The effect of first-lactation calving season, milk production, and morphology on the survival of Simmental cows.

Longevity in dairy and dual-purpose cattle is a complex trait which depends on many individual and managerial factors. The purpose of the present study was to investigate the survival (SURV) rate of Italian Simmental dual-purpose cows across different parities. Data of this study referred to 2 173 primiparous cows under official milk recording that calved between 2002 and 2020. Only cows linearly classified for type traits, including muscularity (MU) and body condition score (BCS) were kept. Survival analysis was carried out, through the Cox regression model, for different pairwise combinations of classes of milk productivity MU, BCS, and calving season. Herd-year of first calving was also considered in the model. SURV (0 = culled; 1 = survived) at each lactation up to the 6th were the dependent variables, so that, for example, SURV2 equal to 1 was attributed to cows that entered the 2nd lactation. Survival rates were 98, 71, 63, 56, and 53% for 2nd, 3rd, 4th, 5th, and 6th lactation, respectively. Results revealed that SURV2 was not dependent on milk yield, while in subsequent parities, low-producing cows were characterized by higher SURV compared to high-producing ones. Additionally, cows starting the lactation in autumn survived less (47.38%) than those starting in spring (53.49%), suggesting that facing the late gestation phase in summer could increase the culling risk. The present study indicates that SURV in Italian Simmental cows is influenced by various factors in addition to milk productivity. However, it is important to consider that in this study all first-calving cows culled before the linear evaluation - carried out between mid- and late lactation in this breed - were not accounted for. Finding can be transferred to other dual-purpose breeds, where the cows' body conformation and muscle development - i.e. meat-related features - are often considered as important as milk performance by farmers undertaking culling decisions.

Quantum biochemical analysis of the TtgR regulator and effectors.

The recent expansion of multidrug-resistant (MDR) pathogens poses significant challenges in treating healthcare-associated infections. Although antibacterial resistance occurs by numerous mechanisms, active efflux of the drugs is a critical concern. A single species of efflux pump can produce a simultaneous resistance to several drugs. One of the best-studied efflux pumps is the TtgABC: a tripartite resistance-nodulation-division (RND) efflux pump implicated in the intrinsic antibiotic resistance in Pseudomonas putida DOT-T1E. The expression of the TtgABC gene is down-regulated by the HTH-type transcriptional repressor TtgR. In this context, by employing quantum chemistry methods based on the Density Functional Theory (DFT) within the Molecular Fragmentation with Conjugate Caps (MFCC) approach, we investigate the coupling profiles of the transcriptional regulator TtgR in complex with quercetin (QUE), a natural polyphenolic flavonoid, tetracycline (TAC), and chloramphenicol (CLM), two broad-spectrum antimicrobial agents. Our quantum biochemical computational results show the: [i] convergence radius, [ii] total binding energy, [iii] relevance (energetically) of the ligands regions, and [iv] most relevant amino acids residues of the TtgR-QUE/TAC/CLM complexes, pointing out distinctions and similarities among them. These findings improve the understanding of the binding mechanism of effectors and facilitate the development of new chemicals targeting TtgR, helping in the battle against the rise of resistance to antimicrobial drugs. These advances are crucial in the ongoing fight against rising antimicrobial drug resistance, providing hope for a future where healthcare-associated infections can be more beneficially treated.

Unlocking bacterial defense: Exploring the potent inhibition of NorA efflux pump by coumarin derivatives in Staphylococcus aureus.

