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Behçet's disease (BD) is an autoinflammatory disease with multifactorial and polygenic etiology, potentially involving arteries and veins of any size resulting in variable vessel vasculitis. We report a case of an Iranian male who presented with porto-sinusoidal vascular disorder due to venous vasculitis as initial manifestation of BD. Despite immunosuppression, anticoagulation and venous recanalization, he subsequently developed severe nephrotic-range proteinuria mimicking a primary renal disease which was completely and immediately ameliorated by stenting of the vena cava. This demonstrates that the proteinuria was caused by increased intraglomerular pressure due to venous outflow obstruction as a consequence of venous vasculitis. To our knowledge, this is the first report of massive proteinuria caused by venous obstruction of the caval vein in the context of BD. Altogether, this case demonstrates the extensive spectrum of vascular disease in BD.
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Síndrome de Behçet , Proteinuria , Humanos , Masculino , Síndrome de Behçet/complicaciones , Proteinuria/etiología , Vasculitis/etiologíaRESUMEN
Asthma is a highly prevalent chronic allergic inflammatory disease of the airways affecting people worldwide. House dust mite (HDM) is the most common allergen implicated in human allergic asthma. HDM-induced allergic responses are thought to depend upon activation of pathways involving Toll-like receptors and their adaptor protein myeloid differentiation factor 88 (MyD88). We sought here to determine the role of MyD88 in myeloid and type II lung epithelial cells in the development of asthma-like allergic disease using a mouse model. Repeated exposure to HDM caused allergic responses in control mice characterized by influx of eosinophils into the bronchoalveolar space and lung tissue, lung pathology and mucus production and protein leak into bronchoalveolar lavage fluid. All these responses were abrogated in mice with a general deficiency of MyD88 but unaltered in mice with MyD88 deficiency, specifically in myeloid or type II lung epithelial cells. We conclude that cells other than myeloid or type II lung epithelial cells are responsible for MyD88-dependent HDM-induced allergic airway inflammation.
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Asma/inmunología , Células Epiteliales/inmunología , Hipersensibilidad/inmunología , Células Mieloides/fisiología , Factor 88 de Diferenciación Mieloide/metabolismo , Neumonía/inmunología , Pyroglyphidae/inmunología , Animales , Antígenos Dermatofagoides/inmunología , Movimiento Celular , Células Epiteliales/patología , Humanos , Pulmón/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Factor 88 de Diferenciación Mieloide/genéticaRESUMEN
BACKGROUND: Asthma is an inflammatory disease that involves airway hyper-responsiveness and mucus hypersecretion. The LIM-only protein FHL2 is a crucial modulator of multiple signal transduction pathways and functions as a scaffold in specific protein-protein interactions. OBJECTIVE: We sought to investigate the role of FHL2 in airway inflammation. METHODS: Allergic airway inflammation was induced in WT and FHL2-knock out (FHL2-KO) mice with ovalbumin (OVA). Lung tissue, bronchoalveolar lavage fluid (BALF) and draining lymph node cells were analysed for inflammation. FHL2 loss and gain of function studies were performed in lung epithelial cells. RESULTS: FHL2-deficient mice challenged with OVA show significantly reduced airway inflammation as evidenced by reduced infiltration of inflammatory cells including eosinophils, dendritic cells, B cells and T cells. Furthermore, mucus production was decreased in FHL2-KO mice. In BALF, the levels of IL-5, IL-13, eotaxin-1 and eotaxin-2 were significantly lower in FHL2-KO mice. In addition, draining lymph node cells from FHL2-KO mice show reduced levels of IL-5 and IL-13. Consistent with this, OVA-specific serum IgG and IgE levels were reduced in FHL2-KO mice. We also found that phosphorylation of ERK1/2 is markedly attenuated in FHL2-KO lung. Knock-down of FHL2 in human lung epithelial cells resulted in a striking decrease in ERK1/2 phosphorylation and mRNA levels of inflammatory cytokines and MUC5AC, whereas FHL2 overexpression exhibited opposite effects. Finally, the SNP rs4851765 shows an association with the severity of bronchial hyper-responsiveness. CONCLUSION: These results highlight functional involvement of FHL2 in airway inflammation and identify FHL2 as a novel gene associated with asthma severity in human.
