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The brain undergoes ionizing radiation (IR) exposure in many clinical situations, particularly during radiotherapy for malignant brain tumors. Cranial radiation therapy is related with the hazard of long-term neurocognitive decline. The detrimental ionizing radiation effects on the brain closely correlate with age at treatment, and younger age associates with harsher deficiencies. Radiation has been shown to induce damage in several cell populations of the mouse brain. Indeed, brain exposure causes a dysfunction of the neurogenic niche due to alterations in the neuronal and supporting cell progenitor signaling environment, particularly in the hippocampus—a region of the brain critical to memory and cognition. Consequent deficiencies in rates of generation of new neurons, neural differentiation and apoptotic cell death, lead to neuronal deterioration and lasting repercussions on neurocognitive functions. Besides neural stem cells, mature neural cells and glial cells are recognized IR targets. We will review the current knowledge about radiation-induced damage in stem cells of the brain and discuss potential treatment interventions and therapy methods to prevent and mitigate radiation related cognitive decline.

The central dogma of radiation biology, that biological effects of ionizing radiation are a direct consequence of DNA damage occurring in irradiated cells, has been challenged by observations that genetic/epigenetic changes occur in unexposed \"bystander cells\" neighboring directly-hit cells, due to cell-to-cell communication or soluble factors released by irradiated cells. To date, the vast majority of these effects are described in cell-culture systems, while in vivo validation and assessment of biological consequences within an organism remain uncertain. Here, we describe the neonatal mouse cerebellum as an accurate in vivo model to detect, quantify, and mechanistically dissect radiation-bystander responses. DNA double-strand breaks and apoptotic cell death were induced in bystander cerebellum in vivo. Accompanying these genetic events, we report bystander-related tumor induction in cerebellum of radiosensitive Patched-1 (Ptch1) heterozygous mice after x-ray exposure of the remainder of the body. We further show that genetic damage is a critical component of in vivo oncogenic bystander responses, and provide evidence supporting the role of gap-junctional intercellular communication (GJIC) in transmission of bystander signals in the central nervous system (CNS). These results represent the first proof-of-principle that bystander effects are factual in vivo events with carcinogenic potential, and implicate the need for re-evaluation of approaches currently used to estimate radiation-associated health risks.

Gastroptosis is a condition in which the stomach is displaced downward and is a condition affects the spontaneous muscle mobility in the stomach. The reason for its current prevalence remains unclear as the medical literature is scarce on the condition in children. In this study, we describe the case of a 17-year-old girl suffering from chronic, position-dependent epigastric pain. The symptoms were observed during post-meal activity, with a significant increase in pain intensity while in an upright position. An inferior stomach displacement was noted in an upper gastrointestinal X-ray study using barium.

Background/purpose of the study Epidemiological evidence suggests that low doses of ionising radiation (≤1.0 Gy) produce persistent alterations in cognition if the exposure occurs at a young age. The mechanisms underlying such alterations are unknown. We investigated the long-term effects of low doses of total body gamma radiation on neonatally exposed NMRI mice on the molecular and cellular level to elucidate neurodegeneration. Results Significant alterations in spontaneous behaviour were observed at 2 and 4 months following a single 0.5 or 1.0 Gy exposure. Alterations in the brain proteome, transcriptome, and several miRNAs were analysed 6–7 months post-irradiation in the hippocampus, dentate gyrus (DG) and cortex. Signalling pathways related to synaptic actin remodelling such as the Rac1-Cofilin pathway were altered in the cortex and hippocampus. Further, synaptic proteins MAP-2 and PSD-95 were increased in the DG and hippocampus (1.0 Gy). The expression of synaptic plasticity genes Arc, c-Fos and CREB was persistently reduced at 1.0 Gy in the hippocampus and cortex. These changes were coupled to epigenetic modulation via increased levels of microRNAs (miR-132/miR-212, miR-134). Astrogliosis, activation of insulin-growth factor/insulin signalling and increased level of microglial cytokine TNFα indicated radiation-induced neuroinflammation. In addition, adult neurogenesis within the DG was persistently negatively affected after irradiation, particularly at 1.0 Gy. Conclusion These data suggest that neurocognitive disorders may be induced in adults when exposed at a young age to low and moderate cranial doses of radiation. This raises concerns about radiation safety standards and regulatory practices.

