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Abstract The p53 protein, encoded by the TP53 gene, serves as a critical tumor suppressor, playing a vital role in maintaining genomic stability and regulating cellular responses to stress. Dysregulation of p53 is frequently observed in hematological malignancies, significantly impacting disease progression and patient outcomes. This review aims to examine the regulatory mechanisms of p53, the implications of TP53 mutations in various hematological cancers, and emerging therapeutic strategies targeting p53. We conducted a comprehensive literature review to synthesize recent findings related to p53's multifaceted role in hematologic cancers, focusing on its regulatory pathways and therapeutic potential. TP53 mutations in hematological malignancies often lead to treatment resistance and poor prognosis. Current therapeutic strategies, including p53 reactivation and gene therapy, show promise in improving treatment outcomes. Understanding the intricacies of p53 regulation and the consequences of its mutations is essential for developing effective diagnostic and therapeutic strategies in hematological malignancies, ultimately enhancing patient care and survival.

In this study, we discuss the existence and impact of microplastics in different ecosystems, including water, soil, air, and the human body, as well as the absorption of pollutants into these microplastic particles. Airborne microplastics have been detected in the atmosphere as well as indoors and outdoors. Microplastics in the air, in addition to inherent toxicity, may cause more risks to human health and the environment than virgin microplastics through the absorption of pollutants and chemicals. Due to the widespread use of plastics around the world, the abundance of microplastics in aquatic environments has increased. Microplastics can be ingested by a wide range of marine organisms, so it is possible that contaminated microplastics cause mechanical damage to organisms and there is also the possibility of contamination being transmitted to marine organisms and the marine food web. Accumulation of microplastics in the soil can cause them to be absorbed by plants and transport these microplastic particles and pollutants absorbed by them along the food chain. Highly populated urban centers, industries or large-scale agriculture are the main causes of soil contamination by microplastics. Microplastics can find their way into the food we eat, the water we drink, and even the air we breathe. Researchers were able to find microplastic particles in all human tissues studied.

Background: Radon is a colorless and odorless radioactive gas that is considered a leading cause of lung cancer. Given this need, the main objective of this policy brief was to discuss the need to pay attention to the prevention and control of indoor radon (IRD) in Iran. Methods: To prepare this policy summary, which is similar to a narrative review, scientific reports and studies conducted in Iran over the past two decades were first obtained by searching reliable national and international databases. Then, based on the main results of the above studies, the general level of IRD concentration in the main regions of Iran was determined. Finally, by using the experiences and measures in other countries, necessary recommendations for the prevention and mitigation of IRD were made Results: By evaluating the findings of previous studies conducted in Iran, it was found that the level of IRD in residential and non-residential buildings evaluated in Iran, in most cases, was higher than the global average (40 bq/m3). In addition, in some cases, it was higher than the acceptable level by World Health Organization (100 bq/m3). Conclusion: Based on the findings, it can be concluded that it is very necessary to educate the public, engineers and health and municipal inspectors about the health risks of exposure to radon. In addition, it is necessary to take basic and preventive measures to mitigation radon in homes.

Most of the scientific and economic observers expect electric vehicles (EVs) to reach more than one-third of new vehicle sales, by 2022 [1]. This growth will be even more pronounced in 2040, when it’s expected that more than 40 million of electric vehicles will be sold each year worldwide, leading to a considerable need for electrical energy (the equivalent of the production of about twenty nuclear power plants). This growth cannot be ensured if we do not radically transform our power supply technologies (new generations of batteries, new engines, new supply strategies, etc.) especially since the principal materials for batteries are projected to disappear in the next thirty years. Fortunately, new technologies for charging EVs are appearing (fast charging stations, inductive charging stations), which could help to reducing the need for larger batteries. However, these technologies require significant investment and heavy urban redevelopment. It is therefore important to find a way to optimize these investments both economically and technologically. In this paper, we will focus on electric vehicles and propose a model to optimize the urban infrastructure planning of energy supply stations. we have developed a new approach of infrastructure optimization based on battery charging platform existing technologies and their location in a city. A decision support tool applied to territorial planning is developed in this study.

