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Jaagsiekte sheep retrovirus (JSRV) causes ovine pulmonary adenocarcinoma. JSRV can be transmitted via infected colostrum or milk, which contain somatic cells (SCs) harboring JSRV provirus. Nevertheless, the cell types involved in this form of transmission and the involvement of the mammary gland remain unknown. We separated adherent cells (macrophages and monocytes) by plastic adherence, and lymphocytes (CD4+ and CD8+ T cells, and B cells) by flow cytometry, from SCs in milk samples from 12 naturally infected, PCR blood test JSRV–positive, subclinical ewes. These cell populations were tested by PCR to detect JSRV provirus. The ewes were euthanized, and mammary gland samples were analyzed immunohistochemically to detect JSRV surface protein. We did not detect JSRV provirus in any milk lymphocyte population, but milk adherent cells were positive in 3 of 12 sheep, suggesting a potential major role of this population in the lactogenic transmission of JSRV. Immunohistochemistry did not reveal positive results in mammary epithelial cells, pointing to a lack of participation of the mammary gland in the biological cycle of JSRV and reducing the probability of excretion of free viral particles in colostrum or milk.

Resumen La neumonia intrahospitalaria (NIH) es la segunda causa de infeccion nosocomial y la que conlleva mayor movilidad y mortalidad. Hoy en dia se clasifica en tres grupos: NIH que no requiere ventilacion artificial, NIH que requiere ventilacion artificial y NIH adquirida durante la ventilacion artificial (NAV). Las ultimas normativas para el manejo de la NIH se han publicado en 2016 (IDSA/ATS) y el 2017 (ERS/ESCMID/ESICM y ALAT). Las ultimas normativas espanolas se publicaron en el ano 2011 en Archivos de Bronconeumologia. Las normativas americanas del 2016 y las internacionales del 2017 presentan sus recomendaciones en un marco de gran aumento de resistencias de los microorganismos a los antibacterianos, tanto para Gram positivos y muy especialmente para Gram negativos. La SEPAR celebro en el 2019 el ano de la neumonia y creyo conveniente actualizar las normativas publicadas en el 2011.En estas normativas han participado neumologos, intensivistas,infectologos y metodologos. Se consensuo realizar las normativas con el siguiente esquema 1. Formulacion de preguntas - ?Son similares la epidemiologia y microbiologia de la NIH y la NAV - Son validos los factores de riesgo para predecir la etiologia de las NIH y NAV causada por microorganismos multirresistentes (MDR) y extremadamente resistentes (XDR) - ?Son efectivos los biomarcadores para el diagnostico y para guiar la duracion del tratamiento? - Cual es el algoritmo de tratamiento empirico actual? - ?Influye la duracion del tratamiento antibiotico de 7-8 dias vs 14 dias en el desenlace de los pacientes? - Cual es la indicacion mas adecuada de los nuevos antibioticos? 2. Cada pregunta contiene los siguientes apartados - Controversia - Evidencia - Directrices - Estudios para recomendados para resolver la controversia - Todas las directrices se consensuaron por el 100% de los expertos

BackgroundHigh-flow nasal cannula (HFNC) has become a frequently used noninvasive form of respiratory support in acute settings; however, evidence supporting its use has only recently emerged. These guidelines provide evidence-based recommendations for the use of HFNC alongside other noninvasive forms of respiratory support in adults with acute respiratory failure (ARF).Materials and methodologyThe European Respiratory Society task force panel included expert clinicians and methodologists in pulmonology and intensive care medicine. The task force used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methods to summarise evidence and develop clinical recommendations for the use of HFNC alongside conventional oxygen therapy (COT) and noninvasive ventilation (NIV) for the management of adults in acute settings with ARF.ResultsThe task force developed eight conditional recommendations, suggesting the use of 1) HFNC over COT in hypoxaemic ARF; 2) HFNC over NIV in hypoxaemic ARF; 3) HFNC over COT during breaks from NIV; 4) either HFNC or COT in post-operative patients at low risk of pulmonary complications; 5) either HFNC or NIV in post-operative patients at high risk of pulmonary complications; 6) HFNC over COT in nonsurgical patients at low risk of extubation failure; 7) NIV over HFNC for patients at high risk of extubation failure unless there are relative or absolute contraindications to NIV; and 8) trialling NIV prior to use of HFNC in patients with COPD and hypercapnic ARF.ConclusionsHFNC is a valuable intervention in adults with ARF. These conditional recommendations can assist clinicians in choosing the most appropriate form of noninvasive respiratory support to provide to patients in different acute settings.

The Neospora caninum Calcium-dependent protein kinase 1 (NcCDPK1) inhibitor BKI-1294 had demonstrated excellent efficacy in a pregnant mouse model of neosporosis, and was also highly efficacious in a pregnant sheep model of toxoplasmosis. In this work, we present the efficacy of BKI-1294 treatment (dosed 5 times orally every 48 h) starting 48 h after intravenous infection of sheep with 105 Nc-Spain7 tachyzoites at mid-pregnancy. In the dams, BKI-1294 plasma concentrations were above the IC50 for N. caninum for 12–15 days. In treated sheep, when they were compared to untreated ones, we observed a minor increase in rectal temperature, higher IFNγ levels after blood stimulation in vitro, and a minor increase of IgG levels against N. caninum soluble antigens through day 28 post-infection. Additionally, the anti-NcSAG1 and anti-NcSAG4 IgGs were lower in treated dams on days 21 and 42 post-infection. However, BKI-1294 did not protect against abortion (87% foetal mortality in both infected groups, treated and untreated) and did not reduce transplacental transmission, parasite load or lesions in placentomes and foetal brain. The lack of foetal protection was likely caused by short systemic exposure in the dams and suboptimal foetal exposure to this parasitostatic drug, which was unable to reduce replication of the likely established N. caninum tachyzoites in the foetus at the moment of treatment. New BKIs with a very low plasma clearance and good ability to cross the blood-brain and placental barriers need to be developed., Graphical abstract Image 1, Highlights • BKI-1294 triggers a transiently decrease in anti-N. caninum IgG levels in sheep. • BKI-1294 does not protect against abortion and vertical transmission of N. caninum. • The efficacy of BKI-1294 is different in pregnant mice and sheep models of neosporosis.

— Epidermotropic cutaneous T-cell lymphoma was diagnosed in six Syrian hamsters (Mesocricetus auratus) with a generalised dermatosis characterised by pruritus, alopecia and exfoliative erythroderma. Plaques and nodules were evident in one animal. Clinical and histopathological findings were suggestive of mycosis fungoides and electron microscopical investigations in one case were supportive. Immuno-histochemical stains for CD3 antigen were strongly positive in all cases. Resume— Un lyphome T cutane a ete diagnostique chez six hamsters de Siberie (Mesocricetus auratus) avec une dermatose generalisee, caracterisee par un prurit, une alopecle et une erythrodermie exfoliative. Des plaques et des nodules ont ete observees sur un animal. Les donnees cliniques et histopathologiques etaient evocatrices d'un mycosis fungoides et les examens en microscopie electronique etaient compatibles dans un cas. Les marquages immuno-histochimiques de l'antigene CD3 etaient tres positifs dans tous les cas. Zusammenfassung— Bei sechs Syrischen Goldhamstern (Mesocricetus auratus) wurde ein epidermotropes kutanes T-Zell-Lymphom mit einer generalisierten Dermatose diagnostiziert, die durch Pruritus, Alopezie und eine exfoliative Erythrodermie gekennzeichnet war. Bei einem Tier traten auch Plagues und Knoten auf. Die klinischen und histopathologischen Befunde deuteten auf Mycosis fungoides hin. Elektronenmikroskopische Untersuchungen unterstutzten diesen Verdacht in einem Fall. Immunhistochemische Farbungen auf CD3-Antigen waren bei alien Fallen stark positiv. Resumen En un grupo de seis hamsters de siria, (Mesocricetus auratus), se diagnostico limfoma epidermotropico cutaneo de linfocitos T, presentando una dermatosis generalizada de tipo pruriginoso, acompanada de alopecia y eritroderma exfoliativo. Las placas y nodulos fueron evidentes en uno de los animales. Los estudios clinicos e histopatologicos indicaron una micosis fungoide, y las investigaciones de microscopia, en uno de los caseos, parecio indicar lo mismo. La tintura inmuno-histoquimica para el antigeno CD3 resulto claramente positiva en todod los casos.

