Replicability of simulation studies for the investigation of statistical methods: the RepliSims project.

Results of simulation studies evaluating the performance of statistical methods can have a major impact on the way empirical research is implemented. However, so far there is limited evidence of the replicability of simulation studies. Eight highly cited statistical simulation studies were selected, and their replicability was assessed by teams of replicators with formal training in quantitative methodology. The teams used information in the original publications to write simulation code with the aim of replicating the results. The primary outcome was to determine the feasibility of replicability based on reported information in the original publications and supplementary materials. Replicasility varied greatly: some original studies provided detailed information leading to almost perfect replication of results, whereas other studies did not provide enough information to implement any of the reported simulations. Factors facilitating replication included availability of code, detailed reporting or visualization of data-generating procedures and methods, and replicator expertise. Replicability of statistical simulation studies was mainly impeded by lack of information and sustainability of information sources. We encourage researchers publishing simulation studies to transparently report all relevant implementation details either in the research paper itself or in easily accessible supplementary material and to make their simulation code publicly available using permanent links.

Association of tyrosine hydroxylase 01 (TH01) microsatellite and insulin gene (INS) variable number of tandem repeat (VNTR) with type 2 diabetes and fasting insulin secretion in Mexican population.

PURPOSE: A variable number of tandem repeats (VNTR) in the insulin gene (INS) control region may be involved in type 2 diabetes (T2D). The TH01 microsatellite is near INS and may regulate it. We investigated whether the TH01 microsatellite and INS VNTR, assessed via the surrogate marker single nucleotide polymorphism rs689, are associated with T2D and serum insulin levels in a Mexican population. METHODS: We analyzed a main case-control study (n = 1986) that used univariate and multivariate logistic regression models to calculate the risk conferred by TH01 and rs689 loci for T2D development; rs689 results were replicated in other case-control (n = 1188) and cross-sectional (n = 1914) studies. RESULTS: TH01 alleles 6, 8, 9, and 9.3 and allele A of rs689 were independently associated with T2D, with differences between sex and age at diagnosis. TH01 alleles with ≥ 8 repeats conferred an increased risk for T2D in males compared with ≤ 7 repeats (odds ratio, ≥ 1.46; 95% confidence interval, 1.1-1.95). In females, larger alleles conferred a 1.5-fold higher risk for T2D when diagnosed ≥ 46 years but conferred protection when diagnosed ≤ 45 years. Similarly, rs689 allele A was associated with T2D in these groups. In males, larger TH01 alleles and the rs689 A allele were associated with a significant decrease in median fasting plasma insulin concentration with age in T2D cases; the reverse occurred in controls. CONCLUSION: Larger TH01 alleles and rs689 A allele may potentiate insulin synthesis in males without T2D, a process disabled in those with T2D.

Detecting hidden transient events in noisy nonlinear time-series.

The information impulse function (IIF), running Variance, and local Hölder Exponent are three conceptually different time-series evaluation techniques. These techniques examine time-series for local changes in information content, statistical variation, and point-wise smoothness, respectively. Using simulated data emulating a randomly excited nonlinear dynamical system, this study interrogates the utility of each method to correctly differentiate a transient event from the background while simultaneously locating it in time. Computational experiments are designed and conducted to evaluate the efficacy of each technique by varying pulse size, time location, and noise level in time-series. Our findings reveal that, in most cases, the first instance of a transient event is more easily observed with the information-based approach of IIF than with the Variance and local Hölder Exponent methods. While our study highlights the unique strengths of each technique, the results suggest that very robust and reliable event detection for nonlinear systems producing noisy time-series data can be obtained by incorporating the IIF into the analysis.

SELNET clinical practice guidelines for bone sarcoma.

Bone sarcoma are infrequent diseases, representing < 0.2% of all adult neoplasms. A multidisciplinary management within reference centers for sarcoma, with discussion of the diagnostic and therapeutic strategies within an expert multidisciplinary tumour board, is essential for these patients, given its heterogeneity and low frequency. This approach leads to an improvement in patient's outcome, as demonstrated in several studies. The Sarcoma European Latin-American Network (SELNET), aims to improve clinical outcome in sarcoma care, with a special focus in Latin-American countries. These Clinical Practice Guidelines (CPG) have been developed and agreed by a multidisciplinary expert group (including medical and radiation oncologist, surgical oncologist, orthopaedic surgeons, radiologist, pathologist, molecular biologist and representatives of patients advocacy groups) of the SELNET consortium, and are conceived to provide the standard approach to diagnosis, treatment and follow-up of bone sarcoma patients in the Latin-American context.

