Real-world treatment patterns in patients with nontuberculous mycobacterial lung disease in the Netherlands based on medication dispensing data.

PURPOSE: Real-world data on antibiotic management of nontuberculous mycobacterial lung disease (NTM-LD) is limited for many countries. This study aimed to evaluate real-world treatment practices of NTM-LD in the Netherlands using medication dispensing data. METHODS: A retrospective longitudinal real-world study was conducted using IQVIA's Dutch pharmaceutical dispensing database. The data are collected monthly and include approximately 70% of all outpatient prescriptions in the Netherlands. Patients initiated on specific NTM-LD treatment regimens between October 2015 and September 2020 were included. The main areas of investigation were initial treatment regimens, persistence on treatment, treatment switching, treatment compliance in terms of medication possession rate (MPR) and restarts of treatment. RESULTS: The database included 465 unique patients initiated on triple- or dual-drug regimens for the treatment of NTM-LD. Treatment switches were common and occurred approximately 1.6 per quarter throughout the treatment period. The average MPR of patients initiated on triple-drug therapy was 90%. The median time on therapy for these patients was 119 days; after six months and one year, 47% and 20% of the patients, respectively, were still on antibiotic therapy. Of 187 patients initiated on triple-drug therapy, 33 (18%) patients restarted antibiotic therapy after the initial treatment had been stopped. CONCLUSION: When on therapy, patients were compliant with the NTM-LD treatment; however, many patients stopped their therapy prematurely, treatment switches often occurred, and part of patients had to restart their therapy after a longer treatment gap. NTM-LD management should be improved through greater guideline adherence and appropriate involvement of expert centers.

Treatment persistence in paediatric and adolescent patients with psoriasis followed into young adulthood. From topical to systemic treatment: a prospective, longitudinal, observational cohort study of 448 patients.

BACKGROUND: Although solely topical treatment often suffices, patients with psoriasis may require more intensive treatment (phototherapy and/or systemic treatments) to control their disease. However, in paediatric, adolescent and young adult patients, little is known about persistence of topical treatment and time until switch to systemic treatment. OBJECTIVES: To determine the median time from psoriasis onset until (i) discontinuation of solely topical agents and (ii) switch to systemic treatment, and to identify patient characteristics associated with switching to systemic treatments. METHODS: Data were extracted from the Child-CAPTURE registry, a prospective, observational cohort of patients with paediatric-onset psoriasis followed into young adulthood from 2008 to 2018. Data prior to inclusion in the registry were collected retrospectively. Median times were determined through Kaplan-Meier survival analyses. Cox regression analysis was used to identify patient characteristics associated with switch to systemic treatment. RESULTS: Of 448 patients, 62·3% stayed on solely topical treatment until data lock; 14·3% switched from topicals to phototherapy, but not to systemic treatment; and 23·4% switched to systemic treatment. The median time from psoriasis onset until discontinuation of solely topical treatment was 7·3 years, and until switch to systemics was 10·8 years. Higher Psoriasis Area and Severity Index and (Children's) Dermatology Life Quality Index > 5 were independently associated with switching to systemic treatment. CONCLUSIONS: In a population of paediatric and adolescent patients with mild-to-severe psoriasis, one-third needed more intensive treatment than solely topical therapy to control their disease. We consider the median time until switching to systemics to be long.

Observational evidence for interhemispheric hydroxyl-radical parity.

The hydroxyl radical (OH) is a key oxidant involved in the removal of air pollutants and greenhouse gases from the atmosphere. The ratio of Northern Hemispheric to Southern Hemispheric (NH/SH) OH concentration is important for our understanding of emission estimates of atmospheric species such as nitrogen oxides and methane. It remains poorly constrained, however, with a range of estimates from 0.85 to 1.4 (refs 4, 7-10). Here we determine the NH/SH ratio of OH with the help of methyl chloroform data (a proxy for OH concentrations) and an atmospheric transport model that accurately describes interhemispheric transport and modelled emissions. We find that for the years 2004-2011 the model predicts an annual mean NH-SH gradient of methyl chloroform that is a tight linear function of the modelled NH/SH ratio in annual mean OH. We estimate a NH/SH OH ratio of 0.97 ± 0.12 during this time period by optimizing global total emissions and mean OH abundance to fit methyl chloroform data from two surface-measurement networks and aircraft campaigns. Our findings suggest that top-down emission estimates of reactive species such as nitrogen oxides in key emitting countries in the NH that are based on a NH/SH OH ratio larger than 1 may be overestimated.

