Induction of the pro-myelocytic leukaemia gene by type I and type II interferons.

The physiological role of the pro-myelocytic leukaemia (PML) gene product is poorly defined. Among other functions, PML is involved in haematopoietic differentiation and in control of cell growth and tumorigenesis. We investigated the regulation of human PML expression by interferons (IFNs) and IL-1 in various human haematopoietic lines (U937, THP1, HL60, NB4), in human diploid fibroblasts and in human peripheral blood leukocytes. Cytokine-induced modulation of PML expression was assessed by Northern blot analyses, flow cytometry studies and in situ immunolabelling. Our data show that IFNs and IL-1 upregulate PML transcript and protein expression in a time and dose-dependent manner. In situ immunolabelling revealed that upregulation of protein expression by IFN-alpha is a consequence of a marked increase in both the number and the intensity of the staining of so-called PML nuclear bodies. Our data suggest that stimulation of PML expression by interferons and IL-1 may account for upregulation of PML proteins observed in inflammatory tissues and in proliferative states

Time, institutional support and quality of decision making in child protection:A cross-country analysis

This paper examines perceptions of time and institutional support for decision making and staff confidence in child welfare staffs ultimate decisions – examining differences and similarities between and within the service-oriented Nordic countries (Norway and Finland) and the risk-oriented Anglo-American countries (England and California). The study identifies a high degree of work pressure across all the countries, lines of predominantly vertical institutional support and relatively high confidence in decisions. Finland stands out with higher perceived work pressure and with a horizontal support line, whereas England stands out with workers having a lower degree of confidence in their own and others’ decisions

Pharmacological inhibition of c-Abl compromises genetic stability and DNA repair in Bcr-Abl-negative cells

Imatinib inhibits the kinase activity of Bcr-Abl and is currently the most effective drug for treatment of chronic myeloid leukemia (CML). Imatinib also blocks c-Abl, a physiological tyrosine kinase activated by a variety of stress signals including damaged DNA. We investigated the effect of pharmacological inhibition of c-Abl on the processing of irradiation-induced DNA damage in Bcr-Abl-negative cells. Cell lines and peripheral blood mononuclear cells (PBMCs) from healthy volunteers were treated with imatinib or dasatinib before gamma-irradiation. Inhibition of c-Abl caused an enhanced irradiation-induced mutation frequency and slowdown of DNA repair, whereas imatinib was ineffective in cells expressing a T315I variant of c-Abl. Mutation frequency and repair kinetics were also studied in c-Abl-/- murine embryonic fibroblasts (MEFs) retransfected with wild-type c-Abl (wt-Abl) or a kinase-defect variant of Abl (KD-Abl). Enhanced mutation frequency as well as delayed DNA repair was observed in cells expressing KD-Abl. These data indicate that pharmacological inhibition of c-Abl compromises DNA-damage response

Marker-free cell discrimination by holographic optical tweezers

We introduce a method for marker-free cell discrimination based on optical tweezers. Cancerous, non-cancerous, and drug-treated cells could be distinguished by measuring the trapping forces using holographic optical tweezers. We present trapping force measurements on different cell lines: normal pre-B lymphocyte cells (BaF3; "normal cells"), their Bcr-Abl transformed counterparts (BaF3-p185; "cancer cells") as a model for chronic myeloid leukaemia (CML) and Imatinib treated BaF3-p185 cells. The results are compared with reference measurements obtained by a commercial flow cytometry system

Issues concerning the implementation of the CCS Directive in the Netherlands

In June 2009, the EU Directive on the Geological Storage of Carbon Dioxide entered into force. The European Member states are obliged to transpose the directive in their national legislations no later than 25 June 2011. The EU legislator has applied a regime of minimum harmonisation when drafting the CCS Directive, amongst others to achieve that an agreement could be reached on the CCS Directive by a majority of Member States. In other words; Member States have considerable discretionary powers while implementing the Directive. The CO2 Storage Directive is mainly transposed into Dutch legislation by means of adaptation of the Dutch Mining Act. There are, however, still some issues in the implementation of this directive that need further clarification. The way these issues are addressed may impact the deployment of large-scale CO2 capture and storage (CCS) in the Netherlands and Europ

Spiritual well-being and associated factors in Dutch patients with advanced cancer

CONTEXT: Palliative care aims to support patients' spiritual needs with the intention of promoting their spiritual well-being (SWB), an important dimension of quality of life. SWB is one of the less-studied dimensions of QoL, particularly in a secular country such as the Netherlands. OBJECTIVES: In this study we aimed to get a better understanding of SWB in Dutch patients with advanced cancer. We therefore examined its prominence and associated factors. METHODS: We used the baseline data of a cohort study on experienced quality of care and quality of life (eQuiPe study), which included 1,103 patients with advanced cancer. In addition to sociodemographic and religious/spiritual characteristics, study measures comprised the SWB subscales Meaning, Peace, and Faith of the revised FACIT-Sp-12, spiritual problems and needs (PNPCsv), quality of life (EORTC-QLQ-C30) and satisfaction with healthcare professionals' interpersonal skills (INPATSAT-32). RESULTS: On average, patients experienced quite a bit of Meaning (8.9, SD 2.3), a little bit to somewhat Peace (6.8, SD 2.7), and very low levels of Faith (2.9, SD 3.7). Two-thirds (71%) of patients reported one or more spiritual problems, for which the majority (54%) wanted to receive attention. In the final multivariable models, only a few factors were associated with SWB, such as greater spiritual needs with lower levels of Meaning and Peace. CONCLUSION: Dutch patients with advanced cancer experience medium to low levels of Meaning, Peace, and Faith. More attention for their SWB is warranted

