Intention to leave, depersonalisation and job satisfaction in physicians and nurses: a cross-sectional study in Europe.

The European healthcare sector faces a significant shortage of healthcare workers. Assessing the prevalence of this issue and understanding its direct and indirect determinants are essential for formulating effective recruitment programs and enhancing job retention strategies for physicians and nurses. A multicentric cross-sectional study was conducted, involving 381 physicians and 1351 nurses recruited from eight European hospitals in Belgium, the Netherlands, Italy, and Poland. The study focused on assessing turnover intentions among healthcare workers based on the Job Demands-Resources model, using an online questionnaire. Structural equation models were employed to test the data collection questionnaires' construct validity and internal consistency. The turnover intention was assessed by agreement with the intention to leave either the hospital or the profession. Among physicians, 17% expressed an intention to leave the hospital, while 9% intended to leave the profession. For nurses, the figures were 8.9% and 13.6%, respectively. The internal consistency of the questionnaires exceeded 0.90 for both categories of health workers. Depersonalization and job dissatisfaction were identified as direct determinants of turnover intention, with work engagement being particularly relevant for nurses. We found a higher intention to leave the hospital among physicians, while nurses were more prone to leave their profession. To mitigate turnover intentions, it is recommended to focus on improving job satisfaction, work engagement and fostering a positive working climate, thereby addressing depersonalisation and promoting job retention.

Comprehensive Analysis of Scientific Output in Hip and Knee Arthroscopy.

PURPOSE OF THE STUDY A global bibliometric comparison of the level of scientific interest and output in the two research areas hip and knee arthroscopy (H-ASC and K-ASC) was carried out. In addition, the different degrees of publication activity in the countries and institutes performing this research were investigated. MATERIAL AND METHODS Publications from 1945-2020 listed in the Web of Science Core Collection were included in the study. Using the web application Science Performance Evaluation (SciPE), quantitative and qualitative aspects were evaluated. Subsequently, the date of publication, author information, and other metadata were analysed. RESULTS Since 1945, 3,924 studies have been published on K-ASC and 2,163 on H-ASC. The majority of the publications which have appeared since 2016 dealt with the topic of H-ASC (H-ASC: 241.2 publications/year; K-ASC: 217.4 publications/year). The USA published the most on both topics (H-ASC: 1,123 publications; K-ASC: 1,078 publications). More countries and institutes participated in K-ASC (3,008 institutes, 82 countries) than in H-ASC (103 institutes, 57 countries). The ten institutes with the most publications accounted for 36.71% and 12.34% of all publications on H-ASC and K-ASC, respectively. H-ASC received 78.12% of its funding from private sponsors while K-ASC was supported mainly by governmental/nonprofit sponsors (70.92%). CONCLUSIONS This study provides the first scientific comparison between H-ASC and K-ASC. Measured by qualitative and quantitative aspects, K-ASC was the most flourishing research area overall. In the last ten to five years, interest has shifted towards HASC with an increasing number of publications and a higher rate of citations. Key words: knee arthroscopy, hip arthroscopy, bibliometric comparison.

Anti-FcαRI Monoclonal Antibodies Resolve IgA Autoantibody-Mediated Disease.

Immunoglobulin A (IgA) is generally considered as a non-inflammatory regulator of mucosal immunity, and its importance in diversifying the gut microbiota is increasingly appreciated. IgA autoantibodies have been found in several autoimmune or chronic inflammatory diseases, but their role in pathophysiology is ill-understood. IgA can interact with the Fc receptor FcαRI on immune cells. We now established a novel IgA autoimmune blistering model, which closely resembles the human disease linear IgA bullous disease (LABD) by using genetically modified mice that produce human IgA and express human FcαRI. Intravital microscopy demonstrated that presence of IgA anti-collagen XVII, - the auto-antigen in LABD-, resulted in neutrophil activation and extravasation from blood vessels into skin tissue. Continued exposure to anti-collagen XVII IgA led to massive neutrophil accumulation, severe tissue damage and blister formation. Importantly, treatment with anti-FcαRI monoclonal antibodies not only prevented disease, but was also able to resolve existing inflammation and tissue damage. Collectively, our data reveal a novel role of neutrophil FcαRI in IgA autoantibody-mediated disease and identify FcαRI as promising new therapeutic target to resolve chronic inflammation and tissue damage.

