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Loneliness is more complex and multi-faceted than it may appear at first glance. Most of the characterizations that we have of loneliness in the extant literature tend to focus on the absence of other people and on the social, mental, and physical distress that can be caused by this type of absence. Although the experience of absence may be a fundamental and encompassing aspect of loneliness, loneliness may also reflect a deeper, more complex experience. This paper integrates data from a qualitative study on the phenomenology of loneliness with philosophical theories on the self. It argues that there is a connection between the experience of absence and the impossibility to appear in the world and that this may consequentially lead to the disruption of self-experience.

Altered patterns of gene expression mediate the effects of particulate matter (PM) on human health, but mechanisms through which PM modifies gene expression are largely undetermined. MicroRNAs (miRNAs) are highly conserved, noncoding small RNAs that regulate the expression of broad gene networks at the posttranscriptional level. We evaluated the effects of exposure to PM and PM metal components on candidate miRNAs (miR-222, miR-21, and miR-146a) related with oxidative stress and inflammatory processes in 63 workers at an electric-furnace steel plant. We measured miR-222, miR-21, and miR-146a expression in blood leukocyte RNA on the first day of a workweek (baseline) and after 3 days of work (postexposure). Relative expression of miRNAs was measured by real-time polymerase chain reaction. We measured blood oxidative stress (8-hydroxyguanine) and estimated individual exposures to PM1 (< 1 microm in aerodynamic diameter), PM10 (< 10 microm in aerodynamic diameter), coarse PM (PM10 minus PM1), and PM metal components (chromium, lead, cadmium, arsenic, nickel, manganese) between the baseline and postexposure measurements. Expression of miR-222 and miR-21 (using the 2-DeltaDeltaCT method) was significantly increased in postexposure samples (miR-222: baseline = 0.68 +/- 3.41, postexposure = 2.16 +/- 2.25, p = 0.002; miR-21: baseline = 4.10 +/- 3.04, postexposure = 4.66 +/- 2.63, p = 0.05). In postexposure samples, miR-222 expression was positively correlated with lead exposure (beta = 0.41, p = 0.02), whereas miR-21 expression was associated with blood 8-hydroxyguanine (beta = 0.11, p = 0.03) but not with individual PM size fractions or metal components. Postexposure expression of miR-146a was not significantly different from baseline (baseline = 0.61 +/- 2.42, postexposure = 1.90 +/- 3.94, p = 0.19) but was negatively correlated with exposure to lead (beta = -0.51, p = 0.011) and cadmium (beta = -0.42, p = 0.04). Changes in miRNA expression may represent a novel mechanism mediating responses to PM and its metal components.

Young people are particularly at risk of developing mental health problems, a challenge exacerbated by the COVID-19 pandemic. Digital tools such as apps and chatbots show promise in providing accessible, cost-effective, and less stigmatized ways of strengthening their mental health. However, while these interventions offer benefits, they extend mental health measures beyond traditional therapeutic settings and relationships, which raises ethical concerns due to the absence of established guidelines and regulations. This is particularly notable for technologies incorporating serious gaming elements. In addition, adolescents are in a sensitive and at times vulnerable phase, which shows great potential for the effective use of preventive and sensitizing mental health measures. Considering the lack of an integration into existing mental health structures among many young users, ethical considerations become crucial. This scoping review aims to build a knowledge base on the ethical aspects of developing and implementing gamified digital mental health interventions for young people. We conducted a search on research articles and conference papers from 2015 to 2023 in English, German, and Spanish. We identified 1815 studies using a unique combination of keywords in the databases Scopus, Web of Science, MEDLINE, and PsycINFO. After removing duplicates (741/1816, 40.8%), we included a total of 38 publications in this review following a double screening process. This review found that ethically relevant aspects were discussed with regard to (1) research ethics, (2) ethical principles (including privacy, accessibility, empowerment and autonomy, cultural and social sensitivity, and co-design), (3) vulnerable groups, and (4) social implications (including implementation using facilitators in specific social contexts, relationship with other therapeutic options, economic aspects, and social embeddedness of technologies). This scoping review identified a prevailing limited interpretation of \"ethics\" as research ethics across the included publications. It also shows a lack of discussion on the social embeddedness of technologies and that co-design is frequently viewed in instrumental terms and vulnerability is mostly addressed pragmatically. Through providing concrete examples of how mental health researchers and game designers thus far have addressed and mitigated ethical challenges in specific interventions, this review illustrates how ethical issues do or do not prompt diverse reflections, mitigation strategies, and actions. It advocates for ethics to be integrated as an ongoing practice throughout all stages of developing and implementing serious game elements in mental health interventions for young people.