Triggered electromyography (tEMG) in the lumbar spine It́s reliable? Correlation of tEMG with postoperative CT images in lumbar instrumentation. / Electromiografía evocada (tEMG) en la columna lumbar. ¿Es confiable? Correlación de tEMG con imágenes de TC posoperatorias en la instrumentación lumbar.

INTRODUCTION: Instrumentation with pedicle screws (PS) can compromise the adjacent neural structures. Triggered electromyography (tEMG) is a modality of intraoperative neuromonitoring, used to assist in the placement of these. The objective of the present study is to evaluate the reliability of this tool. METHOD: Retrospective review of patients underwent posterior lumbar fusions from January 2017 to December 2019, correlating postoperative CT images (postop CT) with tEMG results for each PS with a threshold of 10mA, establishing sensitivity and specificity of this tool. Diagnostic test and receiver operating characteristic curve were performed to evaluate the area under the curve. RESULT: A total of 275 PS were evaluated between L1 to S1; 5 PS showed concordance for an inadequate trajectory, while 10PS, with tEMG <10mA, were correctly positioned. The postoperative CT identified 17 pedicle gaps not noticed by the tEMG. Sensitivity and specificity were 23% (95% CI: 8-45) and 96% (95% CI: 93-98), respectively, with a PPV of 33.3% and a NPV of 93.6%. The area under the curve was 0.74 (95% CI: 0.62-0.86) with a cut-off point of 24mA, showing a sensitivity of 77% (95% CI: 0.55-0.92) and specificity of 69% (95% CI: 0.63-0.75). CONCLUSION: Given its low sensitivity, we do not recommend tEMG as the sole test in the verification of PS. We recommend using a cut-off point ≤8mA as it demonstrated the highest levels of sensitivity and specificity. We do not recommend using high thresholds to increase sensitivity.

Electromiografía evocada (tEMG) en la columna lumbar. ¿Es confiable? Correlación de tEMG con imágenes de TC posoperatorias en la instrumentación lumbar / Triggered electromyography (tEMG) in the lumbar spine Its reliable? Correlation of tEMG with postoperative CT images in lumbar instrumentation

Introducción: La instrumentación con tornillos pediculares (TP) puede comprometer las estructuras neurales adyacentes. La electromiografía evocada (tEMG) es una modalidad del neuromonitoreo intraoperatorio utilizada para asistir la colocación de estos. El objetivo del presente estudio es evaluar la confiabilidad de esta herramienta. Método: Revisión retrospectiva de pacientes intervenidos de artrodesis lumbar posterolateral instrumentada desde enero del 2017 hasta diciembre del 2019. Se correlacionaron las imágenes de TC postoperatorias (TC-postop) con los resultados de la tEMG para cada TP con un umbral de 10mA, y se establecieron la sensibilidad y especificidad de esta herramienta. Se realizó test diagnóstico y la curva característica operativa del receptor para evaluar el área bajo la curva. Resultado: Se evaluaron 275 TP entre L1 y S1; 5 TP presentaban concordancia para una trayectoria inadecuada, mientras que 10TP, con tEMG <10mA, se encontraban correctamente posicionados. La TC-postop identificó 17 brechas pediculares no advertidas por la tEMG. La sensibilidad y la especificidad fue del 23% (IC 95%: 8-45) y 96% (IC 95%: 93-98), respectivamente, con un VPP del 33,3% y un VPN del 93,6%. El área bajo la curva fue de 0,74 (IC 95%: 0,62-0,86) con punto de corte de 24mA, que mostró una sensibilidad del 77% (IC 95%: 0,55-0,92) y una especificidad del 69% (IC 95%: 0,63-0,75). Conclusión: Dada su baja sensibilidad, no aconsejamos la tEMG como prueba única en la verificación de TP. Recomendamos la utilización de un punto de corte ≤8mA, ya que ha demostrado los niveles más altos de sensibilidad y especificidad. No recomendamos el uso de umbrales elevados para aumentar la sensibilidad.(AU)