The Clinical Outcome of Custom-Made Implants in Primary and Revision Hip Arthroplasty.

PURPOSE OF THE STUDY Facing the increasing number of priary and revision hip arthroplasties, the therapy of complex osseus defects becomes a crucial issue. Large acetabular defects cannot be treated with standard implant. Individual, customized implants based on 3D computed tomography (CT) scans are used for reconstruction. However, high complication and revision rates come along with final favorable outcomes. MATERIAL AND METHODS Eight patients underwent primary or revision total hip arthroplasty by an anterolateral surgical approach using patient matched implants based on 3D CT scans. Six patients with a Paprosky type IIIB acetabular defect, one patient with a nonunion acetabular and femoral neck fracture and one patient with a severe hip dysplasia were included. The clinical data and the Merle d'Aubigné score assessing the clinical outcome pre- and postoperatively were analyzed retrospectively. RESULTS Patient matched implants were used for eight patients (four male and four female). The mean Merle d'Aubigné score improved from 8.1 (range 2-11) pre-operatively to 13 (range 9-17) at the final follow-up (p < 0.01). Postoperative complications were recorded in 3 cases. CONCLUSIONS Customized implants of severe acetabular defects provide a solution with a favorable outcome. Nevertheless, dislocation presents a significant complication. A reduction of complications in order to achieve the optimal custome-made implant is desirable. Key words: revision arthroplasty, patient-matched implants, Paprosky IIIB defects, clinical outcome.

Treatment of discontinuous emission of sewage sludge odours by a full scale biotrickling filter with an activated carbon polishing unit.

A SULPHUSTM biotrickling filter (BTF) and an ACTUSTM polishing activated carbon filter (ACF) were used at a wastewater treatment plant to treat 2,432 m3·h-1 of air extracted from sewage sludge processes. The project is part of Thames Water's strategy to reduce customer odour impact and, in this case, is designed to achieve a maximum discharge concentration of 1,000 ouE·m-3. The odour and hydrogen sulphide concentration in the input air was more influenced by the operation of the sludge holding tank mixers than by ambient temperature. Phosphorus was found to be limiting the performance of the BTF during peak conditions, hence requiring additional nutrient supply. Olfactometry and pollutant measurements demonstrated that during the high rate of change of intermittent odour concentrations the ACF was required to reach compliant stack values. The two stage unit outperformed design criteria, with 139 ouE·m-3 measured after 11 months of operation. At peak conditions and even at very low temperatures, the nutrient addition considerably increased the performance of the BTF, extending the time before activated carbon replacement over the one year design time. During baseline operation, the BTF achieved values between 266-1,647 ouE·m-3 even during a 6 day irrigation failure of the biofilm.

Preparedness activities and research needs in addressing emerging infectious animal and zoonotic diseases.

Emerging infectious animal and zoonotic diseases can inflict significant losses on animal production and public health, and threaten the safety and security of the food system. Threat analysis (forecasting), which monitors the measurable risk indicators of disease emergence, should be in place before the emergence of any threat. Animal and public health authorities develop and regularly re-evaluate disease preparedness, response and recovery plans, based on the 'One Health' principle. These plans should include surveillance, biosecurity measures, communication channels and training for personnel. Scenarios for outbreaks of natural emerging infectious disease or bioterrorist events should be prepared and practised. National and international legislation should be regularly updated to provide a robust legal basis to manage outbreaks. Reference laboratories should have reliable and validated diagnostic tools for rapid, high-throughput testing. Strict biosafety, biocontainment and biosecurity control measures must be implemented in laboratories in order to prevent the accidental or malicious release of pathogens. The pharmaceutical industry should be incentivised to develop vaccines and/or antiviral drugs against disease outbreaks. Conventions between public authorities and the pharmaceutical industry should guarantee adequate stockpiling of the pharmaceuticals needed to control large-scale outbreaks. In the early phase of disease emergence (early warning), veterinarians and stakeholders play an important role in early detection at the farm level. Upon notification, veterinary authorities must take rapid response measures to limit disease spread. National and international short- and medium-term strategic research agendas should be developed, based on a comprehensive gap analysis and horizon scan. This planning will help to guide funding agencies and non-governmental organisations in their quest to support relevant research.

