Questionnaire about the Adverse Events and Side Effects Following Botulinum Toxin A Treatment in Patients with Cerebral Palsy

Botulinum toxin A (BoNT-A) injections for treatment of spasticity in patients with cerebral palsy (CP) have been used for about two decades. The treatment is considered safe but a low frequency of adverse events (AE) has been reported. A good method to report AEs is necessary to verify the safety of the treatment. We decided to use an active surveillance of treatment-induced harm using a questionnaire we created. We studied the incidence of reported AEs and side effects in patients with CP treated with BoNT-A. We investigated the relationship between the incidence of AEs or side effects and gender, age, weight, total dose, dose per body weight, Gross Motor Function Classification System (GMFCS) and number of treated body parts. Seventy-four patients with CP participated in our study. In 54 (51%) of 105 BoNT-A treatments performed in 45 (61%) patients, there were 95 AEs and side effects reported, out of which 50 were generalized and/or focal distant. Severe AEs occurred in three patients (4%), and their BoNT-A treatment was discontinued. Consecutive collection of the AE and side-effect incidence using our questionnaire can increase the safety of BoNT-A treatment in patients with CP.     

Propolis and Organosilanes as Innovative Hybrid Modifiers in Wood-Based Polymer Composites

The article presents characteristics of wood/polypropylene composites, where the wood was treated with propolis extract (EEP) and innovative propolis-silane formulations. Special interest in propolis for wood impregnation is due to its antimicrobial properties. One propolis-silane formulation (EEP-TEOS/VTMOS) consisted of EEP, tetraethyl orthosilicate (TEOS), and vinyltrimethoxysilane (VTMOS), while the other (EEP-TEOS/OTEOS) contained EEP, tetraethyl orthosilicate (TEOS), and octyltriethoxysilane (OTEOS). The treated wood fillers were characterized by Fourier transform infrared spectroscopy (FTIR), atomic absorption spectrometry (AAS), and X-ray diffraction (XRD), while the composites were investigated using differential scanning calorimetry (DSC), X-ray diffraction (XRD), and optical microscopy. The wood treated with EEP and propolis-silane formulations showed resistance against moulds, including Aspergillus niger, Chaetomium globosum, and Trichoderma viride. The chemical analyses confirmed presence of silanes and constituents of propolis in wood structure. In addition, treatment of wood with the propolis-silane formulations produced significant changes in nucleating abilities of wood in the polypropylene matrix, which was confirmed by an increase in crystallization temperature and crystal conversion, as well as a decrease in half-time of crystallization parameters compared to the untreated polymer matrix. In all the composites, the formation of a transcrystalline layer was observed, with the greatest rate recorded for the composite with the filler treated with EEP-TEOS/OTEOS. Moreover, impregnation of wood with propolis-silane formulations resulted in a considerable improvement of strength properties in the produced composites. A dependence was found between changes in the polymorphic structures of the polypropylene matrix and strength properties of composite materials. It needs to be stressed that to date literature sources have not reported on treatment of wood fillers using bifunctional modifiers providing a simultaneous effect of compatibility in the polymer-filler system or any protective effect against fungi.     

Microdeletion of target sites for insulator protein CTCF in a chromosome 11p15 imprinting center in Beckwith-Wiedemann syndrome and Wilms' tumor

We have analyzed several cases of Beckwith-Wiedemann syndrome (BWS) with Wilms' tumor in a familial setting, which give insight into the complex controls of imprinting and gene expression in the chromosome 11p15 region. We describe a 2.2-kbp microdeletion in the H19/insulin-like growth factor 2 (IGF2)-imprinting center eliminating three target sites of the chromatin insulator protein CTCF that we believe here is necessary, but not sufficient, to cause BWS and Wilms' tumor. Maternal inheritance of the deletion is associated with IGF2 loss of imprinting and up-regulation of IGF2 mRNA. However, in at least one affected family member a second genetic lesion (a duplication of maternal 11p15) was identified and accompanied by a further increase in IGF2 mRNA levels 35-fold higher than control values. Our results suggest that the combined effects of the H19/IGF2-imprinting center microdeletion and 11p15 chromosome duplication were necessary for manifestation of BWS.     