Two cases of cutaneous mycobacteriosis in psittacine birds showing featherless, non-painful, non-pruritic nodules are described. Histopathological studies of skin biopsies from both cases demonstrated the presence of a diffuse granulomatous dermatitis with acid- fast organism s inside macrophages, which led to the diagnosis of cutaneous mycobacteriosis. In one case, generalization of the process to internal organs (intestinal and hepatic serosae) was observed. Mycobacterial organisms could not be cultured using conventional isolation media (Coletsos and Lowenstein-Jensen), but polymerase chain reaction (PCR) technique performed on pathological samples from both birds revealed the presence of Mycobacterium genavense. It is thus proposed that cutaneous mycobacteriosis infections, in particular those caused by M.genavense, should be included in the differential diagnosis of skin nodular processes in psittacine birds. The usefulness of PCR techniques for aetiological diagnosis of mycobacterial infections is emphasized.

Oestrus ovis (Linnaeus 1761) is a parasite of sheep and goats, in which the fly larvae are obligatory parasites of nasal and sinus cavities. Oestrosis is endemic in hot and dry regions, especially in Mediterranean areas of Europe, Africa and America. Infected animals firstly suffer from fly strike, when adult flies inject first stage larvae on their nostrils and secondly, hosts will suffer from nasal-sinus myiasis with varying clinical respiratory signs. The disturbance caused to small ruminants while grazing and the effects during development of larvae can have severe consequences on livestock production. The evolution of O. ovis depends on the weather; the parasite is very well-adapted to their environment, being able to undergo hypobiosis either inside or outside the host, according to the climatic environmental conditions and seasonality. Understanding the epidemiology and life cycle of O. ovis is crucial to design effective control measures of this myiasis. Moreover, O. ovis infestation is considered a zoonosis; it causes ophthalmomyiasis in man in many parts of the world. The present article focuses on describing the main information about this parasite gathered in the last 20 years.

'Numerous disorders affect the lower respiratory tract of adult sheep, including Maedi Visna, ovine pulmonary adenocarcinoma and verminous pneumonias as reported elsewhere in this special issue. Herein we examine gangrenous pneumonia, ovine respiratory complex (ORC) and the visceral form of caseous lymphadenitis (CLA). Gangrenous pneumonia is a pulmonary infection commonly caused by inhalation of foreign materials, producing inflammation and necrosis of the lung parenchyma. ORC is a complex disease process involving a range of host-pathogen-environment interactions, where host immunological and physiological mechanisms interact with multiple etiological agents including bacteria, plus environmental factors or stressors. Visceral form of CLA commonly causes lesions in mediastinal lymph nodes and lung parenchyma, producing respiratory clinical signs, particularly the coughing that is responsible for transmission of the disease by aerosol. The economic relevance, etiological, clinical and pathological findings of these diseases are reviewed.

PURPOSE: Ventilator associated-lower respiratory tract infections (VA-LRTIs), either ventilator-associated pneumonia (VAP) or tracheobronchitis (VAT), accounts for most nosocomial infections in intensive care units (ICU) including. Our aim was to determine if appropriate antibiotic treatment in patients with VA-LRTI will effectively reduce mortality in patients who had cardiovascular failure.METHODS: This was a pre-planned subanalysis of a large prospective cohort of mechanically ventilated patients for at least 48 h in eight countries in two continents. Patients with a modified Sequential Organ Failure Assessment (mSOFA) cardiovascular score of 4 (at the time of VA-LRTI diagnosis and needed be present for at least 12 h) were defined as having cardiovascular failure.RESULTS: VA-LRTI occurred in 689 (23.2%) out of 2960 patients and 174 (25.3%) developed cardiovascular failure. Patients with cardiovascular failure had significantly higher ICU mortality than those without (58% vs. 26.8%; p CONCLUSIONS: Patients with VA-LRTI and cardiovascular failure did not show an association to a higher ICU survival with appropriate antibiotic treatment. Additionally, we found that in patients without cardiovascular failure, appropriate antibiotic treatment conferred a survival benefit for patients only with VAP.TRIAL REGISTRY: ClinicalTrials.gov, number NCT01791530.

Simple Summary Different species can harbor coronavirus, including domestic and wild animals. The Coroviridae family is composed of four genera, including Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus. Some domestic animals are susceptible to SARS-CoV-2 in natural and experimental infections. The infection of animals is generally a consequence of close contact with COVID-19 patients. Among domestic animals, SARS-CoV-2 replicates in respiratory ex vivo organ cultures of domestic ruminants. In this context, there is no information about the role sheep can play in the spread of the infection. This study tested the antibody response in 90 serum samples from sheep from the pre-pandemic period and 336 serum samples from sheep from the pandemic period (June 2020 to March 2021). In both cases, the animals were in close contact with a veterinary student community composed of more than 700 members. None of the serum samples analyzed were seroreactive based on an enzyme-linked immunosorbent assay (ELISA) using the receptor-binding domain (RBD) of the spike antigen. In this sense, no statistical difference was observed compared to the pre-pandemic sheep. To the authors’ knowledge, this is the first serosurvey in sheep to detect anti-SARS-CoV-2 antibodies. Future investigations should analyze the epidemiological role of sheep in SARS-CoV-2 infection, including the prevalence of infection. Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the zoonotic causative agent of coronavirus disease 2019 (COVID-19) that has caused a pandemic situation with millions of infected humans worldwide. Among domestic animals, there have been limited studies regarding the transmissibility and exposure to the infection in natural conditions. Some animals are exposed and/or susceptible to SARS-CoV-2 infection, such as cats, ferrets and dogs. By contrast, there is no information about the susceptibility of ruminants to SARS-CoV-2. This study tested the antibody response in 90 ovine pre-pandemic serum samples and 336 sheep serum samples from the pandemic period (June 2020 to March 2021). In both cases, the animals were in close contact with a veterinary student community composed of more than 700 members. None of the serum samples analyzed was seroreactive based on an enzyme-linked immunosorbent assay (ELISA) using the receptor-binding domain (RBD) of the spike antigen. In this sense, no statistical difference was observed compared to the pre-pandemic sheep. Our results suggest that it seems unlikely that sheep could play a relevant role in the epidemiology of SARS-CoV-2 infection. This is the first study to report the absence of evidence of sheep exposure to SARS-CoV-2 in natural conditions.

Ovine anaplasmosis is a vector-borne disease caused by Anaplasma ovis and mainly transmitted through tick bites. In Spain, the first outbreak of ovine anaplasmosis occurred in 2014. An epidemiological study in fifty-one farms was carried out associated with this outbreak in the affected geographical area. An epidemiological questionnaire was performed. In addition, whole blood samples were taken for molecular analysis in 47 of these farms to determine the prevalence of infection of Anaplasma ovis. A. ovis was present in 44 out of 47 PCR-analysed farms (93.6%). However, only 40.4% of the studied farms showed severe clinical signs. The clinical signs affected mainly young animals, which showed severe anaemia, weakness, anorexia, cachexia and epiphora. The early culling of young animals was more frequently reported by severely affected farms than the analysed farms without clinical signs (71.4% vs. 12.5%, p &lt, 0.001). The geographical area where the farm is located seems to be relevant for the presence of clinical signs of the disease. Ovine anaplasmosis is an emerging disease in Europe that spreads rapidly through tick bites and is capable of causing significant economic losses when it spreads in a naive area and causes an epidemic.