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Asma/genética , Proteínas con Homeodominio LIM/metabolismo , Proteínas Musculares/metabolismo , Neumonía/genética , Hipersensibilidad Respiratoria/genética , Factores de Transcripción/metabolismo , Animales , Asma/metabolismo , Western Blotting , Modelos Animales de Enfermedad , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Proteínas con Homeodominio LIM/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Musculares/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Neumonía/metabolismo , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Hipersensibilidad Respiratoria/metabolismo , Factores de Transcripción/genéticaRESUMEN
BACKGROUND: Subthreshold psychotic and bipolar experiences are common in major depressive disorder (MDD). However, it is unknown if effectiveness of psychotherapy is altered in depressed patients who display such features compared with those without. The current paper aimed to investigate the impact of the co-presence of subclinical psychotic experiences and subclinical bipolar symptoms on the effectiveness of psychological treatment, alone or in combination with pharmacotherapy. METHOD: In a naturalistic study, patients with MDD (n = 116) received psychological treatment (cognitive behavioural therapy or interpersonal psychotherapy) alone or in combination with pharmacotherapy. Depression and functioning were assessed six times over 2 years. Lifetime psychotic experiences and bipolar symptoms were assessed at the second time point. RESULTS: Subclinical psychotic experiences predicted more depression over time (ß = 0.20, p < 0.002), non-remission [odds ratio (OR) 7.51, p < 0.016] and relapse (OR 3.85, p < 0.034). Subthreshold bipolar symptoms predicted relapse (OR 1.16, p < 0.037). CONCLUSIONS: In general, subclinical psychotic experiences have a negative impact on the course and outcome of psychotherapy in MDD. Effects of subclinical bipolar experiences were less prominent.
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Trastorno Bipolar/terapia , Trastorno Depresivo Mayor/terapia , Psicoterapia/métodos , Trastornos Psicóticos/terapia , Resultado del Tratamiento , Adulto , Trastorno Bipolar/epidemiología , Terapia Cognitivo-Conductual/métodos , Terapia Combinada , Comorbilidad , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/psicología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Trastornos Psicóticos/epidemiología , Recurrencia , Inducción de Remisión , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality. Specific therapy is lacking. We assessed whether C1-inhibitor attenuates lung injury in a 'two-hit' TRALI model. METHODS: Mice were primed with lipopolysaccharide, subsequently TRALI was induced by MHC-I antibodies. In the intervention group, C1-inhibitor was infused concomitantly. Mice were supported with mechanical ventilation. After 2 h, mice were killed, lungs were removed and bronchoalveolar lavage fluid (BALF) was obtained. RESULTS: Injection of MHC-I antibodies induced TRALI, illustrated by an increase in wet-to-dry ratio of the lungs, in BALF protein levels and in lung injury scores. TRALI was further characterized by complement activation, demonstrated by increased BALF levels of C3a and C5a. Administration of C1-inhibitor resulted in increased pulmonary C1-inhibitor levels with high activity. C1-inhibitor reduced pulmonary levels of complement C3a associated with improved lung injury scores. However, levels of pro-inflammatory mediators were unaffected. CONCLUSION: In a murine model of TRALI, C1-inhibitor attenuated pulmonary levels of C3a associated with improved lung injury scores, but with persistent high levels of inflammatory cytokines.
