Deleterious action of azadirachtin against the mutualistic fungus of leaf-cutting ants

Leaf-cutting ants have a beneficial and obligatory relationship with the fungus that they grow. This mutualism allowed the evolutionary success of these ants. The great defoliation capacity of these insects, which often exceeds the level of tolerable economic damage, includes them as severe pests in many cultures. However, given the close relationship between these two agents of mutualism, it is expected that an impact on the fungus will reflect on the performance of the colony as a whole. Therefore, the effect of azadirachtin on the development, and the macronutrient composition of Leucoagaricus gongylophorus was evaluated. Azadirachtin reduced the final fungal mass at the end of treatment at all concentrations tested, but did not reduce the final growth area. A reduction in the amount of hyphae produced with increasing azadirachtin concentration was also observed. Regarding macronutrients, the compound did not affect their total amount in the fungus. Thus, it is observed that azadirachtin did not alter the composition of L. gongylophorus macronutrients, but inhibited its growth by reducing the number of hyphae produced. This reduction reflects directly on the amount of nutrients offered to the workers and the queen and may improve the management of these insects.     

Next‐generation sequencing for the diagnosis of MYH9‐RD: Predicting pathogenic variants

The heterogeneous manifestations of MYH9‐related disorder (MYH9‐RD), characterized by macrothrombocytopenia, Döhle‐like inclusion bodies in leukocytes, bleeding of variable severity with, in some cases, ear, eye, kidney, and liver involvement, make the diagnosis for these patients still challenging in clinical practice. We collected phenotypic data and analyzed the genetic variants in more than 3,000 patients with a bleeding or platelet disorder. Patients were enrolled in the BRIDGE‐BPD and ThromboGenomics Projects and their samples processed by high throughput sequencing (HTS). We identified 50 patients with a rare variant in MYH9. All patients had macrothrombocytes and all except two had thrombocytopenia. Some degree of bleeding diathesis was reported in 41 of the 50 patients. Eleven patients presented hearing impairment, three renal failure and two elevated liver enzymes. Among the 28 rare variants identified in MYH9, 12 were novel. HTS was instrumental in diagnosing 23 patients (46%). Our results confirm the clinical heterogeneity of MYH9‐RD and show that, in the presence of an unclassified platelet disorder with macrothrombocytes, MYH9‐RD should always be considered. A HTS‐based strategy is a reliable method to reach a conclusive diagnosis of MYH9‐RD in clinical practice.     

Transfusion in Sickle cell disease: best practice and understanding of its utility

Transfusion therapy remains an important treatment modality for patients with sickle cell disease (SCD). Transfusions are given not only to treat symptomatic anaemia, but also to decrease SCD‐related complications by lowering the percentage of circulating sickle red cells, thus decreasing blood viscosity and vaso‐occlusion. The strongest evidence of the effectiveness of transfusion is in primary and secondary stroke prophylaxis, where transfusion reduces the risk of overt stroke by about 90–70%, and in pre‐operative transfusion, where transfusion reduces the risk of acute chest syndrome by at least 30%. Most other indications for transfusion in SCD are based on expert opinion or less well‐controlled studies. In this brief overview, we discuss methods of transfusion, the evidence and expert opinion regarding various indications in sickle cell disease and our current pathophysiologic understanding of how transfusions may work in SCD.     

Hippocampal degeneration in patients with amyotrophic lateral sclerosis

There is increasing appreciation of non-motor system involvement in amyotrophic lateral sclerosis (ALS), although its full extent and clinical significance remains to be established. This study tested the hypothesis that memory impairment in patients with ALS is related to hippocampal degeneration. Consecutive patients with ALS (58) and 29 matched controls participated in standardized neuropsychological assessment and magnetic resonance imaging. Patients with ALS performed worse in global cognitive functioning and executive and verbal memory tests (p < 0.05). The hippocampus was manually segmented in each hemisphere, and volumes were calculated with correction for intracranial volume. Analysis of covariance, controlled for the effect of age and education years, showed significantly smaller hippocampal volume on the right (p = 0.004) in patients with ALS. Verbal memory test performance correlated with the left hippocampal volume in patients with ALS (p < 0.05), although there was no significant correlation with tests of executive function and clinical variables underscoring the specificity of the present findings. Hippocampal volume loss and its correlation with the severity of verbal memory impairment highlight significant hippocampal involvement which can occur as a non-motor deficit in patients with ALS.     