Background A better understanding of locally advanced cervical cancer (LACC) is mandatory for further improving the rates of disease control, since a significant proportion of patients still fail to respond or undergo relapse after concurrent chemoradiation treatment (CRT), and survival for these patients has generally remained poor. Methods To identify specific markers of CRT response, we compared pretreatment biopsies from LACC patients with pathological complete response (sensitive) with those from patients showing macroscopic residual tumor (resistant) after neoadjuvant CRT, using a proteomic approach integrated with gene expression profiling. The study of the underpinning mechanisms of chemoradiation response was carried out through in vitro models of cervical cancer. Results We identified annexin A2 (ANXA2), N-myc downstream regulated gene 1 (NDRG1) and signal transducer and activator of transcription 1 (STAT1) as biomarkers of LACC patients’ responsiveness to CRT. The dataset collected through qPCR on these genes was used as training dataset to implement a Random Forest algorithm able to predict the response of new patients to this treatment. Mechanistic investigations demonstrated the key role of the identified genes in the balance between death and survival of tumor cells. Conclusions Our results define a predictive gene signature that can help in cervical cancer patient stratification, thus providing a useful tool towards more personalized treatment modalities.

Introduction and objective The COVID-19 pandemic has affected the lives of people worldwide. The aim of the study was to find out whether at the first stage of pandemic in Poland there occurred differences in the level of anxiety caused by the COVID-19 pandemic between different social groups. Material and methods The study included 499 respondents, conducted using the Google Forms package, based on which the authors constructed a questionnaire, subsequently distributed by social media. For the purpose of the study 8 questions were selected from the above-mentioned questionnaire, and the results statistically analyzed. Results The study showed that females experienced greater anxiety of COVID-19 than males (p<0.001). Chronically ill respondents had a significantly higher level of anxiety due to COVID-19 than healthy individuals (p<0.001). Those who had the level of education lower than secondary school showed a lower level of anxiety than respondents with full secondary and higher education (p < 0.001). In addition, anxiety caused by the COVID-19 increased with respondents’ age (p = 0.014). It was also observed that respondents who obtained information about COVID-19 from the Internet and the media showed a higher level of anxiety towards COVID-19, compared to those who used information from the medical community and other sources. It was found that the respondents’ place of residence, the size of the city in which they live, and the fact of contracting COVID-19 by themselves or their significant others did not exert any significant impact on the level of anxiety of COVID-19. Conclusions The pandemic and the resulting restrictions caused changes in the functioning of many people worldwide. The study demonstrated the presence of factors which correlated with a higher level of fear of developing COVID-19.

Many genes controlling neuronal development also regulate adult neurogenesis. We investigated the effect of Sonic hedgehog (Shh) signaling activation on patterning and neurogenesis of the hippocampus and behavior of ( ) heterozygous mice ( ). We demonstrated for the first time, that mice exhibit morphological, cellular and molecular alterations in the dentate gyrus (DG), including elongation and reduced width of the DG as well as deregulations at multiple steps during lineage progression from neural stem cells to neurons. By using stage-specific cellular markers, we detected reduction of quiescent stem cells, newborn neurons and astrocytes and accumulation of proliferating intermediate progenitors, indicative of defects in the dynamic transition among neural stages. Phenotypic alterations in mice were accompanied by expression changes in Notch pathway downstream components and nuclear receptor, as well as perturbations in inflammatory and synaptic networks and mouse behavior, pointing to complex biological interactions and highlighting cooperation between Shh and Notch signaling in the regulation of neurogenesis.