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Lesión Pulmonar Aguda/tratamiento farmacológico , Proteína Inhibidora del Complemento C1/administración & dosificación , Reacción a la Transfusión , Reacción a la Transfusión/tratamiento farmacológico , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/patología , Análisis de Varianza , Animales , Anticuerpos/inmunología , Líquido del Lavado Bronquioalveolar/inmunología , Activación de Complemento/inmunología , Complemento C3a/inmunología , Complemento C5a/inmunología , Citocinas/inmunología , Modelos Animales de Enfermedad , Lipopolisacáridos , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Reacción a la Transfusión/patologíaRESUMEN
In the current study, the development in reading comprehension performance of students in lower-SES versus higher-SES schools during and after school closures due to Covid-19 lockdowns was examined, and compared to a normed reference group. Furthermore, we explored protective factors against negative effects at the time of school closures, by pinpointing successful practices in a sub sample of resilient lower-SES schools. The total sample consisted of 2202 students followed from grade 2-4. Overall, we found that students in lower-SES schools made less progress over time than students in higher-SES schools. On average, students made less progress during the lockdowns, but here, the interaction with SES was not significant. Students' reading comprehension levels partially recovered after the lockdowns. Questionnaire-data revealed that schools were better prepared during the second lockdown, with teachers making more use of digital means, and providing more online reading instruction. In addition, collaboration with the parents seemed to have improved. The in depth interviews with resilient lower-SES schools revealed that the introduction of online education and investing in educational partnerships with parents may have helped to minimize the negative impact of lockdowns. We conclude that lockdowns have a negative effect on the development of reading education, but that students are resilient. Digital means and partnership with parents may be seen as protective factors to attenuate the negative effects of emergency remote teaching.
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Rectal suction biopsy (RSB) is a gold standard for diagnosing Hirschsprung disease (HD). Calretinin staining of RSB is increasingly used by experienced pathologists due to non-complex examination and comparable diagnostic accuracy with acetylcholinesterase (AChE). However, the diagnostic accuracy of calretinin examined by unexperienced pathologists remains to be elucidated. Therefore, we aim to compare diagnostic accuracy of calretinin with AChE on RSB for diagnosing HD when examined by unexperienced pathologists. We prospectively analyzed sections from RSB stained with AChE + HE and calretinin. Blinded examination was done by five unexperienced pathologists (pathology residents) and three experienced pathologists (senior pediatric gastro-enterology pathologists) assessing for the presence of HD. Cases for the study included ones proven to be HD on resection specimens and cases without HD. Diagnostic accuracy was determined calculating area under the curve (AUC), sensitivity, specificity, likelihood ratio, and posttest probability. Fleiss' kappa analysis was performed to assess interobserver agreement between reviewers. Eleven of 18 included patients (61%) were diagnosed with HD. Comparing the diagnostic accuracy of unexperienced pathologists, calretinin versus AChE + HE showed sensitivity of 80.0% versus 74.5% and specificity of 100% versus 65.4%, AUC of 0.87 (0.78-0.96) versus 0.59 (0.45-0.72). Unexperienced pathologists showed substantial agreement with calretinin (kappa 0.72 [0.61-0.84]) and fair agreement with AChE + HE (kappa 0.34 [0.23-0.44]). We found calretinin having higher diagnostic accuracy in diagnosing HD compared to AChE + HE when examined by unexperienced pathologists. Therefore, we recommend to use calretinin as the standard technique for staining RSB in diagnosing HD.
