Main-chain flexibility and hydrophobicity of ionenes strongly impact their antimicrobial activity: an extended study on drug resistance strains and Mycobacterium

The spread of antibiotic-resistant pathogens and the resurgence of tuberculosis disease are major motivations to search for novel antimicrobial agents. Some promising candidates in this respect are cationic polymers, also known as synthetic mimics of antimicrobial peptides (SMAMPs), which act through the membrane-lytic mechanism. Development of resistance toward SMAMPs is less likely than toward currently employed antibiotics; however, further studies are needed to better understand their structure–activity relationship. The main objective of this work is to understand the cross-influence of hydrophobicity, main-chain flexibility, and the topology of ionenes (polycations containing a cationic moiety within the main-chain) on activity. To fulfill this goal, a library of ionenes was developed and compared with previously investigated molecules. The obtained compounds display promising activity against the model microorganisms and drug-resistance clinical isolates, including Mycobacterium tuberculosis. The killing efficiency was also investigated, and results confirm a strong effect of hydrophobicity, revealing higher activity for molecules possessing the flexible linker within the polymer main-chain.

A high significance of the main chain flexibility and an unexpected effect of hydrophobicity on the biological activity in series of ionenes was observed. The most potent among the tested polycations showed high activity toward clinical bacterial isolates.     

The Assessment of the Hypothalamic-Pituitary-Adrenal Axis After Oncological Treatment in Pediatric Patients with Acute Lymphoblastic Leukemia

Objective:Oncologic treatment can affect the adrenal glands, which in stressful situations may lead to life threatening adrenal crisis. The aim of the study was to assess adrenal function in pediatric acute lymphoblastic leukemia (ALL) survivors and to identify the best markers for this assessment.Methods:Forty-three ALL survivors, mean age 8.5±3.6 years and 45 age and sex-matched healthy controls were recruited to the study. ALL patients were assessed once within five years following oncological treatment completion. Fasting blood samples were collected from all participants to measure: fasting blood glucose (FBG); cortisol; aldosterone; plasma renin activity (PRA); dehydroepiandrostendione-sulfate (DHEA-S); and adrenocorticotropic hormone (ACTH). Moreover, diurnal profile of cortisol levels and 24-hour urinary free cortisol (UFC) were assessed. ALL survivors underwent a test with 1 ug of synthetic ACTH.Results:The study revealed lower level of PRA (1.94±0.98 ng/mL/h vs 3.61±4.85 ng/mL/h, p=0.029) and higher FBG (4.6±0.38 mmol/L vs 4.41±0.39 mmol/L, p=0.018) in the ALL group compared to controls. UFC correlated with evening cortisol (p=0.015, r=0.26), midnight cortisol (p=0.002, r=0.33), and DHEA-S (p=0.004, r=0.32). UFC also correlated with systolic and diastolic blood pressure (p=0.033, r=0.23 and p=0.005, r=0.31, respectively). The ACTH test confirmed impaired adrenal function in 4/43 ALL survivors (9%). Two of the patients who needed permanent hydrocortisone replacement had low UFC, midnight cortisol and DHEA-S levels.Conclusion:These results highlight the importance of reviewing adrenal gland functionality after chemo/radiotherapy in ALL survivors. DHEA-S proved to be a good marker to assess the adrenal glands after oncological therapy. Post-treatment disturbances of the adrenal axis could be associated with metabolic complications.     

Polyaniline and Polyaniline-Based Materials as Sorbents in Solid-Phase Extraction Techniques

Polyaniline (PANI) is one of the best known and widely studied conducting polymers with multiple applications and unique physicochemical properties. Due to its porous structure and relatively high surface area as well as the affinity toward many analytes related to the ability to establish different types of interactions, PANI has a great potential as a sorbent in sample pretreatment before instrumental analyses. This study provides an overview of the applications of polyaniline and polyaniline composites as sorbents in sample preparation techniques based on solid-phase extraction, including conventional solid-phase extraction (SPE) and its modifications, solid-phase microextraction (SPME), dispersive solid-phase extraction (dSPE), magnetic solid-phase extraction (MSPE) and stir-bar sorptive extraction (SBSE). The utility of PANI-based sorbents in chromatography was also summarized. It has been shown that polyaniline is willingly combined with other components and PANI-based materials may be formed in a variety of shapes. Polyaniline alone and PANI-based composites were successfully applied for sample preparation before determination of various analytes, both metal ions and organic compounds, in different matrices such as environmental samples, food, human plasma, urine, and blood.     

Tests of Dental Properties of Composite Materials Containing Nanohybrid Filler

Complex composite materials are used in many areas of dentistry. Initially, chemically hardened materials were also used, and in this group nanohybrid composites are highly valued. They are often used today, mainly for the direct reconstruction of damaged hard tooth tissue materials for rebuilding damaged tissues using indirect adhesive techniques. The research was conducted to determine the mechanical properties of materials with nanofillers. The article focuses on methods of important test methods for dental prosthetics: resilience, abrasion, wear test, impact strength, hardness, SEM, and chemical analysis. As part of this work, five different series of hybrid composites with nano-fillers were tested. The mechanical properties of composites, such as compressive strength, microhardness, flexural strength, and modulus of elasticity, depend mainly on the type, particle size, and amount of filler introduced. The obtained test results showed that the type and amount of nanofiller have a significant influence on the mechanical and tribological properties. The introduction of nanofillers allowed us to obtain higher mechanical properties compared to classic materials discussed by other researchers. The study observed a change in vibrations in the IR spectrum, which allowed a comparison of the organic structures of the studied preparations.     