Les maladies animales infectieuses et les zoonoses émergentes ont un coût élevé pour la santé animale et la santé publique, en plus d'entraîner d'importantes pertes de production dans les élevages et de menacer la sécurité des systèmes de production alimentaire. Une analyse des menaces (anticipation), grâce au suivi d'indicateurs mesurables du risque d'émergence des maladies animales, devrait être en place avant que ces menaces n'émergent. Les autorités en charge de la santé animale et de la santé publique développent et réévaluent régulièrement des plans de préparation, de réponse et de récupération vis-à-vis de maladies, sur la base du principe « Une seule santé ¼. Ces plans doivent inclure des mesures de surveillance et de biosécurité, en plus de se doter de moyens de communication et de formation du personnel. Il convient d'élaborer et de mettre en pratique des scénarios d'émergence de maladies infectieuses, que celle-ci soit d'origine naturelle ou d'origine bioterroriste. Les législations nationales et internationales en la matière doivent être actualisées régulièrement afin de fournir un fondement juridique solide à la gestion des émergences. Les laboratoires de référence doivent disposer d'outils diagnostiques fiables et validés permettant la réalisation de tests rapides et à haut débit. Des mesures strictes de contrôle de la biosécurité, du bioconfinement et de la biosûreté doivent être appliquées dans les laboratoires pour prévenir toute libération accidentelle ou malintentionnée d'agents pathogènes. L'industrie pharmaceutique doit être incitée au développement de vaccins et d'antiviraux pour maîtriser les maladies émergentes. Les conventions entre les autorités publiques et l'industrie pharmaceutique doivent permettre de garantir la constitution de stocks suffisants de produits pharmaceutiques pour maîtriser les émergences de grande ampleur. Lors des premières phases d'émergence d'un foyer (alerte précoce), les vétérinaires et autres acteurs de terrain jouent un rôle important dans la détection précoce au niveau des élevages. Dès la notification d'un foyer, les autorités vétérinaires doivent réagir rapidement afin d'en limiter la propagation. Il convient de développer des programmes nationaux et internationaux de recherche stratégique à court et moyen terme, basés sur un examen exhaustif des lacunes et sur une analyse prospective complète. Cette planification contribuera à fournir aux agences de financement et aux organisations non gouvernementales des orientations leur permettant de déterminer quel soutien apporter à la recherche.