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Enfermedad de Hirschsprung , Acetilcolinesterasa/análisis , Acetilcolinesterasa/metabolismo , Biopsia/métodos , Calbindina 2/análisis , Niño , Enfermedad de Hirschsprung/diagnóstico , Humanos , Lactante , Patólogos , Recto/patología , Coloración y Etiquetado , SucciónRESUMEN
Influenza A is a major cause of mortality. Knowledge on coagulation activation in influenza infection is limited. The factor V Leiden (FVL) mutation is possibly subject to positive selection pressure. It is unknown whether this mutation impacts on the outcome of severe influenza. In the present study, the effect of lethal influenza on pulmonary and systemic coagulation activation and whether or not FVL mutation alters coagulation activation in and the course of lethal influenza, was determined. Wild-type mice, and mice heterozygous or homozygous for FVL were infected intranasally with a lethal dose of H1N1 (haemagglutinin 1 and neuraminidase 1) influenza A. Mice were sacrificed after 48 or 96 h for determination of coagulation activation, histopathology, pulmonary inflammatory parameters and viral load, or were observed in a survival study. Extensive local and systemic coagulation activation during lethal influenza was demonstrated by increased lung and plasma levels of thrombin-antithrombin complexes and fibrin degradation products, and by pulmonary fibrin deposition. FVL mutation did not influence the procoagulant response, lung histopathology or survival. FVL mice demonstrated elevated viral loads 48 h after infection. In conclusion, coagulation is activated locally and systemically during lethal murine influenza A infection. The FVL mutation does not influence coagulation activation, lung inflammation or survival in lethal influenza A.
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Trastornos de la Coagulación Sanguínea/genética , Factor V/genética , Subtipo H1N1 del Virus de la Influenza A , Infecciones por Orthomyxoviridae/sangre , Infecciones por Orthomyxoviridae/mortalidad , Animales , Antitrombinas/análisis , Factores de Coagulación Sanguínea/análisis , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Heterocigoto , Homocigoto , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Mutación Puntual , Índice de Severidad de la Enfermedad , Trombina/análisis , Carga ViralRESUMEN
A 46-year-old woman was referred for orthodontic surgery consultation because ofa retrognathic maxilla, unilateral cross bite and functional, aesthetic and speech problems. The maxilla was widened unilaterally by unilateral surgically assisted rapid maxillary expansion with a bone-borne transpalatal distractor. During post-operative orthodontic treatment, a temporary anchorage device was administered. With the help of composite veneers, crowns and a removable partial denture, a functionally and aesthetically satisfying result was achieved.
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Maxilar/cirugía , Osteogénesis por Distracción/métodos , Osteotomía Le Fort/métodos , Técnica de Expansión Palatina/instrumentación , Femenino , Humanos , Maxilar/anomalías , Persona de Mediana Edad , Aparatos Ortodóncicos , Osteogénesis por Distracción/instrumentación , Osteotomía Le Fort/instrumentación , Resultado del TratamientoRESUMEN
Changes in human balance control can objectively be assessed using system identification techniques in combination with support surface translations. However, large, expensive and complex motion platforms are required, which are not suitable for the clinic. A treadmill could be a simple alternative to apply support surface translations. In this paper we first validated the estimation of the joint stiffness of an inverted pendulum using system identification methods in combination with support surface translations, by comparison with the joint stiffness calculated using a linear regression method. Second, we used the system identification method to investigate the effect of horizontal ground reaction forces on the estimation of the ankle torque and the dynamics of the stabilizing mechanism of 12 healthy participants. Ankle torque and resulting frequency response functions, which describes the dynamics of the stabilizing mechanism, were calculated by both including and excluding horizontal ground reaction forces. Results showed that the joint stiffness of an inverted pendulum estimated using system identification is comparable to the joint stiffness estimated by a regression method. Secondly, within the induced body sway angles, the ankle torque and frequency response function of the joint dynamics calculated by both including and excluding horizontal ground reaction forces are similar. Therefore, the horizontal ground reaction forces play a minor role in calculating the ankle torque and frequency response function of the dynamics of the stabilizing mechanism and can thus be omitted.