Microorganisms involved in ovine mandibular osteomyelitis (OMO) have not yet been deeply studied. The aim of the present study is to elucidate the microorganisms involved in OMO, comparing them with the microorganisms found in the healthy oral cavity of sheep. Two hundred and five samples were taken from mandibular osteomyelitis lesions, and they were compared with the microbiological results of samples obtained from twelve periodontally healthy sheep. Sixty-four samples (32.98%) of OMO lesions showed pure growths, while 130 (67.01%) were mixed cultures. Microorganisms of the genus Streptococcus were the most frequently isolated (20.95%), followed by bacteria of the genus Pseudomonas (8.50%), Trueperella pyogenes (7.26%), Staphylococcus (6.63%) and Escherichia coli (6.22%). Ninety-one different isolates were obtained from healthy mouths, and again, microorganisms of the genus Streptococcus were the most frequent (16.48%), followed by bacteria of the genus Staphylococcus (13.18%), Pseudomonas (9.89%) and Moraxella (6.59%). Based on these and previous results, it could be concluded that the normal microbiota of the oral cavity could be involved in the development of OMO lesions when there is an injury of the gingiva that enables the entry of bacteria to the oral mucosa that eventually settle locally in bony tissues, causing mandibular osteomyelitis.

Delia Lacasta,1 Ramses Reina,2 Marta Ruiz de Arcaute,1 Luis Miguel Ferrer,1 Alfredo Angel Benito,3 Maria Teresa Tejedor,4 Irache Echeverria,2 Hector Ruiz,1 Silvia Martinez Cardenas,1 Peter Andrew Windsor5 1Animal Pathology Department, Instituto Agroalimentario de Aragón-IA2 (Universidad de Zaragoza-CITA), Veterinary Faculty of Zaragoza, Zaragoza, 50013, Spain; 2Instituto de Agrobiotecnología (CSIC-Gobierno de Navarra), Mutilva, 31192, Navarra, Spain; 3EXOPOL S.L, San Mateo de Gállego, Zaragoza, Spain; 4Anatomy, Embryology and Animal Genetics Department, CIBER CV (Universidad de Zaragoza-IIS), Veterinary Faculty of Zaragoza, Zaragoza, 50013, Spain; 5Sydney School of Veterinary Science, The University of Sydney, Camden, NSW, 2570, AustraliaCorrespondence: Delia LacastaFacultad de Veterinaria de Zaragoza, C/Miguel Servet 177, Zaragoza, 50013, SpainTel +34 609676727Email dlacasta@gmail.comIntroduction: Orf is a highly contagious eruptive viral disease of the skin and mucosa of sheep and goats. Although vaccination with live or attenuated orf virus is the preferred option for disease control, the vaccine is unavailable in many countries. Treatment of orf lesions involves standard hygiene and in numerous cases, management of presumptive secondary infections with antibiotics, increasing risks of antimicrobial resistance (AMR). The wound dressing formulation Tri-Solfen® containing two local anaesthetics (lignocaine and bupivacaine), adrenaline and an antiseptic (cetrimide) in a gel formulation was developed for pain relief in sheep undergoing surgical husbandry procedures in Australia. Recently, TS therapy was found to reduce suffering and enhance recovery in cattle and buffalo with oral and skin lesions due to foot-and-mouth disease (FMD) virus infection. It was noted that TS has a low pH and is potentially viricidal, potentially aiding disease control.Methods: One-month-old lambs (n=14), naturally infected with orf, were recruited from a farm during a natural outbreak of the disease. The animals were selected at the early stages of the infection and randomly divided into two cohorts: Group A (n=11) treated with the topical wound gel formulation (TS); and Group B (n=3) an untreated control group. Swabs were obtained before treatment (T0) and on days one (T1), 3 (T2) and 5 (T3) post-treatment, then submitted to direct DNA extraction with real-time PCR quantification, plus incubation with primary tissue cultures from ovine skin fibroblasts (OSF) and T-immortalized goat embryonic fibroblasts (TIGEF).Results: Although no significant differences were found in the clinical progression of the lesions and PCR quantification (p=0.722) between these small cohorts, there was a significant difference (p< 0.05) in reduction in infective viral load between the groups when assessed in OSF cell cultures between T0 and T3.Conclusion: These preliminary findings suggest that treatment of early stage lesions with this TS may reduce the infective viral load present in orf lesions.Keywords: sheep, contagious ecthyma, wound formulation, local therapy

Background Usefulness of noninvasive ventilation (NIV) in weaning patients with non-hypercapnic hypoxemic acute respiratory failure (hARF) is unclear. The study aims to assess in patients with non-hypercapnic hARF, the efficacy of NIV after early extubation, compared to standard weaning. Methods In this individual patient data meta-analysis, we searched EMBASE, Medline and Cochrane Central Register of Controlled Trials to identify potentially eligible randomized controlled trials published from database inception to October 2020. To be eligible, studies had to include patients treated with NIV after early extubation and compared to conventional weaning in adult non-hypercapnic hARF patients. Anonymized individual patient data from eligible studies were provided by study investigators. Using one-step and two-step meta-analysis models we tested the difference in total days spent on invasive ventilation. Results We screened 1605 records. Six studies were included in quantitative synthesis. Overall, 459 participants (mean [SD] age, 62 [15] years; 269 [59%] males) recovering from hARF were included in the analysis (233 in the intervention group and 226 controls). Participants receiving NIV had a shorter duration of invasive mechanical ventilation compared to control group (mean difference, − 3.43; 95% CI − 5.17 to − 1.69 days, p p = 0.024), a reduced risk of ventilatory associated pneumonia (odds ratio, 0.24; 95% CI 0.08 to 0.71, p = 0.014), a reduction of time spent in ICU (time ratio, 0.81; 95% CI 0.68 to 0.96, p = 0.015) and in-hospital (time ratio, 0.81; 95% CI 0.69 to 0.95, p = 0.010), with no difference in ICU mortality. Conclusions Although primary studies are limited, using an individual patient data metanalysis approach, NIV after early extubation appears useful in reducing total days spent on invasive mechanical ventilation. Trial registration The protocol was registered to PROSPERO database on 12/06/2019 and available at PROSPERO website inserting the study code i.e., CRD42019133837.

Aluminium (Al) hydroxide use as adjuvant induces local formation of long‐lasting subcutaneous granulomas in sheep. Macrophages within these granulomas have been identified as a new small ruminant lentivirus (SRLV) replication site in naturally infected animals. Diagnosis of Al hydroxide‐induced granulomas in sheep is mostly based on postmortem observations but little information is available on in vivo detection. Computed tomography (CT) is used for studying these reactions in other animal species. To determine if CT could be a tool for in vivo diagnosis and research of subcutaneous Al hydroxide‐induced granulomas in sheep. A retrospective survey on thoracic CT scans was performed on 46 adult sheep. Analysis included absence or presence, number and location of subcutaneous nodules. Thoracic CT scans and pathological studies were prescribed to two further sheep. Single or multiple subcutaneous nodules were detected in 26 (56.52%) sheep. One or two nodules per animal were most often observed (36.95%). Size ranged between 1.5 and 4.5 cm. Pre‐contrast two‐dimensional (2D) CT images showed focal or multifocal increases in subcutaneous tissue thickness. Post‐contrast 2D CT images revealed hypointense areas in the centre. Histopathology indicated the presence of granulomas composed by a large number of activated macrophages, surrounding a central core of necrosis. Large intracytoplasmic Al‐positive aggregates were demonstrated by lumogallion staining. CT is a useful tool to detect subcutaneous Al hydroxide‐induced granulomas in vivo in sheep. CT provides a diagnostic and research tool that can be very useful in future works in Al hydroxide‐induced pathology, SRLV infection, or both., We describe the usefulness of CT for in vivo diagnose of subcutaneous granulomas in sheep. CT is an excellent tool to advance the diagnosis of subcutaneous Al‐induced granulomas in vivo and to boost further research in SRLV infections in sheep.