Impaired synaptic transmission in dorsal dentate gyrus increases impulsive alcohol seeking

Both human and animal studies indicate that the dentate gyrus (DG) of the hippocampus is highly exploited by drug and alcohol abuse. Yet, it is poorly understood how DG dysfunction affects addiction-related behaviors. Here, we used an animal model of alcohol use disorder (AUD) in automated IntelliCages and performed local genetic manipulation to investigate how synaptic transmission in the dorsal DG (dDG) affects alcohol-related behaviors. We show that a cue light induces potentiation-like plasticity of dDG synapses in alcohol-naive mice. This process is impaired in mice trained to drink alcohol. Acamprosate (ACA), a drug that reduces alcohol relapse, rescues the impairment of dDG synaptic transmission in alcohol mice. A molecular manipulation that reduces dDG synaptic AMPAR and NMDAR levels increases impulsive alcohol seeking during cue relapse (CR) in alcohol mice but does not affect alcohol reward, motivation or craving. These findings suggest that hindered dDG synaptic transmission specifically underlies impulsive alcohol seeking induced by alcohol cues, a core symptom of AUD.Subject terms: Addiction, Cellular neuroscience     

Bending Strength of Wood Treated with Propolis Extract and Silicon Compounds

The modification of wood and its treatment with various preservatives may affect its mechanical properties, hence the knowledge of the character changes in wood caused by impregnation is of great importance. Therefore, the aim of the research was to determine the effect of impregnation, with the propolis-silane preparation (EEP-MPTMOS/TEOS) consisting of the propolis extract (EEP) and silicon compounds: 3-(trimethoxysilyl)propyl methacrylate (MPTMOS) and tetraethoxysilane (TEOS), on the bending strength of treated wood. Moreover, in the study wood treated with components of the propolis-silane formulation was used, namely 70% ethanol, the propolis extract, and silanes (MPTMOS/TEOS). In order to determine whether the impregnation of wood affects its long-term bending, creep tests were performed depending on the humidity. The impregnation of wood with the propolis extract and the propolis-silane preparation (EEP-MPTMOS/TEOS) contributed to the increase in modulus of rapture and work to maximum load values compared to the untreated wood. In dry wood condition, the wood treated with EEP and EEP-MPTMOS/TEOS was characterized by lower modulus of elasticity values than the control samples. In turn, in wet wood condition, wood treated with the propolis-silane preparation showed an increase in the MOE value. Moreover, the impregnation of wood had an influence on the wood creep process under bending loads. The treated wood was characterized by higher relative creep compliance than the untreated wood. The exception was the wood impregnated with EEP-MPTMOS/TEOS, which showed comparable relative creep compliance to the control samples. The presented results indicate that wood treated with a bio-friendly preparation based on propolis and silicon compounds can be used in various application and also in variable humidity conditions.     

High throughput sequencing reveals high specificity of TNFAIP3 mutations in ocular adnexal marginal zone B-cell lymphomas

The majority of ocular adnexal (OA) lymphomas (OAL) are extranodal marginal zone lymphomas (MZL). First high throughput sequencing (HTS) studies on OA-MZL showed inconsistent results and the distribution of mutations in reactive lymphoid lesions of this anatomic region has not yet been sufficiently addressed. We characterized OAL and lymphoid lesions of the OA by targeted HTS. The study included 34 OA-MZL, 11 chronic conjunctivitis, five mature small cell B-cell lymphomas spreading to the OA, five diseases with increase of IgG4+ plasma cells, three Burkitt lymphomas (BL), three diffuse large B-cell lymphomas (DLBCL), three mantle cell lymphomas, three idiopathic orbital inflammations/orbital pseudo tumors (PT), and three OA lymphoid hyperplasia. All cases were negative for Chlamydia. The mutational number was highest in BL and lowest in PT. The most commonly (and exclusively) mutated gene in OA-MZL was TNFAIP3 (10 of 34 cases). Altogether, 20 out of 34 patients harbored mutually exclusive mutations of either TNFAIP3, BCL10, MYD88, ATM, BRAF, or NFKBIE, or nonexclusive mutations of IRF8, TNFRSF14, KLHL6, and TBL1XR1, all encoding for NK-κB pathway compounds or regulators. Thirteen patients (38%) had, to a great part, mutually exclusive mutations of chromatin modifier-encoding genes: KMT2D, CREBBP, BCL7A, DNMT3A, EP300, or HIST1H1E. Only four patients harbored co-occurring mutations of genes encoding for NK-κB compounds and chromatin modifiers. Finally, PTEN, KMT2D, PRDM1, and HIST1H2BK mutations were observable in reactive lymphoid lesions too, while such instances were devoid of NF-κB compound mutations and/or mutations of acetyltransferase-encoding genes. In conclusion, 80% of OA-MZL display mutations of either NK-κB compounds or chromatin modifiers. Lymphoid lesions of the OA bearing NF-κB compound mutations and/or mutations of acetyltransferase-encoding genes highly likely represent lymphomas.     

Using amyloid PET imaging to diagnose Alzheimer’s disease in patients with multiple sclerosis

Journal of Neurology - Cognitive dysfunction affects 40–60% of individuals with multiple sclerosis (MS). The neuropsychological profile commonly consists of a subcortical pattern of deficits,...     

Impact of comorbidities and co-medication on disease onset and progression in a large German ALS patient group

Journal of Neurology - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with loss of muscle function. The pathogenesis is still unclear and the heterogeneity of ALS...