Evaluation of Ointments with Daldinia eschscholtzii in Wound Healing in an In Vivo Model.

Fungi are a source of a variety of secondary metabolites of importance in different areas of biotechnology. Several compounds have been characterized with antioxidant, antimicrobial, and anti-inflammatory activity from fungi of the division of the Ascomycota, among which is the species Daldinia eschscholtzii, an endophyte fungus of pantropical distribution. In this study, we evaluated the effect of an ointment made with D. eschscholtzii on the wound healing of BALB/c mice. The species was corroborated using a molecular marker Internal Transcribed Spacer (ITS1 and ITS4). The extracts and dust of the fungus were considered nontoxic as they caused a mortality of <15% in the nematode Panagrellus redivivus, and experimental ointments had no adverse effects on the skin of BALB/c mice. Wounds treated with the D. eschscholtzii ointments had 99.9-100% wound contraction after 17 days, which was similar to commercial healing (positive control). As such, the ointment of D. eschscholtzii is a natural alternative to improve wound healing.

Zika emergence, persistence, and transmission rate in Colombia: a nationwide application of a space-time Markov switching model.

Zika, a viral disease transmitted to humans by Aedes mosquitoes, emerged in the Americas in 2015, causing large-scale epidemics. Colombia alone reported over 72,000 Zika cases between 2015 and 2016. Using national surveillance data from 1121 municipalities over 70 weeks, we identified sociodemographic and environmental factors associated with Zika's emergence, re-emergence, persistence, and transmission intensity in Colombia. We fitted a zero-state Markov-switching model under the Bayesian framework, assuming Zika switched between periods of presence and absence according to spatially and temporally varying probabilities of emergence/re-emergence (from absence to presence) and persistence (from presence to presence). These probabilities were assumed to follow a series of mixed multiple logistic regressions. When Zika was present, assuming that the cases follow a negative binomial distribution, we estimated the transmission intensity rate. Our results indicate that Zika emerged/re-emerged sooner and that transmission was intensified in municipalities that were more densely populated, at lower altitudes and/or with less vegetation cover. Warmer temperatures and less weekly-accumulated rain were also associated with Zika emergence. Zika cases persisted for longer in more densely populated areas with more cases reported in the previous week. Overall, population density, elevation, and temperature were identified as the main contributors to the first Zika epidemic in Colombia. We also estimated the probability of Zika presence by municipality and week, and the results suggest that the disease circulated undetected by the surveillance system on many occasions. Our results offer insights into priority areas for public health interventions against emerging and re-emerging Aedes-borne diseases.

Crude Extracts of Pleurotus Spp. and the Presence of Their Proteins in the Ovicidal and Larvicidal Activity of Haemonchus contortus.

Mushrooms of the genus Pleurotus have shown nematophagous activity as it produces many chemical compounds and enzymes affecting parasitic nematodes. This study aimed to extract the inhibitory activity of the five strains of the fungus Pleurotus spp. It was evaluated against eggs and larvae of Haemonchus contortus. The extract of P. ostreatus obtained the highest level of inhibition of eggs at 97.6% (1341 µg/mL) followed by P. pulmonarius (EPP) at 81.2% (774 µg/mL). The extract selected for evaluation against larvae was P. pulmonarius, showing no effect for L3 larvae, but for L4 larvae an immobility effect of 56.93% was observed at 900 µg/mL. The protein profile showed the presence of 23 protein bands in the extract. The crude extract of P. pulmonarius showed degradation of tissues both inside the eggs and larvae L1. Metabolites produced by Pleurotus mushrooms can consider using in agriculture sustainable by utilizing in producing of ovicidal and larvicidal against H. contortus instead of chemical compounds.

A Qualitative Analysis of the Perceptions of Stakeholders Involved in Vector Control and Vector-Borne Disease Research and Surveillance in Orinoquia, Colombia.