Although vitamin D insufficiency has been correlated with an increased risk of cardiovascular disease (CVD), there are few data on the association between 25-hydroxyvitamin D (25(OH)D) and atherogenic indices predictive of CVD. This study investigated the relationship of vitamin D status with lipid profile and atherogenic indices in adult women in Morocco. Three hundred women aged 18 to 50 years from Meknes were included. Fasting 25(OH)D and lipid concentrations were assayed by a one-step electrochemiluminescence-based immunoassay and an enzymatic method, respectively. Atherogenic indices (atherogenic index of plasma (AIP), atherogenic coefficient (AC), non-HDL cholesterol (non-HDL-C), Castelli risk indices I and II (CRI-I and II), and CHOLIndex (CI)) were calculated using conventional lipid parameters. Logistic regression models and operating characteristic curve (ROC) analysis were used to assess the relationship of the variables and estimate the threshold of 25(OH)D levels associated with high atherogenic indices. 25(OH) D below 20 ng/mL was significantly associated with an enhanced risk of hypertriglyceridemia and elevated values of AIP, AC, non-HDL-C, and CRI-I with an OR (95% CI) of 4.904 (1.856–12.959), 3.637 (2.149–6.158), 3.589 (1.673–7.700), 2.074 (1.215–3.540), and 2.481 (1.481–4.123), respectively. According to the ROC analysis, the likelihood of hypertriglyceridemia and high values of AIP, AC, non-HDL-C, and CRI-I were associated with 25(OH)D thresholds ≤15.15 ng/mL, ≤17.5 ng/mL, ≤19.8 ng/mL, ≤20.1 ng/mL, and ≤19.5 ng/mL, respectively, all p < 0.01. Based on the atherogenic indices, this study indicates that vitamin D below 20 ng/mL may increase the risk of cardiovascular disease in adult women. Additional health measures are essential to raise awareness among women and health professionals of preventing and controlling cardiovascular risk factors, particularly among young individuals.

Abstract Background It is believed that loss of p53 function plays a crucial role in the progression of well to poorly differentiated thyroid cancers including anaplastic thyroid carcinoma (ATC). Given the poor prognosis of ATC due to its strong therapeutic resistance, there is a need to establish new therapeutic targets to extend the survival of ATC patients. Activating transcription factor 3 (ATF3) can inhibit the oncogenic activity of mutant p53 and, as a result, contribute to tumor suppression in several TP53-mutated cancers. Herein, we demonstrate that the ectopic overexpression of ATF3 leads to the suppression of oncogenic mutant p53 activity in chemo-resistant 8305 C thyroid cancer cells harboring R273C p53 gene mutation. Methods The biological behavior of 8305 C cells was assessed pre- and post-transfection with pCMV6-ATF3 plasmid using MTT assay, fluorescent microscopy, cell cycle, and annexin V/PI flow cytometric analysis. The effect of ectopic ATF3 overexpression on the cellular level of p53 was examined by western blotting assay. The mRNA expression levels of TP53, TAp63, ΔNp63, and SHARP1 were evaluated in ectopic ATF3-expressing cells compared to controls. Results The overexpression of ATF3 in 8305 C thyroid cancer cells significantly decreased cell viability and induced apoptosis and cell cycle arrest in vitro. The immunoblotting of p53 protein revealed that ATF3 overexpression significantly increased the level of mutant p53 in 8305C cells compared to mock-transfected control cells. Additionally, elevated mRNA levels of TAp63 and SHARP1 and a decreased mRNA level of ΔNp63 were observed in PCMV6-AC-ATF3-transfected 8305 C cells with significant differences compared to the mock and untreated cells. Conclusion In light of our findings, it is evident that therapeutic strategies aimed at increasing ATF3 expression or enhancing the interaction between ATF3 and mutant p53 can be a promising approach for the treatment of p53-mutated metastatic thyroid cancer.

In this study, the sources of microplastics in the environment, the ways of human exposure to microplastics, how to deal with them, and the policies and laws of different countries in this regard are discussed. Most of the microplastic pollution comes from textiles, tires and urban dust, which make up more than 80% of the microplastics in the environment. The human body is exposed to microplastics through eating food containing microplastics, inhaling microplastics in the air, and skin contact with these particles in products, textiles, or in dust. The main route of human exposure to microplastic particles in human diet is food and drink. Microplastics can enter food during food processing, storage, transportation and packaging process. Airborne microplastics are an underestimated hazard, potentially reaching deep into human lungs because they can pass through the defensive respiratory system. Humans may also be exposed to microplastics through skin contact, following the atmospheric fallout, in this case hair follicles, sweat glands or damaged skin are all ways of entry. Some researchers have suggested burning plastics and recovering the resulting energy. Nevertheless, plastic recycling is considered a more efficient solution because this method reduces the amount of plastic waste produced as opposed to burning.

