Toxoplasma gondii, an obligate intracellular parasite, is the aetiological agent of toxoplasmosis, a disease that affects approximately 25% - 30% of the world's population. At present, no safe and effective vaccine exists for the prevention of toxoplasmosis. Current treatment options for toxoplasmosis are active only against tachyzoites and may also cause bone marrow toxicity. To contribute to the global search for novel agents for the treatment of toxoplasmosis, we herein report the in vitro activities of previously synthesised benzyltriazole derivatives. The effects of these compounds against T. gondii in vitro were evaluated by using a expressing green fluorescent protein (GFP) type I strain parasite (RH-GFP) and a type II cyst-forming strain of parasite (PruΔku80Δhxgprt). The frontline antitubercular drug isoniazid, designated as Frans J. Smit -isoniazid (FJS-INH), was also included in the screening as a preliminary test in view of future repurposing of this agent. Of the compounds screened, FJS-302, FJS-303, FJS-403 and FJS-INH demonstrated > 80% parasite growth inhibition with IC50 values of 5.6 µg/mL, 6.8 µg/µL, 7.0 µg/mL and 19.8 µg/mL, respectively. FJS-302, FJS-303 and FJS-403 inhibited parasite invasion and replication, whereas, sulphadiazine (SFZ), the positive control, was only effective against parasite replication. In addition, SFZ induced bradyzoite differentiation in vitro, whilst FJS-302, FJS-303 and FJS-403 did not increase the bradyzoite number. These results indicate that FJS-302, FJS-303 and FJS-403 have the potential to act as a viable source of antiparasitic therapeutic agents.

Tick-borne diseases (TBDs) caused by Theileria, Babesia, Anaplasma and Ehrlichia species are common in tropical and subtropical regions. In this study, we investigated the presence and genetic diversity of Theileria spp., Anaplasma ovis, B. ovis, E. ruminantium and Anaplasma spp. in sheep from the Machakos and Homa Bay counties of Kenya. In order to improve the diagnosis and control of ovine TBDs, a total of 76 blood samples from apparently healthy sheep were screened using a polymerase chain reaction (PCR). The assays were conducted using primers based on Theileria spp. 18S rRNA, Anaplasma ovis Major surface protein-4 (AoMSP4), B. ovis 18S rRNA, E. ruminantium pCS20 and Anaplasma spp. 16S rRNA. The overall infection rates for Theileria spp., A. ovis, E. ruminantium and Anaplasma spp. were 39/76 (51.3%), 26/76 (34.2%), 6/76 (7.9%) and 31/76 (40.8%), respectively. The overall co-infection was 47/76 (61.8%). All Theileria spp. positive samples were confirmed to be of Theileria ovis on sequencing. A phylogenetic analysis of the 18S rRNA gene sequences of T. ovis revealed that all isolates of this study clustered with T. ovis sequences extracted from the GenBank suggesting this gene is highly conserved. E. ruminantium pCS20 sequences were in the same clade on the phylogenetic tree. However, three AoMSP4 sequences from this study appeared in the same clade, while one sequence formed a separate branch revealing genetic divergence. The 16S rRNA sequencing revealed uncharacterised Anaplasma spp. and A. ovis. The phylogenetic analyses of the uncharacterised Anaplasma spp. revealed that the two sequences from this study appear in an independent clade from other sequences extracted from the GenBank. This study provides important information regarding the occurrence of tick-borne pathogens and their degree of genetic diversity among sheep in Kenya, which is useful for the diagnosis and control of TBDs.

Abstract Free vibration of a bimaterial circular nano-tube is investigated. The tube is formed by bonding together a Si3N4/SUS304 functionally graded upper semi tube and a ZrO2/Ti-6Al-4V functionally graded lower semi tube. The material properties of the tube are assumed to vary along the radius according to power law with the power index of upper semi tube differing from that of lower semi tube. Based on non-local elasticity theory and Hamilton’s principle, a refined beam model considering the effect of transverse shear deformation is used to derive the governing equations, then analytical solution is obtained by using a two-steps perturbation method. Our results were compared with the existing ones. The effects on tube’s linear and non-linear frequency are analyzed of the factors, including small scale parameter, temperature, the double volume fraction indexes, slenderness ratio and different types of beam model. A new approach is suggested in this article to change the natural frequency of the tubes by adjusting constituent materials. In contrast to conventional approach, the new one can result in more accurate frequency control in the same dimensionless size of tubes.