Las enfermedades animales infecciosas y las zoonosis emergentes pueden causar pérdidas cuantiosas en los ámbitos de la producción animal y la salud pública, además de amenazar la higiene y la seguridad de los sistemas alimentarios. El análisis (pronóstico) de amenazas, que consiste en seguir de cerca indicadores cuantificables del riesgo de aparición de enfermedades animales, es algo que debería estar implantado antes de que surja toda amenaza. Las autoridades sanitarias y zoosanitarias definen y periódicamente reevalúan planes de preparación, respuesta y recuperación frente a enfermedades, basándose para ello en el principio de «Una sola salud¼. Estos planes deben incluir labores de vigilancia y medidas de seguridad biológica, además de prever cauces de comunicación y actividades de formación del personal. También hay que elaborar y aplicar planes para hipotéticos brotes infecciosos, ya sean de origen natural u obra de bioterroristas. Asimismo, a fin de contar con sólidas bases jurídicas para combatir la aparición de enfermedades, es preciso actualizar periódicamente la legislación nacional e internacional. Los laboratorios de referencia deben contar con herramientas de diagnóstico fiables y validadas que permitan efectuar pruebas rápidas y de alto rendimiento. Es preciso implantar en los laboratorios estrictas medidas de control de la protección, la contención y la seguridad biológicas para evitar toda liberación accidental o malintencionada de patógenos. Hay que incentivar asimismo a la industria farmacéutica para que desarrolle vacunas y fármacos antivirales contra las enfermedades emergentes. Por otra parte, las autoridades públicas deben suscribir con el sector farmacéutico convenios que garanticen la constitución de reservas suficientes de los productos farmacéuticos requeridos para hacer frente a la aparición de brotes de grandes dimensiones. En las primeras fases de la aparición de un foco (alerta rápida), los veterinarios y otros interlocutores cumplen una importante función para detectar con prontitud la patología dentro de las explotaciones. Al recibir notificación, las autoridades veterinarias deben reaccionar con rapidez para poner coto a la propagación de la enfermedad. Por último, a partir de un análisis exhaustivo de las carencias existentes y de un estudio prospectivo completo, es preciso elaborar planes nacionales e internacionales de investigación estratégica a corto y medio plazo. Tal planificación ayudará a orientar a los organismos de financiación y las organizaciones no gubernamentales (ONG) en su labor de apoyo a las investigaciones de interés.

Avoidable Compartment Syndrome! High Index of Suspicion for a Newly Presenting Haemophiliac: A Case Series.

Bleeding disorders can present at any age and vary in their severity. Haemophilia, which is characterised by its x-linked recessive inheritance, can present with a spontaneous mutation and therefore no family history will be evident. Three cases of trauma induced thigh haematomas as an initial presenting feature for people with haemophilia are discussed. The cases highlight the importance of a coagulation screen if the patients bleeding phenotype does not match the injury sustained. An isolated prolonged APTT with no offending anticoagulant cause should always be investigated to look for underlying haemophilia. Interestingly the cases demonstrate the limitations of a coagulation screen. Factor VIII being an acute phase reactant can result in the fact that the initial coagulation screen may be temporarily normal. Therefore, if there is a high index of suspicion for a bleeding disorder, consider repeating the coagulation screen and seeking haematology opinion. Early diagnosis and appropriate specific factor replacement for an injured haemophiliac prevent haematomas expanding thus avoiding potential complications like compartment syndrome or unnecessary surgical input.

Plexin-B1 signalling promotes androgen receptor translocation to the nucleus.

Semaphorins and their receptors plexins have diverse roles in many cancers affecting tumour growth, metastasis and angiogenesis. Plexin-B1, the receptor for semaphorin4D (Sema4D), has been implicated in prostate cancer where mutation of the gene and overexpression of the protein occur. It is not clear, however, as to which of the several Sema4D-activated signalling pathways downstream of plexin-B1 function in prostate cancer progression. We show here that Sema4D/plexin-B1 increases the expression of androgen-responsive genes and activates the transcriptional activity of the androgen receptor (AR). Activation of plexin-B1 results in phosphorylation of AR at Serine 81, a site that is phosphorylated by nuclear kinases. Cell fractionation and immunocytochemistry studies demonstrated that the proportion of cells with AR in the nucleus increases significantly upon Sema4D treatment. The N-terminal (AF-1) domain of AR, which contains binding sites for transcription regulators, is not required for this response. Depletion of AR suppressed Sema4D-induced anchorage-independent growth of LNCaP and LNCaP-LN3 cells, demonstrating the functional significance of these findings. These results show that Sema4D/plexin-B1 signalling promotes the translocation of AR to the nucleus and thereby enhances AR transcriptional activity. Plexin-B1 is therefore a promising target for cancer therapy, especially in low androgen situations such as those imposed by androgen deprivation therapy.

All in the blink of an eye: new insight into cerebellar and brainstem function in DYT1 and DYT6 dystonia.

