Compartmental stress responses correlate with cell survival in bystander effects induced by the DNA damage agent, bleomycin

In collaboration with Horia Hulubei National Institute of Physics and Nuclear Engineering - IFIN HH, 30 Reactorului St., P.O.BOX MG-6, Magurele, Bucharest, ROMANIA The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link

Bystander effects and compartmental stress response to X-ray irradiation in L929 cells.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Bystander effects are indirect consequences of radiation and many other stress factors. They occur in cells that are not directly exposed to these factors, but receive signals from affected cells either by gap junctions or by molecules released in the medium. Characterizing these effects and deciphering the underlying mechanisms involved in radiation-induced bystander effects are relevant for cancer radiotherapy and radioprotection. At doses of X-ray radiation 0.5 and 1 Gy, we detected bystander effects as increased numbers of micronuclei shortly after the treatment, through medium transfer and by co-cultures. Interestingly, bystander cells did not exhibit long-term adverse changes in viability. Evaluation of several compartmental stress markers (CHOP, BiP, mtHsp60, cytHsp70) by qRT-PCR did not reveal expression changes at transcriptional level. We investigated the involvement of ROS and NO in this process by addition of specific scavengers of these molecules, DMSO or c-PTIO in the transferred medium. This approach proved that ROS but not NO is involved in the induction of lesions in the acceptor cells. These results indicate that L929 cells are susceptible to stress effects of radiation-induced bystander signaling

Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026

Background The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. Methods In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. Findings In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95$7·3 trillion (95% UI 7·2–7·4) in 2019; 293·7 times the $24·8 billion (95$43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and$37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11–21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP. Interpretation There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained

The Role of MiR-124 in Bladder Cancer – A Review of the Literature

MicroRNAs (miRNAs) are a group of non-coding RNA molecules that have an important role in modulating the expression of genes involved in regulating cellular functions. A growing number of studies suggest the abnormal expression of microRNAs in different types of cancer cells. MiRNA-124 is a microRNA that is down-regulated in many types of cancer cells, including bladder cancer. Our objective is to provide a review of the key publications that studied the effect of miR-124 on bladder cancer. This review focus on the targets and different pathways of miR-124 that were identified in various studies and differences between their expressions in normal urothelium and tumor tissues. We also include data regarding urinary methylations levels of miR-124 and their role in bladder cancer diagnosis and prognosis. Subsequently, we establish future perspectives of miR-124 research and its promising role in bladder cancer

Chromosomal radiosensitivity in secondary-progressive multiple sclerosis patients

Purpose: To investigate chromosomal radiosensitivity of secondary progressive (SP) multiple sclerosis (MS) patients in comparison to a group of healthy individuals. Material and methods: Chromosomal radiosensitivity was assessed in vitro with the G2 assay and the GO-micronucleus (MN) assay. For the G2 assay phytohaemagglutinin (PHA) stimulated blood cultures were irradiated with a close of 0.4 Gy Co-60 gamma rays in the G2 phase of the cell cycle. For the MN assay unstimulated diluted blood samples were exposed to 3.5 Gy (CO)-C-60 gamma rays delivered at a high dose-rate (HDR = 1 Gy/min) or low dose-rate (LDR = 4 mGy/mim). Results: No significant differences in the number of chromatid breaks were observed between MS patients and healthy individuals. With the G0-MN assay a higher spontaneous MN yield was found in MS patients. At HDR irradiation no significant differences were shown, while at LDR irradiation, MS patients were found less sensitive than healthy controls. The dose-rate sparing index was higher for MS patients, pointing to a better repair capacity. Conclusions: MS patients are not characterised by an enhanced in vitro chromosomal radiosensitivity. The radioresistant response, which was only observed with the MN assay after LDR irradiation, may point to an adaptive response induced by in vivo oxidative stress in SPMS patients

Emergency Care for Burn Patients—A Single-Center Report

Burns, one of the main public health problems, lead to significant mortality and morbidity. Epidemiological studies regarding burn patients in Romania are scarce. The aim of this study is to identify the burn etiology, demographics, clinical characteristics, and outcomes in patients requiring treatment in a regional burn unit. Design. We performed a retrospective observational study of 2021. Patients. All patients admitted to our six-bed intensive care unit (ICU) were included. Interventions. The following data were collected for further analysis: demographics, burn pattern (etiology, size, depth, affected body region), type of ventilation, ABSI (Abbreviated Burn Severity Index) score, comorbidities, bioumoral parameters, and hospitalization days. Results. There were 93 burned patients included in our study that were divided into two groups: alive patients’ group (63.4%) and deceased patients’ group (36.6%). The mean age was 55.80 ± 17.16 (SD). There were 65.6% male patients, and 39.8% of the patients were admitted by transfer from another hospital. Further, 59 patients presented third-degree burns, from which 32.3% died. Burns affecting >37% of the total body surface area (TBSA) were noticed in 30 patients. The most vulnerable regions of the body were the trunk (p = 0.003), the legs (p = 0.004), the neck (p = 0.011), and the arms (p = 0.020). Inhalation injury was found in 60.2% of the patients. The risk of death in a patient with an ABSI score > 9 points was 72 times higher. Comorbidities were present in 44.1% of the patients. We observed a median LOS (length of stay) of 23 days and an ICU-LOS of 11 days. Logistic regression analysis showed that admission protein, creatinkinase, and leukocytes were independent risk factors for mortality. The general mortality rate was 36.6%. Conclusion. A thermal factor was responsible for the vast majority of burns, 94.6% of cases being accidents. Extensive and full-thickness burns, burns affecting the arms, inhalation injuries, the need for mechanical ventilation, and a high ABSI score represent important risk factors for mortality. Considering the results, it appears that prompt correction of protein, creatinkinase, and leukocytes levels may contribute to improvement in severe burn patients’ outcomes

Epidemiological Characteristics and Mortality Risk Factors Comparison in Dialysis and Non-Dialysis CKD Patients with COVID-19—A Single Center Experience

(1) Background: Despite some controversies between studies, chronic kidney disease (CKD) has a negative impact on COVID-19 outcomes, with patients presenting a higher mortality risk than in the general population. Studies have shown an association between COVID-19 severe cases and different inflammatory biomarkers. The aim of this study was to emphasize the epidemiological characteristics of CKD patients diagnosed with COVID-19 and to determine if the risk of mortality, and the severity of this infection might be influenced by different parameters. (2) Methods: Our retrospective study included CKD patients with COVID-19—362 in the non-dialysis group and 132 in the dialysis group. (3) Results: There were significant statistical differences between our groups regarding age (p < 0.001), hemoglobin (p < 0.001), interleukin-6 (p < 0.001), serum albumin (p = 0.016), procalcitonin (p = 0.002), ferritin (p < 0.001), and of course serum creatinine (p < 0.001). Even if the risk of death was higher in the dialysis group (Exp(b) = 1.839), the survival proportions were similar in both groups. (4) Conclusions: High values of hemoglobin, serum creatinine, and LDH at admission, age, length of hospital stay ≤ 10 days, and a pulmonary impairment > 25% are responsible for an adverse outcome in non-dialysis and dialysis patients diagnosed with COVID-19