Simple Summary Caseous lymphadenitis is a widespread disease, which has been noticed in most sheep farming countries, causing important economic losses. This disease produces emaciation and weakness in the animals and has to be considered in the differential diagnosis of the so-called ‘’thin ewe syndrome’’, especially when sheep are affected by the visceral presentation of the disease. The present study analysed the prevalence of the disease in the Ebro valley area in Spain and its implication as a cause of culling in adult sheep. Abstract Four hundred and ninety-eight culled sheep received at the Ruminant Clinical Service of the Veterinary Faculty of Zaragoza, Spain, were examined in life and after humanitarian sacrifice in order to reach the final diagnosis of the cause of culling and to evaluate the presence of caseous lymphadenitis (CLA) lesions. One hundred and forty-seven of the 498 studied animals (29.52%) showed CLA compatible lesions that were subsequently confirmed by Corynebacterium pseudotuberculosis isolation. One hundred and seven of the 147 CLA affected animals presenting the visceral clinical form of the disease (72.79%), while only 32 animals were affected by the superficial form (21.77%). In addition, eight animals were found to be affected in both the visceral and the superficial presentations (5.44%). Eighty-four of the 147 CLA-affected animals (57.14%) did not show any concurrent disease, considering, in this case, CLA the main cause of culling (84/498: 16.87%). In the superficial presentation, the retropharyngeal lymph node, as a sole lesion, was the most frequently affected (13/32: 40.63%). Further, in the visceral form of the disease, 85.06% of the affected animals had the lesions located in the respiratory system (91/107: 85.06%). CLA was revealed as an important cause of culling in sheep production.

In spring and summer 2020, six outbreaks of condemnation of jaundiced lamb carcasses were diagnosed in different farms in Arag&oacute, n region, Spain. Anaplasma ovis was identified in all affected farms. Four hundred and ninety-two lambs from two affected farms were more closely examined. Clinical examination, haematologies, biochemistries, histopathology and microbiological and molecular analyses were performed. After slaughter, 34.84% of the lambs showed jaundiced carcasses and 79.64% presented splenomegaly at the abattoir. All tested lambs with icteric carcasses showed positive A. ovis PCR, although 72.72% of the unaffected lambs also tested positive. However, the bacterial load was significantly higher in the animals that showed jaundiced carcasses (Cq: 25.00 vs 26.16, p = 0.004). Moreover, all the tested lambs that showed severe anaemia were PCR positive. On the contrary, the PCR negative lambs did not show anaemia. Lambs that presented icteric carcasses displayed severe regenerative anaemia with significantly lower erythrocyte count (7.18 vs. 11.97), haematocrit (26.89 vs. 34.82) and haemoglobin (8.50 vs. 11.10) than unaffected lambs. Reticulocyte count (18.80 vs. 5.65) was also significantly increased in affected animals. This article describes a new disorder caused by Anaplasma ovis that is producing significant economic losses associated with the carcass condemnation of apparently healthy lamb.

Simple Summary Oral injuries are widespread disorders of sheep that can cause significant economic losses in farms. These usually painful conditions prevent animals from feeding properly, leading to chronic weight loss and, very often, causing the final culling of the animals. This study analyses the management risk factors associated with the presence of mandibular and maxillary disorders in a representative cohort of sheep in Spain. These lesions are usually the external and final manifestation of underdiagnosed oral disorders. It was concluded that hard foods with sharp edges such as maize straw as well as acidic foods such as silages, favor the development of these disorders. Furthermore, the study shows that the use of mineral supplementation prevents the appearance of oral lesions. Abstract Oral disorders constitute a significant cause of weight loss in sheep. In a study of disorders of the oral cavity of 36,033 sheep from 60 meat sheep flocks in Spain, we looked for management risk factors associated with chronic oral lesions. Mandibular and maxillary disorders were assessed as an external manifestation of oral lesions by palpation, searching for tissue swellings, fistulae, or open wounds. The prevalence of flocks containing sheep with jaw disorders was 98.3%, with an average individual prevalence of 5.5%. The majority of lesions were located in in the mid-region of the mandible, and the most relevant risk factor was increasing age. Use of acidic diets based on silage and inclusion of hard foods, such as maize straw or hay, was associated with the occurrence of jaw inflammation. It was concluded that hard diets containing plant material with edges and sharp areas, plus acidic foods including silage, are more likely to cause lesions of the gingiva, enabling entry of pathogens to the oral mucosa that eventually establish locally in bony tissues, usually as mandibular osteomyelitis. It was also observed that mineral supplementation appears to prevent the occurrence of these lesions.

Respiratory diseases are one of the main causes of death and economic losses in sheep farming. The prevention and treatment of these diseases must be based on a correct diagnosis, which improves the results of health plans and optimizes the responsible use of medicines. Diagnostic imaging techniques are important working tools to diagnose this kind of disorders but have not always been sufficiently used in sheep. X-ray, although widely used in small animals, is not a valuable tool in field conditions. Ultrasonography is a noninvasive technique easily applied in sheep farms and very useful for the diagnosis of respiratory diseases; however, many articles have been already published on this topic. The present paper proposes and illustrates the use of thermography and computed tomography (CT) to support and improve the aforementioned techniques, taking into consideration that thermography is only useful for upper respiratory tract disorders and CT scan is an expensive technique for routine use but very illustrative to understand the pathogenesis of the different disorders and to improve the in vivo diagnosis.

Background While the efficacy of allergen-specific immunotherapy (ASIT) to treat canine atopic dermatitis has been well established, it remains unclear why not all dogs show the same response to treatment. The goal of the study was to determine the relationship between duration of ASIT and two measurements of success: disease severity and concomitant medication sparing effect. Methods Data were retrospectively compiled for 145 dogs with atopic dermatitis treated with ASIT. As a measure of treatment compliance, cases were stratified into dogs treated for less than 12 months or for at least 12 months. Treatment efficacy, defined as a reduction in disease severity score (scale 0–10), was compared between both groups, and correlations between treatment success and several related factors were examined. Results ASIT treatment duration was strongly correlated with treatment efficacy. Animals treated for less than 12 months showed lower efficacy rates (22 per cent) than those treated for at least 12 months (65 per cent). Further, in animals treated for at least 12 months, concomitant medications were reduced more (87 per cent) than in animals treated for less than 12 months (39 per cent). Conclusion A lack of owner compliance emerged as the main factor explaining the reduced effectiveness of ASIT. To improve treatment adherence, veterinarians and owners need to be better informed about ASIT mechanisms of action before starting treatment.

The tick Ixodes uriae is an ectoparasite widely distributed among seabirds throughout circumpolar regions, usually associated with seabird colonies. Nevertheless, potential effects of infestations, especially in chicks, are not well documented. In this article, we studied factors associated with probability and intensity of infestations in Black-browed Albatross Thalassarche melanophrys nestlings in a colony at the Falklands Islands. We compared the body measurements, physiological parameters, distance to other nests and position inside the colony between infested and non-infested 40 Black-browed Albatross nestlings. Ticks were present in 60% of the nestlings with a mean number per nestlings of 1.47. None of the 12 analysed blood parameters but LDH (Lactate dehydrogenase) showed significant differences between infested and not infested nestlings. Nestlings infected showed significant higher level of LDH than those without ticks. The number of ticks found on each nestling was positively and significantly correlated with their LDH blood levels. Tarsus length (as a proxy of age) and distance to the nearest nest showed a significant effect, with younger nestlings with closer nests showing higher probability to be infected. These variables also affect intensity of infestation. No effects of nutritional condition (butyrate or urea levels) or body condition (residuals of cubic root of mass/tarsus length regression) on probability or intensity of infestation were found. Both small anaemias and tick scars would explain the different values of LDH between infected/non-infected chicks. The low level of infestation found in our colony could be the cause of a non-detectable effect of the presence of ticks on nestling body condition and other blood parameters related to metabolism of fat or protein.