The occurrence of bacterial resistance has been increasing, compromising the treatment of various infections. The high virulence of Staphylococcus aureus allows for the maintenance of the infectious process, causing many deaths and hospitalizations. The MepA and NorA efflux pumps are transporter proteins responsible for expelling antimicrobial agents such as fluoroquinolones from the bacterial cell. Coumarins are phenolic compounds that have been studied for their diverse biological actions, including against bacteria. A pharmacokinetic in silico characterization of compounds C10, C11, C13, and C14 was carried out according to the principles of Lipinski's Rule of Five, in addition to searching for similarity in ChemBL and subsequent search for publications in CAS SciFinder. All compounds were evaluated for their in vitro antibacterial and modulatory activity against standard and multidrug-resistant Gram-positive and Gram-negative strains. The effect of coumarins C9, C10, C11, C13, and C14 as efflux pump inhibitors in Staphylococcus aureus strains was evaluated using the microdilution method (MepA or NorA) and fluorimetry (NorA). The behavior of coumarins regarding the efflux pump was determined from their interaction properties with the membrane and coumarin-protein using molecular docking and molecular dynamics simulations. Only the isolated coumarin compound C13 showed antibacterial activity against standard strains of Staphylococcus aureus and Escherichia coli. However, the other tested coumarins showed modulatory capacity for fluoroquinolone and aminoglycoside antibacterials. Compounds C10, C13, and C14 were effective in reducing the MIC of both antibiotics for both multidrug-resistant strains, while C11 potentiated the effect of norfloxacin and gentamicin for Gram-positive and Gram-negative bacteria and only norfloxacin for Gram-negative. Only coumarin C14 produced synergistic effects when associated with ciprofloxacin in MepA-carrying strains. All tested coumarins have the ability to inhibit the NorA efflux pump present in Staphylococcus aureus, both in reducing the MIC and inducing increased ethidium bromide fluorescence emission in fluorimetry. The findings of this study offer an atomistic perspective on the potential of coumarins as active inhibitors of the NorA pump, highlighting their specific mode of action mainly targeting protein inhibition. In molecular docking, it was observed that coumarins are capable of interacting with various amino acid residues of the NorA pump. The simulation showed that coumarin C10 can cross the bilayer; however, the other coumarins interacted with the membrane but were unable to cross it. Coumarins demonstrated their potentiating role in the effect of norfloxacin through a dual mechanism: efflux pump inhibition through direct interaction with the protein (C9, C10, C11, and C13) and increased interaction with the membrane (C10 and C13). In the context of pharmacokinetic prediction studies, the studied structures have a suitable chemical profile for possible oral use. We suggest that coumarin derivatives may be an interesting alternative in the future for the treatment of resistant bacterial infections, with the possibility of a synergistic effect with other antibacterials, although further studies are needed to characterize their therapeutic effects and toxicity.

Depression and cognition are associated with lipid dysregulation in both a multigenerational study of depression and the National Health and Nutrition Examination Survey.

Chronic dysregulation of peripheral lipids has been found to be associated with depression and cognition, but their interaction has not been investigated. Growing evidence has highlighted the association between peripheral lipoprotein levels with depression and cognition with inconsistent results. We assessed the association between peripheral lipids, depression, and cognition while evaluating their potential interactions using robust clinically relevant predictors such as lipoprotein levels and chronic medical disorders that dysregulate lipoproteins. We report an association between peripheral lipids, depression, and cognition, suggesting a common underlying biological mechanism driven by lipid dysregulation in two independent studies. Analysis of a longitudinal study of a cohort at high or low familial risk for major depressive disorder (MDD) (n = 526) found metabolic diseases, including diabetes, hypertension, and other cardiovascular diseases, were associated with MDD and cognitive outcomes. Investigating a cross-sectional population survey of adults in the National Health and Nutrition Examination Survey 2011-2014 (NHANES) (n = 2377), depression was found to be associated with high density lipoprotein (HDL) and cognitive assessments. In the familial risk study, medical conditions were found to be associated with chronic lipid dysregulation and were significantly associated with MDD using the structural equation model. A positive association between chronic lipid dysregulation and cognitive scores was found in an exploratory analysis of the familial risk study. In a complementary study, analysis of NHANES revealed a positive association of HDL levels with cognition. Further analysis of the NHANES cohort indicated that depression status mediated the interaction between HDL levels and cognitive tests. Importantly, the protective effect of HDL on cognition was absent in those with depressive symptoms, which may ultimately result in worse outcomes leading to cognitive decline. These findings highlight the potential for the early predictive value of medical conditions with chronic lipid dyshomeostasis for the risk of depression and cognitive decline.

Acute amnestic syndrome in fornix lesions: a systematic review of reported cases with a focus on differential diagnosis.

