Selective treatment of clinical mastitis: Assessment of the Net Cash Impact on Dairy Farms Under Diverse Scenarios. A European Perspective.

Selective treatment of clinical mastitis (STCM) potentially reduces antimicrobial use without negative implications on cow's milk production or health. However, this approach comes with additional costs. The aim of this study was to evaluate the net cash impact (NCI) of implementing STCM compared with blanket treatment of clinical mastitis (BTCM) under different diagnostic-test turnaround times (24 h, 14 h, and 8 h) using a stochastic partial budget analysis with Monte Carlo simulation. The target population was European commercial dairy herds; therefore, the model inputs were primarily from European sources. Additionally, variables associated with dairy management programs were obtained from USDA sources, worldwide multisite clinical trials, and expert opinion. The output was calculated by subtracting the cost of STCM from the cost of BTCM and it represented the expected NCI if a herd switched from BTCM to STCM. Depending on the time-to-treatment efficiency and diagnostic-test turnaround time, the expected mean NCI, assuming that STCM has no impact on the cow's future health or production, ranged from +€8.7 to +€12.4 per case with 72.4% to 84.8% of the iterations being ≥ €0. Moreover, using the numerically favorable health and production effects of STCM reported in the literature, the expected mean NCI ranged from +€44.5 to +€48.1 per case with 93.6% to 95.4% of the iterations being ≥ €0. The variables with the greatest contribution to NCI variance were proportion of gram-positive cases (39.2% of the variance) and days out of the tank for treated cows (22.0%). However, if future cow's health and production were accounted for, culling risk (24.6%), recurrence risk (19.4%), and milk yield (10.6%) would have the greatest contribution to NCI. The sensitivity analysis indicated that farms with high clinical mastitis incidence, low proportion of gram-positive cases, large number of days out of the tank for treated cows, higher milking frequency or using automatic milking systems, not using the highest priced diagnostic tests, and having high antimicrobial treatment costs are the best candidates for STCM. Improving time-to-treatment efficiency, for example, by using a rapid diagnostic test, leads to a favorable NCI, while high daily milk yield and milk price enhances the NCI in already positive scenarios. Finally, the cash flow entirely depends on future cow's health and milk yield. In conclusion, results indicate that overall, STCM is a practice that positively impacts the NCI of many herds.

Determinants of diversity and composition of the tapeworm fauna of blue sharks, Prionace glauca: a geographical and host-specificity analysis.

Blue sharks, Prionace glauca, are cosmopolitan, extremely vagile sharks and the species among elasmobranchs for which most surveys containing tapeworm community data are available worldwide. In this study we report on the tapeworm fauna of three samples of blue sharks (n = 37) from two new regions (one sample from Galicia, north-east Atlantic, and two from Valencia, western Mediterranean), and compared it with previous studies, assessing the relative role of the ecological and evolutionary factors in structuring local tapeworm assemblages. Nine cestode taxa were identified, of which four included adult specimens, that is, Platybothrium auriculatum, Prosobothrium armigerum, Anthobothrium caseyi and Molicola horridus. The abundance of these species, and Brillouin's diversity index, differed significantly among samples without a clear geographical signal. A comparison with six previous surveys revealed that tapeworm assemblages were composed of the same 'core' taxa, with mean species richness typically ranging from two to four species. Global records of adult tapeworms in blue sharks included: 15 taxa identified at species level, of which only eight (generalist trypanorhynchs) were shared with other sympatric host species; five mostly with other carcharhinids; and three with large lamnid sharks sharing the blue sharks' habitat. The composition of tapeworm communities of blue sharks is thus highly constrained by strong host specificity, with composition and abundance varying across localities depending on idiosyncratic environmental conditions.

Affiliation Bias in Peer Review of Abstracts by a Large Language Model.

This study assesses affiliation bias in peer review of medical abstracts by a commonly used large language model.

Gene therapy approaches in the non-human primate model of Parkinson's disease.

