Enhancing chlamydospore production in Duddingtonia flagrans on solid substrate: The impact of mannitol and varied cultivation conditions.

Duddingtonia flagrans is a nematophagous fungus which has shown promising results as a non-chemical parasitic control tool. The fungus disrupts the parasite's life cycle by trapping larvae in the environment through the networks generated from chlamydospores, thus preventing the reinfection of animals. One barrier to the development of a commercial product using this tool is the need to increase chlamydospore production in the laboratory for its administration to livestock. The purpose of this study was to evaluate the addition of mannitol to an enriched culture medium and the effect of adverse cultivation conditions on chlamydospore production. D. flagrans was cultivated on Petri dishes with corn agar for 4 weeks at 27 °C and 70% relative humidity (RH). Four groups were then formed, all with Sabouraud agar as a base, to which different growth inducers were added: GSA (glucose Sabouraud agar), GSA-MI (glucose Sabouraud agar + meso inositol), GSA-E (enriched glucose Sabouraud agar), and AE-M (enriched agar + mannitol). After 4 weeks, chlamydospores were recovered by washing the surface of each plate with distilled water and then quantified. The medium that yielded the highest amount of chlamydospores was subjected to different cultivation conditions: NC (normal conditions): 70% RH and 27 °C, AC (adverse conditions) 1: 20% RH and 40 °C, CA2: 60% RH and 27 °C, and CA3: 55% RH and 24 °C. It was determined that mannitol increases chlamydospore production (65x106 chlamydospores/plate), and when reducing humidity by 10% under cultivation conditions it resulted in an approximately 10% increase in chlamydospore production compared to the control group. These results suggest that the addition of polyols, as well as its cultivation under certain environmental conditions, can improve chlamydospore production on a laboratory scale.

Real-life analysis on safety and efficacy of asciminib for ponatinib pretreated patients with chronic myeloid leukemia.

Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.

Effect of macrocyclic lactones on nontarget coprophilic organisms: a review.

Macrocyclic lactones are frequently used dewormers in livestock farms around the world. Due to their wide spectrum of action against nematodes and arthropods and their practicality of application at very low doses, their use has become massive since their discovery. These compounds are eliminated in a large percentage in the feces of animals, causing adverse effects on coprophilic fauna. Several research groups around the world have been devoted to evaluating these effects on this fauna. The aim of this review is to register the adverse effects of the concentrations in which macrocyclic lactones are eliminated in the feces of domestic animals and the importance of the coprophilic and edaphilous fauna on the degradation of the feces of the animals. The documented data shows that the use of macrocyclic lactones has a high toxicological risk for the different species that colonize the dung, thus causing an adverse effect on its disintegration and its subsequent incorporation into the soil. Even so, more studies at the regional level and their standardization are necessary to make the comparison between different areas possible.

Lack of negative effects of the biological control agent Duddingtonia flagrans on soil nematodes and other nematophagous fungi.

The possible environmental effects of the massive use of Duddingtonia flagrans for controlling sheep nematodes were evaluated in two regions. Non-supplemented faeces and faeces from sheep supplemented with D. flagrans were deposited three times on pasture plots and samples were collected 7 and 14 days post-deposition. Samples were cultured in agar-water (2%) with Panagrellus spp. to recover D. flagrans and other nematophagous fungi, and soil nematodes were extracted using Baermann funnels and counted. No significant differences in the populations of soil nematodes and fungi colonizing sheep faeces (P > 0.05) were observed between supplemented and non-supplemented groups, except in one sample. The topsoil in contact with the faeces was sampled 1-4 months post-deposition, revealing that, with one exception, D. flagrans did not persist in soil beyond 2 months post-deposition. Duddingtonia flagrans does not affect faecal colonization by other fungi and soil nematodes and, once deployed on pasture, does not survive for long periods in the environment.

The use of soy protein polymers as a release device for nematophagous fungi in the control of parasitic nematodes in ruminants.