Introduction: Instrumentation with pedicle screws (PS) can compromise the adjacent neural structures. Triggered electromyography (tEMG) is a modality of intraoperative neuromonitoring, used to assist in the placement of these. The objective of the present study is to evaluate the reliability of this tool. Method: Retrospective review of patients underwent posterior lumbar fusions from January 2017 to December 2019, correlating postoperative CT images (postop CT) with tEMG results for each PS with a threshold of 10mA, establishing sensitivity and specificity of this tool. Diagnostic test and receiver operating characteristic curve were performed to evaluate the area under the curve. Result: A total of 275 PS were evaluated between L1 to S1; 5 PS showed concordance for an inadequate trajectory, while 10PS, with tEMG <10mA, were correctly positioned. The postoperative CT identified 17 pedicle gaps not noticed by the tEMG. Sensitivity and specificity were 23% (95% CI: 8-45) and 96% (95% CI: 93-98), respectively, with a PPV of 33.3% and a NPV of 93.6%. The area under the curve was 0.74 (95% CI: 0.62-0.86) with a cut-off point of 24mA, showing a sensitivity of 77% (95% CI: 0.55-0.92) and specificity of 69% (95% CI: 0.63-0.75). Conclusion: Given its low sensitivity, we do not recommend tEMG as the sole test in the verification of PS. We recommend using a cut-off point ≤8mA as it demonstrated the highest levels of sensitivity and specificity. We do not recommend using high thresholds to increase sensitivity.(AU)

Triggered electromyography (tEMG) in the lumbar spine it's reliable? Correlation of tEMG with postoperative CT images in lumbar instrumentation / Electromiografía evocada (tEMG) en la columna lumbar. ¿Es confiable? Correlación de tEMG con imágenes de TC posoperatorias en la instrumentación lumbar

Introduction: Instrumentation with pedicle screws (PS) can compromise the adjacent neural structures. Triggered electromyography (tEMG) is a modality of intraoperative neuromonitoring, used to assist in the placement of these. The objective of the present study is to evaluate the reliability of this tool. Method: Retrospective review of patients underwent posterior lumbar fusions from January 2017 to December 2019, correlating postoperative CT images (postop CT) with tEMG results for each PS with a threshold of 10mA, establishing sensitivity and specificity of this tool. Diagnostic test and receiver operating characteristic curve were performed to evaluate the area under the curve. Result: A total of 275 PS were evaluated between L1 to S1; 5 PS showed concordance for an inadequate trajectory, while 10PS, with tEMG <10mA, were correctly positioned. The postoperative CT identified 17 pedicle gaps not noticed by the tEMG. Sensitivity and specificity were 23% (95% CI: 8-45) and 96% (95% CI: 93-98), respectively, with a PPV of 33.3% and a NPV of 93.6%. The area under the curve was 0.74 (95% CI: 0.62-0.86) with a cut-off point of 24mA, showing a sensitivity of 77% (95% CI: 0.55-0.92) and specificity of 69% (95% CI: 0.63-0.75). Conclusion: Given its low sensitivity, we do not recommend tEMG as the sole test in the verification of PS. We recommend using a cut-off point ≤8mA as it demonstrated the highest levels of sensitivity and specificity. We do not recommend using high thresholds to increase sensitivity.(AU)

Introducción: La instrumentación con tornillos pediculares (TP) puede comprometer las estructuras neurales adyacentes. La electromiografía evocada (tEMG) es una modalidad del neuromonitoreo intraoperatorio utilizada para asistir la colocación de estos. El objetivo del presente estudio es evaluar la confiabilidad de esta herramienta. Método: Revisión retrospectiva de pacientes intervenidos de artrodesis lumbar posterolateral instrumentada desde enero del 2017 hasta diciembre del 2019. Se correlacionaron las imágenes de TC postoperatorias (TC-postop) con los resultados de la tEMG para cada TP con un umbral de 10mA, y se establecieron la sensibilidad y especificidad de esta herramienta. Se realizó test diagnóstico y la curva característica operativa del receptor para evaluar el área bajo la curva. Resultado: Se evaluaron 275 TP entre L1 y S1; 5 TP presentaban concordancia para una trayectoria inadecuada, mientras que 10TP, con tEMG <10mA, se encontraban correctamente posicionados. La TC-postop identificó 17 brechas pediculares no advertidas por la tEMG. La sensibilidad y la especificidad fue del 23% (IC 95%: 8-45) y 96% (IC 95%: 93-98), respectivamente, con un VPP del 33,3% y un VPN del 93,6%. El área bajo la curva fue de 0,74 (IC 95%: 0,62-0,86) con punto de corte de 24mA, que mostró una sensibilidad del 77% (IC 95%: 0,55-0,92) y una especificidad del 69% (IC 95%: 0,63-0,75). Conclusión: Dada su baja sensibilidad, no aconsejamos la tEMG como prueba única en la verificación de TP. Recomendamos la utilización de un punto de corte ≤8mA, ya que ha demostrado los niveles más altos de sensibilidad y especificidad. No recomendamos el uso de umbrales elevados para aumentar la sensibilidad.(AU)