Introduction: Acute amnestic syndrome is an uncommon clinical presentation of neurological disease. Differential diagnosis encompasses several syndromes including Wernicke-Korsakoff and transient global amnesia (TGA). Structural lesions of the fornix account for a minority of cases of acute amnestic syndromes. Etiology varies from iatrogenic injury to ischemic, inflammatory, or neoplastic lesions. A prompt diagnosis of the underlying pathology is essential but challenging. The aim of this review is to systematically review the existing literature regarding cases of acute amnestic syndrome associated with non-iatrogenic lesions of the fornix. Methods: We performed a systematic literature search on PubMed, Scopus, and Web of Science up to September 2023 to identify case reports and case series of patients with amnestic syndrome due to fornix lesions. The systematic review was conducted according to PRISMA guidelines. The research was limited to articles written in English. Cases of fornix damage directly ascribable to a surgical procedure were excluded. Results: A total of 52 publications reporting 55 cases were included in the review. Focusing on acute/subacute onset, vascular etiology was highly prevalent, being responsible for 78% of cases, 40/55 (74%) of which were due to acute ischemic stroke. The amnestic syndrome was characterized by anterograde amnesia in all patients, associated with retrograde amnesia in 27% of cases. Amnesia was an isolated presentation in most cases. Up to two thirds of patients had persistent memory deficits of any severity at follow-up. Discussion: Acute amnestic syndrome can be rarely caused by fornix lesions. In most cases of acute/subacute presentation, the etiology is ischemic stroke, mainly caused by strokes involving the subcallosal artery territory. The differential diagnosis is challenging and a distinction from common mimics is often difficult on a clinical basis. A high index of suspicion should be maintained to avoid misdiagnosis and provide adequate acute treatment to patients with time-dependent disease, also employing advanced neuroimaging. More research is needed to better understand the outcome and identify prognostic factors in patients with amnestic syndrome due to fornix lesions.

Does the age of milk affect its mid-infrared spectrum and predictions?

Milk of dairy species commonly undergo standardized official analyses, these that may require chemical preservation and transportation to a certified laboratory. In this context, storage duration is an important factor that can potential affect both milk chemical analyses and its mid-infrared spectrum. We analysed milk samples at different time points/ages to assess repeatability and reproducibility of mid-infrared predicted traits (e.g., fat and protein). Using spectral data, we also evaluated the ability of spectroscopy coupled with chemometrics to discriminate samples according to their age. Although the main components of milk remained consistently reproducible across age (days), changes in the spectrum due to sample aging and deterioration of the matrix were detectable. Using a discriminant analysis, we achieved a classification accuracy of 77% in validation. Predicting milk age using mid-infrared spectra is feasible, allowing for sample monitoring within circuits where maximum reliability is needed, e.g., bulk or individual milk samples for legal/official use or payment systems.

HPV-related oropharyngeal carcinoma remains infrequent over 25 years in a Brazilian Oral Pathology Center: A cross-sectional study with literature review.

BACKGROUND: The aim was to evaluate the frequency, clinicopathological features, and HPV status of oropharyngeal squamous cell carcinoma (OP-SCC) and benign HPV-related epithelial lesions of the oropharynx over the last 25 years. Moreover, a literature review was performed to investigate HPV frequency in OP-SCC samples diagnosed in Brazilian Centers. MATERIAL AND METHODS: A cross-sectional study analyzed OP-SCC, squamous papilloma, verruca vulgaris, and condyloma accuminatum, diagnosed from 1997 to 2021. HPV status of OP-SCC was determined by immunohistochemistry and "in situ" hybridization. Bivariate statistics were performed (p≤0.05). For the literature review, MEDLINE/PubMed, Web of Science, EMBASE, and Scopus were searched. Two independent reviewers assessed the studies for eligibility. RESULTS: Cross-sectional: 211 OP-SCC (63.0%) and 124 benign lesions (37.0%) were included. OP-SCC frequency increased gradually over time, whereas benign lesions had steady trends. OP-SCC affected more males (n= 171; 81.0%), though the relative frequency in females rose over time. Smoking (n= 127; 60.2%) was common in OP-SCC. Nineteen OP-SCC (13.0%) were positive for HPV. HPV-positive and HPV-negative tumors had similar clinicopathological features (p>0.05). Benign lesions predominated in middle-aged (n= 32; 26.7%) women (n= 71; 57.3%), in the soft palate (n=101; 81.5%). LITERATURE REVIEW: 32 studies were included, and in 60% of them, HPV frequency in OP-SCC was less than 25%. CONCLUSIONS: OP-SCC prevalence has been increasing, and it was mostly associated with smoking and alcohol rather than with HPV infection in Brazil. Benign lesions had a stationary frequency over the evaluated period.

Effects of different temperature-humidity indexes on milk traits of Holstein cows: a 10-yr retrospective study.