This trial was conducted to evaluate the predatory activity of Duddingtonia flagrans incorporated into soy protein-based polymers as a controlled-release device (CRD). The rate of fungal release from the polymers and time of residence of the CRD in the rumen of a cannulated sheep was also determined. After administration to the sheep, the CRD was extracted at weekly intervals over a month for observation of its physical structure and faeces were collected to observe the subsequent predatory activity of the fungus in Petri dishes with water-agar 2% and Panagrellus spp. as bait. The CRD slowly degraded in the rumen over 4 weeks and liberated D. flagrans into the faeces. The formulation of the soy protein-based polymers did not affect the predatory activity of the fungus. The study demonstrates that biodegradable soy protein polymers could potentially improve the use of nematophagous fungi for controlling nematode parasites of ruminants.

Experimental demonstration of lossy mode resonance generation for transverse-magnetic and transverse-electric polarizations.

This Letter, presents the fabrication of lossy mode resonance (LMR) devices based on titanium dioxide (TiO2)/ poly(sodium 4-styrenesulfonate) (PSS) coatings deposited on side-polished D-shaped optical fibers. TiO2 thin films have been obtained by means of the layer-by-layer (LbL) self-assembly technique. LbL enables us to produce smooth and homogeneous coatings on the polished side of the fiber. This permits us to couple light from the waveguide to the TiO2-coating/external medium region at specific wavelength ranges. The generation of LMRs depends on the coating thickness, so that thicker coatings can produce more resonances. LMRs are sensitive to the external medium refractive index, which allows its utilization as refractometers. The characteristic D-shaped architecture of the devices employed in this Letter enables us to distinguish TE and TM polarizations, which had not been possible before with regular optical fibers due to their cylindrical symmetry. The results presented here show for the first time the experimental demonstration of the generation of LMRs produced by both TM and TE polarizations. More specifically, for these TiO2/PSS thin films, the TM and TM modes of the LMRs show a wavelength shift of 226 nm for the first-order LMR and 56 nm for the second-order LMR.

Is there a change in cytomegalovirus seroepidemiology in Spain?

The aim of this paper is to compare the seroprevalence of cytomegalovirus (CMV) in women in the Autonomous Region of Madrid (ARM) obtained in two different years (1993 and 1999), according to age and seroprevalence of a virus transmitted by the faecal-oral route (hepatitis A virus, HAV) and another virus of respiratory transmission (varicella zoster virus, VZV). A total of 1813 serum samples were studied, taken from females aged 2-40 in two different serosurveys which were representative of the general population in the ARM. Of these, 933 were taken in 1993, and 880 in 1999. In each survey the samples were distributed over six groups, according to age group (2-5, 6-10, 11-15, 16-20, 21-30 and 31-40 years). CMV- and VZV-specific IgG was tested by indirect ELISA (Dade-Behring, Germany); and HAV-IgG by ImX (Abbott, USA) in the 1993 samples, or by Vidas (BioMérieux, France) in the case of those taken in 1999. A significant age-related rise in CMV seroprevalence was observed in both serosurveys. The seroprevalence obtained was lower in all age groups in 1999 than in 1993. The differences were statistically significant in two age groups: 6-10 years old (43.7 vs. 56.7%) and 31-40 years old (79.1 vs. 90.3%). In the younger age groups concurrent seroprevalence of CMV and VZV was significant lower in 1999. In older age groups a significant decrease in concurrent seroprevalence of both CMV and HAV was also seen. Agreement between serological results for CMV-HAV, CMV-VZV and HAV-VVZ during the two time periods and in every age group was poor or fair (kappa index < or = 0.2 or between 0.21 and 0.4) in all age groups. To conclude, a change in CMV epidemiology seems to be taking place in Madrid. The increase in the proportion of CMV seronegative women of childbearing age may have some impact on the incidence of congenital diseases related to vertical transmission of CMV. Apparently, such a change, among children, could be related to a lower close contact transmission rate (as in VZV), and among adults to improvements in standards of public health (as in HAV). However, due to the poor or fair agreement between serological results for CMV-HAV, CMV-VZV and HAV-VVZ, other independent factors may affect the fall in CMV seroprevalence.