Colombia has a tropical climate and environmental conditions that favour the circulation of most of the known vector-borne diseases (VBDs). Protocols have been established and implemented to address the threats of these diseases, but they are for country-wide use and do not take into consideration the nuances of the different environments of the country. Almost the entire population is vulnerable to infection with one or more VBD. This study aims to characterise the perceptions and experiences of stakeholders involved in vector control and VBDs in the Orinoquia region in Colombia. Two panel discussions, and 12 semi-structured interviews, were conducted. Experts from the Colombian National Health Institute (INS), health secretaries from Meta, Guaviare and Vichada Departments, academic researchers, and individuals from private vector control companies participated. All sessions were recorded, transcribed, and translated, and then subject to thematic analysis. Three major themes emerged: involvement, limitations, and recommendations. Results showed that participants are engaged in vector surveillance activities, education, and vector control research. Participants focused on problems of disjointed efforts towards VBD control between health secretaries and the health ministry, as well as societal issues, such as socioeconomic, cultural, and political issues, which became the rationale for the lack of vector control resources. Responses in the panel discussions and interviews overlapped in opinions, and suggested that vector control could be improved through better communication between vector control bodies, strengthened engagement with vulnerable communities, more collaborative actions, and a more balanced distribution of resources.

Prevalencia de Metástasis torácicas en pacientes con cáncer de Tiroides en el Instituto Nacional de Cancerología entre 2016 y 2019, en Bogotá, Colombia / Prevalence of Thoracic Metastases in Patients with Thyroid Cancer at the National Cancer Institute between 2016 and 2019 in Bogotá, Colombia

RESUMEN Introducción: El cáncer de tiroides es la neoplasia endocrina más prevalente y el tercer tumor más frecuente en las mujeres colombianas. Tiene buen pronóstico en ausencia de metástasis. Los pulmones son el tejido más comprometido por metástasis en pa cientes con cáncer de tiroides. El objetivo del trabajo fue describir la prevalencia de las metástasis torácicas en pacientes con cáncer de tiroides en un centro de referencia en cáncer de la ciudad de Bogotá entre 2016 y 2019. Material y métodos: El estudio fue de corte transversal con muestreo no probabilístico de casos consecutivos en pacientes mayores de 18 años con cáncer de tiroides que asistieron a consulta externa de del Instituto Nacional de Cancerología entre 2016 y 2019. Resultados: Se incluyeron 241 pacientes; 53 presentaron metástasis torácicas. Dentro de los pacientes con metástasis el promedio de edad fue de 59,6 años (DE ± 12,7), 77,3% fueron mujeres, y el 90,5% presentó carcinoma papilar. La prevalencia de metástasis torácicas fue del 21,9%. Las comorbilidades más frecuentes fueron hipertensión arterial (32,08%). El síntoma más frecuente fue la disnea en un 15%. El 34% presentaron tirog lobulina mayor de 38 ng/mL y un 22% tenían anticuerpos antitiroglobulina detectables. Las variables asociadas a metástasis torácicas fueron la edad (p = 0,002), el peso (p = 0,019), adenopatías cervicales (p = 0,007), presencia de disnea (p = 0,004) y tiroglobulina mayor de 38 ng/mL (p < 0,001). La presencia de adenopatías cervicales se encontró en el 86% de los pacientes con metástasis, lo que sugiere que se trata de un marcador de riesgo de metástasis. Conclusiones: El presente estudio permite establecer datos locales, cuyos resultados promueven futuros estudios prospectivos que identifiquen variables asociadas y factores pronósticos en pacientes con cáncer de tiroides.

ABSTRACT Introduction: Thyroid cancer is the most prevalent endocrine neoplasm and the third most common tumor in Colombian women. It has a good prognosis in the absence of metastasis. The lungs are the most affected tissue by metastasis in patients with thyroid cancer. The objective of this work was to describe the prevalence of thoracic metastases in patients with thyroid cancer in a cancer reference hospital from Bogotá, between 2016 and 2019. Materials and methods: The study was cross-sectional, with non-probabilistic sampling of consecutive cases in patients older than 18 with thyroid cancer who were attended at the National Cancer Institute between 2016 and 2019. Results: 241 patients were included in the study; 53 had thoracic metastases. The mean age of patients with metastasis was 59.6 years (SD ± 12.7); 77.3% were female and 90.5% showed papillary carcinoma. The prevalence of thoracic metastases was 21.9%. The most common comorbidity was arterial hypertension (32.08%). The most common symptom was dyspnea, with 15%. 34% of patients had thyroglobulin of more than 38 ng/ml and 22% had detectable anti-thyroglobulin antibodies. Variables associated with thoracic metastases were age (p = 0.002), weight (p = 0.019), cervical adenopathies (p = 0.007), presence of dyspnea (p = 0.004), and thyroglobulin values greater than 38 ng/ml (p < 0.001). Cervical adenopathies were found in 86% of patients with metastasis, suggesting the fact that they are a risk marker for metastasis. Conclusions: This study allows us to establish local data, whose results promote future prospective studies that identify associated variables and prognostic factors in patients with thyroid cancer.