BACKGROUND AND PURPOSE: Traditionally dystonia has been considered a disorder of basal ganglia dysfunction. However, recent research has advocated a more complex neuroanatomical network. In particular, there is increasing interest in the pathophysiological role of the cerebellum. Patients with cervical and focal hand dystonia have impaired cerebellar associative learning using the paradigm eyeblink conditioning. This is perhaps the most direct evidence to date that the cerebellum is implicated in patients. METHODS: Eleven patients with DYT1 dystonia and five patients with DYT6 dystonia were examined and rates of eyeblink conditioning were compared with age-matched controls. A marker of brainstem excitability, the blink reflex recovery, was also studied in the same groups. RESULTS: Patients with DYT1 and DYT6 dystonia have a normal ability to acquire conditioned responses. Blink reflex recovery was enhanced in DYT1 but this effect was not seen in DYT6. CONCLUSIONS: If the cerebellum is an important driver in DYT1 and DYT6 dystonia our data suggest that there is specific cerebellar dysfunction such that the circuits essential for conditioning function normally. Our data are contrary to observations in focal dystonia and suggest that the cerebellum may have a distinct role in different subsets of dystonia. Evidence of enhanced blink reflex recovery in all patients with dystonia was not found and recent studies calling for the blink recovery reflex to be used as a diagnostic test for dystonic tremor may require further corroboration.

Aqueous oxygen peroxide treatment of VLUs in a primary care-based randomised, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate a novel aqueous oxygen peroxide (AOP) wound therapy (BioxyQuell) in a multi-centre, primary care-based, randomised, double-blind, placebo-controlled, parallel-group trial, monitoring long-term healing outcomes over 12 months. METHOD: Sixty-one patients with chronic, stable venous leg ulceration were treated with either AOP solution or sterile water placebo applied as a lavage over 2 weeks. The patients' wounds were dressed weekly and assessed fortnightly over the following 6 weeks. Patients who completed the initial 8-week trial were invited into a 10-month follow-up trial. The primary endpoints of the study were wound healing at 8 weeks, 12 weeks, 6 months and 12 months, and wound size reduction during the treatment phase. Secondary endpoints were reductions in wound bioburden and pain. RESULTS: Patients treated with AOP were more likely to heal at 6 months (p=0.014) and 12 months (p=0.006), but not at 8 weeks (p=0.979) or 12 weeks (p=0.263). Patients treated with AOP had greater wound area reduction (p=0.015), reductions in pain measured on a 100-point scale (p=0.001) and wound bioburden reduction (p=0.005) during the treatment phase. CONCLUSION: The addition of AOP treatment provides substantial benefits to patients with chronic venous leg ulceration compared with current best practice.

Anticardiolipin antibodies are associated with cognitive dysfunction in stroke-free individuals.

BACKGROUND AND PURPOSE: The presence of anticardiolipin antibodies (aCLs) has been associated with vascular occlusive events. The role of aCLs as a risk factor for stroke has been a matter of debate, and scarce information exists on the relationship between aCLs and other cerebral disorders. Reports exist for seizures, chorea and subtle cognitive dysfunction. The association between aCLs and cognition was further explored and the relationship between aCL titres and brain magnetic resonance imaging (MRI) findings was evaluated in a large cohort of community-dwelling individuals. METHODS: The study cohort was drawn from the Austrian Stroke Prevention Study. A total of 1895 subjects had a complete risk factor assessment and measurement of aCL titres in serum. Participants were classified as aCL positive if either the immunoglobulin G (IgG) or IgM aCL titres were elevated (IgG > 21 U/ml, IgM > 12 U/ml). All subjects were also categorized based on the quartile distribution of IgG and IgM isotype titres. All underwent cognitive testing by the Mini Mental State Examination (MMSE) and a random sample of 947 participants also underwent brain MRI. RESULTS: aCL positive participants performed worse on the MMSE. IgG but not IgM isotype titres related to worse performance on the MMSE. No significant association existed with vascular brain abnormalities including lacunes, cortical infarcts and white matter lesions. CONCLUSIONS: These data support the view that in normal elderly persons increasing IgG aCL titres relate to global cognitive dysfunction. It is unlikely that structural brain lesions are responsible for this finding.