Salmonella enterica subsp. diarizonae serotype 61: k: 1,5, (7) (SED) is a microorganism well adapted to sheep; however, it has also been described producing chronic proliferative rhinitis (CPR) in ovine. CPR causes a proliferative inflammation of the ventral nasal turbinates that may totally obstruct the nasal cavity. The main objective of the present study was to investigate the prevalence of SED in nostrils and stool of sheep without CPR clinical signs in commercial sheep farms of Spain with and without previous clinical cases of CPR. Five samplings were performed in 10 commercial sheep farms for one year. Samples from nostrils and faeces were taken from four animals without CPR visible clinical signs that belonged to four different age ranges at each farm visit. The prevalence of positive animals was 45.3 %, and the number of positive samples in nostrils was higher than in faeces (38.5 % vs 22.5 %). Only on one farm was no positive result obtained in the entire study. In almost all positive farms, sheep belonging to the youngest age ranges accounted for more than 50 % of positive isolates. Finally, farms with a previous diagnosis of CPR were 1.784 times more likely to have an animal with positive isolation than farms without a previous diagnosis. This could suggest that the infection pressure in the farm might favour the occurrence of clinical cases of the disease. However, further studies will be necessary to unravel why this saprophytic bacterium is able to cross the epithelial barrier causing severe rhinitis in certain animals.

Hematological studies concerned with the determination of normal values of blood parameters in animals have been increasing. However, studies on normal concentration of blood constituents of free-living birds still are not very common, and less than 5% of the species of birds have been analyzed, mostly in captivity. Avian hematology has been used in ornithological studies, because it provides biological data about these animals, their biology, and can be very important in the understanding of ecological and behavioral issues. The main purpose of the study was to investigate the concentrations of certain plasma biochemical parameters in nestlings of Rockhopper Penguins (Eudyptes chrysocome) at the creche phase and the potential influence of some factors such as sex. We captured 95 nestling Rockhopper during the period 24–31 January 2017. All nestlings were randomly selected from colonies in Saunders Island (Falkland Islands). All the sampled birds were between 25 and 45 days of age, with mean weight of 1.778 ± 0.314 kg and mean bill length of 36.0 ± 2.8 mm. No differences in blood parameters or body condition between sexes were found. No parameters but total protein and urea were related to body index. Body index showed a negative significant relationship with urea levels in blood, with penguins in worse condition (those relatively lighter) showing higher levels of urea in blood than those that were relatively heavier. Same trend was observed for total proteins. Urea concentration in blood would be used as a tool in future studies, particularly in young Rockhoppers when they are in creche phase, a period of high level of mortality mainly by predation. Plasma urea was the single variable that reflects the best body index and also has a rationale background explaining this relationship.

15 páginas, 2 tablas, 7 figuras., Experimental infections in pregnant sheep have been focused on studying the effect of the time of challenge on the outcome of N. caninum infection, whereas the impact of the dose and route of challenge has not been studied in depth. Therefore, clinical outcome, immune responses, parasite detection and burden, and lesion severity in placental tissues and foetal brains were investigated in 90-day-pregnant sheep inoculated intravenously with 10(5) (G1), 10(4) (G2), 10(3) (G3), or 10(2) (G4) tachyzoites or subcutaneously with 10(4) (G5) tachyzoites of the virulent Nc-Spain7 isolate and an uninfected group (G6). Comparing challenge doses, G1 was the only group that had 100% abortion. Likewise, IFN gamma levels in G1 increased earlier than those in other intravenously infected groups, and IgG levels on day 21 post-infection (pi) were higher in G1 than those in other intravenously infected groups. Concerning vertical transmission, G1 shows a higher parasite burden in the foetal brain than did G2 and G3. Comparing routes of administration, no differences in foetal survival rate or parasite load in the foetal brain were found. Although G2 had higher IFN gamma levels than G5 on day 10 pi, no differences were found in humoral immune responses. Because the outcome after intravenous infection with 10(5) tachyzoites was similar to that observed after intravenous infection with 10(6) tachyzoites used in a previous work (100% abortion and vertical transmission), we conclude that it may be reasonable to use 10(5) tachyzoites administered by the intravenous route in further experiments when assessing drugs or vaccine candidates., We gratefully acknowledge Neus Callizo Esteve from Clinical Veterinary Hospital (Complutense University of Madrid, Spain) and Jose Maria Gonzalez (University of Zaragoza, Spain) for their excellent technical assistance. The Animal Experimentation Service (SEA) at the University of Zaragoza is acknowledged for using their facilities to carry out the reproduction programme. Roberto Sanchez Sanchez is supported by a fellowship from the Spanish Ministry of Education, Culture and Sports (MECD) as a part of the Programme of Training of University Teaching Staff (FPU, Grant Number FPU13/03438). This work was supported by the Ministry of Economy and Competitiveness (AGL2016-75935-C2) and Community of Madrid, Spain (PLATESA, S2013/ABI2906).

13 páginas, 2 tablas, 7 figuras., Neospora caninum is one of the main causes of abortion in cattle, and recent studies have highlighted its relevance as an abortifacient in small ruminants. Vaccines or drugs for the control of neosporosis are lacking. Bumped kinase inhibitors (BKIs), which are ATP-competitive inhibitors of calcium dependent protein kinase 1 (CDPK1), were shown to be highly efficacious against several apicomplexan parasites in vitro and in laboratory animal models. We here present the pharmacokinetics, safety and efficacy of BKI-1553 in pregnant ewes and foetuses using a pregnant sheep model of N. caninum infection. BKI-1553 showed exposure in pregnant ewes with trough concentrations of approximately 4 mu M, and of 1 mu M in foetuses. Subcutaneous BKI-1553 administration increased rectal temperatures shortly after treatment, and resulted in dermal nodules triggering a slight monocytosis after repeated doses at short intervals. BKI-1553 treatment decreased fever in infected pregnant ewes already after two applications, resulted in a 37-50% reduction in foetal mortality, and modulated immune responses; IFN. levels were increased early after infection and IgG levels were reduced subsequently. N. caninum was abundantly found in placental tissues; however, parasite detection in foetal brain tissue decreased from 94% in the infected/untreated group to 69-71% in the treated groups. In summary, BKI-1553 confers partial protection against abortion in a ruminant experimental model of N. caninum infection during pregnancy. In addition, reduced parasite detection, parasite load and lesions in foetal brains were observed., We gratefully acknowledge Jacobo Sampere from the SALUVETgroup (Complutense University of Madrid, Spain), Teresa Navarro andJosé María González (University of Zaragoza, Spain), Isabel Ayala,Lucas Troya, Clara Colmenero, Dolores González, Natalia Peral,Verónica Pérez, Ignacio Gómez and Isabel Santiago from the Clinical Veterinary Hospital (Complutense University of Madrid, Spain) for their excellent technical assistance, and also Rama Subba Rao Vidadala and Dustin Maly (Department of Chemistry, University of Washington) fortheir assistance in further purification of the study drug. The AnimalExperimentation Service (SEA) at the University of Zaragoza is ac-knowledged for providing their facilities to carry out the reproduction programme. Roberto Sánchez Sánchez is supported by a fellowship from the Spanish Ministry of Education, Culture and Sports (MECD), asa part of the Program of Training of University Teaching Staff (FPU,grant number FPU13/03438). Patricia Vázquez has a Juan de la Cierva-Formación post-doctoral contract (FJCI-2014-20982) from the Spanish Ministry of Economy and Competitiveness (MINECO). Andrew Hemphill is supported by the Swiss National Science Foundation grant(No. 310030 165782). This work was supported by the Public Health Service, National Institutes of Health, Bethesda, MD (grants R01 AI111341 and R01 HD 080670), the U.S. Department of Agriculture(grant 2014-67015-22106) and the Community of Madrid, Spain(PLATESA, S2013/ABI2906).

