Jaagsiekte sheep retrovirus found in milk macrophages but not in milk lymphocytes or mammary gland epithelia of naturally infected sheep.

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.

Effects of Transportation Stress on Complete Blood Count, Blood Chemistry, and Cytokine Gene Expression in Heifers.

Blood samples were obtained from 16 high-risk heifers; eight were newly arrived from a 40 h road trip (0 days post-arrival (DPA)), whereas the other eight heifers had been in the feedlot at 25 DPA. Both groups were transported from the southeast tropical region of Mexico to a feedlot in the northeast and were sampled on the same day. The complete blood count, blood chemistry, and cytokine gene expression were analyzed. Gene expression was analyzed using specific primers to amplify and quantify the cDNA reverse transcribed from the mRNA transcripts for tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-2. Higher values for hematocrit (p = 0.029), hemoglobin (p = 0.002), eosinophils (0.029), albumin (p = 0.014), alanine aminotransferase (p = 0.004), bilirubin (p = 0.003), cholesterol (p = 0.014), and cortisol (p = 0.051) were observed in the 0 DPA group than the 25 DPA group. In the electrophoresis of TNF-α amplification products, two non-specific bands were observed in the 0 DPA group. These bands were sequenced, and BLAST analysis suggested that they corresponded to bovine lymphotoxin and have not been reported previously related to stress. The TNF-α expression level was higher (p = 0.001) in the 25 DPA group than the 0 DPA group according to the semi-quantitative expression analysis. This may indicate a persistent inflammatory process that could be related to trauma and disease, which can negatively impact their subsequent health and growth performance. In conclusion, homeostatic disruption was apparent in the 0 DPA heifers, which showed higher cortisol and reductions in TNF-α levels and stress-induced bovine lymphotoxin (SIBL) co-expression.

Natural and Synthetic Naphthoquinones as Potential Anti-Infective Agents.

BACKGROUND: Naphthoquinones are a class of aromatic compounds relevant for their chemical characteristics, structural properties, and biological activity. These compounds are found in nature with a wide range of effects, highlighting their antibacterial, antifungal, and antiprotozoal properties. Additionally, naphthoquinones are used as a scaffold to obtain new derivatives with pharmacological potential, mainly compounds against parasitic diseases. OBJECTIVE: The purpose of this work was to carry out a comprehensive review of naphthoquinones and their derivatives obtained from both natural and synthetic sources, also, to analyze their biological activity against Leishmania spp. (Leishmaniasis), Trypanosoma cruzi (Chagas disease), Plasmodium falciparum (Malaria), Toxoplasma gondii (Toxoplasmosis), and Toxocara canis (Toxocariasis). All of these agents are responsible for relevant diseases worldwide. RESULTS: Natural naphthoquinones, such as plumbagin, diospyrin, burmanin, lapachol, lawsone and psychorubrin, show an antiprotozoal activity similar or enhanced antiprotozoal activity to reference drugs. Some naphthoquinones obtained by synthesis or semi-synthesis showed better biological activity or less toxic effects than natural compounds. CONCLUSION: In this review, natural and synthetic naphthoquinones showed antiparasitic activity, in most cases, with improved results than current drugs currently used in clinical trials. A modification of their structure with different functional groups can enhance their biological effects, improve solubility, and reduce undesirable side effects. Therefore, naphthoquinones are important molecules in the development of new chemotherapeutic agents against parasitic diseases.

Factors associated with mortality in patients hospitalized with COVID-19: A prospective cohort in a Peruvian national referral hospital. / Factores asociados a mortalidad en pacientes hospitalizados con COVID-19: cohorte prospectiva en un hospital de referencia nacional de Perú.