Utility of the combination of hederagenin glucoside saponins and chromane hydrazone in the topical treatment of canine cutaneous leishmaniasis. An observational study.

Canine cutaneous leishmaniasis (CCL) is an emerging zoonotic infection endemic in several countries of the world. Due to variable response to therapy and frequency of relapses, a more effective, safer, and inexpensive treatment is needed. Recently, it was reported that the hederagenin glucoside saponins (SS) and chromane-derived hydrazone (TC2) combined in a 1:1 ratio has high potential in antileishmanial therapy since both compounds alter the survival of Leishmania and the ability to infect adjacent macrophage. Not only the skin permeation and the absorption of an ointment containing 2% TC2 and 2% SS (w/w) was determined in this work, but also the acute dermal toxicity in both in vitro and in vivo assays. Last, the effectiveness and safety of the topical therapy with 2% TC2-2% SS ointment was evaluated in an observational study in dogs with diagnosis of cutaneous leishmaniasis (CL). Both TC2 and SS diffused through pig ear skin and traces of TC2 (but not SS) were detected in the stratum corneum of mice at 6-24 h. Neither TC2 nor SS was detected in plasma. The acute dermal toxicity was negative. Treatment with 2% TC2-2% SS ointment produced a complete long-term clinical cure in 56 dogs (24 females and 32 males) from the Orinoco and Amazonas regions in southeastern Colombia without adverse effects. All dogs have remained disease-free for the last 24 months. In conclusion, these results support the use of this topical therapy as a safer and new first-line local treatment of CCL that could help limit the spread of CL from dogs to humans.

End-of-life transfusions in patientswith an oncological diagnosis / Transfusiones al final de la vida en pacientes con diagnóstico oncológico

Introduction: Cancer patients in terminal stages present symptoms related to anemia, other cytopenias, and coagulopathies that deteriorate the quality of life. These symptoms can be multicausal and do not improve in most cases. Objective: Describe the use of blood transfusions in the six months before death as an alternative palliative treatment in patients with an oncological diagnosis in the city of Medellin during the period 2013-2018. Methods: Retrospective cohort, in patients with a cancer diagnosis who received transfusions in the last six months of life, a non-probabilistic sampling of consecutive cases was executed. The analysis was carried out in SPSS, estimating absolute and relative frequencies and median with interquartile ranges. Results: Out of 3,254 medical records of cancer pa­tients, 151 were included. The time to oncological diagnosis had a median of 2 years (IQR 1 and 3). The symptoms observed in patients before and after the first transfusion were pain, present in 32.1 % (46) and 16.9 % (25) respectively, besides drowsiness was distinguished in 25 % (36) before transfusion and 14.3 % (21) after. Finally, the clinical outcomes before and after the last transfusion prior to death, were a decrease in pain, asthenia/adynamia, drowsiness, among others. Conclusions: The findings of this research allow us to appreciate the current panorama in the institutions in which palliative care medical services are being provided and consider when to offer the blood products to a patient at the end of life as a therapeutic measure in the context of a human being cared by physicians.(AU)