Previously not recognized deletion in presenilin-1 (p.Leu174del.) in a patient with early-onset familial Alzheimer's disease.

We report on a previously not recognized mutation in exon 6 of presenilin-1 (PSEN1) (c.520_522delCTG) in a male patient with early onset familial Alzheimer disease. The mutation results in the deletion of a leucine at amino acid position 174 of the protein. The index patient presented with progressive memory loss at 50 years of age. Initially, depression was the only ancillary symptom. At age 53 clinical diagnosis of early Alzheimer disease was made based on neuropsychological, neuroimaging, and CSF findings. The patient's father and his paternal grandmother also suffered from memory loss and cognitive decline. The clinical findings in the patient are similar to signs and symptoms in previously reported patients with missense mutations at codon 174 of PSEN1.

Existential behavioural therapy for informal caregivers of palliative patients: a randomised controlled trial.

BACKGROUND: Existential behavioural therapy (EBT) was developed to support informal caregivers of palliative patients in the last stage of life and during bereavement as a manualised group psychotherapy comprising six sessions. We tested the effectiveness of EBT on mental stress and quality of life (QOL). METHODS: Informal caregivers were randomly assigned (1:1) to EBT or a treatment-as-usual control group using computer-generated numbers in blocks of 10. Primary outcomes were assessed with the Brief Symptom Inventory (subscales somatisation, anxiety and depression), the Satisfaction with Life Scale (SWLS), the WHOQOL-BREF and a numeric rating scale for QOL (QOL-NRS, range 0-10). Data were collected at baseline, pre-treatment, post-treatment and follow-ups after 3 and 12 months. Treatment effects were assessed with a multivariate analysis of covariance. RESULTS: Out of 160 relatives, 81 were assigned to EBT and 79 to the control group. Participants were 54.5 ± 13.2 years old; 69.9% were female. The multivariate model was significant for the pre-/post-comparison (p=0.005) and the pre-/12-month comparison (p=0.05) but not for the pre-/3-month comparison. Medium to large effects on anxiety and QOL (SWLS, WHOQOL-BREF, QOL-NRS) were found at post-treatment; medium effects on depression and QOL (QOL-NRS) emerged in the 12-month follow-up. No adverse effects of the intervention were observed. CONCLUSION: Existential behavioural therapy appears to exert beneficial effects on distress and QOL of informal caregivers of palliative patients. Further longitudinal evidence is needed to confirm these findings.

Measurement of muon capture on the proton to 1% precision and determination of the pseudoscalar coupling gP.

The MuCap experiment at the Paul Scherrer Institute has measured the rate Λ(S) of muon capture from the singlet state of the muonic hydrogen atom to a precision of 1%. A muon beam was stopped in a time projection chamber filled with 10-bar, ultrapure hydrogen gas. Cylindrical wire chambers and a segmented scintillator barrel detected electrons from muon decay. Λ(S) is determined from the difference between the µ(-) disappearance rate in hydrogen and the free muon decay rate. The result is based on the analysis of 1.2 × 10(10) µ(-) decays, from which we extract the capture rate Λ(S) = (714.9 ± 5.4(stat) ± 5.1(syst)) s(-1) and derive the proton's pseudoscalar coupling g(P)(q(0)(2) = -0.88 m(µ)(2)) = 8.06 ± 0.55.

Measurement of the positive muon lifetime and determination of the Fermi constant to part-per-million precision.

We report a measurement of the positive muon lifetime to a precision of 1.0 ppm; it is the most precise particle lifetime ever measured. The experiment used a time-structured, low-energy muon beam and a segmented plastic scintillator array to record more than 2×10(12) decays. Two different stopping target configurations were employed in independent data-taking periods. The combined results give τ(µ(+)) (MuLan)=2 196 980.3(2.2) ps, more than 15 times as precise as any previous experiment. The muon lifetime gives the most precise value for the Fermi constant: G(F) (MuLan)=1.166 378 8(7)×10(-5) GeV(-2) (0.6 ppm). It is also used to extract the µ(-)p singlet capture rate, which determines the proton's weak induced pseudoscalar coupling g(P).