Systemic lupus erythematosus and antiphospholipid syndrome after COVID-19 vaccination. A case report.

Coronavirus disease 2019 (COVID-19) vaccines have some adverse effects, mostly mild. However, by presenting an immunological challenge to the individual, they could infrequently trigger immune-mediated diseases (IMDs). We report the case of a 42-year-old woman, with no previous medical history, who received the first dose of vaccine against COVID-19 and developed inflammatory arthralgias, associated with sudden-onset dyspnoea and hypoxemia. Pulmonary thromboembolism was documented, and the diagnosis of systemic lupus erythematosus (SLE) and secondary antiphospholipid syndrome (APS) was suspected. Autoantibodies were measured confirming this suspicion. After a few days, she presented a massive pericardial effusion with cardiac tamponade that required surgical management. Treatment with azathioprine, hydroxychloroquine, corticosteroids, and anticoagulation was indicated with improvement of all her symptoms. There is controversy regarding the potential of COVID-19 vaccines to induce autoimmunity. Studies addressing the safety of using these vaccines have reported the occurrence of mild local and systemic reactions, most frequently in young adults. So far, there are few reports of patients who have developed autoimmune or autoinflammatory diseases after getting vaccinated with any of the COVID-19 vaccines. To the best of our knowledge, to date, this is one of the first cases of new-onset SLE and secondary APS after COVID-19 vaccination.

Dinámicas comunitarias y gubernamentales sobre la malaria en Guaviare-Colombia / Community and governmental dynamics related to malaria in Guaviare-Colombia

OBJETIVO: El objetivo del estudio fue describir las dinámicas comunitarias y gubernamentales en torno a la malaria, su control y prevención en el Municipio de San José del Guaviare, en el departamento de Guaviare (Colombia). MÉTODOS: Se realizó un estudio de métodos mixtos utilizando una encuesta que constaba de 45 preguntas sobre conocimientos, actitudes y prácticas y entrevistas semiestructuradas con personal médico y trabajadores del gobierno. RESULTADOS: Aceptaron realizar la encuesta 103 personas, el 72% fueron mujeres, edad promedio de 40,8 años, tiene acueducto el 60% y alcantarillado 53,4%. El 59% reportó haber tenido malaria, 76% reconoció un mosquito como el vector de la enfermedad, 6% reconoce al Anopheles como el vector. El 16,5% de los encuestados asegura que la malaria no es un problema de salud para ellos y sus familias. El uso de toldillos (74%) es considerado una eficaz protección. CONCLUSIONES: Se evidencia un buen conocimiento de la malaria después de los acuerdos de paz, sin embargo, los determinantes relacionados con suministro de agua, alcantarillado, difícil atención en zona rural y las escasas acciones interdisciplinarias son posibles elementos de riesgo para esta población.

The objective of the study was to describe the community and government dynamics around malaria, especially its control and prevention, in the Municipality of San José del Guaviare, in the sector of Guaviare (Colombia). METHODS: We conducted a mixed methods study using a survey consisting of 45 questions on knowledge, attitudes, and practices, and semi-structured interviews with medical personnel and government workers. RESULTS: 103 people responded to the survey. 72% were women, and the average age was 40.8 years. 60% had an aqueduct and 53.4% had sewers. 59% reported having had malaria, 76% recognized a mosquito as the vector of the disease, and 6% recognized Anopheles as the vector. 16.5% of those surveyed said that malaria was not a health problem for them and their families. 74% considered the use of mosquito nets an effective protection. CONCLUSIONS: While there is a good knowledge of malaria, difficulties related to water supply, sewage, care in rural areas and lack of interdisciplinary solutions pose possible risk factors for this population.