Natural and anthropogenic variations in methane sources during the past two millennia.

Methane is an important greenhouse gas that is emitted from multiple natural and anthropogenic sources. Atmospheric methane concentrations have varied on a number of timescales in the past, but what has caused these variations is not always well understood. The different sources and sinks of methane have specific isotopic signatures, and the isotopic composition of methane can therefore help to identify the environmental drivers of variations in atmospheric methane concentrations. Here we present high-resolution carbon isotope data (δ(13)C content) for methane from two ice cores from Greenland for the past two millennia. We find that the δ(13)C content underwent pronounced centennial-scale variations between 100 BC and AD 1600. With the help of two-box model calculations, we show that the centennial-scale variations in isotope ratios can be attributed to changes in pyrogenic and biogenic sources. We find correlations between these source changes and both natural climate variability--such as the Medieval Climate Anomaly and the Little Ice Age--and changes in human population and land use, such as the decline of the Roman empire and the Han dynasty, and the population expansion during the medieval period.

Doubly Dressed Bosons: Exciton Polaritons in a Strong Terahertz Field.

We demonstrate the existence of a novel quasiparticle, an exciton in a semiconductor doubly dressed with two photons of different wavelengths: a near infrared cavity photon and terahertz (THz) photon, with the THz coupling strength approaching the ultrastrong coupling regime. This quasiparticle is composed of three different bosons, being a mixture of a matter-light quasiparticle. Our observations are confirmed by a detailed theoretical analysis, treating quantum mechanically all three bosonic fields. The doubly dressed quasiparticles retain the bosonic nature of their constituents, but their internal quantum structure strongly depends on the intensity of the applied terahertz field.

DNA damage and oxidative stress response to selenium yeast in the non-smoking individuals: a short-term supplementation trial with respect to GPX1 and SEPP1 polymorphism.

PURPOSE: Selenium, both essential and toxic element, is considered to protect against cancer, though human supplementation trials have generated many inconsistent data. Genetic background may partially explain a great variability of the studies related to selenium and human health. The aim of this study was to assess whether functional polymorphisms within two selenoprotein-encoding genes modify the response to selenium at the level of oxidative stress, DNA damage, and mRNA expression, especially in the individuals with a relatively low selenium status. METHODS: The trial involved 95 non-smoking individuals, stratified according to GPX1 rs1050450 and SEPP1 rs3877899 genotypes, and supplemented with selenium yeast (200 µg) for 6 weeks. Blood was collected at four time points, including 4 weeks of washout. RESULTS: After genotype stratification, the effect of GPX1 rs1050450 on lower GPx1 activity responsiveness was confirmed; however, in terms of DNA damage, we failed to indicate that individuals homozygous for variant allele may especially benefit from the increased selenium intake. Surprisingly, considering gene and time interaction, GPX1 polymorphism was observed to modify the level of DNA strand breaks during washout, showing a significant increase in GPX1 wild-type homozygotes. Regardless of the genotype, selenium supplementation was associated with a selectively suppressed selenoprotein mRNA expression and inconsistent changes in oxidative stress response, indicating for overlapped, antioxidant, and prooxidant effects. Intriguingly, DNA damage was not influenced by supplementation, but it was significantly increased during washout. CONCLUSIONS: These results point to an unclear relationship between selenium, genotype, and DNA damage.

Immunosuppression in Dogs During Mammary Cancer Development.