Summary Objective: Dermal papilla cells (DPCs) are located in the hair follicles and play an important role in hair growth. These cells have the ability to induce hair follicle formation when they display aggregative behavior. DPCs derived from the androgenetic alopecia (AGA) area undergo premature senescence in vitro, associated with p16INK4a expression. The aim of the current study was to investigate the expression of p16INK4a in aggregative and non-aggregative DPCs and the effect of p16INK4a down-regulation in these cells by adenovirus-mediated RNA interference (RNAi). Method: DPCs were isolated and cultured from healthy human scalp. p16INK4a gene and protein were detected in aggregative and non-aggregative cells. Expression of p16INK4a in DPCs was silenced by infection with rAd5-CDKN1A-1p2shRNA. Cell fate was monitored after infection. The growth of cells was measured by MTT assay. Cell cycle was evaluated by flow cytometry (FCM). Results: DPCs were isolated by digestion and showed aggregative behavior for six passages. The expression of p16INK4a showed a clear upward trend in non-aggregative cells when compared with aggregative group. p16INK4a expression was silenced by rAd5-CDKN1A-1p2shRNA (p<0.05). The p16INK4a-silenced cells grew more rapidly and exhibited a trend towards aggregative growth. There was an increase in the proportion of cells in G1 phase, while those in S phase were reduced after p16INK4a gene silencing (p<0.05). Conclusion: Our results suggest that p16INK4a plays an important role in the premature senescence and aggregative behavior of DPCs. These observations can lead to novel therapeutic strategies for treatment of AGA.

Abstract: Aflatoxin B1 (AFB1), produced by Aspergillus flavus and Aspergillus parasiticus, is one of the major mycotoxins to affect animal health. AFB1 contamination of aquafeed is widespread, especially in countries with humid, tropical climates. The most applied method for protecting animals against aflatoxicosis is the use of clay minerals. Growth performance, immunosuppressive effects (bactericidal activity, lysozyme activity, albumin/globulin ratio, alternative complement pathway activity, and protein content), and pathology parameters were used to evaluate the response of yellow catfish (Pelteobagrus fulvidraco) to increasing concentrations of AFB1 and test the protective effect of dietary supplementation with a bentonite (dioctahedral montmorillonite) based AFB1 binder. Triplicate groups of yellow catfish with an average weight of 2.0 ± 0.1 g were fed diets containing 0, 200, 500, and 1,000 μg/kg of AFB1 alone, or diets containing 0, 200, 500, and 1,000 μg/kg of AFB1 along with 2 g/kg AFB1 binder, for 12 weeks. Results showed that diets containing increasing amounts of AFB1 had a significantly lower (P = 0.002) survival rate. There was a statistical significant reduction in weight gain, final body weight, and specific growth rate, and an increase in feed conversion ratio (FCR) influenced by the levels of AFB1 in the diet (P < 0.001 for all parameters), as well as increasing protection due to the presence of the binder (P = 0.046, P = 0.014, P = 0.038, and P = 0.485, respectively). The immunosuppressive nature of AFB1 in yellow catfish diets was confirmed through observation of lower bactericidal activity (P = 0.001), lower lysozyme activity (P = 0.006), reduced total protein (P = 0.002), and enhanced albumin/globulin ratio (P = 0.004). Fish fed diets contaminated with AFB1 and supplemented with the AFB1 binder showed better improvement in FCR (P = 0.019). These results indicate that AFB1 has a negative impact on yellow catfish growth and survival rate. The AFB1 binder protected fish from the toxic effects of AFB1.

Resumen: La aflatoxina B1 (AFB1), producida por Aspergillus flavus y Aspergillus parasiticus, es una de las principales micotoxinas que afectan la salud animal. La contaminación de alimentos acuícolas con AFB1 es común, especialmente en países con climas húmedos y tropicales. El método más usado para proteger a los animales contra la aflatoxicosis es el uso de arcillas. Para evaluar la respuesta del bagre amarillo (Pelteobagrus fulvidraco) a concentraciones crecientes de AFB1 y evaluar el efecto protector de una bentonita (montmorillonita dioctaédrica), se analizaron el crecimiento, efectos inmunosupresores (actividad bactericida, relación albúmina/globulina, actividad de la lisozima, actividad de la vía alternativa del complemento y contenido de proteínas) y parámetros patológicos. Grupos triplicados de P. fulvidraco, con un peso promedio de 2.0 ± 0.1 g, fueron alimentados durante 12 semanas con dietas que contenían 0, 200, 500 y 1,000 μg/kg de AFB1 pura, o dietas que contiendan 0, 200, 500 y 1,000 μg/kg de AFB1 junto con 2 g/kg de bentonita. Los resultados mostraron que las dietas con mayores cantidades de AFB1 tenían una tasa de supervivencia significativamente menor (P = 0.002). Hubo una reducción estadísticamente significativa del aumento de peso, el peso corporal final y la tasa de crecimiento específico y un aumento de la tasa de conversión alimenticia debido a los niveles de AFB1 en la dieta (P < 0.001 para todos los parámetros), así como mayor protección por la presencia de la bentonita (P = 0.046, P = 0.014, P = 0.038 y P = 0.485, respectivamente). La naturaleza inmunosupresora de AFB1 en las dietas del bagre amarillo se confirmó mediante la observación de una menor actividad bactericida (P = 0.001), una menor actividad de la lisozima (P = 0.006), una disminución de la proteína total (P = 0.002) y una mayor relación albúmina/globulina (P = 0.004). Los peces alimentados con dietas contaminadas con AFB1 y complementadas con la bentonita mostraron una mejora de la tasa de conversión alimenticia (P = 0.019). Estos resultados indican que la AFB1 tiene un impacto negativo en el crecimiento del bagre amarillo y la tasa de supervivencia. La bentonita protegió a los individuos de los efectos tóxicos de la AFB1.