Test-day records (n = 723,091) collected between 2012 and 2021 from 43,015 Holsteins in 157 farms located in Northern Italy were used to study the effects of heat load on milk production and composition a posteriori. The data consisted of milk yield (kg/d), traditional gross composition traits, somatic cell score (SCS), differential SCC (%), milk ß-hydroxybutyrate (BHB, mmol/L), milk urea (mg/dL), and milk FA composition (g/100 g milk). Test-day records were then associated to their relative temperature-humidity indexes (THI) calculated using historical environmental data registered by weather stations. Indexes were created using either yearly or summer THI data: the first included the average daily THI (adTHI) and the maximum daily THI (mdTHI) measured throughout the whole year, whereas summer indexes were focused on 3 mo only (June to August) and included the average daily THI (adTHIs), the maximum daily THI (mdTHIs), and the average daily THI of the hottest 4 h of the day (adTHI4h, 12:00 to 4:00 p.m.). All indexes had significant effects on the majority of milk traits analyzed, with in particular adTHI and mdTHI being highly significant in explaining the variation of all traits. Milk yield started to decline at a higher THI compared with protein and fat content. The reduction in fat ceased in the elevated THI experienced during the summer months as demonstrated by adTHIs, mdTHIs, and adTHI4h. The cows had a tendency for increased BHB concentration with elevated THI, suggesting that there is a greater risk of negative energy balance in presence of heat stress. What is more, the concentration of the de-novo fatty acids C14:0 and C16:0 was reduced in higher THI, reflecting the altered mammary gland activity upon elevated heat load and stress. Milk SCS tended to increase with higher adTHIS, mdTHIS, and adTHI4h. The use of yearly indexes is recommended when investigating the effects of heat load on milk composition, while summer indexes are suggested when investigating traits influenced by extreme conditions, such as SCS and milk yield. With global temperatures set to further rise in the upcoming decades, early and easy identification of cows or herds suffering from heat stress, as through changes in milk composition, is crucial for timely intervention. Adapting measures to mitigate such effects of elevated THI on milk yield and composition is a necessity for the dairy industry to prevent detrimental impacts on dairy production.

Head injury in older adults presenting to the ambulance service: who do we convey to the emergency department, and what clinical variables are associated with an intracranial bleed? A retrospective case-control study.

OBJECTIVE: Most older adults with traumatic brain injuries (TBI) reach the emergency department via the ambulance service. Older adults, often with mild TBI symptoms, risk being under-triaged and facing poor outcomes. This study aimed to identify whether sufficient information is available on the scene to an ambulance clinician to identify an older adult at risk of an intracranial haemorrhage following a head injury. METHODS: This was a retrospective case-control observational study involving one regional ambulance service in the UK and eight emergency departments. 3545 patients aged 60 years and over presented to one regional ambulance service with a head injury between the 1st of January 2020 and the 31st of December 2020. The primary outcome was an acute intracranial haemorrhage on head computed tomography (CT) scan in patients conveyed to the emergency department (ED). A secondary outcome was factors associated with conveyance to the ED by the ambulance clinician. RESULTS: In 2020, 2111 patients were conveyed to the ED and 162 patients were found to have an intracranial haemorrhage on their head CT scan. Falls from more than 2 m (adjusted odds ratio (aOR) 3.45, 95% CI 1.78-6.40), chronic kidney disease (CKD) (aOR 2.80, 95% CI 1.25-5.75) and Clopidogrel (aOR 1.98, 95% CI 1.04-3.59) were associated with an intracranial haemorrhage. Conveyance to the ED was associated with patients taking anticoagulant and antiplatelet medication or a visible head injury or head injury symptoms. CONCLUSION: This study highlights that while most older adults with a head injury are conveyed to the ED, only a minority will have an intracranial haemorrhage following their head injury. While mechanisms of injury such as falls from more than 2 m remain a predictor, this work highlights that Clopidogrel and CKD are also associated with an increased odds of tICH in older adults following a head injury. These findings may warrant a review of current ambulance head injury guidelines.

Proportions of sewage sludge in the production and quality of Malpighia emarginata DC. seedlings.