Cancer immunosuppression that facilitates tumor progression and metastasis evolves by development of an immunosuppressive network. The aim of this study was to assess this network in dogs with benign or malignant tumors with or without confirmed metastasis. The authors showed that the number of various T cell subpopulations was constant during tumor development; however the number of regulatory T cells (Tregs) was significantly higher in tumor-bearing dogs than in healthy individuals. The number of myeloid-derived suppressor cells (MDSCs) and their p-STAT3 expression (which is a negative regulator of hematopoiesis and regulates VEGF expression) were higher in cancer patients than in control dogs, however their number increased significantly in late-stage cancer patients. Canine mammary carcinomas with confirmed metastases to either lymph nodes or internal organs had greater MDSCs and Treg infiltration than benign mammary tumors or malignant mammary tumors for which metastases had not been detected. Similarly, expression of p-STAT3 and VEGF-C was the highest in tumors with confirmed metastases. This research shows changes occurring in the blood (n = 30 patients) and tumor tissue of patients (n = 100) during canine mammary tumor development. The findings should be considered preliminary because of the small number of samples. Nonetheless, the findings suggest that a high level of Tregs and MDSCs as well as high expression of p-STAT3 and VEGF-C may significantly contribute to mammary tumor progression and metastasis in dogs.

Consumer Quality Index Chronic Skin Disease (CQI-CSD): a new instrument to measure quality of care from the patient's perspective.

BACKGROUND: Assessing quality of care from the patient's perspective is considered to be highly relevant. As a standardized instrument in dermatology was lacking, we developed a patient experience questionnaire regarding chronic skin disease care: the Consumer Quality Index Chronic Skin Disease (CQI-CSD). OBJECTIVES: (i) To evaluate the dimensional structure of the CQI-CSD, (ii) to assess its ability to distinguish between hospitals according to patients' experiences with quality of care, (iii) to explore patients' experiences with dermatological care and priorities for quality improvement according to the patients, and (iv) to optimize the questionnaire based on psychometric results and stakeholders' input. METHODS: In a cross-sectional study 5647 adult patients who received dermatological care in the past 12 months in 20 hospitals were randomly selected and invited to fill out the questionnaire. RESULTS: Overall 1160 of 3989 eligible respondents (29% response rate, 30-87 per hospital) were included for analysis. The CQI-CSD comprised seven scales with high internal consistency (Cronbach's α = 0·74-0·92). The instrument's discriminative power was limited. Patients were positive about the care provided by nurses and doctors, but the provision of information by healthcare providers, accessibility of care and patient involvement could be improved. We optimized the CQI-CSD, resulting in a revised questionnaire containing 65 items. CONCLUSIONS: In conclusion, the CQI-CSD is a useful instrument to measure patient experiences with dermatological care.

Intraoperative arterial blood pressure lability is associated with improved 30 day survival.

BACKGROUND: Arterial blood pressure lability, defined as rapid changes in arterial blood pressure, occurs commonly during anaesthesia. It is believed that hypertensive patients exhibit more lability during surgery and that lability is associated with poorer outcomes. Neither association has been rigorously tested. We hypothesized that hypertensive patients have more blood pressure lability and that increased lability is associated with increased 30 day mortality. METHODS: This was a retrospective single-centre study of surgical patients from July 2008 to December 2012. Intraoperative data were extracted from the electronic anaesthesia record. Lability was calculated as the modulus of the percentage change in mean arterial pressure between consecutive 5 min intervals. The number of episodes of lability >10% was tabulated. Multivariate logistic regression was performed to determine the association between lability and 30 day mortality using derivation and validation cohorts. RESULTS: Inclusion criteria were met by 52 919 subjects. Of the derivation cohort, 53% of subjects were hypertensive and 42% used an antihypertensive medication. The median number of episodes of lability >10% was 9 (interquartile range 5-14) per patient. Hypertensive subjects demonstrated more lability than normotensive patients, 10 (5-15) compared with 8 (5-12), P<0.0001. In subjects taking no antihypertensive medication, lability >10% was associated with decreased 30 day mortality, odds ratio (OR) per episode 0.95 [95% confidence interval (CI) 0.92-0.97], P<0.0001. This result was confirmed in the validation cohort, OR 0.96 (95% CI 0.93-0.99), P=0.01, and in hypertensive patients taking no antihypertensive medication, OR 0.96 (95% CI 0.93-0.99), P=0.002. Use of any antihypertensive medication class reduced this effect. CONCLUSIONS: Intraoperative arterial blood pressure lability occurs more often in hypertensive patients. Contrary to common belief, increased lability was associated with decreased 30 day mortality.