OBJECTIVES: To describe and assess clinical characteristics and factors associated with mortality in adult patients with COVID-19 admitted to a national referral hospital in Peru. METHODS: We conducted a prospective cohort study that included hospitalized patients older than 18 years with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosis. Patients with a positive rapid serological test on admission but no respiratory symptoms nor compatible images were excluded. We collected the data from clinical records. RESULTS: A total of 813 adults were included, 544 (66.9%) with confirmed COVID-19. The mean age was 61.2 years (standard deviation: 15.0), and 575 (70.5%) were male. The most frequent comorbidities were hypertension (34.1%) and obesity (25.9%). On admission, the most frequent symptoms were dyspnea (82.2%) and cough (53.9%). A total of 114 (14.0%) patients received mechanical ventilation, 38 (4.7%) were admitted to the intensive care unit, and 377 (46.4%) died. The requirement for ventilatory support, greater lung involvement, and inflammatory markers were associated with higher mortality. It was found that for every 10-year age increase, the risk of dying increased 32% (relative risk: 1.32; 95% confidence interval: 1.25 to 1.38). Those who were admitted to the intensive care unit and and were placed on mechanical ventilation had 1.39 (95% confidence interval: 1.13 to 1.69) and 1.97 (95% confidence interval: 1.69 to 2.29) times the risk of dying compared to those who did not, respectively. CONCLUSION: We found a high mortality rate among hospitalized patients associated with older age, higher inflammatory markers, and greater lung involvement.

OBJETIVOS: Describir las características clínicas y evaluar los factores asociados con la mortalidad de los pacientes adultos con la nueva enfermedad causada por coronavirus 2019 (COVID-19) ingresados a un hospital de referencia nacional de Perú. MÉTODOS: Se realizó un estudio de cohorte prospectivo. Se incluyó a pacientes mayores de 18 años hospitalizados con el diagnóstico de infección por coronavirus 2 del síndrome respiratorio agudo severo (SARS-CoV-2). Se excluyó a quienes ingresaron con prueba rápida serológica positiva al ingreso, sin clínica sugestiva ni imágenes compatibles. Los datos se recolectaron a partir de la historia clínica. RESULTADOS: Se incluyó un total de 813 adultos, 544 (66,9%) tuvieron COVID-19 confirmado. La media de la edad fue de 61,2 años (desviación estándar: 15) y 575 (70,5%) fueron de sexo masculino. Las comorbilidades más frecuentes fueron hipertensión arterial (34,1%) y obesidad (25,9%). Los síntomas más frecuentes al ingreso fueron disnea (82,2%) y tos (53,9%). Un total de 114 (14%) pacientes recibieron ventilación mecánica, 38 (4,7%) ingresaron a unidad de cuidados intensivos y 377 (46,4%) fallecieron. Se asociaron a la mortalidad el requerimiento de soporte ventilatorio, el mayor compromiso pulmonar y los marcadores inflamatorios. Encontramos que por cada 10 años que aumentó la edad, el riesgo de morir se incrementó en 32% (riesgo relativo: 1,32; intervalo de confianza 95%: 1,25 a 1,38). Aquellos pacientes que requirieron ingreso a unidad de cuidados intensivos y ventilación mecánica tuvieron 1,39 (intervalo de confianza 95%: 1,13 a 1,69) y 1,97 (intervalo de confianza 95%: 1,69 a 2,29) veces el riesgo de morir, respectivamente. CONCLUSIÓN: La mortalidad encontrada en nuestro estudio fue alta y estuvo asociada a la edad, marcadores inflamatorios y compromiso respiratorio.

Factores asociados a mortalidad en pacientes hospitalizados con COVID-19: cohorte prospectiva en un hospital de referencia nacional de Perú / Factors associated with mortality in patients hospitalized with COVID-19: a prospective cohort in a Peruvian national referral hospital