The field of gene therapy has recently witnessed a number of major conceptual changes. Besides the traditional thinking that comprises the use of viral vectors for the delivery of a given therapeutic gene, a number of original approaches have been recently envisaged, focused on using vectors carrying genes to further modify basal ganglia circuits of interest. It is expected that these approaches will ultimately induce a therapeutic potential being sustained by gene-induced changes in brain circuits. Among others, at present, it is technically feasible to use viral vectors to (1) achieve a controlled release of neurotrophic factors, (2) conduct either a transient or permanent silencing of any given basal ganglia circuit of interest, (3) perform an in vivo cellular reprogramming by promoting the conversion of resident cells into dopaminergic-like neurons, and (4) improving levodopa efficacy over time by targeting aromatic L-amino acid decarboxylase. Furthermore, extensive research efforts based on viral vectors are currently ongoing in an attempt to better replicate the dopaminergic neurodegeneration phenomena inherent to the progressive intraneuronal aggregation of alpha-synuclein. Finally, a number of incoming strategies will soon emerge over the horizon, these being sustained by the underlying goal of promoting alpha-synuclein clearance, such as, for instance, gene therapy initiatives based on increasing the activity of glucocerebrosidase. To provide adequate proof-of-concept on safety and efficacy and to push forward true translational initiatives based on these different types of gene therapies before entering into clinical trials, the use of non-human primate models undoubtedly plays an instrumental role.

Shorter specialist time intervals are associated with advanced stage on symptomatic oral cancer.

OBJECTIVES: As longer times from the first symptom to diagnosis and treatment of oral cancers have been linked to poorer outcomes, this study investigates the contribution of the specialist to this time (STI). SUBJECTS AND METHODS: A series of 228 oral/oropharyngeal squamous cell carcinoma patients were retrospectively studied to determine the STI and its related factors. RESULTS: Patients were mostly males (n = 170; 74.5%), (50.7% stages I-II), mean age = 61.4 ± 12.5 years. The STI median was 6 days (X±SD:6.8 ± 5.6 days). Time first symptom to diagnosis was 64 days (X±SD:91.0 ± 84.6 days). Univariate regression unveiled a significant association between STI and TNM stage, which was confirmed by multivariate regression. CONCLUSIONS: Specialist time interval is a short time interval in oral cancer diagnosis, imposing a limited time burden in the context of the whole interval until diagnosis. However, there seems to be room for improvement and a possible target for future interventions to shorten STI particularly for patients at early stages after their disease has been disclosed.

How much progress has there been in the second-line treatment of multiple sclerosis: A 2017 update.

In 1993, the US Food and Drug Administration (FDA) approved the first drug specifically for treating multiple sclerosis (MS). More than two decades later, a dozen such treatments are now available. Of these, four are considered second-line treatments for use in escalation strategies and two new drugs are currently undergoing accreditation procedures. Soon, they will provide clinicians with a range of six effective disease-modifying treatments (DMTs) to thwart the inflammatory processes in MS patients with active disease. However, while such a large number of DMTs for MS can help to control early inflammation, any decisions to be made by clinicians have also been made substantially more complex. This complexity is increased by the lack of head-to-head studies comparing these second-line therapies and the benefit-risk profiles for each of these drugs, which are likely to vary among patients. Ultimately, good awareness of the benefits and, more important, the risks of each MS DMT is crucial for the effective management of inflammation in MS.

Pathogen-related factors affecting outcome of catheter-related bacteremia due to methicillin-susceptible Staphylococcus aureus in a Spanish multicenter study.