[The cost-effectiveness evaluation of 2 caries prevention strategies compared with the standard approach]. / Een economische evaluatie van 2 cariëspreventieve strategieën vergeleken met standaardzorg.

A cost-effectiveness evaluation was conducted with a randomised controlled clinical trial of caries prevention measures among 6-year-old children who were assigned to either a control group or 1 of 2 experimental groups (IPFA: 2 extra professionally-delivered fluoride applications per year, or NOCTP: a non-operative caries treatment programme, like the one that was previously carried out in Nexø, Denmark. In order to determine the cost of the prevention of 1 DMFS in comparison with the control practice information on expenses incurred was collected for 3 years. The prevention of a single DMFS - depending on whether costs of dental treatment only were taken into consideration or also other social costs - were, in the IPFA programme, 269 and 1,369 euro respectively and, in the NOCTP programme, 30 and 100 euro respectively. On the basis of these results, it can be concluded that from both a dental and cost-effective perspective the NOCTP programme produces the most favourable results. Following the NOCTP strategy - during the 3-year period - just like following the IPFA approach was, however, more expensive than the standard approach.

Value for money: economic evaluation of two different caries prevention programmes compared with standard care in a randomized controlled trial.

A cost-effectiveness analysis was conducted during a 3-year randomized controlled clinical trial in a general dental practice in the Netherlands in which 230 6-year-old children (± 3 months) were assigned to either regular dental care, an increased professional fluoride application (IPFA) programme or a non-operative caries treatment and prevention (NOCTP) programme. Information on resource use during the 3-year period was documented by the dental nurse at every patient visit, such as treatment time, travel time and travel distance. Caries increment scores (at D3MFS level) were used to assess effectiveness. Cost calculations were performed using bottom-up micro-costing. Incremental cost-effectiveness ratios (ICERs) were expressed as additional average costs per prevented DMFS. The ICERs compared with regular dental care from a health care system perspective and societal perspective were, respectively, EUR 269 and EUR 1,369 per prevented DMFS in the IPFA programme, and EUR 30 and EUR 100 in the NOCTP programme. The largest investments for the NOCTP group were made in the first year of the study; they decreased in the second and equalled the costs of control group in third year of the study. From both medical and economic points of view, the NOCTP strategy may be considered the preferred strategy for caries prevention.

Exploring young patients' perspectives on rehabilitation care: methods and challenges of organizing focus groups for children and adolescents.

BACKGROUND: In research on quality of care, the experiences of children and (pre)adolescents are usually assessed by asking their parents. However, these young patients may have preferences of their own, and their experiences do not necessarily concur with those of their parents. Therefore, our research aimed to give young patients an opportunity to speak up for themselves. METHODS: Focus group meetings and online focus groups were organized for two age groups (8­11 and 12­15 years) of young patients from two Dutch rehabilitation centres, with the use of a tailored interview technique. The feasibility and applicability of both types of focus groups were assessed. RESULTS: For both types of focus groups, recruitment proved a major problem. The focus group meetings with (pre)adolescents proved both feasible and applicable in obtaining information regarding the preferences and experiences towards rehabilitation care. Regarding children's meetings, there were mixed results. The setting suited most of them, but some were more anxious. In general, online focus groups were less successful than expected for both age groups. CONCLUSIONS: Possibilities for enhancing the recruitment rate should be considered, as the low participation rates limited generalizability of focus group results. The tailored design proved useful for obtaining relevant input from (pre)adolescents through meetings, but, especially for children, repeated meetings or other locations (e.g. at home) could be considered. This may make participants more at ease. For both age groups, the online focus groups proved far less useful, in terms of participation.