Knowledges, attitudes and practice regarding malaria in a vulnerable municipality in Colombia / Predicción fisicomatemática de la dinámica semestral de la malaria en Antioquia, Colombia

Introduction: In Colombia, malaria affects people in vulnerable conditions. In urban areas, disease control measures have decreased the incidence of malaria in the past 5 years. However, there is some government abandonment in areas with armed conflict. Objective: To determine the knowledges, attitudes and practice regarding malaria in Piñalito, a town located in the municipality of Vista Hermosa in the Meta department (Colombia), in the period 2016-2017. Methods: We conducted a mixed-methods study using a survey consisting of 45 questions on knowledge, attitudes, and practices and semistructured interviews with medical personnel and government workers. Results: Of the respondents, 89.13% said that malaria is a health problem, 63.04% said the disease is transmitted by a mosquito bite, main symptoms were reported to be high fever (78.26%) and headache (60.87%). A total of 73.91% of respondents affirmed using mosquito nets to avoid the disease. The community affirmed that they do not receive good medical attention (65.22%) and did not identify the active participation of the local health secretary to prevent malaria. Conclusions: The inhabitants of Piñalito demonstrated adequate knowledge about the disease and positive attitudes toward preventing malaria. However, they had negative perceptions about the actions of the secretary of health and the government for control and prevention of the disease.

Introducción: En Colombia, la malaria afecta a personas en condiciones de vulnerabilidad. En áreas urbanas, las medidas de control de enfermedades han disminuido la incidencia de malaria en los últimos 5 años. Sin embargo, existe cierto abandono del gobierno en áreas con conflicto armado. Objetivo: Determinar los conocimientos, actitudes y prácticas sobre la malaria en la población del municipio de Piñalito (Meta, Colombia), en el periodo 2016-2017. Métodos: Realizamos un estudio de métodos mixtos utilizando una encuesta de 45 preguntas sobre conocimientos, actitudes y prácticas de la población y entrevistas semiestructuradas con personal médico y trabajadores del gobierno. Resultados: De los encuestados, el 89,13 % dijo que la malaria es un problema de salud, el 63,04 % considera que la enfermedad se transmite por la picadura de un mosquito. Los síntomas principales fueron fiebre alta (78,26 %) y dolor de cabeza (60,87 %). El 73,91 % de los encuestados afirmó utilizar mosquiteros para evitar la enfermedad. La comunidad manifestó que no recibe buena atención médica (65,22 %) y no identificó la participación activa de la secretaría de salud local para prevenir la malaria. Conclusiones: Los habitantes de Piñalito demostraron un adecuado conocimiento sobre la enfermedad y actitudes positivas hacia la prevención de la malaria. Sin embargo, tenían percepciones negativas sobre las acciones de la secretaría de salud y del gobierno para el control y prevención de la enfermedad.

Bio-directed Chemical Study of Pleurotus ostreatus Spent Substrate and Its Nematicidal Activity.

PURPOSE: In the present study, the nematicidal activity of the chemical fractionation of the spent substrate of the edible mushroom Pleurotus ostreatus against eggs and L3 larvae of Haemonchus contortus was evaluated. METHODS: The hydroalcoholic extract of the spent substrate was subjected to a bipartition with ethyl acetate giving two fractions: one aqueous (F. Ac) and one organic (F. AcOET). Both fractions were evaluated against eggs and L3 larvae at different concentrations (5, 2.5, 1.25, 0.625 and 0.3125 mg/mL) and 2% methanol, PBS and thiabendazole (5 mg/mL) as controls. Chemical fractionation of F. AcOET was performed in open column chromatography where 76 fractions were obtained and when analyzed by thin layer chromatography (TLC) were grouped into 11 mixtures (R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11). These mixtures were evaluated at 10 mg/mL against eggs and L3 larvae. The data obtained were analyzed by ANOVA and a Tukey test in the SAS V9 program. RESULTS: The results showed that, in the evaluation of F. AcOET and F. Ac, for the inhibition of egg hatching, the highest percentages were 78.80 and 76.89% at 5 mg/mL, respectively. As for the percentage of larval mortality, F. AcOET obtained 60.91 and F. Ac 29.77% at 5 mg/mL. The results of the evaluations of the mixtures showed that mixtures R4, R5 obtained 100 and 95.41% larval mortality and mixtures R6 and R7 presented 100% inhibitory activity of egg hatching, so these were analyzed by gas chromatography mass spectrometry finding compounds such as vanillin, ß-sitosterol, ρ-methyl ρ-hydroxycinnamate and ρ-hydroxybenzaldehyde. CONCLUSION: The results of the present study demonstrate that the spent substrate of P. ostreatus has potential anthelmintic activity against H. contortus. Moreover, by reusing and taking advantage of this substrate, its environmental pollution effects can be reduced.

