular understandings of metabolism, cellular transport, DNA repair, gene expression and regulation, and the cell division cycle have all been obtained through biochemistry and genetic analysis using different yeasts. In this review, we summarize the role that yeasts have had in biological discoveries, the use of yeasts as biological tools, as well as past and on-going research projects on HMGB proteins along the way from yeast to cancer.

Study of Ferroptosis Transmission by Small Extracellular Vesicles in Epithelial Ovarian Cancer Cells.

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. The current treatment for EOC involves surgical debulking of the tumors followed by a combination of chemotherapy. While most patients achieve complete remission, many EOCs will recur and develop chemo-resistance. The cancer cells can adapt to several stress stimuli, becoming resistant. Because of this, new ways to fight resistant cells during the disease are being studied. However, the clinical outcomes remain unsatisfactory. Recently, ferroptosis, a novel form of regulated cell death trigged by the accumulation of iron and toxic species of lipid metabolism in cells, has emerged as a promising anti-tumor strategy for EOC treatment. This process has a high potential to become a complementary treatment to the current anti-tumor strategies to eliminate resistant cells and to avoid relapse. Cancer cells, like other cells in the body, release small extracellular vesicles (sEV) that allow the transport of substances from the cells themselves to communicate with their environment. To achieve this, we analyzed the capacity of epithelial ovarian cancer cells (OVCA), treated with ferroptosis inducers, to generate sEV, assessing their size and number, and study the transmission of ferroptosis by sEV. Our results reveal that OVCA cells treated with ferroptotic inducers can modify intercellular communication by sEV, inducing cell death in recipient cells. Furthermore, these receptor cells are able to generate a greater amount of sEV, contributing to a much higher ferroptosis paracrine transmission. Thus, we discovered the importance of the sEV in the communication between cells in OVCA, focusing on the ferroptosis process. These findings could be the beginning form to study the molecular mechanism ferroptosis transmission through sEV.

Effects of the Inclusion of Ground Pouteria sapota Kernel on Intake, Digestibility, and Growth Performance in Lambs.

This study determined the effect of replacing ground corn and soybean meal with ground Pouteria sapota kernel (PSSM) in lamb diets on nutrient intake and digestibility, performance, and carcass traits. Twenty-one male hair sheep lambs with an average body weight of 22 ± 3.5 kg were randomly assigned to three treatment diets containing PSSM at 0, 10, and 20% of the total dry matter (DM) inclusion. The study lasted 60 days, which included 15 days for adaption and 45 days for sample collection. The PSSM inclusion did not affect intake or performance (p > 0.05). However, ether extract (EE) digestibility linearly increased (p < 0.0001), while crude protein (CP) and acid detergent fiber (ADF) linearly decreased. Final body weight, total weight gain, average daily weight gain, feeding efficiency, and carcass traits were not affected by PSSM inclusion. In conclusion, these results suggest that PSSM can replace up to 200 g/kg DM of ground corn and soybean meal without affecting intake or animal performance.

Effect of Adding Extra Virgin Olive Oil to Hair Sheep Lambs' Diets on Productive Performance, Ruminal Fermentation Kinetics and Rumen Ciliate Protozoa.

This study determined productive performance, ruminal fermentation kinetics and rumen ciliate protozoa in hair sheep lambs fed different levels of olive oil. Twenty-four growing lambs were used, with an initial live weight of 10.5 ± 2.9 kg, and randomly assigned into four treatments (six animals per treatment) containing increasing levels of extra virgin olive oil (0, 2, 4 and 6% of dry matter). Animals were fed for 80 days, and sampling was carried out weekly. Intake of dry matter (DM), organic matter (OM), crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF) and metabolizable energy (ME) differed between treatments (p < 0.05), with a linear and cubic tendency to decrease when oil concentrations were increased. Digestibility coefficients of OM, CP and NDF were not affected; however, the relationship between total intake and nutrient digestibility (DM, OM, NDF, ADF) increased with 2% DM olive oil. Compared with all treatments, the concentration of propionic acid increased by 16% with 4% olive oil. The intake of olive oil did not affect the protozoa population and live weight gain. Overall, the inclusion of olive oil in low concentrations (2% of DM) positively influences feed intake and nutrient digestibility in hair sheep lambs.

A Fully Integrated, Power-Efficient, 0.07-2.08 mA, High-Voltage Neural Stimulator in a Standard CMOS Process.

This paper presents a fully integrated high-voltage (HV) neural stimulator with on-chip HV generation. It consists of a neural stimulator front-end that delivers stimulation currents up to 2.08 mA with 5 bits resolution and a switched-capacitor DC-DC converter that generates a programmable voltage supply from 4.2 V to 13.2 V with 4 bits resolution. The solution was designed and fabricated in a standard 180 nm 1.8 V/3.3 V CMOS process and occupied an active area of 2.34 mm2. Circuit-level and block-level techniques, such as a proposed high-compliance voltage cell, have been used for implementing HV circuits in a low-voltage CMOS process. Experimental validation with an electrical model of the electrode−tissue interface showed that (1) the neural stimulator can handle voltage supplies up to 4 times higher than the technology's nominal supply, (2) residual charge­without passive discharging phase­was below 0.12% for the whole range of stimulation currents, (3) a stimulation current of 2 mA can be delivered with a voltage drop of 0.9 V, and (4) an overall power efficiency of 48% was obtained at maximum stimulation current.

Residual Feed Intake and Rumen Metabolism in Growing Pelibuey Sheep.

This study was carried out to evaluate the residual feed intake (RFI), volatile fatty acid (VFA) production and enteric methane (CH4) from growing Pelibuey sheep. In this case, 12 non-castrated Pelibuey with an initial average live weight (LW) of 21.17 ± 3.87 kg and an age of 3 months, were housed in individual pens and fed a basal diet with 16% of crude protein and 11 MJ ME for 45 days. Dry matter intake (DMI) was measured and the daily weight gain (DWG) was calculated using a linear regression between the LW and experimental period. Mean metabolic live weight (LW0.75) was calculated. RFI was determined by linear regression with DWG and LW0.75 as independent variables. Lambs were classified as low, medium, and high RFI. Feed efficiency was determined as DWG/DMI. For determining rumen pH, ammonia nitrogen concentration NH3-N), and VFA, ruminal fluid was obtained using an esophageal probe on day 40. Feed intake of low RFI lambs was approximately 16% lower (p < 0.05) while growth rate was not significantly different. Their average energy loss, expressed as CH4 production per kilogram of metabolic weight, was 17% lower (p < 0.05).

HMG Proteins from Molecules to Disease.

High Mobility Group (HMG) proteins are today the focus of interest due to their participation in human degenerative diseases and inflammatory responses [...].