Genetic analysis of clinical mastitis and somatic cell count traits in Austrian Fleckvieh cows.

The objectives of this study were to investigate genetic associations between clinical mastitis (CM) and different somatic cell count traits, and to examine their relationships, in terms of estimated breeding values, with other traits that are routinely evaluated in Austrian Fleckvieh dual-purpose cows. Records on veterinary treatments of CM were available from the Austrian health-monitoring project. For CM, 3 intervals in early lactation were considered: -10 to 50 d, 51 to 150 d, and -10 to 150 d after calving. Within each interval, absence or presence of CM was scored as 1 or 0 based on whether or not the cow had recorded at least one veterinary treatment of CM. The average somatic cell score of the first 2 test-days after calving was defined as early lactation average somatic cell score, and lactation mean somatic cell score was the average of all test-day somatic cell scores from 8 to 305 d after calving. Subclinical mastitis was expressed as a binary trait based on prolonged elevated somatic cell counts. If somatic cell counts on 3 consecutive test-days in the interval from 8 to 305 d after calving were above 200,000 cells/mL, the binary variable subclinical mastitis was defined as 1 and otherwise 0. Records of Austrian Fleckvieh cows, with calving from January 1, 2007, to February 28, 2009, were analyzed using univariate and bivariate sire models. Threshold liability models were applied for binary traits, and Gaussian models were used for early lactation average somatic cell score and lactation mean somatic cell score. A Bayesian approach using Gibbs sampling was applied for genetic analyses. Posterior means of heritability of liability to CM were 0.06 and 0.02 in the first and second interval, respectively, and 0.05 in the full period (-10 to 150 d). Heritability estimates of somatic cell count traits were higher (0.09 to 0.13). The posterior mean of the genetic correlation between CM in lactation period 1 (-10 to 50 d after calving) and 2 (51 to 150 d after calving) was close to unity. Posterior means of genetic correlations between CM and somatic cell count traits ranged from 0.64 to 0.77. Because CM and somatic cell count describe different aspects of udder health, information on both traits should be considered for selection of bulls. Correlations of sire breeding values revealed that especially the udder conformation trait udder depth may be useful as additional information to reduce both CM and somatic cell count.

Celecoxib treatment restores pharmacosensitivity in a rat model of pharmacoresistant epilepsy.

BACKGROUND AND PURPOSE: A functional link between seizure-induced P-glycoprotein overexpression at the blood-brain barrier and therapeutic failure has been suggested by several studies using rodent epilepsy models and human epileptic tissue. Recently, we reported that interference with the mechanisms that up-regulate P-glycoprotein in response to seizure activity might provide a novel approach to control its expression in the epileptic brain. Based on these data, we hypothesized that blocking the appropriate signalling cascade by cyclooxygenase-2 inhibition should improve brain penetration of antiepileptic drugs and help to overcome drug resistance. EXPERIMENTAL APPROACH: Effects of the selective cyclooxygenase-2 inhibitor celecoxib on the response to the P-glycoprotein substrate, phenobarbital, was evaluated in a chronic model of drug-resistant temporal lobe epilepsy in rats. Drug-resistant rats selected from this model exhibit a marked overexpression of P-glycoprotein in the hippocampus and other limbic brain regions. KEY RESULTS: Responders and non-responders were selected from a group of rats with spontaneous recurrent seizures after prolonged treatment with phenobarbital at maximum tolerated doses. The efficacy of phenobarbital was re-evaluated following a 6 day treatment with celecoxib and the frequency of spontaneous recurrent seizures was significantly reduced in both groups of rats, phenobarbital responders or non-responders selected from the previous drug trial. CONCLUSIONS AND IMPLICATIONS: Pretreatment with the cyclooxygenase-2 inhibitor restored the anticonvulsant activity of phenobarbital in rats that failed to exhibit a relevant response before celecoxib treatment. Our data provide further support for a novel therapeutic approach to overcome transporter-mediated drug resistance in epilepsies.