Abstract Background Burnout is a growing problem in medical education, and is usually characterised by three dimensions: emotional exhaustion, cynicism, and reduced professional efficacy. Currently, the majority of burnout studies have been conducted in western high-income countries, overshadowing findings from low- and middle-income countries. Our objective is to investigate burnout and its associated predictive factors in Morocco, aiming to guide intervention strategies, while also assessing differences between the preclinical and clinical years. Methods A cross-sectional, self-administered online survey assessing burnout dimensions and its main determinants was distributed among medical students at Université Mohammed VI des Sciences et de la Santé (UM6SS, Casablanca, Morocco). Descriptive analyses involved computing mean scores, standard deviations and Pearson correlations. Further, t-tests were performed to check for significant differences in burnout dimensions across the preclinical and clinical learning phase, and stepwise linear regression analyses were conducted using a backward elimination method to estimate the effects of the selected variables on the three burnout dimensions. Results A t-test assessing the difference in cynicism found a significant difference between students at the preclinical phase and the clinical phase, t(90) = -2.5, p = 0.01. For emotional exhaustion and reduced professional efficacy no significant difference was observed. A linear regression analysis showed that emotional exhaustion was significantly predicted by workload, work-home conflict, social support from peers and neuroticism. Cynicism was predicted by the learning phase, workload, meaningfulness and neuroticism; and reduced professional efficacy by neuroticism only. Conclusions Our findings suggest a potential gradual increase in cynicism during medical education in Morocco. Conducting this study in a low- and middle income country has enhanced the scientific understanding of burnout in these regions. Given the identified predictive factors for burnout, such as workload, work-home conflict, support from peers, neuroticism, and meaningfulness, it is necessary to focus on these elements when developing burnout interventions.

Abstract Background Designing and preparing a co-delivery system based on polymeric micelles have attracted in recent years. Co-delivery of anti-cancer agents within pH-sensitive polymeric micelles could provide superior advantages over the co-administration of free drugs, since it enables simultaneous delivery of drugs to reach an optimum synergistic dose right to the tumor. Methods DOX was conjugated to the polymer through a hydrazine linker by Schiff’s base reaction. Then, DTX was encapsulated into the core of the polymer to the resulting DOX-Hyd-PM/DTX micelle with optimum molar ratios of 1:1 and 1:5 (DOX/DTX). Results The final formulations showed the desired particle size and increased release of DOX and DTX in acidic media (pH 5.5). The cytotoxicity assay of DOX-Hyd-PM/DTX indicated the highest synergistic effect on both 4T1 and TUBO cell lines over other formulations. Interestingly, in accordance with in vitro results, DOX-Hyd-PM/DTX revealed a promising anti-tumor activity in mice-bearing 4T1 breast cancer tumor with higher tumor accumulation of DOX and DTX after 24 h compared to free drugs combination. Conclusions These findings point to the potential use of such smart nanodrug delivery systems in cancer treatment, where the synergistic effect of both drugs may be used to enhance therapeutic response. Graphical Abstract

Objective(s): Currently, the most important treatment approach for hemophilia type A is recombinant Factor VIII. However, due to its low retention time in the blood, the patients usually need successive injections. In addition, neutralization of injected proteins by antibodies complicates treatment. We examined the prolongation of the persistence time of injectable FVIII in the blood and the potential effects on survival using promising PEGylated liposomes (PEGLip) utilizing hydrogenated soy phosphatidylcholine (HSPC, Tm= 54.5 ºC) and 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC, Tm= – 2 ºC).Materials and Methods: Nanoliposomes with different percentages of PEG (3% and 5%) were obtained via the thin film hydration procedure and extrusion. Liposomal FVIII formulation was prepared and characterization was done.Results: The results revealed that the formulations are in the 80–120 nm range with uniform dispersion, which was confirmed using transmission electron microscopy (TEM) imaging. The phase transition temperature (Tm) of the liposomes was obtained by differential scanning calorimetry (DSC). With an attachment efficacy of approximately 87%, proteins bind non-covalently yet with a strong affinity to the exterior of PEGLip. The final formulations underwent additional examination. No significant change was observed in size, charge, and PDI between the FVIII-conjugated liposomal formulations and their liposomal nanoparticles. The selected formulations were injected into BALB/c mice. The circulation time and potential clotting effectiveness of PEGLip-FVIII are vastly improved over free protein, in non-hemophilic mice. Conclusion: The obtained results showed that using phospholipids with high Tm (HSPC) can improve the hemostatic efficiency of liposomes more than phospholipids with low Tm (POPC).