Sewage sludge (SS) has nutritional contents and has been implemented in the cultivation of seedlings. This study aimed to evaluate the quality of Malpighia emarginata DC. seedlings produced in different substrates with SS. Treatments were implemented with the addition of SS, and after 180 days seedling the characteristics were measured: aerial part and root system length, stem base diameter, number of leaves, fresh and dry mass of aerial part and root, and total biomass. The Dickson Quality Index (DQI) was calculated and the macro and micronutrient content of the aerial part and root. The accumulation of macronutrients in the root system followed the order of N>K>P>Ca>Mg>S, and aerial part of N>Ca>K>P>Mg>S, in the two vegetative structures N and S were in lower concentration. For micronutrients, the accumulation in the root system occurred with Fe>Zn>Mn>Cu>B, and aerial part with Fe>Mn>Zn>B>Cu. It was noted that in the two vegetative structures the Fe content was more concentrated. The use of SS in the substrate formulation proved effective in obtaining viable seedlings for field planting, being recommended the treatment with 60% SS + 40% organic compost.

Association between torquetenovirus in vaginal secretions and infertility: An exploratory metagenomic analysis.

PROBLEM: The association of viruses with infertility remains incompletely evaluated. METHOD OF STUDY: Vaginal secretions from 46 women seeking treatment in the Center for Reproductive Medicine and Infertility at Weill Cornell Medicine were tested for viruses by metagenomic analysis by lab personnel blinded to all clinical data. RESULTS: Torquetenovirus (TTV) was identified in 16 women, alphapapillomavirus in seven women and most were positive for bacteriophages. Twelve of the subjects were fertile and sought to freeze their oocytes for future implantation. These women were all negative for TTV. In contrast, 16 of the 34 women (47.1%) being treated for infertility were TTV-positive (p = .0035). Evaluating the women by cause of infertility, five of nine women (55.6%) whose male partner had inadequate sperm parameters and six of 14 women (42.9%) with defective ovulation were TTV positive (p = .0062 and p = .0171, respectively, vs. the fertile women). Alphapapillomavirus was identified in one (8.3%) fertile woman, five (35.7%) women with ovulation deficiency, and one (11.1%) woman with male factor infertility. These differences were not statistically significant. There were no differences in bacteriophage families or the presence of Lactobacillus phages between fertile or infertile women or between different causes of infertility. There was a negative association between TTV detection and Lactobacillus crispatus dominance in the vaginal microbiota (p = .0184), but no association between TTV detection and the presence of alphapapillomavirus or Candida species. CONCLUSION: Detection of TTV in the vagina might be a biomarker for specific causes of infertility.

How animal milk and plant-based alternatives diverge in terms of fatty acid, amino acid, and mineral composition.

The decline in fresh milk in the Western world has in part been substituted by an increased consumption of plant-based beverages (PBB). These are often marketed as healthy and sustainable alternatives to milk and dairy foodstuff, although studies have suggested PBB to be of lower nutrient quality. The current study considered different brands of almond-, oat-, rice-, coconut- and soya-based beverages for a comparative analysis and found that they indeed presented lower contents of total protein, lipids, amino acids, and minerals than cow and goat milk. The only exception was given by soya-based beverages which approximated the protein content (3.47% vs. 3.42 and 3.25% in cow and goat milk, respectively) and amino acid composition of animal milk, and also demonstrated high mineral content. The natural presence of phyto-compounds in PBB characterised as antinutrients and their potential to exacerbate the issue of low nutrient quality by lowering bioavailability have been discussed.

Minerals and essential amino acids of bovine colostrum: Phenotypic variability and predictive ability of mid- and near-infrared spectroscopy.

Colostrum quality and volume are fundamental for calves because it is the primary supplier of antibodies and the first source of energy, carbohydrates, lipids, proteins, minerals, and vitamins for the newborn. Assessing the detailed composition (i.e., AA and mineral content) of bovine colostrum (BC) on-line and at a reasonable cost would help dairy stakeholders such as farmers or veterinarians for precision feeding purposes and industries producing preparations containing BC such as foodstuff, supplements, and medicaments. In the present study we evaluated mid- (MIRS) and near-infrared spectroscopy (NIRS) prediction ability for AA and mineral composition of individual BC. Second, we the investigated the major factors affecting the phenotypic variability of such traits also evaluating the correlations with the Ig concentration. Results demonstrated that MIRS and NIRS were able to provide sufficiently accurate predictions for all the AA. The coefficient of determination in external validation (R2V) fell, in fact, within the range of 0.70 to 0.86, with the exception of Ile, His, and Met. Only some minerals reached a sufficient accuracy (i.e., Ca, P, S, and Mg; R2V ≥ 0.66) using MIRS, and also S (R2V = 0.87) using NIRS. Phenotypically, both parity and calving season affected the variability of these BC composition traits. Heifers' colostrum was the one with the greatest concentration of Ca and P, the 2 most abundant minerals. These minerals were however very low in cows calving in summer compared with the rest of the year. The pattern of AA across parities and calving season was not linear, likely because their variability was scarcely (or not) affected by these effects. Finally, samples characterized by high IgG concentration were those presenting on average greater concentration of AA. Findings suggest that infrared spectroscopy has the potential to be used to predict certain AA and minerals, outlining the possibility of implementing on-site analyses for the evaluation of the broad-sense BC quality.