Purpose: The CIGMA study investigated a novel human polyclonal antibody preparation (trimodulin) containing ~ 23% immunoglobulin (Ig) M, ~ 21% IgA, and ~ 56% IgG as add-on therapy for patients with severe community-acquired pneumonia (sCAP). Methods: In this double-blind, phase II study (NCT01420744), 160 patients with sCAP requiring invasive mechanical ventilation were randomized (1:1) to trimodulin (42 mg IgM/kg/day) or placebo for five consecutive days. Primary endpoint was ventilator-free days (VFDs). Secondary endpoints included 28-day all-cause and pneumonia-related mortality. Safety and tolerability were monitored. Exploratory post hoc analyses were performed in subsets stratified by baseline C-reactive protein (CRP; ≥ 70 mg/L) and/or IgM (≤ 0.8 g/L). Results: Overall, there was no statistically significant difference in VFDs between trimodulin (mean 11.0, median 11 [n = 81]) and placebo (mean 9.6; median 8 [n = 79]; p = 0.173). Twenty-eight-day all-cause mortality was 22.2% vs. 27.8%, respectively (p = 0.465). Time to discharge from intensive care unit and mean duration of hospitalization were comparable between groups. Adverse-event incidences were comparable. Post hoc subset analyses, which included the majority of patients (58–78%), showed significant reductions in all-cause mortality (trimodulin vs. placebo) in patients with high CRP, low IgM, and high CRP/low IgM at baseline. Conclusions: No significant differences were found in VFDs and mortality between trimodulin and placebo groups. Post hoc analyses supported improved outcome regarding mortality with trimodulin in subsets of patients with elevated CRP, reduced IgM, or both. These findings warrant further investigation. Trial registration: NCT01420744., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

Deep semen deposition, avoiding retrograde flow, lesions and stress, has proved to be very important in the success of sheep AI. The objective of the present study was to develop a new, suitable anti-retrograde flow device for sheep cervical AI (DARIO) that enables deep deposition of semen into the cervix without any modifications to the procedures currently used, and to compare the fertility, fecundity, and prolificacy rates between DARIO and a traditional catheter. Field tests were performed on 16 farms actively participating in the non-profit National Association of Rasa Aragonesa Breeders´ genetic selection scheme and where sheep management was similar. A total of 242 AI lots were considered, including 1,299 ewes; 126 lots (662 ewes) were inseminated using DARIO, and 116 lots (637 ewes) using a traditional commercially-available catheter (control group). Several factors affecting AI results were included in the model for mean comparison between DARIO and control groups (farm and ram as random factors; catheter, year and photoperiod as fixed effects; catheter × photoperiod interaction). The type of catheter had a significant effect on fertility ( 0.05). Overall, the use of DARIO instead of the traditional commercially-available catheter increased both fertility and fecundity rates; the marginal mean differences were 9.05 pregnant ewes per 100 inseminated and 0.15 lambs per inseminated ewe, respectively.

The aim of the present study was to investigate the clinical, pathological and immunological changes in lambs infected experimentally with Salmonella enterica subsp. diarizonae serotype 61:k:1,5,(7) (SED) that causes chronic proliferative rhinitis (CPR) in sheep. Eleven four-month-old lambs were infected with 3.2 × 10 8 UFC of SED by nasal route and four lambs with the same age were kept as placebo group. Clinical explorations were carried out monthly and vaginal, nasal swaps and fecal samples were taken for microbiological study during one year. Furthermore, a postmortem investigation was performed. Ventral turbinates of both nostrils and submandibular, parotid and retropharyngeal lymph nodes were sampled for histopathological, immunohistochemical and microbiological studies. Cell mediated immune response was assessed by lymphocyte stimulation test (Con A, PWM, PHA and LPS were used as mitogens), DTH test and by measuring IFN-γ concentration in serum and cultured supernatants. SED was isolated from nasal swabs and fecal samples of all infected lambs virtually throughout the study. No isolations were obtained from control group. At necropsy, no lesions associated with SED were recorded; however, the microorganism was isolated in regional lymph nodes in all infected animals. Moreover, infected lambs showed lower stimulation indices to Con A, PHA and PWM and higher for both LPS ( P 0.001). Besides, DTH response was lower in infected lambs than in the control group, but statistical significant differences were not found ( P > 0.05). Serum levels of IFN-γ during the experiment were higher in infected sheep than in the control group, suggesting an active infection. Furthermore, mitogens stimulated the production of IFN-γ in lymphocyte cultures from infected sheep, and the highest level were obtained with Con A. These results demonstrate that after experimental infection of healthy lambs with S. enterica subsp . diarizonae serotype 61:k:1,5,(7) infection was maintained for at least one year in the upper respiratory tract and that digestive route should be taken into account as a possible way of SED elimination. Moreover, SED infection caused a weak response of the T cells; nevertheless, more studies are needed to understand the mechanisms involved in the immunitary response and pathology of CPR in sheep associated with Salmonella enterica subsp. diarizonae infection.

We thank all participants who have agreed to participate in this study. Authors also thank Maria Dolores Casares, Angeles Molina, Carmen Oloriz for the collection of Spanish samples and Hans Jurgen Hoffmann, Marianne Thomsen, Vibeke Ostergaard Thomsen, Malene Rohr Andersen, Lise Lotte B. Laursen, Helle Jorgensen, Ram Benny Christian Dessau, Niels Steen Krogh, Ulla Vogel, Paal Skytt Andersen, Ivan Brandslund, Steffen Bank, Frederik Trier Moller, Nikolai Toft and Niels Moller Andersen for the participation in collection and purification of Danish samples. We also thank the Danish Departments of Rheumatology for their implication in the collection of clinical data from RA patients included in the DANBIO cohort and the Danish Rheumatologic Biobank. Likewise, we would like to thank Teun van Herwaarden for steroid hormone measurements in serum samples from subjects ascertained through the HFGP initiative. This work was partially supported by intramural funds of GENYO and FIBAO foundation (Granada, Spain); Novo Nordisk Fonden (NNF15OC0016932, VA); and Knud og Edith Eriksens Mindefond (VA) and Gigtforeningen (A2037, A3570, VA). MGN was supported by a Spinoza grant from the Netherlands Organization for Scientific Research., All data used in this project have been meticulously cataloged and archived in the BBMRI-NL data infrastructure (https://hfgp.bbmri.nl/) using the MOLGENIS open source platform for scientific data45. This allows flexible data querying and download, including sufficiently rich metadata and interfaces for machine processing (R statistics, REST API) and using FAIR principles to optimize Findability, Accessibility, Interoperability and Reusability46. Genetic data from the discovery and DANBIO populations can be accessed at ftp.genyo.es and data from the DREAM registry are available at https://www.synapse.org/#!Synapse:syn3280809/wiki/194735 and https://www. synapse.org/#!Synapse:syn3280809/wiki/194736., Supplementary information is available for this paper at https://doi.org/10.1038/s41598-020-61331-5., This study sought to evaluate the association of 28 single nucleotide polymorphisms (SNPs) within NFKB and inflammasome pathway genes with the risk of rheumatoid arthritis (RA) and response to TNF inhibitors (TNFi). We conducted a case-control study in a European population of 1194 RA patients and 1328 healthy controls. The association of potentially interesting markers was validated with data from the DANBIO (695 RA patients and 978 healthy controls) and DREAM (882 RA patients) registries. The meta-analysis of our data with those from the DANBIO registry confirmed that anti-citrullinated protein antibodies (ACPA)-positive subjects carrying the NFKB2rs11574851T allele had a significantly increased risk of developing RA (PMeta_ACPA + = 0.0006) whereas no significant effect was found in ACPA-negative individuals (PMeta_ACPA− = 0.35). An ACPA-stratified haplotype analysis including both cohorts (n = 4210) confirmed that ACPA-positive subjects carrying the NFKB2TT haplotype had an increased risk of RA (OR = 1.39, P = 0.0042) whereas no effect was found in ACPA-negative subjects (OR = 1.04, P = 0.82). The meta-analysis of our data with those from the DANBIO and DREAM registries also revealed a suggestive association of the NFKB2rs1056890 SNP with larger changes in DAS28 (OR = 1.18, P = 0.007). Functional experiments showed that peripheral blood mononuclear cells from carriers of the NFKB2rs1005044C allele (in LD with the rs1056890, r2 = 1.00) showed increased production of IL10 after stimulation with LPS (P = 0.0026). These results provide first evidence of a role of the NFKB2 locus in modulating the risk of RA in an ACPA-dependent manner and suggest its implication in determining the response to TNFi. Additional studies are now warranted to further validate these findings., GENYO, FIBAO foundation (Granada, Spain), Novo Nordisk Foundation NNF15OC0016932, Knud og Edith Eriksens Mindefond A2037 A3570, Gigtforeningen A2037 A3570, Spinoza grant from the Netherlands Organization for Scientific Research