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Articulación del Tobillo , Tobillo , Fenómenos Biomecánicos , Humanos , TorqueRESUMEN
We investigated the effects of different ratios of reduced (NH4+) versus oxidised (NO3(-)) nitrogen in deposition on heathland and species-rich grassland vegetation at high nitrogen deposition levels in large mesocosms filled with nutrient-poor soils to which different NH4+/NO3(-) ratios were applied. The response of the forbs, Antennaria dioica, Arnica montana, Gentiana pneumonanthe, Thymus serpyllum, the grasses Danthonia decumbens, Deschampsia flexuosa, Nardus stricta and the shrub Calluna vulgaris was recorded. The forb A. dioica and the grass D.decumbens preferred low NH4+/NO3(-) ratios and were characterised by a negative correlation between NH4+/NO3(-) ratios and biomass and survival, whereas the grasses N. stricta and D. flexuosa showed no correlation with NH4+/NO3(-) ratios. Lime addition eliminated the negative effects of high NH4+ concentrations in deposition for A. dioica and the grass D. decumbens. The implications of these findings for heathland vegetations are discussed.
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Amoníaco/farmacología , Ecología/métodos , Contaminantes Ambientales/farmacología , Óxidos de Nitrógeno/farmacología , Desarrollo de la Planta , Aminoácidos/análisis , Biodiversidad , Biomasa , Calluna/química , Calluna/crecimiento & desarrollo , Clorofila/análisis , Concentración de Iones de Hidrógeno , Plantas/química , Plantas Comestibles/química , Plantas Comestibles/crecimiento & desarrollo , Poaceae/química , Poaceae/crecimiento & desarrollo , Suelo/análisis , EspectrofotometríaRESUMEN
The objective of this study was to investigate whether dairy cows visit and interact with a fenceline-housed bull more during oestrus than outside oestrus and whether fenceline bull contact affects expression of oestrus. At one end of a free stall a fence with vertical open bars was placed behind which a bull could be housed, allowing interactions with the cows. A closed fence with two blinded entrances was placed before the fence, creating a contact area. The experiment consisted of three treatments; it started with the control treatment (no bull on the farm) and was followed by bull treatment (a bull housed behind the fence) and no bull treatment (a bull present on the farm but not housed behind the fence). Signs of oestrus were observed every 4h for 30min and cows were equipped with pedometers. On the day of oestrus, cows were more frequent in the contact area during the bull treatment (12.0+/-9.8 times) and the no bull treatment (13.9+/-10.2 times) than during the control treatment (2.6+/-2.5 times). The frequency of visits to the contact area was low and not different between treatments on the other days (2.2+/-1.9 times). More cows had direct contact with the bull on the day of oestrus (71.4%) compared to the days outside oestrus (21.4-30%). The duration of direct contact with the bull was highly variable between cows and did not differ between oestrus and non-oestrus days. Behaviour and duration of oestrus were not affected by treatment but the relative increase in number of steps during oestrus tended to be higher in the bull (5.5+/-0.2) and no bull treatment (5.3+/-0.3) than in the control treatment (4.6+/-0.3). In conclusion, dairy cows in oestrus seem to be attracted by a bull or by the expectation of the presence of a bull, but fenceline bull exposure does not affect behavioural expression of oestrus.