Characterization of Torquetenovirus in amniotic fluid at the time of in utero fetal surgery: correlation with early premature delivery and respiratory distress.

Torquetenovirus (TTV) is a commensal virus present in many healthy individuals. Although considered to be non-pathogenic, its presence and titer have been shown to be indicative of altered immune status in individuals with chronic infections or following allogeneic transplantations. We evaluated if TTV was present in amniotic fluid (AF) at the time of in utero surgery to correct a fetal neurological defect, and whether its detection was predictive of adverse post-surgical parameters. AF was collected from 27 women by needle aspiration prior to a uterine incision. TTV titer in the AF was measured by isolation of viral DNA followed by gene amplification and analysis. The TTV genomes were further characterized and sequenced by metagenomics. Pregnancy outcome parameters were subsequently obtained by chart review. Three of the AFs (11.1%) were positive for TTV at 3.36, 4.16, and 4.19 log10 copies/mL. Analysis of their genomes revealed DNA sequences similar to previously identified TTV isolates. Mean gestational age at delivery was >2 weeks earlier (32.5 vs. 34.6 weeks) and the prevalence of respiratory distress was greater (100% vs. 20.8%) in the TTV-positive pregnancies. TTV detection in AF prior to intrauterine surgery may indicate elevated post-surgical risk for earlier delivery and newborn respiratory distress.

Sign reversal of the Josephson inductance magnetochiral anisotropy and 0-π-like transitions in supercurrent diodes.

The recent discovery of the intrinsic supercurrent diode effect, and its prompt observation in a rich variety of systems, has shown that non-reciprocal supercurrents naturally emerge when both space-inversion and time-inversion symmetries are broken. In Josephson junctions, non-reciprocal supercurrent can be conveniently described in terms of spin-split Andreev states. Here we demonstrate a sign reversal of the Josephson inductance magnetochiral anisotropy, a manifestation of the supercurrent diode effect. The asymmetry of the Josephson inductance as a function of the supercurrent allows us to probe the current-phase relation near equilibrium, and to probe jumps in the junction ground state. Using a minimal theoretical model, we can then link the sign reversal of the inductance magnetochiral anisotropy to the so-called 0-π-like transition, a predicted but still elusive feature of multichannel junctions. Our results demonstrate the potential of inductance measurements as sensitive probes of the fundamental properties of unconventional Josephson junctions.

Mid-infrared spectroscopy for large-scale phenotyping of bovine colostrum gross composition and immunoglobulin concentration.

Immunoglobulin G is the fundamental antibody for acquisition of passive transfer of immunity in ruminant newborns. Colostrum, in fact, must be administered as soon as possible after birth to ensure a successful transfer of IgG from the dam to the calf. Assessment of colostrum Ig concentration and gross composition via gold standards is expensive, time consuming, and hardly implementable for large-scale investigations. Therefore, in the present study we evaluated the predictive ability of mid-infrared spectroscopy (MIRS) as an indirect determination method. A total of 714 colostrum samples collected within 6 h from parturition from Italian Holstein cows, 30% primiparous and 70% pluriparous, were scanned using a benchtop spectrometer after dilution in pure water. The prediction models were developed by correlating spectral information with the reference measurements: IgG concentration (93.54 ± 33.87 g/L), total Ig concentrations (102.82 ± 35.04 g/L), and content of protein (14.71 ± 3.51%), fat (4.61 ± 3.04%), and lactose (2.36 ± 0.51 mg/100 mg). We found a good to excellent performance in prediction of colostrum IgG concentration and traditional composition traits in cross-validation (R2CV ≥ 0.92) and a promising and good predictive ability in external validation with R2V equal to 0.84, 0.89, and 0.74 for IgG, protein, and fat, respectively. In the case of IgG and protein content, for example, the coefficient of determination in external validation was greater than 0.84. The other Ig fractions, A and M, presented insufficient prediction accuracy likely due to their extremely low concentration compared with IgG (4.56 and 5.06 g/L vs. 93.54 g/L). The discriminant ability of MIRS-predicted IgG and protein content was outstanding when trying to classify samples according to the quality level (i.e., low vs. high concentration of IgG). In particular, the cut-off that better discriminate low- from high-quality colostrum was 75.40 g/L in the case of the MIRS-predicted IgG and 13.32% for the MIRS-predicted protein content. Therefore, MIRS is proposed as a rapid and cheap tool for large-scale punctual IgG, protein, and lactose quantification and for the screening of low-quality samples. From a practical perspective, there is the possibility to install colostrum models in the MIRS benchtop machineries already present in laboratories in charge of official milk testing. Colostrum phenotypes collected on an individual basis will be useful to breeders for the definition of specific selection strategies and to farmers for management scopes. Finally, our findings may be relevant for other stakeholders, given the fact that colostrum is an emerging ingredient for the animal and human food and pharmaceutical industry.