Canine mammary carcinoma cell line are resistant to chemosensitizers: verapamil and cyclosporin A.

Cancer chemotherapy can fail in many ways. One of the most significant is the development of multiple drug resistance (MDR), which constitutes a serious clinical problem. The development of MDR relates to the expression of a major membrane pump, P-glycoprotein (P-gp). Thus, currently one of the goals of experimental and clinical oncology is to decrease its activity. So far, many different P-gp inhibitors are available, but their efficacy is still questionable and requires further study. The aim of our study was to assess an impact of classical P-gp inhibitors (verapamil and cyclosporin A) in the reversion of multidrug resistance in canine mammary cancer cells. We used two cell lines isolated from mammary tumors and two cell lines isolated from their lung metastases. All of them showed P-gp over-expression confirmed using Real-time rt-PCR, Skan(R) screening station and confocal microscopy. The FACS analysis showed that in three of the examined cell lines, treatment with verpamil/cyclosporin A was ineffective to reverse cancer chemoresistance. However, more studies in this field are required.

Structural studies of calcium silicate hydrate modified with heavy metal cations.

This study investigates the immobilization mechanisms of heavy metal ions in the C-S-H phase. Synthetic C-S-H phases were prepared via the precipitation method, incorporating five different ions (Pb(II), Cd(II), Ni(II), Zn(II), and Cr(III)). Structural analysis of the obtained material was conducted using vibrational spectroscopy (both FT-IR and Raman), X-ray photoelectron spectroscopy, and X-ray diffraction. Spectroscopic methods were primarily employed to evaluate the structural effects and polymerization degree of the resulting C-S-H phase. Morphological changes were characterized using scanning and transmission electron microscopy (SEM and TEM, respectively). Our findings reveal several mechanisms for immobilizing heavy metal cations: precipitation of insoluble compounds (particularly notable for Ni(II) and Cr(III)), replacement of Ca(II) ions within the silicate structure (evident in the crystallization of Ca(OH)2 in samples containing Cd(II), Ni(II), and Zn(II) in minimal quantities), and strong bonding of certain metals (such as Pb(II)) with the C-S-H phase structure. These insights contribute to understanding the potential applications of C-S-H phases in heavy metal immobilization.

Effect of compaction on bisulfide diffusive transport through MX-80 bentonite.

Canada's deep geological repository (DGR) design includes an engineered barrier system where highly compacted bentonite (HCB) surrounds the copper-coated used fuel containers (UFCs). Microbial-influenced corrosion is a potential threat to long-term integrity of UFC as bisulfide (HS-) may be produced by microbial activities under anaerobic conditions and transported via diffusion through the HCB to reach the UFC surface, resulting in corrosion of copper. Therefore, understanding HS- transport mechanisms through HCB is critical for accurate prediction of copper corrosion allowance. This study investigated HS- transport behaviour through MX-80 bentonite at dry densities 1070-1615 kg m-3 by performing through-diffusion experiments. Following HS- diffusion, bromide (Br-) diffusion and Raman spectroscopy analyses were performed to explore possible physical or mineralogical alterations of bentonite caused by interacting with HS-. In addition, accessible porosity ε was estimated using extended Archie's law. Effective diffusion coefficient of HS- was found 2.5 × 10-12 m2 s-1 and 5.0× 10-12 m2 s-1 for dry densities 1330 and 1070 kg m-3, respectively. No HS- breakthrough was observed for highly compacted bentonite (1535-1615 kg m-3) over the experimental timeframe (170 days). Raman spectroscopy results revealed that HS- reacted with iron in bentonite and precipitated as mackinawite and, therefore, it was immobilized. Finally, results of this study imply that HS- transport towards UFC will be highly controlled by the available iron content and dry density of the buffer material.

Excess manganese differentially inhibits photosystem I versus II in Arabidopsis thaliana.