Introducción: Los pacientes con cáncer en fase terminal presentan síntomas relacionados con la anemia, otras citopenias y coagulopatías que deterioran la calidad de vida. Estos síntomas pueden ser multicausales y no mejoran en la mayoría de los casos. Objetivo: Describir el uso de transfusiones sanguíneas en los seis meses previos a la muerte como alternativa de tratamiento paliativo en pacientes con diagnóstico oncológico en la ciudad de Medellín durante el periodo 2013-2018. Métodos: Cohorte retrospectiva, en pacientes con diagnóstico de cáncer que recibieron transfusiones en los últimos seis meses de vida, se ejecutó un muestreo no probabilístico de casos consecutivos. El análisis se realizó en SPSS, estimando frecuencias absolutas y relativas y mediana con rangos intercuartílicos.Resultados: De 3254 historias clínicas de pacientes con cáncer, 151 fueron incluidas. El tiempo hasta el diagnóstico oncológico tuvo una mediana de 2 años (IQR 1 y 3). Los síntomas observados en los pacientes antes y después de la primera transfusión fueron el dolor, presente en el 32,1 % (46) y el 16,9 % (25) respectivamente, además de la somnolencia que se distinguió en el 25 % (36) antes de la transfusión y el 14,3 % (21) después. Finalmente, los resultados clínicos antes y después de la última transfusión antes de la muerte, fueron una disminución del dolor, astenia/adinamia, somnolencia, entre otros. Conclusiones: Los hallazgos de esta investigación permiten apreciar el panorama actual en las instituciones en las que se prestan servicios médicos de cuidados paliativos y considerar cuándo ofrecer los hemoderivados a un paciente al final de la vida como medida terapéutica en el contexto de un ser humano atendido por los médicos.(AU)

Risk factors associated with veterinary attrition from clinical practice: a descriptive study.

A sustainable workforce is important for the veterinary profession to meet the demands of society. To maintain a sustainable workforce, it has been recommended to retain veterinary clinicians. However, there seems to be an increasing issue with retention of veterinarians in clinical practice. In the following study, the researchers sought to understand the associations between demographic and work-related factors and attrition of veterinarians from clinical practice. Responses to an online cross-sectional survey of 881 current and former Australian veterinary clinicians were analysed. A logistic regression model was used to identify and describe associations between attrition from veterinary clinical practice and salary, working hours, role in practice, years of experience, field of work, interaction with regulatory authorities, region of work and on-call duties. Lower salary, longer working hours, having on-call duties and having worked in both rural and metropolitan regions were found to significantly (P < 0.05) increase the likelihood of leaving clinical practice. The results may inform intervention strategies to assist the industry to retain veterinarians in clinical practice.

The Effect of Different Species of Eimeria with Clostridium perfringens on Performance Parameters and Induction of Clinical Necrotic Enteritis in Broiler Chickens.

Necrotic enteritis (NE) is a common disease that causes great economic loss to the broiler industry due to mortality and reduced performance. Although Clostridium perfringens (CP) is a necessary component of this disease, coccidia species are a well-defined predisposing factor that exacerbates the condition. Different Eimeria species have been reported to influence NE to different degrees. In a pair of experiments, six different Eimeria species were evaluated in the presence and absence of C. perfringens. Male broiler chicks were housed in battery cages for the duration of both experiments. Feed conversion, body weight gain, and NE mortality were reported in both experiments. Experiment 1 challenged birds with E. maxima, E. acervulina, E. tenella, E. necatrix, and E. brunetti at day 13 and subsequently inoculated birds with CP on days 18, 19, and 20. In the second experiment, E. maxima, E. acervulina, E. tenella, and E. praecox were inoculated on day 15 and challenged with CP on days 17, 18, 19, 20, 21, and 22 of the experiment. In the first experiment, E. acervulina, E. brunetti, E. maxima, and E. necatrix with the addition of CP all stimulated necrotic enteritis mortality. In the second experiment, E. praecox had minimal impact on performance during the challenge (14-23 days) while E. maxima + CP decreased body weight gain and increased mortality compared to the CP alone control. Eimeria maxima had the highest mortality (21.9%) in this experiment followed by E. acervulina (6.3%). The remaining Eimeria with added CP in the second experiment did not induce NE mortality. While the challenge with CP alone did not induce mortality, feed conversion was increased compared to the unchallenged control group. When using isolated Eimeria species in these experiments, disturbances created by E. brunetti and E. maxima resulted in the most-severe challenges. These experiments highlight the NE risk of these species of Eimeria and give insight into how other species interact with the host in a controlled CP challenge model.