Even with appropriate clinical management, complicated methicillin-susceptible Staphylococcus aureus (MSSA) catheter-related bacteremia (CRB) is frequent. We investigated the influence of molecular characteristics of MSSA strains on the risk of complicated bacteremia (CB) in MSSA-CRB. A multicenter prospective study was conducted in Spain between 2011 and 2014 on MSSA-CRB. Optimized protocol-guided clinical management was required. CB included endocarditis, septic thrombophlebitis, persistent bacteremia and/or end-organ hematogenous spread. Molecular typing, agr functionality and DNA microarray analysis of virulence factors were performed in all MSSA isolates. Out of 83 MSSA-CRB episodes included, 26 (31.3%) developed CB. MSSA isolates belonged to 16 clonal complexes (CCs), with CC30 (32.5%), CC5 (15.7%) and CC45 (13.3) being the most common. Comparison between MSSA isolates in episodes with or without CB revealed no differences regarding agr type and functionality. However, our results showed that CC15 and the presence of genes like cna, chp and cap8 were associated with the development of CB. The multivariate analysis highlighted that the presence of cna (Hazard ratio 2.9; 95% CI 1.14-7.6) was associated with the development of CB. Our results suggest that particular CCs and specific genes may influence the outcome of MSSA-CRB.

rAAV-mediated overexpression of sox9, TGF-ß and IGF-I in minipig bone marrow aspirates to enhance the chondrogenic processes for cartilage repair.

Administration of therapeutic gene sequences coding for chondrogenic and chondroreparative factors in bone marrow aspirates using the clinically adapted recombinant adeno-associated virus (rAAV) vector may provide convenient, single-step approaches to improve cartilage repair. Here, we tested the ability of distinct rAAV constructs coding for the potent SOX9, transforming growth factor beta (TGF-ß) and insulin-like growth factor I (IGF-I) candidate factors to modify marrow aspirates from minipigs to offer a preclinical large animal model system adapted for a translational evaluation of cartilage repair upon transplantation in sites of injury. Our results demonstrate that high, prolonged rAAV gene transfer efficiencies were achieved in the aspirates (up to 100% for at least 21 days) allowing to produce elevated amounts of the transcription factor SOX9 that led to increased levels of matrix synthesis and chondrogenic differentiation and of the growth factors TGF-ß and IGF-I that both increased cell proliferation, matrix synthesis and chondrogenic differentiation (although to a lower level than SOX9) compared with control (lacZ) condition. Remarkably, application of the candidate SOX9 vector also led to reduced levels of hypertrophic differentiation in the aspirates, possibly by modulating the ß-catenin, Indian hedgehog and PTHrP pathways. The present findings show the benefits of modifying minipig marrow concentrates via rAAV gene transfer as a future means to develop practical strategies to promote cartilage repair in a large animal model.

GABA (γ-Aminobutyric Acid) Uptake Via the GABA Permease GabP Represses Virulence Gene Expression in Pseudomonas syringae pv. tomato DC3000.

The nonprotein amino acid γ-aminobutyric acid (GABA) is the most abundant amino acid in the tomato (Solanum lycopersicum) leaf apoplast and is synthesized by Arabidopsis thaliana in response to infection by the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 (hereafter called DC3000). High levels of exogenous GABA have previously been shown to repress the expression of the type III secretion system (T3SS) in DC3000, resulting in reduced elicitation of the hypersensitive response (HR) in the nonhost plant tobacco (Nicotiana tabacum). This study demonstrates that the GABA permease GabP provides the primary mechanism for GABA uptake by DC3000 and that the gabP deletion mutant ΔgabP is insensitive to GABA-mediated repression of T3SS expression. ΔgabP displayed an enhanced ability to elicit the HR in young tobacco leaves and in tobacco plants engineered to produce increased levels of GABA, which supports the hypothesis that GABA uptake via GabP acts to regulate T3SS expression in planta. The observation that P. syringae can be rendered insensitive to GABA through loss of gabP but that gabP is retained by this bacterium suggests that GabP is important for DC3000 in a natural setting, either for nutrition or as a mechanism for regulating gene expression. [Formula: see text] Copyright © 2016 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Determination of effective rAAV-mediated gene transfer conditions to support chondrogenic differentiation processes in human primary bone marrow aspirates.

