Comprehensive spatial distribution of patients with first-episode psychosis (FEP) and its relation to socio-economic factors.

BACKGROUND: The functional-cognitive impact of first-episode psychosis (FEP) is extremely relevant and implies dysfunction from early life stages like adolescence and youth. Like other illnesses, FEP incidence is also influenced by environmental factors. It is necessary to attend to this age group with early interventions and to act on the environmental factors that the literature correlates with increased FEP incidence: socio-economic aspects, social adversity, bullying at school or cannabis use. In this context, identifying the areas of cities where FEP patients concentrate is important to perform early interventions. The spatial analysis of patient distribution in a whole city is one way to identify the most vulnerable areas and to propose psycho-social interventions for the possible prevention and/or early detection of FEP by improving urban mental health. METHODS: An epidemiological study of point patterns to determine the areas of a city with a higher incidence of patients with FEP. To do so, the addresses of FEP cases were georeferenced from 1 January 2016 to 31 October 2022, and 109 FEP patients were analysed. Data from a random sample of 383 controls, comprising their addresses, age, and sex, were randomly obtained from the official city council database. By GIS, the areas with higher FEP incidence were analysed to see if they coincided with the zones where inhabitants with lower incomes lived. RESULTS: The risk ratio of the FEP patients was compatible with the constant risk ratio in Albacete (p = 0.22). When performing the process separately with cases and controls only in men and women, the results were not significant for both distributions (p value: 0.12 and 0.57, respectively). Nonetheless, areas within the city had a significantly higher risk. These groups of cases coincided with those who had lower income and more inequality for women, but this pattern was not clear for men. CONCLUSIONS: Classifying city areas per income can help to determine the zones at higher risk of FEP, which would allow early healthcare and preventive measures for these zones.

High dose rate endoluminal brachytherapy in the treatment of endobronchial lesions - experience of a single institution and literature review.

PURPOSE: To evaluate the efficacy and toxicity of Iridium-192 high-dose-rate endobronchial brachytherapy (HDR-EBT) for palliation of symptoms and for curative intent. MATERIAL AND METHODS: This is a retrospective study of a prospectively registered cohort of 31 patients with endobronchial lesions treated with HDR-EBT at our institution between 2008 and 2020. Eighteen patients were treated with palliative intent and 13 curative intent; 4 of them as a boost to external radiation therapy (XRT). The primary objectives of the study were to analyze the symptomatic relief, endoscopic response, and treatment-related toxicity. As a secondary endpoint, survival analyses were performed. RESULTS: In palliative setting, most of the symptomatic patients (80%) presented a significant clinical improvement and 75% presented endoscopic improvement of the lesions. In curative setting, all patients with visible lesions had endoscopic improvement and better survival than palliatively treated patients (median: 78 and 9 months, respectively; p = 0.002). There were no complications in 91.4% of the treatments: only one pneumonia, one pneumothorax and one bronchial stenosis occurred, all in palliative treatments. No fatal hemoptysis happened. Acute toxicity was mild (G ≤ 2) and transitory. DISCUSSION: HDR-EBT is an excellent, safe, and inexpensive palliative treatment of symptoms caused by endobronchial growth of tumors in the proximal airway, either as a single treatment or in combination with XRT. It can also be an alternative in the treatment of initial malignant tumors when surgery or XRT is not possible, and it may also play a role in treating non-malignant bronchial obstructions.

Molecular strategies to increase yeast iron accumulation and resistance.

All eukaryotic organisms rely on iron as an essential micronutrient for life because it participates as a redox-active cofactor in multiple biological processes. However, excess iron can generate reactive oxygen species that damage cellular macromolecules. The low solubility of ferric iron under physiological conditions increases the prevalence of iron deficiency anemia. A common strategy to treat iron deficiency consists of dietary iron supplementation. The baker's yeast Saccharomyces cerevisiae is used as a model eukaryotic organism, but also as a feed supplement. In response to iron deficiency, the yeast Aft1 transcription factor activates cellular iron acquisition. However, when constitutively active, Aft1 inhibits growth probably due to iron toxicity. In this report, we have studied the consequences of using hyperactive AFT1 alleles, including AFT1-1UP, to increase yeast iron accumulation. We first characterized the iron sensitivity of cells expressing different constitutively active AFT1 alleles. We rescued the high iron sensitivity conferred by the AFT1 alleles by deleting the sphingolipid signaling kinase YPK1. We observed that the deletion of YPK1 exerts different effects on iron accumulation depending on the AFT1 allele and the environmental iron. Moreover, we determined that the impairment of the high-affinity iron transport system partially rescues the high iron toxicity of AFT1-1UP-expressing cells. Finally, we observed that AFT1-1UP inhibits oxygen consumption through activation of the RNA-binding protein Cth2. Deletion of CTH2 partially rescues the AFT1-1UP negative respiratory effect. Collectively, these results contribute to understand how the Aft1 transcription factor functions and the multiple consequences derived from its constitutive activation.