Artículo regular­Efecto de diferentes especies de Eimeria con Clostridium perfringens sobre los parámetros de rendimiento y la inducción de enteritis necrótica clínica en pollos de engorde. La enteritis necrótica (NE) es una enfermedad común que causa grandes pérdidas económicas a la industria del pollo de engorde debido a la mortalidad y a la reducción del rendimiento. Aunque Clostridium perfringens (CP) es un componente necesario de esta enfermedad, las especies de coccidia son un factor predisponente bien definido que agrava la enfermedad. Se ha informado que diferentes especies de Eimeria influyen en la enteritis necrótica en diferentes grados. En un par de experimentos, se evaluaron seis especies diferentes de Eimeria en presencia y ausencia de C. perfringens. Pollos de engorde machos se alojaron en jaulas en batería durante la duración de ambos experimentos. En ambos experimentos se analizaron la conversión alimenticia, el aumento de peso corporal y la mortalidad por enteritis necrótica. En el Experimento 1 se desafió a las aves con E. maxima, E. acervulina, E. tenella, E. necatrix y E. brunetti en el día 13 y posteriormente se inoculó a las aves con C. perfringens en los días 18, 19 y 20. En el segundo experimento, E. maxima, E. acervulina, E. tenella y E. praecox se inocularon en el día 15 y se desafiaron con C. perfringens en los días 17, 18, 19, 20, 21 y 22 del experimento. En el primer experimento, E. acervulina, E. brunetti, E. maxima y E. necatrix junto con C. perfringens estimularon la mortalidad por enteritis necrótica. En el segundo experimento, E. praecox tuvo un impacto mínimo en el rendimiento durante el desafío (14 a 23 días) mientras que el tratamiento de E. maxima + C. perfringens disminuyó el aumento de peso corporal y aumentó la mortalidad en comparación con el control con solamente C. perfringens. Eimeria maxima tuvo la mayor mortalidad (21.9%) en este experimento seguida por E. acervulina (6.3%). El resto de las especies de Eimeria junto con C. perfringens en el segundo experimento no indujeron mortalidad por enteritis necrótica. Si bien el desafío con C. perfringens no solo no indujo mortalidad, sino que la conversión alimenticia aumentó en comparación con el grupo de control no desafiado. Cuando se utilizaron especies de Eimeria aisladas en estos experimentos, los problemas creados por E. brunetti y E. maxima resultaron en los desafíos más severos. Estos experimentos destacan el riesgo por enteritis necrótica con estas especies de Eimeria y dan una idea de cómo otras especies interactúan con el hospedador en un modelo de desafío con C. perfringens controlado.

Heart rate dynamics and lactate following high-intensity race-pace continuous vs interval workouts in highly trained athletes.

PURPOSE: The present study aimed to compare the physiological responses of high-intensity race-pace continuous vs. interval workouts commonly used in middle-distance athletics, by means of analyzing post-exercise cardiac autonomic regulation and lactate. METHODS: Nineteen highly-trained 800-m male runners were asked to run a 600-m race-pace continuous workout and a 2 × 4 × 200-m interval training, counterbalanced and randomized within one week of difference. Blood lactate jointly with linear and nonlinear heart rate dynamics were assessed during the immediate 15-min recovery. Age-category (Under23-Senior vs. Juvenile-Junior) was considered as an inter-subject factor. RESULTS: Peak lactate was higher following the interval training (15.51 ± 0.99 vs 13.83 ± 1.77 mmol L-1; P < 0.05) whereas lactate removal was almost nonexistent 15 min after both workouts (between 0 and 16%). Vagal modulation (ln RMSSD and lnRMSSD to RR ratio) remained significantly depressed at the end of recovery following both workouts, although the alteration was larger following the interval training. Detrended Fluctuation Analysis evidenced a more random HR behavior (DFA1 closer to 0.5) during the first 9 min of recovery after the interval training, whereas no significant change was observed in heart rate complexity (SampEn). Neither were differences found in post-exercise lactate and HR dynamics as a function of age-category. CONCLUSIONS: High-intensity workouts commonly used in middle-distance athletics, both race-pace continuous and intervallic approaches, induce a large depression of vagal modulation in highly trained runners, although interval trainings appear to induce even a greater alteration of both linear and nonlinear HR dynamics and a higher post-exercise peak lactate.

Antibodies elicited by the CaniLeish® vaccine: long-term clinical follow-up study of dogs in Spain.