The REWRITE Study - REal-WoRld effectIveness of TrifluridinE/tipiracil in Patients with Previously Treated Metastatic Colorectal Cancer.

AIMS: In the pivotal RECOURSE trial, trifluridine/tipiracil improved survival outcomes in refractory metastatic colorectal cancer (mCRC), while demonstrating an acceptable toxicity profile. Routine clinical practice evidence is important to support the ongoing value of recently approved medicines. Our objective was to assess the utilisation patterns and real-world effectiveness of trifluridine/tipiracil in previously treated mCRC patients. MATERIALS AND METHODS: This was a retrospective observational study including consecutive patients who started trifluridine/tipiracil between 1 April 2018 and 30 September 2019 in the medical oncology departments of three major public hospitals in Portugal. The primary outcome measure was overall survival. Associations between overall survival and patient and tumour characteristics were assessed using multivariate Cox regression analyses. RESULTS: In total, 111 patients were included in the study, with a mean age of 64 years. From these, 45.9% received two prior lines of treatment, 47.8% had three or more previous lines of treatment and 83.6% had Eastern Cooperative Oncology Group (ECOG) performance status 0-1 at baseline. The median duration of trifluridine/tipiracil treatment was 3.7 cycles (95% confidence interval 3.4-4.1). Most patients (80.4%) remained on their planned dose throughout the trifluridine/tipiracil treatment period, fulfilling 100% relative dose intensity. The median overall survival in the total study cohort was 7.9 months (95% confidence interval 6.4-9.8) and the median progression-free survival was 3.4 months (95% confidence interval 3.2-3.9). The median overall survival was significantly higher in patients with a normal serum lactate dehydrogenase (LDH) level (median overall survival 11.2 months for [135, 205] IU/l LDH [95% confidence interval 8.2-NR] and 13.6 months for [205, 251] IU/l LDH [95% confidence interval 8.2-NR]) and in better fitted (ECOG = 0-1) patients (median overall survival 8.0 months; 95% confidence interval 6.7-10.0). The median time to worsening performance status was 6.2 months (95% confidence interval 5.0-8.0). Treatment discontinuation due to adverse events was low (3.1%). CONCLUSION: Our study confirms the effectiveness of trifluridine/tipiracil in real-life mCRC patients. Overall survival and progression-free survival outcomes are consistent with the efficacy profile reported in the earlier randomised RECOURSE clinical trial. Like other real-world studies, we found no additional safety concerns in the use of trifluridine/tipiracil.

Invited review: Bovine colostrum, a promising ingredient for humans and animals-Properties, processing technologies, and uses.