Objetivos Describir las características clínicas y evaluar los factores asociados con la mortalidad de los pacientes adultos con la nueva enfermedad causada por coronavirus 2019 (COVID-19) ingresados a un hospital de referencia nacional de Perú. Métodos Se realizó un estudio de cohorte prospectivo. Se incluyó a pacientes mayores de 18 años hospitalizados con el diagnóstico de infección por coronavirus 2 del síndrome respiratorio agudo severo (SARS-CoV-2). Se excluyó a quienes ingresaron con prueba rápida serológica positiva al ingreso, sin clínica sugestiva ni imágenes compatibles. Los datos se recolectaron a partir de la historia clínica. Resultados Se incluyó un total de 813 adultos, 544 (66,9%) tuvieron COVID-19 confirmado. La media de la edad fue de 61,2 años (desviación estándar: 15) y 575 (70,5%) fueron de sexo masculino. Las comorbilidades más frecuentes fueron hipertensión arterial (34,1%) y obesidad (25,9%). Los síntomas más frecuentes al ingreso fueron disnea (82,2%) y tos (53,9%). Un total de 114 (14%) pacientes recibieron ventilación mecánica, 38 (4,7%) ingresaron a unidad de cuidados intensivos y 377 (46,4%) fallecieron. Se asociaron a la mortalidad el requerimiento de soporte ventilatorio, el mayor compromiso pulmonar y los marcadores inflamatorios. Encontramos que por cada 10 años que aumentó la edad, el riesgo de morir se incrementó en 32% (riesgo relativo: 1,32; intervalo de confianza 95%: 1,25 a 1,38). Aquellos pacientes que requirieron ingreso a unidad de cuidados intensivos y ventilación mecánica tuvieron 1,39 (intervalo de confianza 95%: 1,13 a 1,69) y 1,97 (intervalo de confianza 95%: 1,69 a 2,29) veces el riesgo de morir, respectivamente. Conclusión La mortalidad encontrada en nuestro estudio fue alta y estuvo asociada a la edad, marcadores inflamatorios y compromiso respiratorio.

Objectives To describe and assess clinical characteristics and factors associated with mortality in adult patients with COVID-19 admitted to a national referral hospital in Peru. Methods We conducted a prospective cohort study that included hospitalized patients older than 18 years with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosis. Patients with a positive rapid serological test on admission but no respiratory symptoms nor compatible images were excluded. We collected the data from clinical records. Results A total of 813 adults were included, 544 (66.9%) with confirmed COVID-19. The mean age was 61.2 years (standard deviation: 15.0), and 575 (70.5%) were male. The most frequent comorbidities were hypertension (34.1%) and obesity (25.9%). On admission, the most frequent symptoms were dyspnea (82.2%) and cough (53.9%). A total of 114 (14.0%) patients received mechanical ventilation, 38 (4.7%) were admitted to the intensive care unit, and 377 (46.4%) died. The requirement for ventilatory support, greater lung involvement, and inflammatory markers were associated with higher mortality. It was found that for every 10-year age increase, the risk of dying increased 32% (relative risk: 1.32; 95% confidence interval: 1.25 to 1.38). Those who were admitted to the intensive care unit and and were placed on mechanical ventilation had 1.39 (95% confidence interval: 1.13 to 1.69) and 1.97 (95% confidence interval: 1.69 to 2.29) times the risk of dying compared to those who did not, respectively. Conclusion We found a high mortality rate among hospitalized patients associated with older age, higher inflammatory markers, and greater lung involvement.

Expression of the Wilms' tumour gene and its association with PPARß/δ in healthy skin and melanoma of horses.

The Wilms' tumour gene (WT1) has previously been described as an oncogene in several neoplasms of humans, including melanoma, and its expression increases cancer cell proliferation. Recent reports associate the expression of the PPARß/δ gene (peroxisome proliferator-activated receptor beta/delta) with the downregulation of WT1 in human melanoma and murine melanoma cell lines. The aim of this work was to analyse the expression of WT1 and its association with PPARß/δ in samples of healthy and melanoma-affected skin of horses by immunohistochemistry. WT1 protein expression was detected in healthy skin, mainly in the epidermis, hair follicle, sebaceous gland and sweat gland, while no expression was observed in equine melanoma tissues. Moreover, it was observed that PPARß/δ has a basal expression in healthy skin and that it is overexpressed in melanoma. These results were confirmed by a densitometric analysis, where a significant increase of the WT1-positive area was observed in healthy skin (128.66 ± 19.84 pixels 106) compared with that observed in melanoma (1.94 ± 0.04 pixels 106). On the other hand, a positive area with an expression of PPARß/δ in healthy skin (214.94 ± 11.85 pixels 106) was significantly decreased compared to melanoma (624.86 ± 181.93 pixels 106). These data suggest that there could be a regulation between WT1 and PPARß/δ in this disease in horses.