Measurement of adherence to BCR-ABL inhibitor therapy in chronic myeloid leukemia: current situation and future challenges

BCR-ABL inhibitors for treating chronic myeloid leukemia in chronic phase have transformed a previously incurable malignancy into a manageable condition. However, suboptimal medication adherence has been observed with these agents affecting clinical outcomes and healthcare costs. In order to raise awareness of the problem of adherence, and before developing pragmatic strategies to enhance medication adherence, a deep understanding of the best approaches for measuring adherence in chronic myeloid leukemia patients and identifying non-adherence is required. A systematic literature review on the prevalence, measurement methods, consequences and risk factors for non-adherence to BCR-ABL inhibitors and adherence-enhancing interventions was performed and critically appraised. Of the 19 included articles, 9 were retrospective. Average adherence varied from 19% to almost 100% of the proportion of prescribed drug taken, but it was measured through various different methods and within different study groups. Suboptimal adherence was associated with a negative impact on both clinical and economic outcomes. There is a lack of supportive evidence demonstrating a difference in adherence across BCR-ABL inhibitors and even contradictory results between the 2^nd generation inhibitors. Drug-related adverse events and forgetfulness were common reasons for intentional and unintentional non-adherence, respectively, but further research is required to identify additional reasons behind non-adherence or patients at risk of non-adherence. Non-adherence in chronic myeloid leukemia patients treated with BCR-ABL inhibitors is common and associated with critical outcomes. However, this review highlights important existing gaps, reveals inconsistent definitions, and a lack of standardized methods for measuring adherence in chronic myeloid leukemia. All require further investigation.     

The heterogeneous immune microenvironment in breast cancer is affected by hypoxia-related genes

The immune system constitutes an important first-line defence against malignant transformation. However, cancer mediated immunosuppression inactivates the mechanisms of host immune surveillance. Cancer cells shut down anti-cancer immunity through direct cell–cell interactions with leukocytes and through soluble factors, establishing an immunosuppressive environment for unimpeded cancer growth. The composition of the immunosuppressive microenvironment in breast tumours is not well documented. To address this question, selected immunosuppressive factors were analyzed in tumour specimens from 33 breast cancer patients after surgery. The mRNA expression of selected genes was quantified in fresh tumour samples. Tumour infiltrating leukocytes were characterized by flow cytometry to identify regulatory T cells, myeloid derived suppressor cells, and type 2 macrophages. Statistical analysis revealed several interesting correlations between the studied parameters and clinical features. Overall, a surprisingly high degree of heterogeneity in the composition of the immunosuppressive environment was found across all breast cancer samples which adds to the complexity of this disease. The influence of the hypoxia inducible factors (HIFs) on the immune microenvironment was also addressed. The level of HIFs correlated with hormone receptor status and the expression of several immunosuppressive molecules. Targeting HIFs might not only sensitize breast tumours for radiation and chemotherapies but also interfere with cancer immunosuppression.     

A single nucleotide polymorphism −35 kb T > C (rs9264942) is strongly associated with psoriasis vulgaris depending on HLA-Cw06

HLA class I molecules play a role both in viral infection control and in autoimmune diseases development. rs9264942T > C polymorphism in HLA-C gene was found to impact on HLA-C surface expression level and to be associated with HIV-1 control. It was found that these HLA alleles which protect against AIDS are associated with autoimmune disease e.g. psoriasis vulgaris (PsV). Whether rs9264942 SNP is associated with PsV was investigated here. rs9264942T > C was genotyped in 292 PsV patients, and 254 controls using TaqMan Genotyping Assay.     

