Antibacterial activity of honey samples from Ukraine

The employment of natural substances such as beehive products with a preventive and therapeutic purpose has been a widespread custom since ancient times. In this investigation, the antibacterial activity of 41 honey samples from different Ukraine regions has been evaluated. For each honey, melissopalynological and physico-chemical analysis were performed in order to determine botanical origin, pH, glucose and fructose contents and free acidity. So, antibacterial activity against Staphylococcus aureus CCM 4223, Listeria monocytogenes ATCC 7644, Salmonella enterica serovar Typhimurium CCM 3807 and Escherichia coli ATCC 25922 was assessed through the determination of MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values by the microdilutions method. The results show that the most susceptible bacterial strain was L. monocytogenes. Its growth was inhibited at a honey concentration ranging from 0.094 to 0.188 g/mL. The most resistant bacterial strain was S. aureus. As concerns MBC values, L. monocytogenes was the most susceptible bacteria, while S. aureus was the most resistant. Helianthus spp. honeys was the most effective against all tested bacterial strains, followed by Robinia spp. and multifloral honeys. Promising results for MIC tests have been found for Brassica spp

Microbial profile of the ventriculum of honey bee (apis mellifera ligustica spinola, 1806) fed with veterinary drugs, dietary supplements and non-protein amino acids

The effects of veterinary drugs, dietary supplements and non-protein amino acids on the European honey bee (Apis mellifera ligustica Spinola, 1806) ventriculum microbial profile were investigated. Total viable aerobic bacteria, Enterobacteriaceae, staphylococci, Escherichia coli, lactic acid bacteria, Pseudomonas spp., aerobic bacterial endospores and Enterococcus spp. were determined using a culture-based method. Two veterinary drugs (Varromed® and Api-Bioxal®), two commercial dietary supplements (ApiHerb® and ApiGo®) and two non-protein amino acids (GABA and beta-alanine) were administered for one week to honey bee foragers reared in laboratory cages. After one week, E. coli and Staphylococcus spp. were significantly affected by the veterinary drugs (p < 0.001). Furthermore, dietary supplements and non-protein amino acids induced significant changes in Staphylococcus spp., E. coli and Pseudomonas spp. (p < 0.001). In conclusion, the results of this investigation showed that the administration of the veterinary drugs, dietary supplements and non-protein amino acids tested, affected the ventriculum microbiological profile of Apis mellifera ligustica

Site-specific abnormalities in the visual system of a mouse model of CDKL5 deficiency disorder

CDKL5 deficiency disorder (CDD) is a neurodevelopmental disorder characterized by a severe global developmental delay and early-onset seizures. Notably, patients show distinctive visual abnormalities often clinically diagnosed as cortical visual impairment. However, the involvement of cerebral cortical dysfunctions in the origin of the symptoms is poorly understood. CDD mouse models also display visual deficits, and cortical visual responses can be used as a robust biomarker in CDKL5 mutant mice. A deeper understanding of the circuits underlying the described visual deficits is essential for directing preclinical research and translational approaches. Here, we addressed this question in two ways: first, we performed an in-depth morphological analysis of the visual pathway, from the retina to the primary visual cortex (V1), of CDKL5 null mice. We found that the lack of CDKL5 produced no alteration in the organization of retinal circuits. Conversely, CDKL5 mutants showed reduced density and altered morphology of spines and decreased excitatory synapse marker PSD95 in the dorsal lateral geniculate nucleus and in V1. An increase in the inhibitory marker VGAT was selectively present in V1. Second, using a conditional CDKL5 knockout model, we showed that selective cortical deletion of CDKL5 from excitatory cells is sufficient to produce abnormalities of visual cortical responses, demonstrating that the normal function of cortical circuits is dependent on CDKL5. Intriguingly, these deficits were associated with morphological alterations of V1 excitatory and inhibitory synaptic contacts. In summary, this work proposes cortical circuit structure and function as a critically important target for studying CDD

Effect of honey and syrup diets enriched with 1,3-1,6 β-glucans on honeybee survival rate and phenoloxidase activity (Apis mellifera l. 1758)