Spatio-temporal clusters and patterns of spread of dengue, chikungunya, and Zika in Colombia.

BACKGROUND: Colombia has one of the highest burdens of arboviruses in South America. The country was in a state of hyperendemicity between 2014 and 2016, with co-circulation of several Aedes-borne viruses, including a syndemic of dengue, chikungunya, and Zika in 2015. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the cases of dengue, chikungunya, and Zika notified in Colombia from January 2014 to December 2018 by municipality and week. The trajectory and velocity of spread was studied using trend surface analysis, and spatio-temporal high-risk clusters for each disease in separate and for the three diseases simultaneously (multivariate) were identified using Kulldorff's scan statistics. During the study period, there were 366,628, 77,345 and 74,793 cases of dengue, chikungunya, and Zika, respectively, in Colombia. The spread patterns for chikungunya and Zika were similar, although Zika's spread was accelerated. Both chikungunya and Zika mainly spread from the regions on the Atlantic coast and the south-west to the rest of the country. We identified 21, 16, and 13 spatio-temporal clusters of dengue, chikungunya and Zika, respectively, and, from the multivariate analysis, 20 spatio-temporal clusters, among which 7 were simultaneous for the three diseases. For all disease-specific analyses and the multivariate analysis, the most-likely cluster was identified in the south-western region of Colombia, including the Valle del Cauca department. CONCLUSIONS/SIGNIFICANCE: The results further our understanding of emerging Aedes-borne diseases in Colombia by providing useful evidence on their potential site of entry and spread trajectory within the country, and identifying spatio-temporal disease-specific and multivariate high-risk clusters of dengue, chikungunya, and Zika, information that can be used to target interventions.

Desarrollo de las reflexiones metapragmáticas sobre la función de la ironía verbal en adolescentes

Objetivo. Analizar las reflexiones metapragmáticas que presentan 32 adolescentes de 12 y 15 años de edad (16 por grupo etario) sobre la función de la ironía verbal en dos tipos de actos de habla: agradecimiento y ofrecimiento irónicos. Método. Los participantes se enfrentaron a ocho historias que terminaban con una expresión irónica y mediante un guion de preguntas se indagó sobre las funciones que les atribuían a los enunciados irónicos. Resultados. Se muestran diferencias significativas debidas a la edad, pero no al tipo de enunciado en las reflexiones que hacen los adolescentes, lo que confirma que la capacidad para hacer reflexiones metapragmáticas sobre la ironía verbal se desarrolla de manera muy tardía en el lenguaje infantil.

Objective. Analyse metapragmatic reflections made by adolescents aged 12 and 15 years old (16 per age group) on the functions of verbal irony, in two types of ironic speech acts: ironic thanking and ironic offering. Method. The participants faced eight stories ending with ironic remarks, and through questioning, they were asked about the functions they attributed to the ironic statements. Results. Significant differences are shown due to age, but none related to the type of statement, which confirms that the ability to make metapragmatic reflections on verbal irony develops late in children's language.

A Review of Mammarenaviruses and Rodent Reservoirs in the Americas.

In the Americas, infectious viral diseases caused by viruses of the genus Mammarenavirus have been reported since the 1960s. Such diseases have commonly been associated with land use changes, which favor abundance of generalist rodent species. In the Americas-where the rates of land use change are among the highest worldwide-at least 1326 of all 2277 known rodent species have been reported. We conducted a literature review of studies between 1960 and 2020, to establish the current and historical knowledge about genotypes of mammarenaviruses and their rodent reservoirs in the Americas. Our overall goal was to show the importance of focusing research efforts on the American continent, since the conditions exist for future viral hemorrhagic fever (VHF) outbreaks caused by rodent-borne viruses, in turn, carried by widely distributed rodents. We found 47 species identified down to the species level, and one species identified only down to the genus level (Oryzomys sp.), reported in the Americas as reservoirs of mammarenaviruses, most these are ecological generalists. These species associate with 29 genotypes of Mammarenavirus, seven of which have been linked to VHFs in humans. We also highlight the need to monitor these species, in order to prevent viral disease outbreaks in the region.