Background Mitochondria have small mitochondrial DNA (mtDNA) molecules independent from the nuclear DNA, a separate epigenetic machinery that generates mtDNA methylation, and are primary sources of oxidative-stress generation in response to exogenous environments. However, no study has yet investigated whether mitochondrial DNA methylation is sensitive to pro-oxidant environmental exposures. Methods We sampled 40 male participants (20 high-, 20 low-exposure) from each of three studies on airborne pollutants, including investigations of steel workers exposed to metal-rich particulate matter (measured as PM 1 ) in Brescia, Italy (Study 1); gas-station attendants exposed to air benzene in Milan, Italy (Study 2); and truck drivers exposed to traffic-derived Elemental Carbon (EC) in Beijing, China (Study 3). We have measured DNA methylation from buffy coats of the participants. We measured methylation by bisulfite-Pyrosequencing in three mtDNA regions, i.e., the transfer RNA phenylalanine ( MT-TF ) , 12S ribosomal RNA ( MT-RNR1 ) gene and “D-loop” control region. All analyses were adjusted for age and smoking. Results In Study 1, participants with high metal-rich PM 1 exposure showed higher MT-TF and MT-RNR1 methylation than low-exposed controls (difference = 1.41, P  = 0.002); MT-TF and MT-RNR1 methylation was significantly associated with PM 1 exposure (beta = 1.35, P  = 0.025); and MT-RNR1 methylation was positively correlated with mtDNA copy number (r = 0.36; P  = 0.02). D-loop methylation was not associated with PM 1 exposure. We found no effects on mtDNA methylation from air benzene (Study 2) and traffic-derived EC exposure (Study 3). Conclusions Mitochondrial MT-TF and MT-RNR1 DNA methylation was associated with metal-rich PM 1 exposure and mtDNA copy number. Our results suggest that locus-specific mtDNA methylation is correlated to selected exposures and mtDNA damage. Larger studies are needed to validate our observations.

Loneliness is one of the least conceptualized psychological phenomena (Fromm-Reichman, 1959). The growing awareness that social relations play a fundamental role in psychological well-being has led mental health researchers to integrate work on loneliness and social support. This has influenced most of the definitions we have of loneliness nowadays. Thus, when defining loneliness, there is a tendency to focus on social distress, which is just one aspect of the experience. Various disciplines have provided different definitions: some have focused on the multifaceted nature of loneliness (addressing the interaction between specific behaviors, emotions and thoughts), while others have focused primarily on cognitive aspects. In such definitions, loneliness is also regarded as a subjective experience, but the subjective aspect is often described as something \"private,\" which obscures the experiential features that are essential to loneliness. In this article, I review the most dominant definitions of loneliness and address some of their underlying assumptions and problems. I propose that a starting point for arriving at better definitions and distinguishing between types of loneliness is to focus on the temporal, embodied and attentional dimensions of the phenomenon.