The genetic modification of freshly aspirated bone marrow may provide convenient tools to enhance the regenerative capacities of cartilage defects compared with the complex manipulation of isolated progenitor cells. In the present study, we examined the ability and safety of recombinant adeno-associated virus (rAAV) serotype 2 vectors to deliver various reporter gene sequences in primary human bone marrow aspirates over time without altering the chondrogenic processes in the samples. The results demonstrate that successful rAAV-mediated gene transfer and expression of the lacZ and red fluorescent protein marker genes were achieved in transduced aspirates at very high efficiencies (90-94%) and over extended periods of time (up to 125 days) upon treatment with hirudin, an alternative anticoagulant that does not prevent the adsorption of the rAAV-2 particles at the surface of their targets compared with heparin. Application of rAAV was safe, displaying neither cytotoxic nor detrimental effects on the cellular and proliferative activities or on the chondrogenic processes in the aspirates especially using an optimal dose of 0.5 mg ml(-1) hirudin, and application of the potent SOX9 transcription factor even enhanced these processes while counteracting hypertrophic differentiation. The current findings demonstrate the clinical value of this class of vector to durably and safely modify bone marrow aspirates as a means to further develop convenient therapeutic approaches to improve the healing of cartilage defects.

Use of healthcare resources and costs of acute cardioembolic stroke management in the Region of Madrid: The CODICE Study.

INTRODUCTION: Stroke is the main cause of admission to Neurology departments and cardioembolic stroke (CS) is one of the most common subtypes of stroke. METHODS: A multicentre prospective observational study was performed in 5 Neurology departments in public hospitals in the Region of Madrid (Spain). The objective was to estimate the use of healthcare resources and costs of acute CS management. Patients with acute CS at<48h from onset were recruited. Patients' socio-demographic, clinical, and healthcare resource use data were collected during hospitalisation and at discharge up to 30 days after admission, including data for rehabilitation treatment after discharge. RESULTS: During an 8-month recruitment period, 128 patients were recruited: mean age, 75.3±11.25; 46.9% women; mortality rate, 4.7%. All patients met the CS diagnostic criteria established by GEENCV-SEN, based on medical history or diagnostic tests. Fifty per cent of the patients had a history of atrial fibrillation and 18.8% presented other major cardioembolic sources. Non-valvular atrial fibrillation was the most frequent cause of CS (33.6%). Data for healthcare resource use, given a mean total hospital stay of 10.3±9.3 days, are as follows: rehabilitation therapy during hospital stay (46.9%, mean 4.5 days) and after discharge (56.3%, mean 26.8 days), complications (32%), specific interventions (19.5%), and laboratory and diagnostic tests (100%). Head CT (98.4%), duplex ultrasound of supra-aortic trunks (87.5%), and electrocardiogram (85.9%) were the most frequently performed diagnostic procedures. Average total cost per patient during acute-phase management and rehabilitation was €13,139. Hospital stay (45.0%) and rehabilitation at discharge (29.2%) accounted for the largest part of resources used. CONCLUSIONS: Acute CS management in the Region of Madrid resulted consumes large amounts of resources (€13,139), mainly due to hospital stays and rehabilitation.

A prospective observational post-marketing study of natalizumab-treated multiple sclerosis patients: clinical, radiological and biological features and adverse events. The BIONAT cohort.

BACKGROUND AND PURPOSE: BIONAT is a French multicentric phase IV study of natalizumab (NTZ)-treated relapsing-remitting multiple sclerosis (MS) patients. The purpose of this study was to collect clinical, radiological and biological data on 1204 patients starting NTZ, and to evaluate the clinical/radiological response to NTZ after 2 years of treatment. METHODS: Patients starting NTZ at 18 French MS centres since June 2007 were included. Good response to NTZ was defined by the absence of clinical and radiological activity. Data analysed in this first report on the BIONAT study focus on patients who started NTZ at least 2 years ago (n = 793; BIONAT2Y ). RESULTS: NTZ was discontinued in 17.78% of BIONAT2Y. The proportion of patients without combined disease activity was 45.59% during the first two successive years of treatment. Systematic dosage of anti-NTZantibodies (Abs) detected only two supplementary patients with anti-NTZ Abs compared with strict application of recommendations. A significant decrease of IgG,M concentrations at 2 years of treatment was found. CONCLUSIONS: The efficacy of NTZ therapy on relapsing-remitting MS in a real life setting is confirmed in the BIONAT cohort. The next step will be the identification of biomarkers predicting response to NTZ therapy and adverse events.