Mammalian colostrum, known as "liquid gold," is considered a valuable source of essential nutrients, growth factors, probiotics, prebiotics, antibodies, and other bioactive compounds. Precisely for this reason, bovine colostrum (BC) is an emerging ingredient for the feed, food, and pharmaceutical industries, being nowadays commercially available in a variety of forms in several countries. Moreover, quite a large number of functional foods and supplements for athletes, human medicines, pet nutrition plans, and complementary feed for some livestock categories, such as piglets and calves, contain BC. The amount of BC yielded by a cow after calving represents approximately 0.5% of the yearly output in dairy breeds. For its nutritional properties and low availability, BC is characterized by a greater market value and an increasing demand compared with other by-products of the dairy sector. However, information regarding the market size of BC for the food and pharmaceutical industries, as well as future developments and perspectives, is scarcely available in the scientific literature. This lack can be attributed to industrial secrecy as well as to the relatively small scale of the BC business when compared with other dairy products, which makes the BC market limited, specific, and intended for a restricted audience. From a legal perspective, regulations assign BC to the large family of milk-derived powders; thus, collecting specific production data, as well as import-export trend information, is not straightforward and can result in unprecise estimates. Given that the interest in BC is increasing in different fields, it is important to have an overview of the production steps and of pros and cons of this emerging ingredient. The present narrative review discloses why BC has started to be considered a product rather than a by-product of the dairy industry. Moreover, the present document aims to summarize the existing methodologies used to assess BC quality in terms of immunoglobulin concentration, the different applications of BC in the industry, and the BC processing technologies. Finally, a panoramic view of the current international market is provided for the first time for this dairy product.

Sex-Specific Patterns of Cerebral Atrophy and Enlarged Perivascular Spaces in Patients with Cerebral Amyloid Angiopathy and Dementia.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy is characterized by amyloid ß deposition in leptomeningeal and superficial cortical vessels. Cognitive impairment is common and may occur independent of concomitant Alzheimer disease neuropathology. It is still unknown which neuroimaging findings are associated with dementia in cerebral amyloid angiopathy and whether they are modulated by sex. This study compared MR imaging markers in patients with cerebral amyloid angiopathy with dementia or mild cognitive impairment or who are cognitively unimpaired and explored sex-specific differences. MATERIALS AND METHODS: We studied 58 patients with cerebral amyloid angiopathy selected from the cerebrovascular and memory outpatient clinics. Clinical characteristics were collected from clinical records. Cerebral amyloid angiopathy was diagnosed on MR imaging on the basis of the Boston criteria. Visual rating scores for atrophy and other imaging features were independently assessed by 2 senior neuroradiologists. RESULTS: Medial temporal lobe atrophy was higher for those with cerebral amyloid angiopathy with dementia versus those cognitively unimpaired (P = .015), but not for those with mild cognitive impairment. This effect was mainly driven by higher atrophy in men with dementia, compared with women with and without dementia (P = .034, P = .012; respectively) and with men without dementia (P = .012). Enlarged perivascular spaces in the centrum semiovale were more frequent in women with dementia versus men with and without dementia (P = .021, P = .011; respectively) and women without dementia (P = .011). CONCLUSIONS: Medial temporal lobe atrophy was more prominent in men with dementia, whereas women showed a higher number of enlarged perivascular spaces in the centrum semiovale. Overall, this finding suggests differential pathophysiologic mechanisms with sex-specific neuroimaging patterns in cerebral amyloid angiopathy.

Use of adipose derived stem cells in Treacher Collins syndrome.

OBJECTIVE: Treacher Collins syndrome (TCS) is a rare congenital disorder of craniofacial development. TCS occurs with an incidence of 1:50,000, and more than 60% of TCS cases have no previous family history and arise as the result of de novo mutations. The high rate of de novo mutations, together with the extreme variability in the degree to which individuals can be affected, makes the provision of genetic counseling extremely complicated. Consequently, every case of TCS is unique and needs to be assessed individually. Patients with TCS frequently undergo multiple reconstructive surgeries from birth through adulthood, which rarely are fully corrective in the long-term. The nascent field of regenerative medicine offers the promise to improve some of these treatments. In particular, structural fat grafting (SFG) seems to be a good strategy not only to restore the normal volume and contour of the face, but also to provide a source of adipose-derived stem cells (ADSCs) with a multilineage differentiation potential. In this work, we present genetical analyses of ADSC affected by TCS. MATERIALS AND METHODS: ADSCs from were analyzed for their stemness properties and shared many characteristics with those of a healthy subject. Screening of the genome of the TCS patient using array-Comparative Genomic Hybridization allowed us to identify some chromosomal imbalances that are probably associated with TCS. RESULTS: We found that some alterations, involving the TIMELESS gene, were usually associated with embryonic stem cells. CONCLUSIONS: With the aim to improve the final results, we need to consider combining knowledge of genetic alterations and expression profiles as a fundamental step before starting with surgical procedures.