ObjectiveDepression is often characterized by a persistent sense of failure. Cognitive theories of depression suggest that depressed individuals may exhibit a maladaptive cognitive style, characterized by increased self-focus following personal failure. The validity of this proposition, however, is yet to be fully examined. This study aimed to identify the relation between symptoms in major depressive disorder and increased self-focus in failure situations.MethodsThis clinical study involved a cohort of 30 patients diagnosed with and treated for depression. We used an eye-tracking paradigm to observe and analyze gaze direction – indicative of either self-focus or self-avoidance – after remembering a significant failure event.ResultsContrary to the maladaptive cognitive style hypothesis, a majority of the depressed participants demonstrated an inclination towards self-avoidance following failure. Nevertheless, approximately 30% of the patient group – those with the highest scores of guilt, punishment, and self-blame – displayed a self-focused attentional bias post-failure.ConclusionsThe presence of a maladaptive self-focusing style may be confined to severely depressed patients with high levels of guilt, punishment, and self-blame. These findings could have substantial clinical implications, as attention bias modification interventions could be particularly beneficial for this subgroup of patients.

Abstract Background Rezūm™ is a relatively new bladder outflow obstruction (BOO) procedure that uses thermal energy through water vapour to cause necrosis of prostatic tissue. The standard delivery of this treatment is in an operating theatre under a general or spinal anaesthetic, or under local anaesthetic with sedation that requires patient monitoring. Methods We propose an outpatient daycase method of delivering Rezūm™ under local anaesthetic without sedation, using a prostatic local anaesthetic block and cold local anaesthetic gel instillation into the urethra. Results Preliminary results of our first thirteen patients demonstrate the feasibility of this new technique, with a mean pain score of 2.1 out of 10 on a visual analogue scale, a successful trial without catheter in all 13 patients (one patient voided successfully on second trial), a reduction in mean International Prostate Symptom Score (IPSS) from 20.6 to 5.4, and improvement in maximum flow from 8.8 ml/s to 14.4 ml/s. The complications were minor (Clavien-Dindo less than III) and included a UTI, minor bleeding not requiring admission, and retrograde ejaculation. Conclusions We demonstrate that an outpatient local anaesthetic daycase service without sedation is feasible. This can be delivered in a clinic setting, reduce waiting times for BOO surgery, and increase availability of operating theatre for other general anaesthetic urological procedures.

Introduction and GoalFloods cause loss of life and financial losses every year, and their management is one of the essential elements of watershed management. In this research, an attempt is made to determine the flood susceptibility of the Sirwan watershed and finally the importance of various environmental factors in flood susceptibility based on historical flood events.Materials and MethodsIn this research, the maximum entropy model along with 13 topographical, hydrological, morpho-hydrological, geological, and environmental flood-affecting factors were used to model the flood susceptibility of the Sirwan watershed and determine the importance and percentage of participation of various factors in the state of flooding potential. A cellular computing unit (pixel) was chosen as the criterion for preparing the predictive factors and flood susceptibility maps. A total of 123 historical flood inundation events detected in the last decade were used as target variables in the model, of which 70% were considered for learning and the remaining 30% for validating the model results. To evaluate the performance of the model, the criterion of the area under the receiver operating characteristic curve was also used.Results The results indicate that the accuracy of learning and validation were 98.2% and 97.3%, respectively, indicating the excellent performance of the model. Based on the visual interpretation of the flood susceptibility map, streams with a higher order near the watershed outlet, which are the conduits for the passage of the flow with a larger volume and are located in lower areas, often have a higher proneness to flood inundation. Based on the results of the relative importance test, the four factors of distance from the stream, topographic wetness index, drainage density, and land use were introduced as the most important factors in the modeling flood susceptibility, with of 17, 13, 12 and 10% participation, respectively. These results show that natural hydrological, morpho-hydrological and environmental factors (both natural and man-made) have a mutual effect in increasing flooding susceptibility. Based on the quantitative analysis of modeling, about 0.76% (5600 hectares) of the studied area is in the high and very high flood susceptibility class, which requires planning and flood management.Conclusion and SuggestionsThe high classification of flood susceptibility classes in the Sirwan watershed of Kurdistan province and the determination of the importance of environmental factors in the event of flooding make it possible for managers to take an effective preventive approach by planning relief facilities and infrastructure. To reduce the risk of flooding, flood crisis management in the Sirwan watershed should be defined based on the four main factors identified in this study. Application of the maximum entropy model in flood susceptibility analysis is suggested for flood management of watersheds.