Assessment of targeted selective treatment criteria to control subclinical gastrointestinal nematode infections on sheep farms.

Control of sheep gastrointestinal nematode (GIN) infections mostly relies on the use of anthelmintics. Refugia-based control strategies as targeted selective treatments (TST) can delay anthelmintic resistance development, but the optimal decision criteria for selecting individuals to be treated in subclinical infection scenarios remain unclear. The present study aimed to evaluate the suitability of body condition score (BCS) and faecal egg counts (FEC) as treatment indicators and to determine their optimized threshold values for treatment in TST by determining the relationships of BCS, FEC and anthelmintic treatment with several productive parameters in pre-mating and pre-partum periods at an individual level. Deworming in pre-mating period increased BCS gain, but its magnitude was directly associated with strongyle FEC before treatment. Deworming also increased fertility in ewes with BCS < 2.75 and the proportion of lambing ewes that got pregnant during the first ovulation cycle. Nevertheless, treatment did not yield productive benefits in ewes with higher BCS values. On the other hand, deworming in the pre-partum lowered lamb peri-partum mortality and increased lamb weight at birth and the growth of lambs during lactation, especially in lambs born from ewes with strongyle FEC > 400 epg before treatment. These results showed that FEC and especially BCS can be potential decision criteria for the implementation of TST in these types of scenarios. The TST scheme derived from the present results on the control of GIN infections should include anthelmintic treatment of ewes with BCS lower than ≈ 3 approximately five weeks before mating and lambing. In the pre-lambing period, treatment may be unnecessary if flock mean strongyle FEC is lower than ≈ 200 epg, as the proportion of ewes with individual FEC > 400 epg would be very low. The results suggest that implementation of this TST scheme would provide benefits, such as the improvement of productivity, a rational management of parasites in refugia, and preservation of future efficacy of anthelmintics, in comparison to traditional deworming schemes.

Trypanothione Reductase: A Target for the Development of Anti- Trypanosoma cruzi Drugs.

BACKGROUND & OBJECTIVE: Chagas disease or American trypanosomiasis is a major parasitic disease in Latin America with restricted available treatment: nifurtimox and benznidazole. These two drugs are ineffective in the chronic phase of the disease; therefore, there is a need for the development of new, efficient and safe drugs for the treatment of this pathology. With this goal, one of the promising targets is trypanothione reductase (TR), a key enzyme in the metabolism of Trypanosoma cruzi. CONCLUSION: In this review, we analyse the importance of TR as a drug target, as well as the well-known and new inhibitors reported in the last decade as potential therapeutic agents for Chagas disease.

Histochemical study of Encephalitozoon cuniculi spores in the kidneys of naturally infected New Zealand rabbits.

Encephalitozoon cuniculi is an important microsporidian pathogen that is considered an emergent, zoonotic, and opportunistic. It infects both domestic and laboratory rabbits, generating severe chronic interstitial and granulomatous nephritis with fibrosis and granulomatous encephalitis. Encephalitozoonosis is diagnosed in paraffin-embedded sections by examining the spores in the host tissues. The spores are difficult to observe when the samples are stained with hematoxylin and eosin (H&E), particularly when there is an inflammatory reaction and tissue damage. The spores are easily mistaken for other microorganisms, such as fungi (yeasts), protozoa, and bacteria. In our study, we used kidney samples from E. cuniculi-positive rabbits and employed 14 recommended histologic stains for detecting microsporidia spores: alcian blue, calcofluor white, Giemsa, Gram, Grocott, H&E, Luna, Luxol fast blue, Masson trichrome, modified trichrome stain (MTS), periodic acid-Schiff reaction (PAS), Van Gieson, Warthin-Starry (WS), and Ziehl-Neelsen (ZN).We concluded that MTS and Gram stain, detected by light microscopy, and calcofluor white stain, detected by ultraviolet light microscopy, are the best stains for detecting spores of E. cuniculi in paraffin-embedded tissues from infected rabbits. These stains were superior to WS, ZN, Giemsa, and PAS for identifying spores without background "noise" or monochromatic interference. Also, they allow individual spores to be discerned in paraffin-embedded tissues. MTS allows observation of the polar tube, polaroplast, and posterior vacuole, the most distinctive parts of the spore.