We examined several procedures for surgical tail docking, with and without general anaesthesia (GA), including the use of a topical wound gel formulation to provide pain relief (PR) and improve healing after surgery, containing local anaesthetics lignocaine and bupivacaine, with cetrimide and adrenalin. Forty-four lambs were recruited into four equal cohorts: Groups A and C, the tail was excised with a scalpel without anaesthesia or stitches, Groups B and D, the tail was surgically excised and stitched under GA, Groups C and D wounds were immediately sprayed with PR. Behavioural observations identified that Groups A and C displayed significantly less pain-related behaviours than Groups B and D shortly after the procedure, especially if treated with PR. Similarly, the mean of days when animals showed no signs of wound infection was longer in the groups not undergoing stitching. Finally, treatment with PR appeared to reduce the cortisol response and avoided the elevation of serum amyloid A in lambs where the tail was excised without general anaesthesia. In conclusion, surgical tail-docking without GA but where wounds are immediately sprayed with PR, appears as an affordable and more welfare-appropriate method for conducting tail docking in lambs.

Here, we assessed whether 41 SNPs within steroid hormone genes associated with erosive disease. The most relevant finding was the rheumatoid factor (RF)-specific effect of the CYP1B1, CYP2C9, ESR2, FcγR3A, and SHBG SNPs to modulate the risk of bone erosions (P = 0.004, 0.0007, 0.0002, 0.013 and 0.015) that was confirmed through meta-analysis of our data with those from the DREAM registry (P = 0.000081, 0.0022, 0.00074, 0.0067 and 0.0087, respectively). Mechanistically, we also found a gender-specific correlation of the CYP2C9rs1799853T/T genotype with serum vitamin D3 levels (P = 0.00085) and a modest effect on IL1β levels after stimulation of PBMCs or blood with LPS and PHA (P = 0.0057 and P = 0.0058). An overall haplotype analysis also showed an association of 3 ESR1 haplotypes with a reduced risk of erosive arthritis (P = 0.009, P = 0.002, and P = 0.002). Furthermore, we observed that the ESR2, ESR1 and FcγR3A SNPs influenced the immune response after stimulation of PBMCs or macrophages with LPS or Pam3Cys (P = 0.002, 0.0008, 0.0011 and 1.97•10−7). Finally, we found that a model built with steroid hormone-related SNPs significantly improved the prediction of erosive disease in seropositive patients (PRF+ = 2.46•10−8) whereas no prediction was detected in seronegative patients (PRF− = 0.36). Although the predictive ability of the model was substantially lower in the replication population (PRF+ = 0.014), we could confirm that CYP1B1 and CYP2C9 SNPs help to predict erosive disease in seropositive patients. These results are the first to suggest a RF-specific association of steroid hormone-related polymorphisms with erosive disease.

BACKGROUND High-volume low-pressure (HVLP) endotracheal tube (ETT) cuffs for critically ill patients often deflate during the course of mechanical ventilation. We performed an in-vitro study to comprehensively assess HVLP cuff deflation dynamics and potential preventive measures. METHODS We evaluated 24-hour deflation of seven HVLP cuffs of cylindrical or tapered shape, and made of polyvinylchloride or polyurethane. Experiments were performed within a thermostated chamber set at 37 °C. In the first stage of experiments, the cuff pilot balloon valve was not manipulated. The cuff internal pressure was assessed hourly for 24 hours, via a linear position sensor which monitored cuff deflation displacements. Then, we re-evaluated cuff deflation of the worst-performing ETT cuffs with the cuff pilot balloon valve sealed. Finally, we inflated ETT cuffs within an artificial trachea to evaluate deflation dynamics during mechanical ventilation. RESULTS Initial tests showed an exponential decrease in cuff internal pressure in five out of seven cuffs. Cuffs of cylindrical shape and made of polyurethane demonstrated the fastest deflation rates (P

BACKGROUND: In patients on mechanical ventilation, lung hyperinflation is often performed to reverse atelectasis and clear retained mucus. We evaluated the effects of manual hyperinflation and ventilator hyperinflation on mucus clearance, gas exchange, pulmonary mechanics, and hemodynamics. METHODS: Six mechanically ventilated pigs with severe Pseudomonas aeruginosa pneumonia randomly received either 12 manual hyperinflation breaths over a period of 2 min (through a gradual manual compression of a resuscitation bag within 4 s to achieve 40 cm H2O of airway pressure), or 12 ventilator hyperinflation over 2 min to achieve the same ventilatory end points as in manual hyperinflation. Mucus clearance rate was measured through fluoroscopic tracking of tracheal markers. Prior to each maneuver and 15 min thereafter, we assessed arterial and mixed gas exchange, pulmonary mechanics, and hemodynamics. RESULTS: Both manual hyperinflation and ventilator hyperinflation significantly decreased inspiratory flow by approximately 16 L/min (P CONCLUSIONS: In an animal model of severe P. aeruginosa pneumonia, neither manual hyperinflation nor ventilator hyperinflation improved mucus clearance. If confirmed in comprehensive clinical experimentations, these findings should promote reappraisal of indications for both manual hyperinflation and ventilator hyperinflation as a therapeutic technique for mucus clearance and atelectasis reversal.

At the slaughterhouse, 1465 culled sheep heads were studied in order to identify disorders of the mandibular cheek teeth. Of these, 227 (15.5%) had evidence of osteomyelitis. The lesional profile showed that the mandible was affected in a similar proportion on both sides (46.7% on the right side vs 50.7% on the left side), mainly in the middle region (55.3%) and with most of the lesions closed without fistulisation (89.4%). In addition, swelling was palpable, with an increase in thickness in the area of the affected body (2.65 ± 0.065 cm vs 1.74 ± 0.030 cm). In 78.6% of the animals, the regional lymph nodes were enlarged. Concerning the mandibular cheek teeth, more than half of the animals lacked at least one tooth (57.0%), with the first premolar being the most frequently missing tooth (34.8%) and the third molar the least (8.2%). The impaction of food around the teeth was very common with the posterior molars being more frequently affected. In the knowledge of the authors, this is the first study that analyses the prevalence of mandibular molar and premolar disorders in sheep, and these are revealed as an important condition affecting culled sheep.