Differential expression of the P2X7 receptor in ovarian surface epithelium during the oestrous cycle in the mouse.

Purinergic signalling has been proposed as an intraovarian regulatory mechanism. Of the receptors responsible for purinergic transmission, the P2X7 receptor is an ATP-gated cationic channel that displays a broad spectrum of cellular functions ranging from apoptosis to cell proliferation and tumourigenesis. In the present study, we investigated the functional expression of P2X7 receptors in ovarian surface epithelium (OSE). P2X7 protein was detected in the OSE layer of the mouse, both in situ and in primary cultures. In cultures, 2'(3')-O-(4-Benzoylbenzoyl)adenosine-5'-triphosphate (BzATP) activation of P2X7 receptors increased [Ca(2+)]i and induced apoptosis. The functionality of the P2X7 receptor was investigated in situ by intrabursal injection of BzATP on each day of the oestrous cycle and evaluation of apoptosis 24h using the terminal deoxyribonucleotidyl transferase-mediated dUTP-fluorescein nick end-labelling (TUNEL) assay. Maximum effects of BzATP were observed during pro-oestrus, with the effects being blocked by A438079, a specific P2X7 receptor antagonist. Immunofluorescence staining for P2X7 protein revealed more robust expression during pro-oestrus and in OSE regions behind the antral follicles, strongly supporting the notion that the differences in apoptosis can be explained by increased receptor expression, which is regulated during the oestrous cycle. Finally, P2X7 receptor expression was detected in the OSE layer of human ovaries, with receptor expression maintained in human ovaries diagnosed with cancer, as well as in the human ovarian carcinoma SKOV3 cell line.

How perceived maternal gatekeeping affects fathers: An 8-week study.

Maternal gatekeeping describes mothers' attempts to influence father involvement in child-rearing. While the effect of maternal gatekeeping on the father-child relationship has been explored, less is known about how fluctuations in the perception of maternal gatekeeping influences fathers' family outcomes and whether father's attachment might moderate these associations. Building on family systems theory, this study explores the within-person effect of negative maternal gatekeeping on father's weekly reports of romantic relationship quality and feelings of exclusion from the family and tests father attachment as a moderator of these associations. Two hundred seventy-seven Canadian and German fathers with children under the age of 6 took part in an 8-week online diary study. Data were analyzed using multilevel structural equation modeling. During weeks when fathers perceived more maternal gatekeeping than was typical, they reported lower positive romantic relationship quality, higher negative romantic relationship quality, and felt more excluded from the family system. Avoidant attachment moderated the within-person effect of perceived maternal gatekeeping on negative romantic relationship quality, such that within-person increases in perceived maternal gatekeeping were more strongly linked with higher than-average negative romantic relationship quality among more avoidant fathers. Our findings shed new light on the within-person effects of perceived maternal gatekeeping on fathers' feelings regarding the family system. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Gene expression biomarkers provide sensitive indicators of in planta nitrogen status in maize.

Over the last several decades, increased agricultural production has been driven by improved agronomic practices and a dramatic increase in the use of nitrogen-containing fertilizers to maximize the yield potential of crops. To reduce input costs and to minimize the potential environmental impacts of nitrogen fertilizer that has been used to optimize yield, an increased understanding of the molecular responses to nitrogen under field conditions is critical for our ability to further improve agricultural sustainability. Using maize (Zea mays) as a model, we have characterized the transcriptional response of plants grown under limiting and sufficient nitrogen conditions and during the recovery of nitrogen-starved plants. We show that a large percentage (approximately 7%) of the maize transcriptome is nitrogen responsive, similar to previous observations in other plant species. Furthermore, we have used statistical approaches to identify a small set of genes whose expression profiles can quantitatively assess the response of plants to varying nitrogen conditions. Using a composite gene expression scoring system, this single set of biomarker genes can accurately assess nitrogen responses independently of genotype, developmental stage, tissue type, or environment, including in plants grown under controlled environments or in the field. Importantly, the biomarker composite expression response is much more rapid and quantitative than phenotypic observations. Consequently, we have successfully used these biomarkers to monitor nitrogen status in real-time assays of field-grown maize plants under typical production conditions. Our results suggest that biomarkers have the potential to be used as agronomic tools to monitor and optimize nitrogen fertilizer usage to help achieve maximal crop yields.