Effect of obstacle position in the flow of sheep through a narrow door.

In a recent work [Phys. Rev. E 91, 022808 (2015)PLEEE81539-375510.1103/PhysRevE.91.022808] it was reported that placing an obstacle in front of a gate has a beneficial effect in the flow of sheep through it. Here, we extend such results by implementing three different obstacle positions. We have observed that the flow is improved in two cases, while it worsens in the other one; the last instance happens when the obstacle is too close to the door. In this situation, the outcomes suggest that clogging develops between the doorjamb and the obstacle, contrary to the cases when the obstacle is farther, in which case clogging always occurs at the very door. The effectiveness of the obstacle (a strategy put forward to alleviate clogging in emergency exits) is therefore quite sensitive to its location. In addition, the study of the temporal evolution of the flow rate as the test develops makes evident a steady behavior during the entire duration of the entrance. This result is at odds with recent findings in human evacuation tests where the flow rate varies over time, therefore challenging the fairness of straightforward comparisons between pedestrian behavior and animal experimental observations.

Interferon γ and interleukin 10 responses in immunocompetent and immunosuppressed New Zealand White rabbits naturally infected with Encephalitozoon cuniculi.

Levels of interferon (IFN)-γ and interleukin (IL)-10 were measured in the serum of immunocompetent and immunosuppressed New Zealand White rabbits naturally infected with Encephalitozoon cuniculi. IFN-γ levels were elevated in infected rabbits, and a synergic effect was observed in animals treated with the immunosuppressive agent dexamethasone (Dex). The role of IL-10 in infected rabbits remains unclear, as IL-10 levels were similar to those of negative controls. Dex appeared to exhibit a proinflammatory effect, as IFN-γ levels were elevated in infected immunosuppressed rabbits. Similarly, Dex exhibited a synergic effect in infected immunosuppressed rabbits, as evidenced by the elevation in IFN-γ production. These data indicate that the immune response to this glucocorticoid should be considered in the design of future animal model studies of immunosuppression.

Encephalitozoon cuniculi: Grading the Histological Lesions in Brain, Kidney, and Liver during Primoinfection Outbreak in Rabbits.

This is the first confirmed report of Encephalitozoon cuniculi (E. cuniculi) in farm meat rabbits located in Northern Mexico. Eighty young rabbits exhibited clinical signs of this zoonotic emerging disease, like torticollis, ataxia, paresis, circling, and rolling. Samples of brain, kidney, and liver were examined for histology lesions. For the first time the lesions caused by E. cuniculi were graded according to their severity (I, II, and III) and the size of the granulomas (Types A, B, and C). The main cerebral injuries were Grade III, coinciding with the presence of Type C granulomas. The cerebral lesions were located in the cortex, brain stem, and medulla. The renal lesions were also Grade III distributed throughout cortex and renal medulla, with no granuloma formation. The involvement of hypersensitivity Types III and IV is suggested. All of the rabbits were seropositive to E. cuniculi by CIA testing, suggesting that this zoonotic and emerging pathogen is widely distributed among animals intended for human consumption. We believe this work could be used as a guide when examining E. cuniculi and will provide direction to confirm the diagnosis of this pathogen.

Cells infected with Jaagsiekte sheep retrovirus are detected in the bone marrow of asymptomatic sheep.