The effects of exposure to increasing manganese concentrations (50-1500 µM) from the start of the experiment on the functional performance of photosystem II (PSII) and photosystem I (PSI) and photosynthetic apparatus composition of Arabidopsis thaliana were compared. In agreement with earlier studies, excess Mn caused minimal changes in the PSII photochemical efficiency measured as F(v)/F(m), although the characteristic peak temperature of the S(2/3)Q(B) (-) charge recombinations was shifted to lower temperatures at the highest Mn concentration. SDS-PAGE and immunoblot analyses also did not exhibit any significant change in the relative abundance of PSII-associated polypeptides: PSII reaction centre protein D1, Lhcb1 (major light-harvesting protein of LHCII complex), and PsbO (OEC33, a 33 kDa protein of the oxygen-evolving complex). In addition, the abundance of Rubisco also did not change with Mn treatments. However, plants grown under excess Mn exhibited increased susceptibility to PSII photoinhibition. In contrast, in vivo measurements of the redox transients of PSI reaction centre (P700) showed a considerable gradual decrease in the extent of P700 photooxidation (P700(+)) under increased Mn concentrations compared to control. This was accompanied by a slower rate of P700(+) re-reduction indicating a downregulation of the PSI-dependent cyclic electron flow. The abundance of PSI reaction centre polypeptides (PsaA and PsaB) in plants under the highest Mn concentration was also significantly lower compared to the control. The results demonstrate for the first time that PSI is the major target of Mn toxicity within the photosynthetic apparatus of Arabidopsis plants. The possible involvement mechanisms of Mn toxicity targeting specifically PSI are discussed.

Influence of increased left ventricular myocardial mass on early and late mortality after cardiac surgery.

BACKGROUND: Increased left ventricular mass (LVM) is a well-recognized predictor of cardiovascular morbidity and mortality in epidemiological studies, but its impact on mortality after cardiac surgery is poorly defined. We hypothesized that patients with increased LVM index (LVMI) were more likely to have greater 30 day and 1 yr mortality. METHODS: With IRB approval, intraoperative transoesophageal echocardiography images of 844 cardiac surgical patients were reviewed. LVMI was calculated using the American Society of Echocardiography recommended formula. Outcome variables studied were 30 day and 1 yr mortality. RESULTS: Mortality within 30 days occurred in 28 patients (3.3%) and within 1 yr in 91 patients (10.8%). An almost linear relationship was found between increasing LVMI and the risk of mortality within 30 days of cardiac surgery. The odds ratio (OR) of dying within 30 days of surgery was 1.15 (95% confidence interval 1.01-1.31) per 20 g m(-2) increase in LVMI. This finding remained statistically significant in multivariate analysis controlling for the effects of age, weight, gender, surgery type, LV function, and functional status [OR=1.36 (1.11-1.66) per 20 g m(-2) increase]. Increased LVMI was not found to be a statistically significant predictor of 1 yr mortality. CONCLUSIONS: Increased LVMI, but not LV systolic function as measured by the fractional area of contraction (FAC) was identified as a strong independent predictor of perioperative mortality after adult cardiac surgery. The relationship between LVMI and risk of 30 day mortality was nearly linear. Furthermore, decreased FAC, and not LVMI, was a strong independent predictor of 1 yr mortality.

Circulating endothelial progenitor cells are inversely correlated with in-stent restenosis in patients with non-ST-segment elevation acute coronary syndromes treated with EPC-capture stents (JACK-EPC trial).