β-glucans can activate the animal innate immune system by acting as immune-modulators and inducing various stimulatory effects. The aim of this study was to investigate the effect of 1,3-1,6 β-glucans administered orally for 96 h on Apis mellifera workers (newly emerged and nurse bees). β-glucans were included in honey and syrup. Survival rate and phenoloxidase activity were measured. In both newly emerged and nurse bees, β-glucans supplementation did not affect survival rate (p > 0.05). Conversely, phenoloxidase activity was higher in both newly emerged bees (p = 0.048) and nurse bees (p = 0.014) fed with a honey diet enriched with β-glucans compared to those fed with only honey. In both the newly emerged and nurse bees, no statistical differences in phenoloxidase activity were recorded between the group fed with a syrup-based diet enriched with β-glucans and the control group (p > 0.05). The absence of significant variation in survival suggests that the potential negative effect of β-glucans in healthy bees could be mitigated by their metabolism. Conversely, the inclusion of β-glucans in a honey-based diet determined an increase of phenoloxidase activity, suggesting that the effect of β-glucan inclusion in the diet of healthy bees on phenoloxidase activity could be linked to the type of base-diet. Further investigations on β-glucans metabolism in bees, on molecular mechanism of phenoloxidase activation by 1,3-1,6 β-glucans, and relative thresholds are desirable. Moreover, investigation on the combined action of honey and β-glucans on phenoloxidase activity are needed

Evidence for textile production in Rabati, Georgia, during the Bedeni phase of the Early Kurgan period

Georgian-Australian excavations in the multi-period settlement site of Rabati, located in southwest Georgia, have produced substantial evidence of textile manufacturing in the Early Kurgan, Bedeni period (2400–2000 BCE). The results of Palynological, Non-Pollen Palynomorph (NPP), Archaeobotanical, bone and fired clay tool analyses presented here have identified fibres of flax and hemp. The presence of cotton is the earliest evidence for this fibre in the region, pointing to trade in the commodity rather than its local cultivation. Also identified were coloured fibres and the possible sources of dye found in the Early Kurgan contexts at the site are discussed. The large number of textile manufacturing implements concentrated in one area of Rabati may indicate that this production was commercial rather than a domestic activity. An active, local textile industry during this period of growing social complexity has significant implications for the development of the emerging elite elements in an increasingly stratified society

Mucinous breast cancer: A narrative review of the literature and a retrospective tertiary single-centre analysis

We reviewed literature and our data to find out mucinous breast cancer's overall survival (OS), disease free survival (DFS) and if there are differences between pure mucinous breast cancer and mixed mucinous breast cancer in terms of OS and DFS

Age-related cognitive and motor decline in a mouse model of CDKL5 deficiency disorder is associated with increased neuronal senescence and death

open20noThis work was supported by grants to E.C. and M.G. from Telethon (GGP19045) and from the Italian parent Association “CDKL5 insieme verso la cura”, and to M.G. from the Association “l’Albero di Greta”, from the International Foundation for CDKL5 Research (IFCR 2019), from the CDKL5 Program of Excellence - LouLou Fundation (CDKL5-17-106-01) and from the Association Française du Syndrome de Rett (ASFR 2017).CDKL5 deficiency disorder (CDD) is a severe neurodevelopmental disease caused by mutations in the X-linked CDKL5 gene. Children affected by CDD display a clinical phenotype characterized by early-onset epilepsy, intellectual disability, motor impairment, and autistic-like features. Although the clinical aspects associated with CDKL5 mutations are well described in children, adults with CDD are still under-characterized. Similarly, most animal research has been carried out on young adult Cdkl5 knockout (KO) mice only. Since age represents a risk factor for the worsening of symptoms in many neurodevelopmental disorders, understanding age differences in the development of behavioral deficits is crucial in order to optimize the impact of therapeutic interventions. Here, we compared young adult Cdkl5 KO mice with middle-aged Cdkl5 KO mice, at a behavioral, neuroanatomical, and molecular level. We found an age-dependent decline in motor, cognitive, and social behaviors in Cdkl5 KO mice, as well as in breathing and sleep patterns. The behavioral decline in older Cdkl5 KO mice was not associated with a worsening of neuroanatomical alterations, such as decreased dendritic arborization or spine density, but was paralleled by decreased neuronal survival in different brain regions such as the hippocampus, cortex, and basal ganglia. Interestingly, we found increased β-galactosidase activity and DNA repair protein levels, γH2AX and XRCC5, in the brains of older Cdkl5 KO mice, which suggests that an absence of Cdkl5 accelerates neuronal senescence/death by triggering irreparable DNA damage. In summary, this work provides evidence that CDKL5 may play a fundamental role in neuronal survival during brain aging and suggests a possible worsening with age of the clinical picture in CDD patients.openGennaccaro L.; Fuchs C.; Loi M.; Pizzo R.; Alvente S.; Berteotti C.; Lupori L.; Sagona G.; Galvani G.; Gurgone A.; Raspanti A.; Medici G.; Tassinari M.; Trazzi S.; Ren E.; Rimondini R.; Pizzorusso T.; Zoccoli G.; Giustetto M.; Ciani E.Gennaccaro L.; Fuchs C.; Loi M.; Pizzo R.; Alvente S.; Berteotti C.; Lupori L.; Sagona G.; Galvani G.; Gurgone A.; Raspanti A.; Medici G.; Tassinari M.; Trazzi S.; Ren E.; Rimondini R.; Pizzorusso T.; Zoccoli G.; Giustetto M.; Ciani E