The prevention of canine leishmaniosis in healthy dogs requires a multimodal approach combining repellents with an effective vaccine. A vaccine that modulates the cell-mediated immune response against the protozoan has been available in Europe since 2012 (CaniLeish®, Virbac, France). The aim of the present study was to monitor dogs vaccinated with CaniLeish® to examine the kinetics of the antibody response and the safety and tolerance of CaniLeish®. Dogs vaccinated with CaniLeish® were monitored for 12 months. In follow-up visits at baseline (primovaccination or annual booster) (Visit 1, V1), and 1 (V2), 4 (V3), 8 (V4) and 12 (V5) months later, we examined antibody response kinetics using two serology techniques (IFAT and Speed Leish K™). Tolerance to CaniLeish® and its safety were also monitored. Anti-L. infantum IgG antibodies were determined in 242 dogs (125 dogs after primovaccination (Group P) and 117 dogs after booster vaccination (Group B). In addition, 46, 22 and 19 dogs were followed for 2, 3 and 4 years, respectively. At baseline, 100% of dogs in Group P returned negative IFAT and Speed Leish K™ test results while 9.4% (11/117) in Group B tested IFAT positive though Speed Leish K™ negative. In subsequent visits, seropositivity was detected by IFAT in 31.2% (Group P) and 41% (Group B) of the dogs in V2; 16.8% (Group P) and 10.2% (Group B) in V3; 6.4% (Group P) and 8.5% (Group B) in V4; and 3.2% (Group P) and 5.9% (Group B) in V5. All dogs tested Speed Leish K™ negative except two, in which it was later confirmed by molecular testing that they were not infected. Adverse events that could be associated with the vaccine were detected in 20 out of 314 dogs (6.4%). The good clinical status of all dogs was confirmed in an exhaustive clinical exam and haemato-biochemical profile. The Canileish® vaccine was well-tolerated with exceptions that did not appear to be related to age, sex, race or size of vaccinated dogs. Anti-L. infantum antibodies were detected by IFAT in 31.9-40.3% of the dogs 1 month after vaccination, and these antibodies could still be detected in 3.2% of the dogs 1 year later. This means that veterinarians need to use other tools (eg. PCR) to correctly diagnose seropositive dogs.

Preparation and in vitro evaluation of PLA/biphasic calcium phosphate filaments used for fused deposition modelling of scaffolds.

Ceramic materials such as calcium phosphates (CaPs) with a composition similar to the mineral phase of bones and polymeric polylactic acid (PLA) are potential candidates for the manufacturing of scaffolds to act as bone substitutes and for tissue engineering applications, due to their bioresorbability and biocompatibility. Variables such as porosity, topography, morphology, and mechanical properties play an essential role in the scaffolds response. In this paper, a polymer/ceramic composite filament of 1.7 mm in diameter based on PLA and biphasic calcium phosphates (BCPs) was obtained by hot-melt extrusion in a single screw extruder. The particles of BCP were obtained by solution-combustion synthesis, and the PLA used was commercial grade. The BCPs ceramics were characterized by X-ray diffraction (XRD), scanning electron microscopic (SEM), transmission electron microscopy (TEM), and Brunauer, Emmett, and Teller (BET). It was possible to confirm that the main inorganic phases were hydroxyapatite (HAP) and tricalcium phosphate (TCP) with grain sizes below 100 nm and with high porosity. The Filaments obtained are a bit fragile but were able to be used in fused deposition modelling (FDM) using low-cost commercial printers. The filaments were characterized by SEM and energy dispersive X-ray (EDX). The in-vitro tests of filaments showed deposition of apatite phases on their surface, non-cytotoxic behavior, adequate cell proliferation and cell adhesion.

Evaluación por gastroscopia simple y cromoendoscopia convencional de la superficie gastroesofágica y duodenal proximal del equino. Estudio piloto / Evaluation by simple gastroscopy and conventional chromoendoscopy of the gastro-esophageal and proximal duodenal surface of equine. Preliminary study

RESUMEN Las enfermedades gastrointestinales equinas tienen una alta incidencia con un pronóstico variable en la práctica clínica. La mayoría de los estudios se limitan a describir lesiones ulcerativas y lesiones inflamatorias. El objetivo de este estudio fue evaluar el potencial diagnóstico complementario de la cromoendoscopia convencional en la mucosa gas-troesofágica y duodenal proximal del equino. El estudio incluyó 20 caballos criollos colombianos de ambos sexos (12 hembras y 8 machos), con edades entre 5 y 20 años, peso entre 250 y 350 kilogramos, condición corporal 4-5/9 y con historial de alteraciones digestivas en los últimos 3 meses; quienes previo a la evaluación por gastroscopia y cromoendoscopia se sometieron a ayuno (sólidos 12h y líquidos 4h) y sedación (xilacina 0,5 mg/kg/iv). Se utilizaron tinciones como rojo fenol, lugol, índigo carmín, azul de metileno y ácido acético y se tomaron biopsias de los segmentos que mostraron reacción. El azul de metileno reveló 52% de las lesiones, el lugol 19%; por su parte, el rojo fenol, el índigo carmín y el ácido acético revelaron el 9,5% restante. El epitelio escamoso fue el más afectado (66,6%), el glandular (19%), antro pilórico (9,5%) y duodeno proximal (4,7%). Los hallazgos histopatológicos fueron hiperplasia, hipertrofia, hiperqueratosis, congestión, degeneración vacuolar, infiltrados celulares, fibrosis, necrosis y atrofia en diferentes grados de severidad. La cromoendoscopia reveló lesiones prematuras, que pasaron desapercibidas con las técnicas convencionales de endoscopia del tracto digestivo. Este es el primer estudio que emplea la cromoendoscopia en equinos; a pesar de que la técnica mejoró la visualización y facilitó la ubicación y descripción de lesiones ulcerativas prematuras a través de la histopatología, se recomiendan mayores estudios controlados y con un número más amplio de muestras.