AIM: Aim of the study was to evaluate the association between circulating endothelial progenitor cells (EPCs) and angiographic outcomes after implantation of GenousTM stent in patients with non-ST-segment elevation acute coronary syndromes (ACS) (NSTE-ACS) undergoing urgent percutaneous coronary intervention (PCI). METHODS: Sixty patients treated with EPC-capture stent (N.=30) or bare metal stents (BMS) (N.=30) receiving 80 mg atorvastatin and dual antiplatelet therapy (DAT) for 12 months. Restenosis was assessed after 6 months by quantitative coronary angiography (QCA) and major acute coronary events (MACE) evaluated after 6 and 12 months. INCLUSION CRITERIA: de novo lesion >70% in native vessel, diameter 2.5-4 mm, lesion length <30 mm. EXCLUSION CRITERIA: diabetes, previous revascularization, significant left main stenosis, chronic total occlusions (CTO) and multivessel disease. RESULTS: Majority of patients in EPC-capture stent and BMS groups presented with NSTEMI (73.3% and 70%, respectively). Mean stent length was 20.1±8 and 19.9±10 mm, diameter 3±0.97 and 3.1±0.88 mm in respective groups. The binary restenosis was significantly lower in GenousTM (13 vs. 26.6%, P=0.04). Risk of MACE after 6 and 12 months were comparable in both groups. There was no stent thrombosis. Numbers of circulating EPCs were significantly approximately 2-fold higher during the ACS than after 6 months. Mobilization of EPCs during acute ischemia was significantly lower in patients who developed restenosis after 6 months (3 vs. 4.5 cells/µL, P=0.002) and it was negatively correlated with late-loss after 6 months (R=-0.42; P<0.03). CONCLUSION: Use of GenousTM stents in NSTE-ACS is associated with lower restenosis rate than BMS at 6 months. There was no ST through 1 year. The number of circulating EPCs is inversely correlated with in-stent late loss (LL).

Spectroscopic studies of heavy metal cations influence on the structure of synthetic hydrated calcium aluminosilicates.

Calcium aluminosilicate hydrates (C-(A)-S-H) with two different C/S molar ratios of 1.0 and 1.7 were synthesized by precipitation with the use of the alkali-activation method. The samples were synthesized with solutions of heavy metals nitrates such as nickel (Ni), chromium (Cr), cobalt (Co), lead (Pb), and zinc (Zn). Metal cations were added in the amount of Ca:Me equal to 9:1, while Al/Si was 0.05. The influence of the addition of heavy metal cations on the structure of the C-(A-)S-H phase was investigated. For this purpose, XRD was used to examine the phase composition of the samples, FT-IR and Raman spectroscopy were used to determine the effect of heavy metal cations on the structure of the obtained C-(A)-S-H phase and their degree of polymerization. Using SEM and TEM, changes in the morphology of the obtained materials were determined. Possible mechanisms of immobilization of heavy metal cations have been determined. It was found that some heavy metals (Ni, Zn, and Cr) could be immobilized by precipitation of insoluble compounds. On the other hand, they could remove Ca2+ ions from the structure of aluminosilicate and take their place, as evidenced by the crystallization of Ca(OH)2 in samples with the addition of Cd, but also Ni and Zn in small amounts. A third possibility is the incorporation of heavy metal cations at the silicon and/or aluminum tetrahedral sites, as is the case with Zn.

Targeted therapies for glioblastoma treatment.

Glioblastoma, the most common and aggressive type of brain tumor in adults, poses significant challenges in terms of treatment. Conventional approaches including surgery, chemotherapy, and radiotherapy have yielded limited success, with a median survival of approximately 15 months. However, extensive research into the biology of glioblastoma has identified molecular targets that can be exploited by newly developed drugs, leading to the emergence of precise personalized therapies. Several innovative treatment strategies are currently under development, aiming to enhance effectiveness while minimizing side effects. Clinical trials are underway to evaluate the efficacy of monoclonal antibodies that target glioblastoma cells, either by blocking specific receptors or by modifying molecular interactions that impede cell proliferation. Another promising avenue involves the use of oncolytic viruses designed to selectively infect glioblastoma cells. Additionally, the review explores the utilization of nanocarriers capable of surmounting the formidable obstacle of the blood-brain barrier, enabling efficient drug delivery. Cell therapies represent another promising approach, with dendritic cells, chimeric antigen receptor-T cells, and macrophages emerging as potential treatment modalities. By summarizing recent advances in targeted therapies against glioblastoma, this review aims to provide a comprehensive overview of ongoing efforts to discover effective and safe methods for treating glioblastoma patients. The ultimate goal is to improve patient outcomes and transform the landscape of glioblastoma treatment.