CXCR4/CXCL12 Signaling and Protumor Macrophages in Primary Tumors and Sentinel Lymph Nodes Are Involved in Luminal B Breast Cancer Progression

Luminal B breast cancers (BC) have a more aggressive behavior associated with a higher rate of tumor relapse and worse prognosis compared to luminal A tumors. In this study, we evaluated the involvement of specific epithelial-to-mesenchymal transition-(EMT-) and immune-related pathways in the dissemination of luminal B BC cells. The expression of 42 EMT- and immune-related genes was evaluated in matched sentinel lymph nodes (SLNs) analyzed by the one-step nucleic acid amplification assay (OSNA) and primary tumors of 40 luminal B BC patients by gene array and immunohistochemistry. The results were validated in an independent group of 150 luminal B tumors by immunohistochemistry and immunofluorescence and using gene expression data from 315 luminal B BC patients included in the Metabric dataset. We found that the expression of CXCR4 (p = 3.28E - 02) and CD163 (p = 6.92 E - 03) was significantly upregulated in SLNs of recurrent luminal B BC patients. Luminal B primary tumors overexpressing CXCR4 were characterized by an increased expression of vimentin and a high content of CD163-positive macrophages. Bioinformatics analysis confirmed the correlation of CXCR4 with CXCL12, VIM, and CD163 expression and LN involvement. Our results suggest that the upregulation of the CXCR4/CXCL12 pathway and the presence of protumor macrophages in the primary tumor and SLNs sustain the aggressiveness of an important subgroup of luminal B BC

Preservation of Axillary Lymph Nodes Compared with Complete Dissection in T1–2 Breast Cancer Patients Presenting One or Two Metastatic Sentinel Lymph Nodes: The SINODAR-ONE Multicenter Randomized Clinical Trial

Background: The SINODAR-ONE trial is a prospective noninferiority multicenter randomized study aimed at assessing the role of axillary lymph node dissection (ALND) in patients undergoing either breast-conserving surgery or mastectomy for T1–2 breast cancer (BC) and presenting one or two macrometastatic sentinel lymph nodes (SLNs). The endpoints were to evaluate whether SLN biopsy (SLNB) only was associated with worsening of the prognosis compared with ALND in terms of overall survival (OS) and relapse. Methods: Patients were randomly assigned (1:1 ratio) to either removal of ≥ 10 axillary level I/II non-SLNs followed by adjuvant therapy (standard arm) or no further axillary treatment (experimental arm). Results: The trial started in April 2015 and ceased in April 2020, involving 889 patients. Median follow-up was 34.0 months. There were eight deaths (ALND, 4; SNLB only, 4), with 5-year cumulative mortality of 5.8% and 2.1% in the standard and experimental arm, respectively (p = 0.984). There were 26 recurrences (ALND 11; SNLB only, 15), with 5-year cumulative incidence of recurrence of 6.9% and 3.3% in the standard and experimental arm, respectively (p = 0.444). Only one axillary lymph node recurrence was observed in each arm. The 5-year OS rates were 98.9% and 98.8%, in the ALND and SNLB-only arm, respectively (p = 0.936). Conclusions: The 3-year survival and relapse rates of T1–2 BC patients with one or two macrometastatic SLNs treated with SLNB only, and adjuvant therapy, were not inferior to those of patients treated with ALND. These results do not support the use of routine ALND