Abstract Resistance to punishment is commonly used to measure the difficulty in refraining from rewarding activities when negative consequences ensue, which is a hallmark of addictive behavior. We recently developed a progressive shock strength (PSS) procedure in which individual rats can titrate the amount of punishment that they are willing to tolerate to obtain food rewards. Here, we investigated the effects of a range of delays (0–12 s) on resistance to punishment measured by PSS break points. As expected from delay discounting principles, we found that delayed shock was less effective as a punisher, as revealed by higher PSS breakpoints. However, this discounting effect was not equally distributed in the population of rats, and the introduction of a delay highlighted the existence of two populations: rats that were sensitive to immediate punishment were also sensitive to delayed shock, whereas rats that were resistant to immediate punishment showed strong temporal discounting of delayed punishment. Importantly, shock-sensitive rats suppressed responding even in subsequent non-punishment sessions, and they differed from shock-resistant rats in anxiety-like behavior, but not in sensitivity to pain. These results show that manipulation of temporal contingencies of punishment in the PSS procedure provides a valuable tool to identify individuals with a double vulnerability to addiction: low sensitivity to aversion and excessive discounting of negative future consequences. Conversely, the shock-sensitive population may provide a model of humans who are vulnerable to opportunity loss due to excessive anxiety.

Background and Objectives: Candida parapsilosis is the second most common species causing infectious diseases and can lead to biofilm resistance. This study aims to adjust and synthesize a liposomal compound of Nigella sativa and evaluate its antifungal properties against C. parapsilosis isolates. Materials and Methods: The liposomal formulation of N. sativa was optimized through the utilization of transmission electron microscopy (TEM), particle size analysis, zeta potential measurement, and UV-visible spectrophotometry. Furthermore, an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was conducted on peripheral blood mononuclear cells (PBMCs). The antifungal efficacy was evaluated in accordance with the M27-A3 guideline. Results: The minimum inhibitory concentrations (MICs) of N. sativa oil and the liposomal formulation on C. parapsilosis isolates ranged from 128 to 8 µg/mL and from 250 to 31.25 µg/mL, respectively. The MIC50 and MIC90 values of N. sativa oil and the liposomal formulation were 125, 187, and 32, 96 µg/mL, respectively. The viability percentage of cells treated with the liposomal formulation and free N. sativa oil was 91% and 85%, respectively. Conclusion: The cytotoxicity of free N. sativa was significantly reduced when using nanoliposomes. The liposomal form of N. sativa showed greater antifungal properties compared to the free N. sativa extract against C. parapsilosis isolates.

Protected areas play a crucial role in safeguarding biodiversity and ecosystem services. However, they face mounting challenges from environmental pressures. This study examines the Oshtorankooh Protected Area (OPA) in Iran, evaluating its vulnerability to various environmental hazards from 2010 to 2020.A comprehensive set of variables, including physiographic, climatic, geological, edaphic, vegetative, hydrological, and socio-economic factors, were utilized to compute 45 vulnerability indicators across three dimensions: exposure, sensitivity, and adaptive capacity for 2010 and 2020. Maps of these indicators were created and standardized, with weights assigned using the Fuzzy Analytic Hierarchy Process (FAHP). Composite indices for exposure, sensitivity, and adaptive capacity were then developed by integrating these weighted and standardized maps.The vulnerability indices for grid cells within the OPA enabled the identification of spatial vulnerability patterns, highlighting heightened vulnerability in the northern and western sectors influenced by factors such as drought variability, social vulnerability, evapotranspiration rates, spring discharge, and runoff dynamics. Results indicate a notable increase in vulnerability over the study period, with index values rising from 0.76 in 2010 to 2.04 in 2020. This spatially explicit vulnerability assessment underscores the dynamic nature of vulnerabilities within protected areas, emphasizing the necessity for adaptive management strategies. The findings stress the importance of tailored, evidence-based management approaches to mitigate risks and preserve ecological and socio-economic values. Implementing adaptive management strategies informed by this assessment can bolster the resilience of protected areas against environmental threats, thereby advancing global conservation efforts.

Primary bone lymphoma of the spine (PBL) is a rare entity that may be misdiagnosed due to its atypical location and clinical and imaging features mimicking certain pathologies as infectious processes, which complicates and delays diagnosis. Our case reports a patient in her sixties who had been suffering from chronic low back pain for a year, and had gradually started to develop cruralgia. She underwent a blood sample, magnetic resonance imaging (MRI), and positron emission tomography (18F-FDG-PET/CT) which revealed inflammatory syndrome, and an image of spondylodiscitis of the lumbar spine associated with a morphological and metabolical widespread invasion posteriorly suggesting epiduritis. No other lesions were found on the rest of the body. Neurosurgical management was performed and a biopsy was made. Histological results showed aggressive and diffuse large B-cell lymphoma, suggesting a diagnosis of PBL. This case highlights the first case of spondylodiscitis mimicking PBL in the lumbar spine, the intricacies of the diagnostic work-up, and the complexity of discriminating with an infectious process in the spine, as both have a similar, non-specific clinical presentation, while morphological and metabolic findings can be alike.