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Estro/fisiología , Conducta Sexual Animal/fisiología , Animales , Bovinos , Femenino , MasculinoRESUMEN
BACKGROUND: People with depression often experience interpersonal problems. Family therapy for depression is a widely used intervention, but it is unclear whether this is an effective therapy for the treatment of depression. OBJECTIVES: To assess the efficacy of family therapy for depression. SEARCH STRATEGY: The following electronic databases were searched using a specific search strategy: CCDANCTR-Studies and CCDANCTR-References searched on 21/10/2005, The Cochrane Central Register of Controlled Trials, Medline (1966 to January 2005), EMBASE (1980 to January 2005), Psycinfo (1974 to January 2005). Reference lists of articles were also searched. Handsearches of relevant journals and bibliographies were conducted and first authors of included studies and experts in the field were contacted for further information. SELECTION CRITERIA: Included studies were randomised controlled and controlled clinical trials comparing family therapy with no intervention or an alternative intervention in which depression symptomatology was a main outcome measure. DATA COLLECTION AND ANALYSIS: Methodological quality was independently assessed by two review authors using the Maastricht-Amsterdam Criteria List. The qualitative and quantitative characteristics of the selected trials were independently extracted by three review authors using a standardised data extraction form. Levels of evidence were used to determine the strength of the evidence available. It was not possible to perform meta-analyses because of the heterogeneity of the selected studies. MAIN RESULTS: Three high-quality and three low-quality studies, involving 519 people with depression, were identified. The studies were very heterogeneous in terms of interventions, participants, and measuring instruments. Despite fairly good methodological quality and positive findings of some studies, evidence for the effectiveness of family therapy for depression did not exceed level 3 (limited or conflicting evidence), except for moderate evidence (level 2), based on the non-combined findings from three studies, indicating that family therapy is more effective than no treatment or waiting list condition on decreasing depression, and on increasing family functioning. AUTHORS' CONCLUSIONS: The current evidence base is too heterogeneous and sparse to draw conclusions on the overall effectiveness of family therapy in the treatment of depression. At this point, use of psychological interventions for the treatment of depression for which there is already an evidence-base would seem to be preferable to family therapy. Further high quality trials examining the effectiveness and comparative effectiveness of explicitly defined forms of family therapy are required.
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Depresión/terapia , Salud de la Familia , Terapia Familiar/métodos , Femenino , Humanos , Masculino , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The objective of this study was to investigate whether bull exposure affects LH profiles in postpartum, anoestrous dairy cows. Eight cows between 10 and 17 days after parturition were used. On Day 1, blood samples were taken at 10 min intervals for 8 h. On Day 2, blood sampling continued at 10 min intervals and after 2 h a bull was introduced behind a fence, and blood sampling continued for another 8 h. Time of resumption of luteal activity was between 25 and more than 80 days after parturition for these animals and was not related (P>0.1) with frequency of LH pulses, amplitude of pulses and basal LH concentration on either Day 1 or Day 2. In 6 of the 8 cows, average and basal LH concentration were greater (P<0.001) during the 8 h of bull presence (0.56 +/- 0.33 and 0.39 +/- 0.26 ng/ml, respectively) compared to the 8 h without a bull (0.50 +/- 0.30 and 0.35 +/- 0.24 ng/ml, respectively). Pulse amplitude did not differ (P=0.85) between Day 2 (0.45 +/- 0.24 ng/ml) or Day 1 (0.45 +/- 0.14 ng/ml). LH pulse frequency was greater (P<0.1) on Day 2 (5.3 pulses/8h) compared to the Day 1 (4.6 pulses/8h). In conclusion, fenceline bull exposure early postpartum seems to have an acute effect on LH-release in anoestrous dairy cows. Whether sustained bull exposure can hasten first ovulation after calving through an effect on LH release in dairy cows is an interesting area of research.
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Anestro/sangre , Industria Lechera , Vivienda para Animales , Hormona Luteinizante/sangre , Periodo Posparto/sangre , Anestro/fisiología , Animales , Bovinos , Femenino , Lactancia/fisiología , Masculino , Apareamiento , Periodo Posparto/fisiologíaRESUMEN
When the daily routine of a cow is disturbed, it may have a detrimental effect on the performance of activity meters to detect estrus. It is possible that during the pasture period, the daily routine of cows is disturbed, adversely affecting the performance of activity meters to detect estrus which does not happen when the cows are housed indoors. The objective of this study was to investigate whether housing conditions (pasture or indoor) affected the performance of activity meters to detect estrus in dairy cows. In this research, two types of activity meters were used, an activity meter attached to the leg and one mounted on the neck. Cows of two different herds were equipped with the Smarttag Leg and the Smarttag Neck (Nedap livestock management, Groenlo, the Netherlands). The study began during the pasture period (September) and ended during the indoor period (January). The pasture period ended at the beginning of November. So, about two months of pasture period and two months of indoor period were studied. Milk samples were collected twice a week during the morning milking and true estrus was determined by milk progesterone concentrations. In total, the dataset consisted of 95 true estrous periods and 1992 true non-estrous days of 56 cows for the pasture period and 138 true estrous periods and 3164 true non-estrous days of 65 cows for the indoor period. Overall, no differences in sensitivity, positive predictive value (PPV) and specificity were found between the pasture and indoor period for both types of sensors. There was also no difference in the performance between leg and neck activity meters. Sensitivity was between 76 and 82%, PPV was between 87 and 92% and specificity was between 99 and 100%. In conclusion, the sensitivity, PPV and specificity did not differ between the pasture and indoor period. This means that, in our study, the performance of both types of activity meters to detect estrus is not affected by housing conditions.