ABSTRACT Equine gastrointestinal diseases have a high occurrence with a variable prognostic in clinic practice. Most of the studies limits to describe ulcerative and inflammatory lesions. The objective of this study was to evaluate the potential complementary diagnostic of conventional chromoendoscopy on the gastroesophageal and proximal duodenal mucosa of the equine. 20 Colombian creole horses, of both sexes (12 females and 8 males), with ages between 5 and 20 years old, weight between 250 and 350 kilograms, body condition 4-5/9, that had presented digestive alterations in the last 3 months, were subjected to fasting (solids 12h and liquids 4h) and sedated (xylazine 0,5 mg/kg/iv) to be evaluated by gastroscopy and chromoendoscopy, using for stains phenol red, lugol, indigo carmine, methylene blue and acetic acid, taking biopsy samples of the segments that showed reaction. The methylene blue revealed 52%, lugol 19%, and phenol red, indigo carmine and acetic acid revealed only 9,5% of the lesions, being the squamous epithelium the most affected (66,6%), glandular epithelium (19%), pyloric antrum (9,5%) and proximal duodenum (4,7%), where histopathological findings were hyperplasia, hypertrophy, hyperkeratosis, congestion, vacuolar degeneration, cellular infiltrates, fibrosis, necrosis and atrophy in different degrees of severity. Chromoendoscopy revealed lesions premature, which go unnoticed with conventional light endoscopy techniques. This is the first study using chromoscopy in horses to show that the reagents used allow a better visualization of injuries than the conventional technique, helping histopathological studies and molecular biology to understand ulcerative premature injuries and possible pathophysiological pathways. However, larger controlled studies and a larger number of samples are needed.

Overweight and obesity status from the prenatal period to adolescence and its association with non-alcoholic fatty liver disease in young adults: cohort study.

OBJECTIVE: To examine the associations of maternal and child overweight status across multiple time-points with liver fat content in the offspring during young adulthood. DESIGN: Cohort study. SETTING: ELEMENT Cohort in Mexico City. POPULATION: Pregnant women with singleton births (n = 97). METHODS: We quantified hepatic triglyceride content (liver fat content) by proton magnetic resonance spectroscopy (1H MRS) and conventional T2-weighted MRIs (3T scanner) in 97 young adults from the ELEMENT birth cohort in Mexico City. Historical records of the cohort were used as a source of pregnancy, and childhood and adolescence anthropometric information, overweight and obesity (OWOB) were defined. Adjusted structural equation models were run to identify the association between OWOB in different life stages with liver fat content (log-transformed) in young adulthood. MAIN OUTCOME: Maternal OWOB at the time of delivery was directly and indirectly associated with the liver fat content in the offspring at young adulthood. RESULTS: Seventeen percent of the participants were classified as having NAFLD. We found a strong association of OWOB between all periods assessed. Maternal OWOB at time of delivery (ß = 1.97, 95% CI 1.28-3.05), and OWOB status in the offspring at young adulthood (ß = 3.17, 95% CI 2.10-4.77) were directly associated with the liver fat content in the offspring. Also, maternal OWOB was indirectly associated with liver fat content through offspring OWOB status. CONCLUSION: We found that maternal OWOB status is related to fatty liver content in the offspring as young adults, even after taking into account OWOB status and lifestyle factors in the offspring. TWEETABLE ABSTRACT: There was an association between pre-pregnancy overweight and the development of NAFLD in adult offspring.