A Review of the Impact of Climate Change on the Epidemiology of Gastrointestinal Nematode Infections in Small Ruminants and Wildlife in Tropical Conditions.

Climate change is causing detrimental changes in living organisms, including pathogens. This review aimed to determine how climate change has impacted livestock system management, and consequently, what factors influenced the gastrointestinal nematodes epidemiology in small ruminants under tropical conditions. The latter is orientated to find out the possible solutions responding to climate change adverse effects. Climate factors that affect the patterns of transmission of gastrointestinal parasites of domesticated ruminants are reviewed. Climate change has modified the behavior of several animal species, including parasites. For this reason, new control methods are required for controlling parasitic infections in livestock animals. After a pertinent literature analysis, conclusions and perspectives of control are given.

Excess all-cause mortality and COVID-19-related mortality: a temporal analysis in 22 countries, from January until August 2020.

BACKGROUND: This study aimed to investigate overall and sex-specific excess all-cause mortality since the inception of the COVID-19 pandemic until August 2020 among 22 countries. METHODS: Countries reported weekly or monthly all-cause mortality from January 2015 until the end of June or August 2020. Weekly or monthly COVID-19 deaths were reported for 2020. Excess mortality for 2020 was calculated by comparing weekly or monthly 2020 mortality (observed deaths) against a baseline mortality obtained from 2015-2019 data for the same week or month using two methods: (i) difference in observed mortality rates between 2020 and the 2015-2019 average and (ii) difference between observed and expected 2020 deaths. RESULTS: Brazil, France, Italy, Spain, Sweden, the UK (England, Wales, Northern Ireland and Scotland) and the USA demonstrated excess all-cause mortality, whereas Australia, Denmark and Georgia experienced a decrease in all-cause mortality. Israel, Ukraine and Ireland demonstrated sex-specific changes in all-cause mortality. CONCLUSIONS: All-cause mortality up to August 2020 was higher than in previous years in some, but not all, participating countries. Geographical location and seasonality of each country, as well as the prompt application of high-stringency control measures, may explain the observed variability in mortality changes.

Nematocidal activity of hydroalcoholic extracts of spent substrate of Pleurotus djamor on L3 larvae of Haemonchus contortus.

The objective of this study was to evaluate and compare the in vitro lethal effect of the hydroalcoholic extract of the spent substrate of Pleurotus djamor ECS-123, obtained at 15 days of colonization (SPS) and at the first (SPS1) and second (SPS2) harvests, against infective larvae L3 of Haemonchus contortus. The in vitro lethal effect was evaluated by the L3 larval mortality test (LM) using six concentrations: 1.25, 2.5, 5, 10, 20, and 40 mg/mL, with ivermectin and thiabendazole (5 mg/mL) as controls. The first harvest extract (SPS1) of strain ECS-123 was subjected to liquid-liquid bipartition, which resulted in two fractions: aqueous (PdAcO) and ethyl acetate (PdAct). The chemical fractionation of PdAct with the highest mortality rate (80.11 %) was carried out with open-column chromatography, giving a total of 13 fractions, which were analyzed by thin-layer chromatography (TLC) and grouped into 5 mixtures (R1;1-3, R2;4-7, R3;8-9, R4;10-11 and R5;12-13). Subsequently, the mixtures were evaluated against H. contortus L3 larvae. Finally, the components of the mixtures with the highest nematocidal effects were evaluated by gas chromatography coupled to mass spectrometry (GC-MS). The data were analyzed with a completely randomized design through ANOVA using the generalized linear model (GLM) with the "R" program. The purification and characterization of R4 and R5 by GC-MS revealed the presence of the following compounds: veratryl alcohol, 4-hydroxy-3,5,5 trimethyl-4-[3-oxo-1-butenyl]-2- cyclohexen-1-one, caffeine and 5,6-dimethoxy-1(3 H) isobenzofuranone. This information allowed for the identification of nematocidal compounds in the degraded substrate of P. djamor, an activity that had not been reported previously.