Ovine pulmonary adenocarcinoma (OPA) is a transmissible lung cancer caused by Jaggsiekte sheep retrovirus (JSRV). It is difficult to identify animals infected with JSRV but are clinically healthy. The virus does not induce a specific antibody response and, although proviral DNA sequences of JSRV can be found in mononuclear blood cells, the detection is inconsistent. The aim of this study was to investigate the presence of JSRV in the bone marrow of infected sheep and develop a more consistent screening method. Immunohistochemical examination of bone marrow samples from 8 asymptomatic JSRV-infected sheep revealed the presence of positively labelled cells. However, JSRV could not be detected by a highly sensitive polymerase chain reaction (PCR) in bone marrow aspirates periodically collected from these animals. Results suggest that JSRV-infected cells may be present in the bone marrow of symptomless animals, but the number is below the detectable level for PCR. Therefore, this technique does not seem to be helpful for preclinical diagnosis of OPA.

L'adénocarcinome pulmonaire ovin (OPA) est un cancer pulmonaire transmissible causé par le rétrovirus ovin de Jaggsiekte (JSRV). Il est difficile d'identifier les animaux infectés par le JSRV mais qui sont cliniquement en santé. Le virus n'entraine pas la production d'anticorps spécifiques et, bien que des séquences d'ADN provirales de JSRV peuvent être retrouvées dans les mononucléaires du sang, la détection est inconstante. L'objectif de la présente étude était d'examiner la présence de JSRV dans la moelle osseuse de moutons infectés et de développer une méthode de tamisage plus constante. L'examen par immunohistochime d'échantillons de la moelle osseuse de huit moutons asymptomatiques mais infectés par JSRV a révélé la présence de cellules positivement marquées. Toutefois, le JSRV ne put être révélé par une épreuve d'amplification en chaine par la polymérase (PCR) très sensible à partir d'aspirations de la moelle osseuse récolées périodiquement à partir de ces animaux. Les résultats suggèrent que les cellules infectées par JSRV peuvent être présentes dans la moelle osseuse d'animaux asymptomatiques, mais le nombre se situe sous le seuil détectable pas PCR. Ainsi, cette technique ne semble pas utile pour le diagnostic préclinique d'OPA.(Traduit par Docteur Serge Messier).

Combined distemper-adenoviral pneumonia in a dog.

A 3 1/2-month-old pug with oculonasal discharge and seizures was submitted for postmortem examination. Grossly, the lungs had cranioventral consolidation, and microscopically, 2 distinct types of inclusion bodies compatible with Canine distemper virus and Canine adenovirus type 2. Presence of both viruses was confirmed via immunohistochemical staining.

Horner's syndrome associated with parotid duct obstruction in a sheep.

A 9-year old, Rasa Aragonesa ewe was presented with a left-sided, facial, soft fluctuant swelling. The postmortem examination showed grass awns filling the entire length of the parotid gland duct. The presence of parotid duct obstruction with Horner's syndrome, previously unreported in sheep, is discussed.

Insuficiencia renal aguda: experiencia en seis años

La insuficiencia renal aguda (I.R.A), constituye una emergencia médica que cobra un alto número de vidas, por lo que resulta importante conocer la etiología, el comportamiento clínico y la evolución final de este síndrome. Se estudiaron noventa y cinco historias clínicas de pacientes con I.R.A. ingresados en el hospital provincial Saturnino Lora, de Santiago de Cuba, entre julio de 1974 y julio de 1980. Entre los resultados obtenidos tenemos que las causas más frecuentes fueron: nefrotoxicidad por drogas, sepsis generalizada y accidentes obstétricos en un 12, 4 por ciento cada uno, y que la bronconeumonía fue la causa principal de muerte. La supervivencia global fue de un 75, 9 por ciento. En nuestra serie la Furosemida a altas dosis no modificó la evolución de la I.R.A. en forma significativa (p mayor 0, 05). Consideramos que la atención integral especializada mejora la supervivencia y se alerta sobre los cuidados del uso de drogas nefrotóxicas(AU)