Fluazuron-induced morphological changes in Rhipicephalus sanguineus Latreille, 1806 (Acari: Ixodidae) nymphs: An ultra-structural evaluation of the cuticle formation and digestive processes

Rhipicephalus sanguineus is a species of tick which is widely distributed in America, Africa and Australia and is probably the most prevalent among all the other ixodid tick species. The present study demonstrated the effects of the arthropod growth regulator fluazuron (Acatak^®), in the formation of the integument and the digestive processes of R. sanguineus nymphs fed on rabbits treated with different doses of this chemical acaricide. For this, three different doses of fluazuron (20 mg/kg, 40 mg/kg and 80 mg/kg) were applied “pour on” to the hosts divided into three different treated-groups (II, III, IV) of three animals each. A fourth group (I) of rabbits (n = 3) was given distilled water as control. On the first day after treatment (24 h), the hosts were artificially infested with R. sanguineus nymphs. After full engorgement (7 days), the nymphs were removed and placed on labeled Petri dishes and kept in BOD incubator for 7 days. The engorged nymphs were then taken to ultra-structural analysis. Results revealed the following main ultra-structural changes in the nymphs integument and midgut of the different treated groups (II, III, IV): cuticle disorganization and the absence of subdivisions, damages in the integument epithelial cells, size of digestive cells, amount of endosomes, autophagic and digestive vacuoles, accumulated digestive residues, lipid droplets and organelles found in the digestive cells’ cytoplasm, as well as the presence of microvilli in their plasma membranes. It is concluded that fluazuron may act on the integument and midgut cells of R. sanguineus engorged nymphs by impairing the synthesis of the new cuticle and the digestive processes (absorption of the blood ingested from the host, digestion – hemolysis, formation of digestive residues and release of nutrients to be converted into lipid, as well as for the synthesis of structural protein), which interfere in the development of nymphs, being able to prevent the emergence of adults after periodical ecdysis. These data indicate the possibility to use this arthropod growth regulator (AGR) in the control of R. sanguineus, at least in the nymphal stage of its biological cycle.     

Response Surface Methodology and Artificial Neural Network Modelling of Membrane Rotating Biological Contactors for Wastewater Treatment

Membrane fouling is a major hindrance to widespread wastewater treatment applications. This study optimizes operating parameters in membrane rotating biological contactors (MRBC) for maximized membrane fouling through Response Surface Methodology (RSM) and an Artificial Neural Network (ANN). MRBC is an integrated system, embracing membrane filtration and conventional rotating biological contactor in one individual bioreactor. The filtration performance was optimized by exploiting the three parameters of disk rotational speed, membrane-to-disk gap, and organic loading rate. The results showed that both the RSM and ANN models were in good agreement with the experimental data and the modelled equation. The overall R² value was 0.9982 for the proposed network using ANN, higher than the RSM value (0.9762). The RSM model demonstrated the optimum operating parameter values of a 44 rpm disk rotational speed, a 1.07 membrane-to-disk gap, and a 10.2 g COD/m² d organic loading rate. The optimization of process parameters can eliminate unnecessary steps and automate steps in the process to save time, reduce errors and avoid duplicate work. This work demonstrates the effective use of statistical modeling to enhance MRBC system performance to obtain a sustainable and energy-efficient treatment process to prevent human health and the environment.     

Magnesium as an Important Factor in the Pathogenesis and Treatment of Migraine—From Theory to Practice

So far, no coherent and convincing theory has been developed to fully explain the pathogenesis of migraine, although many researchers and experts emphasize its association with spreading cortical depression, oxidative stress, vascular changes, nervous excitement, neurotransmitter release, and electrolyte disturbances. The contribution of magnesium deficiency to the induction of cortical depression or abnormal glutamatergic neurotransmission is a likely mechanism of the magnesium–migraine relationship. Hence, there is interest in various methods of assessing magnesium ion deficiency and attempts to study the relationship of its intra- and extracellular levels with the induction of migraine attacks. At the same time, many clinicians believe that magnesium supplementation in the right dose and form can be a treatment to prevent migraine attacks, especially in those patients who have identified contraindications to standard medications or their different preferences. However, there are no reliable publications confirming the role of magnesium deficiency in the diet as a factor causing migraine attacks. It also seems interesting to deepen the research on the administration of high doses of magnesium intravenously during migraine attacks. The aim of the study was to discuss the probable mechanisms of correlation of magnesium deficiency with migraine, as well as to present the current clinical proposals for the use of various magnesium preparations in complementary or substitute pharmacotherapy of migraine. The summary of the results of research and clinical observations to date gives hope of finding a trigger for migraine attacks (especially migraine with aura), which may turn out to be easy to diagnose and eliminate with pharmacological and dietary supplementation.