The effect of a toothpaste containing oleanolic acid in reducing plaque and gingivitis: a proof-of-concept randomized trial.

OBJECTIVES: To assess the safety and efficacy of an oleanolic acid (OA)-containing toothpaste in reducing gingival inflammation and plaque in patients with gingivitis. METHODS: This proof-of-concept parallel, double-blind, randomized controlled clinical trial included 99 patients. Following a 1-week washout, patients were randomized into three groups: OA group (fluoride toothpaste containing 0.1% OA and placebo mouthwash); negative control (fluoride toothpaste and placebo mouthwash); and CHX group (fluoride toothpaste and 0.12% chlorhexidine mouthwash). Patients were clinically assessed at inclusion, pre-washout visit, baseline and after 4 days, 1 week and 2 weeks of twice-daily use of the products. Patients received a diary for documentation of bleeding on brushing and provided unstimulated saliva samples. RESULTS: After two weeks, all groups showed significant reductions in all clinical parameters. The CHX group exhibited significantly greater reductions in gingival index and interproximal gingival index scores at week 2, as compared to patients in the negative control (p = 0.04). In contrast, reductions in gingival index scores did not differ between CHX and OA groups and between OA and negative control groups at week 2. The CHX group had significantly greater reductions in plaque index scores at day-4, 1-week and 2-week evaluations, as compared to the negative control and OA groups. The frequency of adverse events was similar among the groups. None of the groups reduced salivary transferrin levels. Finally, the OA group had the lowest percentage of self-reported bleeding events. CONCLUSION: OA toothpaste failed to provide antiplaque and antigingivitis effects superior to those of a fluoride toothpaste after 2 weeks of use.

In vitro Evaluation of the Nutraceutical Potential of Theobroma cacao pod Husk and Leaf Extracts for Small Ruminants.

PURPOSE: Some agroindustrial by-products could be used as nutraceutical materials for small ruminants helping with their nutrition while controlling their gastrointestinal nematodes. This study evaluated the potential in vitro nutraceutical value of pod husks and leaves of three varieties of Theobroma cacao using two Haemonchus contortus isolates with different polyphenol susceptibility. METHODS: Leaves and husks from three T. cacao varieties (AZT, CAL and CEY) were evaluated for their bromatological composition, in vitro dry matter digestibility and polyphenol content. Acetone:water extracts (70:30) of each plant variety were evaluated using the egg hatch and larval exsheathment inhibition tests, using two isolates (FESC and PARAISO) of H. contortus. Effective concentrations 50% (EC50) were determined for both tests. The role of polyphenols was confirmed using polyvinylpolypyrrolidone. L3 exposed to CAL leaf extract were submitted to transmission electron microscopy. RESULTS: Both plant materials showed a good nutritional value to complement protein-rich diets for small ruminants. Extracts inhibited exsheathment of H. contortus L3 more effectively than the egg hatching, and the leaf extracts were more active than husk extracts in the L3 exsheathment inhibition. The FESC isolate was more sensitive to extracts. Polyphenols blocked exsheathment inhibition of leaf extracts. Structural damage was observed in the sheath and muscles of L3 exposed to CAL leaf extracts. CONCLUSION: The two T. cacao materials tested showed their potential to be used as ruminant feeds. Extracts affected H. contortus by blocking L3 exsheathment, particularly with the leaf extracts. The in vivo nutraceutical value should be confirmed in small ruminants.

Assessing the reporting of Dengue, Chikungunya and Zika to the National Surveillance System in Colombia from 2014-2017: A Capture-recapture analysis accounting for misclassification of arboviral diagnostics.