Reduction in potentially inappropriate end-of-life hospital care for cancer patients during the COVID-19 pandemic:A retrospective population-based study

Background: The COVID-19 pandemic impacted cancer diagnosis and treatment. However, little is known about end-of-life cancer care during the pandemic. Aim: To investigate potentially inappropriate end-of-life hospital care for cancer patients before and during the COVID-19 pandemic. Design: Retrospective population-based cohort study using data from the Netherlands Cancer Registry and the Dutch National Hospital Care Registration. Potentially inappropriate care in the last month of life (chemotherapy administration, &gt;1 emergency room contact, &gt;1 hospitalization, hospitalization &gt;14 days, intensive care unit admission or hospital death) was compared between four COVID-19 periods and corresponding periods in 2018/2019. Participants: A total of 112,919 cancer patients (⩾18 years) who died between January 2018 and May 2021 were included. Results: Fewer patients received potentially inappropriate end-of-life care during the COVID-19 pandemic compared to previous years, especially during the first COVID-19 peak (22.4% vs 26.0%). Regression analysis showed lower odds of potentially inappropriate end-of-life care during all COVID-19 periods (between OR 0.81; 95% CI 0.74–0.88 and OR 0.92; 95% CI 0.87–0.97) after adjustment for age, sex and cancer type. For the individual indicators, fewer patients experienced multiple or long hospitalizations, intensive care unit admission or hospital death during the pandemic. Conclusions: Cancer patients received less potentially inappropriate end-of-life care during the COVID-19 pandemic. Because several factors may have contributed, it is unclear whether this reflects better quality care. However, these findings raise important questions about what pandemic-induced changes in care practices can help provide appropriate end-of-life care for future patients in the context of increasing patient numbers and limited resources.</p

Зміни активності NO-синтаз та аргінази у тканині підшлункової залози при введенні L-аргініну або аміногуанідину за умов стрептозотоцин-індукованої гіперглікемії

При стрептозотоцин-индуцированной гипергликемии у крыс изучали влияние L-аргинина и селективного блокатора индуцибельной NO-синтазы аминогунидина на активность NO-синтаз и аргиназы в ткани поджелудочной железы. Показано, что как L-аргинин, так и аминогуанидин снижают активность индуцибельной NO-синтазы, при этом L-аргинин выражено понижает концентрацию глюкозы в крови и повышает активность аргиназы, что свидетельствует об усилении неокислительного пути его метаболизма.The influence of L-arginine and selective inducible NO-synthase blocker aminoguanidine on the activity of NO-synthases and arginase in pancreatic tissue in rats under conditions of streptozotocin-induced hyperglycemia was investigated. It was shown, that both L-arginine and aminoguanidine decrease the activity of inducible NO-synthase, whereas L-arginine supplementation significantly decreases the glucose concentration in blood and increases the activity of arginase, giving evidence about the enhancement of nonoxidative pathway of its metabolism

Continuity of care for patients with de novo metastatic cancer during the COVID-19 pandemic:A population-based observational study

During the COVID-19 pandemic recommendations were made to adapt cancer care. This population-based study aimed to investigate possible differences between the treatment of patients with metastatic cancer before and during the pandemic by comparing the initial treatments in five COVID-19 periods (weeks 1–12 2020: pre-COVID-19, weeks 12–20 2020: 1st peak, weeks 21–41 2020: recovery, weeks 42–53 2020: 2nd peak, weeks 1–20 2021: prolonged 2nd peak) with reference data from 2017 to 2019. The proportion of patients receiving different treatment modalities (chemotherapy, hormonal therapy, immunotherapy or targeted therapy, radiotherapy primary tumor, resection primary tumor, resection metastases) within 6 weeks of diagnosis and the time between diagnosis and first treatment were compared by period. In total, 74,208 patients were included. Overall, patients were more likely to receive treatments in the COVID-19 periods than in previous years. This mainly holds for hormone therapy, immunotherapy or targeted therapy and resection of metastases. Lower odds were observed for resection of the primary tumor during the recovery period (OR 0.87; 95% CI 0.77–0.99) and for radiotherapy on the primary tumor during the prolonged 2nd peak (OR 0.84; 95% CI 0.72–0.98). The time from diagnosis to the start of first treatment was shorter, mainly during the 1st peak (average 5 days, p &lt;.001). These findings show that during the first 1.5 years of the COVID-19 pandemic, there were only minor changes in the initial treatment of metastatic cancer. Remarkably, time from diagnosis to first treatment was shorter. Overall, the results suggest continuity of care for patients with metastatic cancer during the pandemic.</p