Clustering of body composition,blood pressure and physical activity in Portuguese families

Aim: The purposes of this study were: (i) to identify familial resemblances in body fat, blood pressure (BP) and total physical activity (TPA); (ii) to estimate the magnitude of their genetic and environmental influences; and (iii) to investigate shared familial aggregation among these phenotypes.

Subjects and methods: The sample comprised 260 nuclear families from Portugal. Body fat was assessed by bioelectrical impedance. BP was measured by an oscillometric device. TPA was estimated by the Baecke questionnaire. Familial correlation analyses were performed using Generalized Estimating Equations. Quantitative genetic modelling was used to estimate maximal heritability, genetic and environmental correlations.

Results: Familial intra-trait correlations ranged from 0.15–0.38. Genetic and common environmental factors explained from 30%--44% of fat mass depots and BP and 24% of TPA. Genetic correlations were significant between BP and the fat mass traits (p?p?Conclusions: The results suggest familial resemblance in the variation of body fat, BP and TPA, showing partial pleiotropic effects in the variation in body fat phenotypes and BP. TPA only shares common environmental influences with BP and body fat traits.     

Micromorphology of the Dental Pulp Is Highly Preserved in Cancer Patients Who Underwent Head and Neck Radiotherapy

Introduction

Teeth are often included in the radiation field during head and neck radiotherapy, and recent clinical evidence suggests that dental pulp is negatively affected by the direct effects of radiation, leading to impaired sensitivity of the dental pulp. Therefore, this study aimed to investigate the direct effects of radiation on the microvasculature, innervation, and extracellular matrix of the dental pulp of patients who have undergone head and neck radiotherapy.

Methods

Twenty-three samples of dental pulp from patients who finished head and neck radiotherapy were analyzed. Samples were histologically processed and stained with hematoxylin-eosin for morphologic evaluation of the microvasculature, innervation, and extracellular matrix. Subsequently, immunohistochemical analysis of proteins related to vascularization (CD34 and smooth muscle actin), innervation (S-100, NCAM/CD56, and neurofilament), and extracellular matrix (vimentin) of the dental pulp was performed.

Results

The morphologic study identified preservation of the microvasculature, nerve bundles, and components of the extracellular matrix in all studied samples. The immunohistochemical analysis confirmed the morphologic findings and showed a normal pattern of expression for the studied proteins in all samples.

Conclusions

Direct effects of radiotherapy are not able to generate morphologic changes in the microvasculature, innervation, and extracellular matrix components of the dental pulp in head and neck cancer patients.     

Photodynamic therapy of tumours with hexadecafluoro zinc phthalocyanine formulated in PEG-coated poly(lactic acid) nanoparticles

Hexadecafluoro zinc phthalocyanine (ZnPcF₁₆), a second-generation sensitizer for the photodynamic therapy (PDT) of cancer, was formulated in polyethylene-glycol-coated poly(lactic acid) nanoparticles (PEG-coated PLA-NP) and tested in EMT-6 tumour-bearing mice for its photodynamic activity. The tumour response was compared to that induced by the same dye formulated as a Cremophor EL (CRM) emulsion. Formulation in the biodegradable NP improved PDT response of the tumour while providing prolonged tumour sensitivity towards PDT. © 1996 Wiley-Liss, Inc.     

POTENTIAL FALSE-POSITIVE RESULTS WITH ANTIGEN ENHANCEMENT FOR IMMUNOHISTOCHEMISTRY OF THE p53 GENE PRODUCT IN COLORECTAL NEOPLASMS

Aberrant crypt foci (ACF) are putative precursor lesions of colon cancer, recently identified on the methylene blue-stained mucosal surface of human colon. No mutations in K- ras or p53 genes were found by non-radioactive single-strand conformation polymorphism analysis in 14 ACF collected from five patients. Using the more sensitive method of allele-specific polymerase chain reaction (PCR) for K- ras , 8 of 14 ACF were found to contain K- ras mutations, suggesting that mutated cells are present in minute clones in ACF. No dysplasia was observed in any of the ACF containing a mutated clone. The presence of K- ras mutations in ACF suggests that these lesions occur at a very early stage in human colorectal carcinogenesis.