BACKGROUND: Chikungunya, dengue, and Zika are three different arboviruses which have similar symptoms and are a major public health issue in Colombia. Despite the mandatory reporting of these arboviruses to the National Surveillance System in Colombia (SIVIGILA), it has been reported that the system captures less than 10% of diagnosed cases in some cities. METHODOLOGY/PRINCIPAL FINDINGS: To assess the scope and degree of arboviruses reporting in Colombia between 2014-2017, we conducted an observational study of surveillance data using the capture-recapture approach in three Colombian cities. Using healthcare facility registries (capture data) and surveillance-notified cases (recapture data), we estimated the degree of reporting by clinical diagnosis. We fit robust Poisson regressions to identify predictors of reporting and estimated the predicted probability of reporting by disease and year. To account for the potential misclassification of the clinical diagnosis, we used the simulation extrapolation for misclassification (MC-SIMEX) method. A total of 266,549 registries were examined. Overall arboviruses' reporting ranged from 5.3% to 14.7% and varied in magnitude according to age and year of diagnosis. Dengue was the most notified disease (21-70%) followed by Zika (6-45%). The highest reporting rate was seen in 2016, an epidemic year. The MC-SIMEX corrected rates indicated underestimation of the reporting due to the potential misclassification bias. CONCLUSIONS: These findings reflect challenges on arboviruses' reporting, and therefore, potential challenges on the estimation of arboviral burden in Colombia and other endemic settings with similar surveillance systems.

Isolation of pure Trichostrongylus colubriformis strains from naturally infected sheep using two methodologies.

Two methodologies were tested to isolate pure Trichostrongylus colubriformis strains from naturally infected sheep. Also, the in vitro susceptibility status to commercial anthelmintic (AH) drugs was determined in these strains. These methods were performed in a tropical region of Mexico where naturally infected sheep and goats host Haemonchus contortus, T. colubriformis and Oesophagostomum columbianum. For the first strain, a group of 6 naturally infected lambs from the "Paraiso" farm were treated with closantel (subcutaneous (SC), 10 mg/kg). On day 10 post-treatment, the eggs per gram (EPG) of faeces were determined with the McMaster technique. The faeces from the two lambs with the highest EPG were used for coprocultures (4 days, 28 °C). The L3 larvae were recovered and identified as T. colubriformis (69%) and O. columbianum (31%). The latter was removed by 10-day refrigeration (4-5 °C) followed by sieving (25 µm), resulting in 100% T. colubriformis (PARAISO strain). The second strain was isolated using repeated doses of levamisole (LEV, SC 7.5 mg/kg) in an 8-year-old sheep. The sheep had 1700 EPG before the LEV treatments and maintained 1300 EPG after both LEV treatments (day 10). The coproculture (4 days, 28 °C) after the second treatment contained 100% T. colubriformis (FMVZ-UADY strain). The in vitro AH susceptibility was determined using the egg hatch test for benzimidazole (BZ), and the larval migration inhibition test for ivermectin (IVM) and LEV. The PARAISO strain was BZ- and LEV-susceptible, and IVM-resistant. Meanwhile, the FMVZ-UADY strain was BZ- and IVM-susceptible, and LEV-resistant. The conditions where these two protocols could be used in other parts of the world were discussed.

Machine learning and dengue forecasting: Comparing random forests and artificial neural networks for predicting dengue burden at national and sub-national scales in Colombia.

The robust estimate and forecast capability of random forests (RF) has been widely recognized, however this ensemble machine learning method has not been widely used in mosquito-borne disease forecasting. In this study, two sets of RF models were developed at the national (pooled department-level data) and department level in Colombia to predict weekly dengue cases for 12-weeks ahead. A pooled national model based on artificial neural networks (ANN) was also developed and used as a comparator to the RF models. The various predictors included historic dengue cases, satellite-derived estimates for vegetation, precipitation, and air temperature, as well as population counts, income inequality, and education. Our RF model trained on the pooled national data was more accurate for department-specific weekly dengue cases estimation compared to a local model trained only on the department's data. Additionally, the forecast errors of the national RF model were smaller to those of the national pooled ANN model and were increased with the forecast horizon increasing from one-week-ahead (mean absolute error, MAE: 9.32) to 12-weeks ahead (MAE: 24.56). There was considerable variation in the relative importance of predictors dependent on forecast horizon. The environmental and meteorological predictors were relatively important for short-term dengue forecast horizons while socio-demographic predictors were relevant for longer-term forecast horizons. This study demonstrates the potential of RF in dengue forecasting with a feasible approach of using a national pooled model to forecast at finer spatial scales. Furthermore, including sociodemographic predictors is likely to be helpful in capturing longer-term dengue trends.