BACKGROUND: Prevention of childhood obesity is an international public health priority given the significant impact of obesity on acute and chronic diseases, general health, development and well-being. The international evidence base for strategies that governments, communities and families can implement to prevent obesity, and promote health, has been accumulating but remains unclear. OBJECTIVE: This review primarily aims to update the previous Cochrane review of childhood obesity prevention research and determine the effectiveness of evaluated interventions intended to prevent obesity in children, assessed by change in Body Mass Index (BMI). Secondary aims were to examine the characteristics of the programs and strategies to answer the questions "What works for whom, why and for what cost?" METHODS: Search methods: The searches were re-run in CENTRAL, MEDLINE, EMBASE, PsychINFO and CINAHL in March 2010 and searched relevant websites. Non-English language papers were included and experts were contacted. Selection criteria: The review includes data from childhood obesity prevention studies that used a controlled study design (with or without randomisation). Studies were included if they evaluated interventions, policies or programs in place for twelve weeks or more. If studies were randomized at a cluster level, six clusters were required. Data collection and analysis: Two review authors independently extracted data and assessed the risk of bias of included studies. Data was extracted on intervention implementation, cost, equity and outcomes. Outcome measures were grouped according to whether they measured adiposity, physical activity (PA)-related behaviours or diet-related behaviours. Adverse outcomes were recorded. A meta-analysis was conducted using available BMI or standardized BMI (zBMI) score data with subgroup analysis by age group (0-5, 6-12, 13-18 years, corresponding to stages of developmental and childhood settings). MAIN RESULTS: This review includes 55 studies (an additional 36 studies found for this update). The majority of studies targeted children aged v 6-12 years. The meta-analysis included 37 studies of 27,946 children and demonstrated that programmes were effective at reducing adiposity, although not all individual interventions were effective, and there was a high level of observed heterogeneity (I2 = 82%). Overall, children in the intervention group had a standardised mean difference in adiposity (measured as BMI or zBMI) of -0.15kg/m2 (95% confidence interval (CI): -0.21 to -0.09). Intervention effects by age subgroups were -0.26kg/m2 (95% CI -0.53 to 0.00) (0- 5 years), - 0.15 kg/m2 (95% CI -0.23 to -0.08) (6-12 years), and -0.09 kg/m2 (95% CI -0.20 to 0.03) (13-18 years). Heterogeneity was apparent in all three age groups and could not explained by randomisation status or the type, duration or setting of the intervention. Only eight studies reported on adverse effects and no evidence of adverse outcomes such as unhealthy dieting practices, increased prevalence of underweight or body image sensitivities was found. Interventions did not appear to increase health inequalities although this was examined in fewer studies. AUTHORS' CONCLUSIONS: We found strong evidence to support beneficial effects of child obesity prevention programmes on BMI, particularly for programmes targeted to children aged six to 12 years. However, given the unexplained heterogeneity and the likelihood of small study bias, these findings must be interpreted cautiously. A broad range of programme components were used in these studies and whilst it is not possible to distinguish which of these components contributed most to the beneficial effects observed, our synthesis indicates the following to be promising policies and strategies: school curriculum that includes healthy eating, physical activity and body image; increased sessions for physical activity and the development of fundamental movement skills throughout the school week; improvements in nutritional quality of the food supply in schools; environments and cultural practices that support children eating healthier foods and being active throughout each day; support for teachers and other staff to implement health promotion strategies and activities (e.g. professional development, capacity building activities); parent support and home activities that encourage children to be more active, eat more nutritious foods and spend less time in screen based activities. However, study and evaluation designs need to be strengthened, and reporting extended to capture process and implementation factors, outcomes in relation to measures of equity, longer term outcomes, potential harms and costs. Childhood obesity prevention research must now move towards identifying how effective intervention components can be embedded within health, education and care systems and achieve long term sustainable impacts.