Background An update of evidence-based guidelines concerning liberation from mechanical ventilation is needed as new evidence has become available. The American College of Chest Physicians (CHEST) and the American Thoracic Society (ATS) have collaborated to provide recommendations to clinicians concerning liberation from the ventilator. Methods Comprehensive evidence syntheses, including meta-analyses, were performed to summarize all available evidence relevant to the guideline panel's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, and the results were summarized in evidence profiles. The evidence syntheses were discussed and recommendations developed and approved by a multidisciplinary committee of experts in mechanical ventilation. Results Recommendations for three population, intervention, comparator, outcome (PICO) questions concerning ventilator liberation are presented in this document. The guideline panel considered the balance of desirable (benefits) and undesirable (burdens, adverse effects, costs) consequences, quality of evidence, feasibility, and acceptability of various interventions with respect to the selected questions. Conditional (weak) recommendations were made to use inspiratory pressure augmentation in the initial spontaneous breathing trial (SBT) and to use protocols to minimize sedation for patients ventilated for more than 24 h. A strong recommendation was made to use preventive noninvasive ventilation (NIV) for high-risk patients ventilated for more than 24 h immediately after extubation to improve selected outcomes. The recommendations were limited by the quality of the available evidence. Conclusions The guideline panel provided recommendations for inspiratory pressure augmentation during an initial SBT, protocols minimizing sedation, and preventative NIV, in relation to ventilator liberation.

Background This clinical practice guideline addresses six questions related to liberation from mechanical ventilation in critically ill adults. It is the result of a collaborative effort between the American Thoracic Society (ATS) and the American College of Chest Physicians (CHEST). Methods A multidisciplinary panel posed six clinical questions in a population, intervention, comparator, outcomes (PICO) format. A comprehensive literature search and evidence synthesis was performed for each question, which included appraising the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The Evidence-to-Decision framework was applied to each question, requiring the panel to evaluate and weigh the importance of the problem, confidence in the evidence, certainty about how much the public values the main outcomes, magnitude and balance of desirable and undesirable outcomes, resources and costs associated with the intervention, impact on health disparities, and acceptability and feasibility of the intervention. Results Evidence-based recommendations were formulated and graded initially by subcommittees and then modified following full panel discussions. The recommendations were confirmed by confidential electronic voting; approval required that at least 80% of the panel members agree with the recommendation. Conclusions The panel provides recommendations regarding liberation from mechanical ventilation. The details regarding the evidence and rationale for each recommendation are presented in the American Journal of Respiratory and Critical Care Medicine and CHEST.

Background: Interventions that lead to earlier liberation from mechanical ventilation can improve patient outcomes. This guideline, a collaborative effort between the American Thoracic Society and the American College of Chest Physicians, provides evidence-based recommendations to optimize liberation from mechanical ventilation in critically ill adults. Methods: Two methodologists performed evidence syntheses to summarize available evidence relevant to key questions about liberation from mechanical ventilation. The methodologists appraised the certainty in the evidence (i.e., the quality of evidence) using the Grading of Recommendations, Assessment, Development, and Evaluation approach and summarized the results in evidence profiles. The guideline panel then formulated recommendations after considering the balance of desirable consequences (benefits) versus undesirable consequences (burdens, adverse effects, and costs), the certaintyintheevidence,andthefeasibilityandacceptabilityofvarious interventions. Recommendations were rated as strong or conditional. Results:Theguidelinepanelmadefourconditionalrecommendations related to rehabilitation protocols, ventilator liberation protocols, and cuff leak tests. The recommendations were for acutely hospitalized adults mechanically ventilated for more than 24 hours to receive protocolized rehabilitation directed toward early mobilization, be managed with a ventilator liberation protocol, be assessed with a cuff leak test if they meet extubation criteria but are deemed high risk for postextubation stridor, and be administered systemic steroids for at least 4 hours before extubation if they fail the cuff leak test. Conclusions: The American Thoracic Society/American College of Chest Physicians recommendations are intended to support healthcare professionals in their decisions related to liberating critically ill adults from mechanical ventilation.

Background: This clinical practice guideline addresses six questions related to liberation from mechanical ventilation in critically ill adults. It is the result of a collaborative effort between the American Thoracic Society and the American College of Chest Physicians. Methods: A multidisciplinary panel posed six clinical questions in a Population, Intervention, Comparator, and Outcomes format. A comprehensive literature search and evidence synthesis was performed for each question, which included appraising the certainty in the evidence (i.e., the quality of evidence) using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The Evidence-to-Decision framework was applied to each question, requiring the panel to evaluate and weigh the importance of the problem, the confidence in the evidence, the certainty about how much the public values the main outcomes, the magnitude and balance of desirable and undesirable outcomes, the resources and costs associated with the intervention, the impact on health disparities, and the acceptability and feasibility of the intervention. Results: Evidence-based recommendations were formulated and graded initially by subcommittees and then modified after full-panel discussions. The recommendations were confirmed by confidential electronic voting; approval required that at least 80% of the panel members agree with the recommendation. Conclusions: The panel provides recommendations regarding liberation from mechanical ventilation. The details regarding the evidence and rationale for each recommendation are presented in the American Journal of Respiratory and Critical Care Medicine and Chest.

Ovine pulmonary adenocarcinoma (OPA) is a contagious lung cancer of sheep caused by jaagsiekte sheep retrovirus (JSRV). It is generally accepted that transmission by the respiratory route occurs under natural conditions. However recent studies strongly indicate that JSRV can also be transmitted to lambs perinatally via colostrum and milk (C/M). The aim of this work was to confirm that C/M can transmit JSRV infection to lambs under natural conditions and investigate the initial events associated with this transmission route. We have analyzed the presence of JSRV in C/M samples from 22 naturally infected, asymptomatic ewes throughout a lactation period, and in various tissues collected from a group of 36 of their lambs that were fed naturally. The lambs were euthanized at 12, 24, 48, and 72 hours and at 5 and 10 days after birth. We detected JSRV-provirus by PCR in the somatic C/M cells from 10/22 ewes (45.45%). The virus was also detected in 9/36 lambs (25%). JSRV-infected cells, with lymphoreticular-like morphology, were observed by immunohistochemistry (IHC) and in situ hybridization (ISH) in Peyer’s patches (PP) from the small intestine of the youngest lambs and in mesenteric lymph nodes (MLN) from lambs older than 72 hours. The virus was also detected by PCR in white blood cells (WBC) in 2/36 lambs (5.5%). These results confirm colostral transmission of JSRV to lambs under natural conditions. Infected lymphoreticular cells contained in C/M appear to be involved. These cells can cross the intestinal barrier of newborn lambs, reach the MLN and enter into circulation.

There has been development of an antiretrograde flow device (DARIO), for sheep cervical artificial insemination (CAI). There, however, needs to be optimization of sperm volume and concentration of insemination doses when the DARIO is used for CAI. Objectives were to compare fertility rates (proportion of ewes lambing as a result of CAI) when there was use of the DARIO for CAI: two sperm volumes containing equal numbers of spermatozoa: 0.25 mL of 1,600 × 106 spermatozoa/mL and 0.50 mL of 800 × 106 spermatozoa/mL (Test 1 group), and two sperm volumes with a different number of spermatozoa/AI dose: 0.25 mL and 0.50 mL of 1,600 × 106 spermatozoa/mL (Test 2 group). There were 335 ewes from seven farms assigned to 60 batches (equally divided into a Control and Test 1 group). For the Test 2 group, 462 ewes from nine farms were assigned to 88 batches (equally proportioned into Control group and Test 2 groups). For the Test 1 group, proportion of ewes lambing as a result of CAI were 0.701 ± 0.2679 and 0.595 ± 0.2393 for the Control and Test 1 groups, respectively (P = 0.163). For the Test 2 group, proportions of ewes lambing were 0.550 ± 0.2598 and 0.658 ± 0.2412 for the Control and Test 2 group, respectively (P = 0.041). An inclusion of a larger number of spermatozoa per insemination in a 0.50 mL dose volume resulted improved proportion of ewes lambing as a result of CAI when there was used of the DARIO.