The male-to-female sex ratio for medulloblastoma (MB) is approximately 1.5∶1, female gender being also a favorable prognostic factor. This study aimed at evaluating the impact of gender on MB tumorigenesis. In vitro activity of 17β-estradiol (E2), DPN [2,3-bis(4-hydroxyphenyl)-propionitrile, a selective estrogen receptor β (ERβ)-agonist], PPT [4,4',4″-(4-Propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol, a selective ERα-agonist] or DHT (5 alpha-dihydrotestosterone) was evaluated in three human MB cell lines. D283 Med cells were transplanted into athymic mice. A significant expression of ERβ, with little or no ERα, and low AR (androgen receptor) was found in MB cell lines. The compounds tested did not affect cell proliferation. In vivo, we observed a significantly lower growth of D283 Med in nude female mice compared to males. At microscopic examination, tumors from females showed a shift towards differentiation, as evaluated by lower nestin, and higher NSE (neuron-specific enolase) and GFAP (glial fibrillary acidic protein) expression compared to males. Tumors from females also showed lower Ki67 and p53 expression. The wild-type ERβ protein (ERβ1) was lost in male tumors, while it was a permanent feature in females, and a strong negative correlation was found between Ki67 and ERβ1 expression. Conversely, tumor levels of ERβ2 and ERβ5 did not significantly differ between genders. Increased levels of cyclin-dependent kinase inhibitor p21 were observed in females, suggesting that estrogen may decrease tumor growth through blocking cell cycle progression. An inhibition of the insulin-like growth factor I (IGF-I) signaling was also evident in females. We provides mechanistic evidence supporting the idea that ERβ1 signaling may have pro-differentiation and tumor suppressive function in medulloblastomas.

Background Persistent structural changes of the lungs in anorexia nervosa (AN) patients are rarely described in contemporary medical literature. The objective of our paper is to report a rare case of severe bronchiectasis and inflammatory changes to the lungs resulting from chronic malnutrition in a AN patient. Case presentation We describe a patient with severe inflammatory lung disease caused by malnutrition, resulting in persistent bronchiectasis accompanying AN. We performed an analysis of the patient’s medical records including radiological findings and laboratory results. A review of available literature shows very little data available on this topic. Conclusion Bronchiectasis and other structural changes of the lungs are rare, but severe complications of severe, chronic malnutrition. As exemplified by our case report, they may require extensive differential diagnosis and pose a significant clinical challenge due to their non-reversible character. A successful treatment relies heavily on the patient’s compliance and may be hard to achieve. Clinicians managing patients with anorexia nervosa should be wary of early respiratory tract dysfunction-related symptoms and always consider malnutrition bronchiectasis as a differential diagnosis option.

Background In humans, in utero exposure to ionising radiation results in an increased prevalence of neurological aberrations, such as small head size, mental retardation and decreased IQ levels. Yet, the association between early damaging events and long-term neuronal anomalies remains largely elusive. Methods Mice were exposed to different X-ray doses, ranging between 0.0 and 1.0 Gy, at embryonic days (E) 10, 11 or 12 and subjected to behavioural tests at 12 weeks of age. Underlying mechanisms of irradiation at E11 were further unravelled using magnetic resonance imaging (MRI) and spectroscopy, diffusion tensor imaging, gene expression profiling, histology and immunohistochemistry. Results Irradiation at the onset of neurogenesis elicited behavioural changes in young adult mice, dependent on the timing of exposure. As locomotor behaviour and hippocampal-dependent spatial learning and memory were most particularly affected after irradiation at E11 with 1.0 Gy, this condition was used for further mechanistic analyses, focusing on the cerebral cortex and hippocampus. A classical p53-mediated apoptotic response was found shortly after exposure. Strikingly, in the neocortex, the majority of apoptotic and microglial cells were residing in the outer layer at 24 h after irradiation, suggesting cell death occurrence in differentiating neurons rather than proliferating cells. Furthermore, total brain volume, cortical thickness and ventricle size were decreased in the irradiated embryos. At 40 weeks of age, MRI showed that the ventricles were enlarged whereas N-acetyl aspartate concentrations and functional anisotropy were reduced in the cortex of the irradiated animals, indicating a decrease in neuronal cell number and persistent neuroinflammation. Finally, in the hippocampus, we revealed a reduction in general neurogenic proliferation and in the amount of Sox2-positive precursors after radiation exposure, although only at a juvenile age. Conclusions Our findings provide evidence for a radiation-induced disruption of mouse brain development, resulting in behavioural differences. We propose that alterations in cortical morphology and juvenile hippocampal neurogenesis might both contribute to the observed aberrant behaviour. Furthermore, our results challenge the generally assumed view of a higher radiosensitivity in dividing cells. Overall, this study offers new insights into irradiation-dependent effects in the embryonic brain, of relevance for the neurodevelopmental and radiobiological field.