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Bovinos/fisiología , Detección del Estro/instrumentación , Vivienda para Animales , Animales , Conducta Animal , Industria Lechera , Estro/fisiología , Extremidades , Femenino , Leche/química , Cuello , Países Bajos , Progesterona/análisis , Estaciones del Año , Sensibilidad y EspecificidadRESUMEN
Essentials Immunity and coagulation are linked during sepsis but the role of thrombin is not fully elucidated. We investigated the effect of thrombin inhibition on murine Klebsiella pneumosepsis outcome. Thrombin is crucial for survival and limiting bacterial growth in pneumonia derived sepsis. Thrombin improves host defense via fibrin and enhancement of platelet-neutrophil interactions. SUMMARY: Background Innate immunity and coagulation are closely linked during sepsis. Their interaction can be detrimental to the outcome because of microvascular failure but can also enhance host defense. The role of thrombin therein has not been fully elucidated. Objective We aimed to investigate the contribution of thrombin to the host response during pneumonia-derived sepsis. Methods Mice treated with the specific thrombin inhibitor dabigatran or control chow were infected with the common human sepsis pathogen Klebsiella (K.) pneumoniae via the airways. In subsequent infection experiments, mice were additionally treated with ancrod to deplete fibrinogen. Ex vivo Klebsiella growth was assessed by incubating human whole blood or specific blood components in various conditions with Klebsiella. Results Thrombin inhibition by dabigatran enhanced bacterial outgrowth and spreading, and accelerated mortality. Thrombin inhibition did not influence neutrophil recruitment to the lung or activation or neutrophil extracellular trap formation. Dabigatran reduced D-dimer formation and fibrin deposition in the lung. Fibrin depletion also enhanced bacterial outgrowth and spreading, and thrombin inhibition had no additional effect. Both thrombin and fibrin polymerization inhibited ex vivo Klebsiella outgrowth in human whole blood, which was neutrophil dependent, and the effect of thrombin required the presence of platelets and platelet protease activated receptor-1. In vivo thrombin inhibition reduced platelet-neutrophil complex formation and endothelial cell activation, but did not prevent sepsis-induced thrombocytopenia or organ damage. Conclusions These results suggest that thrombin plays an important role in protective immunity during pneumonia-derived sepsis by fibrin polymerization and enhancement of platelet-neutrophil interactions.