Transcript-based cloning of RRP46, a regulator of rRNA processing and R gene-independent cell death in barley-powdery mildew interactions.

Programmed cell death (PCD) plays a pivotal role in plant development and defense. To investigate the interaction between PCD and R gene-mediated defense, we used the 22K Barley1 GeneChip to compare and contrast time-course expression profiles of Blumeria graminis f. sp hordei (Bgh) challenged barley (Hordeum vulgare) cultivar C.I. 16151 (harboring the Mla6 powdery mildew resistance allele) and its fast neutron-derived Bgh-induced tip cell death1 mutant, bcd1. Mixed linear model analysis identified genes associated with the cell death phenotype as opposed to R gene-mediated resistance. One-hundred fifty genes were found at the threshold P value < 0.0001 and a false discovery rate <0.6%. Of these, 124 were constitutively overexpressed in the bcd1 mutant. Gene Ontology and rice (Oryza sativa) alignment-based annotation indicated that 68 of the 124 overexpressed genes encode ribosomal proteins. A deletion harboring six genes on chromosome 5H cosegregates with bcd1-specified cell death and is associated with misprocessing of rRNAs but segregates independent of R gene-mediated resistance. Barley stripe mosaic virus-induced gene silencing of one of the six deleted genes, RRP46 (rRNA-processing protein 46), phenocopied bcd1-mediated tip cell death. These findings suggest that RRP46, a critical component of the exosome core, mediates RNA processing and degradation involved in cell death initiation as a result of attempted penetration by Bgh during the barley-powdery mildew interaction but is independent of gene-for-gene resistance.

Effect of laser remelting on the tribological performance of thermal barrier coatings.

Gas turbine's efficiency improves as operating temperature is increased. For this reason, metallic components used in turbine engines, for propulsion and power generation, are protected by thermal barrier coatings (TBC). Laser glazing has been used to enhance the oxidation and corrosion resistance of thermally sprayed TBC, but there is no information about the effect of this treatment on the tribological performance. ZrO2(CaO) top coat and NiAIMo bond coating were flame sprayed onto an AlSI 1045 carbon steel. The top coat was laser remelted and a densified ceramic layer was induced in the top surface of the ceramic coating. Both, the as sprayed and the laser remelted top coatings, were formed by cubic ZrO2 with some tetragonal precipitates. The grain size was reduced by the laser treatment. The mechanical properties and the local wear rate were evaluated by depth sensing indentation and scratch tests respectively. The nanoscale wear behaviour was always improved by the laser treatment.

[Clinical management of the new anticoagulants]. / Manejo clínico de los nuevos anticoagulantes.

The vitamin K antagonists (VKA) available for stroke prevention in patients with atrial fibrillation have many drawbacks due to their difficult clinical use and high risk of bleeding. Currently, several drugs are being developed as possible substitutes for VKA that have many advantages such as the lack of monitoring requirement and scarce pharmacologic and food interactions. The present article provides an update on the new oral anticoagulants that are in a more advanced stage of clinical research, their pharmacologic properties, advantages and disadvantages and their results in recent clinical trials.

Mechanical characterisation of hydrophobic and hydrophilic acrylates used in intraocular lenses through depth sensing indentation.

In this work, the mechanical behaviour of hydrophilic and hydrophobic acrylates has been characterised by depth sensing indentation. Time-dependent behaviour has been studied using load-relaxation tests. Experiments have been simulated with a finite element software using a visco-hyperelastic material model. The parameters of this model have been determined using deep learning techniques. The developed material models have been used to mechanically simulate a standard compression test of a prototype intraocular lens.