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Plaquetas/citología , Fibrina/química , Neutrófilos/citología , Neumonía Bacteriana/inmunología , Sepsis/inmunología , Trombina/inmunología , Animales , Coagulación Sanguínea , Comunicación Celular , Dabigatrán/administración & dosificación , Trampas Extracelulares , Femenino , Fibrinógeno/química , Citometría de Flujo , Humanos , Sistema Inmunológico , Inmunidad Innata , Infecciones por Klebsiella/inmunología , Klebsiella pneumoniae , Pulmón/patología , Ratones , Ratones Endogámicos C57BL , Microcirculación , Sepsis/microbiologíaRESUMEN
Groundwater-fed fens are known sources of methane (CH4 ) emissions to the atmosphere, and these are known to be mediated by the vegetation. In a fen located in the Bale Mountains, Ethiopia, we assessed the effects of a cushion plant (Eriocaulon schimperi) and a sedge (Carex monostachya) on rhizosphere biogeochemistry. Methane and CO2 concentrations and pH were measured in pore-water at different depths in the profile. Redox potentials and NaCl-extractable element concentrations were analysed in soil samples from sites dominated by either E. schimperii or C. monostachya. Nutrient and element concentration were analysed in plant tissues. At Carex-dominated sites, CH4 concentrations increased from 70 µmol·l-1 at a depth of 10 cm to 130 µmol·l-1 at a depth of 100 cm. CH4 concentrations at Eriocaulon-dominated sites were almost zero (<1 µmol·l-1 ) to a depth of 100 cm. Simultaneously, soil redox potentials and CO2 concentrations were higher at Eriocaulon-dominated sites, indicating a low potential for CH4 production and a high potential for CH4 oxidation. Eriocaulon schimperi displayed a root investment strategy to cope with the harsh environment, similar to the cushion plant Astelia pumila in Patagonian bogs. This strategy is characterised by high root/shoot ratios, high root porosity and density under high redox conditions. Both cushion plant species create an aerobic rhizosphere through radial oxygen loss from deep roots, which strongly reduce CH4 fluxes to the atmosphere.
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Eriocaulaceae/metabolismo , Metano/metabolismo , Oxígeno/metabolismo , Dióxido de Carbono/metabolismo , Etiopía , RizosferaRESUMEN
The objective of this study was to investigate whether monitoring progesterone concentrations in milk and blood plasma can be used to predict time of ovulation in dairy cattle. Whole milk was sampled twice daily and blood samples were collected once a day before the morning milking. Ovulation was assessed by trans-rectal ultrasonography at 4h intervals beginning from the end of estrus. For a parameter to be useful as predictor for time of ovulation, it should be precise (i.e. variation between animals should not exceed 12h). In milk, progesterone concentration dropped <15 ng/ml at 97.7+/-17.8h (range: 54-126 h) before ovulation, to <5 ng/ml at 79.7+/-11.2h (range: 54-98) before ovulation to decline further to <2n g/ml at 70.7+/-16.8h (range: 38-90 h) before ovulation (n=20). In plasma, progesterone concentration dropped to <4ng/ml 90.5+/-19.6h (range: 66-138 h) before ovulation and to <2 ng/ml at 75.0+/-12.2 h (range: 50-98) before ovulation. These intervals were not influenced by parity, milk production or days in milk. In conclusion, monitoring of progesterone alone is not sufficient to predict ovulation because of the large variation in timing of decrease of progesterone concentrations relative to ovulation between animals. At best the range is about 2 days.
Asunto(s)
Bovinos/fisiología , Leche/química , Ovulación , Progesterona/análisis , Progesterona/sangre , Animales , Femenino , Ovario/diagnóstico por imagen , Factores de Tiempo , UltrasonografíaRESUMEN
The objective of the present study was to examine whether different intervals between insemination and ovulation have an influence on the sex of seven-day-old embryos in dairy cattle. Cows were inseminated once with semen of one of two bulls of proven fertility between 36 h before ovulation and 12 h after ovulation. Time of ovulation was assessed by ultrasound at 4-h intervals. In total, 64 embryos were determined to be male or female. Of these 64 embryos, 51.6% were female. The sex ratio in the various insemination-ovulation intervals (early: between 36 and 20 h before ovulation; intermediate: between 20 and 8 h before ovulation; late: between 8 h before and 12 h after ovulation) did not significantly differ from the expected 1:1 sex ratio (50, 50 and 55% females, respectively). Bull (Bull A and B) and Parity (primiparous and multiparous) had no influence on the expected 1:1 sex ratio either. The number of cell cycles was similar for male and female (P = 0.23) embryos when quality of the embryo (P < 0.0001) was included in the model. The results of this study indicate that, in cattle, the interval between insemination and ovulation does not influence the sex ratio of seven-day-old embryos.