One of the cells of Palazzo Chiaramonte Steri's prisons in Palermo still bears the marks of drawings depicting saints and martyrs accompanied by hand-written prayers and hymns in Latin. Interestingly, each single drawing is marked with a letter B. According to Giuseppe Pitrè, these graffiti should be attributed to Francesco Baronio Manfredi, an erudite priest who was arrested by the Spanish Inquisition in 1647 after the revolt of Palermo. What are the reasons behind his arrest? Why is he considered to be the author of graffiti depicting saints and martyrs? Starting from Pitrè's hypothesis, I will investigate Baronio's past in order to understand the reasons for his imprisonment. At the same time, I intend to shed new light on the graffiti that he supposedly drew during his imprisonment.

In this study on 90 individuals we aimed at evaluating the microRNAs (miRNAs) expression profile associated with personal levels of Titanium (Ti) and Zirconium (Zr) traced in hair samples. Ti and Zr materials are broadly used for dental implants but the biological reactions triggered by a long term presence of these materials in the oral cavity still need to be assessed. MiRNAs are mechanisms that need to be investigated as they play a fundamental role in the control of gene expression following external stimuli and contribute to a wide range of pathophysiological processes. Using the TaqMan® Low-Density Array, we assessed the expression levels of 377 human miRNAs in peripheral blood of 90 subjects. Hair samples were analyzed for Ti and Zr content using Inductively Coupled Plasma-Mass Spectrometry. We performed multivariable regression analysis to investigate the effects of Ti and Zr exposure on miRNA expression levels. We used the Ingenuity Pathway Analysis (IPA) software to explore the functional role of the investigated miRNAs and the related target genes. Seven miRNAs (miR-99b, miR-142-5p, miR-152, miR-193a-5p, miR-323-3p, miR-335, miR-494) resulted specifically associated with Zr levels. The functional target analysis showed that miRNAs are involved in mechanisms such as inflammation, skeletal and connective tissue disorders. Our data suggest that Zr is more bioactive than Ti and show that miRNAs are relevant molecular mechanisms sensitive to Zr exposure.

Blood pressure (BP) is a complex, multifactorial clinical outcome driven by genetic susceptibility, behavioral choices, and environmental factors. Many molecular mechanisms have been proposed for the pathophysiology of high BP even as its prevalence continues to grow worldwide, increasing morbidity and marking it as a major public health concern. To address this, we evaluated miRNA profiling in blood leukocytes as potential biomarkers of BP and BP-related risk factors. The Beijing Truck Driver Air Pollution Study included 60 truck drivers and 60 office workers examined in 2008. On two days separated by 1-2 weeks, we examined three BP measures: systolic, diastolic, and mean arterial pressure measured at both pre- and post-work exams for blood NanoString nCounter miRNA profiles. We used covariate-adjusted linear mixed-effect models to examine associations between BP and increased miRNA expression in both pooled and risk factor-stratified analyses. Overall 43 miRNAs were associated with pre-work BP (FDR<0.05). In stratified analyses different but overlapping groups of miRNAs were associated with pre-work BP in truck drivers, high-BMI participants, and usual alcohol drinkers (FDR<0.05). Only four miRNAs were associated with post-work BP (FDR<0.05), in ever smokers. Our results suggest that many miRNAs were significantly associated with BP in subgroups exposed to known hypertension risk factors. These findings shed light on the underlying molecular mechanisms of BP, and may assist with the development of a miRNA panel for early detection of hypertension.

Background Repetitive elements take up >40% of the human genome and can change distribution through transposition, thus generating subfamilies. Repetitive element DNA methylation has associated with several diseases and environmental exposures, including exposure to airborne pollutants. No systematic analysis has yet been conducted to examine the effects of exposures across different repetitive element subfamilies. The purpose of the study is to evaluate sensitivity of DNA methylation in differentially‒evolved LINE, Alu, and HERV subfamilies to different types of airborne pollutants. Methods We sampled a total of 120 male participants from three studies (20 high-, 20 low-exposure in each study) of steel workers exposed to metal-rich particulate matter (measured as PM 10 ) (Study 1); gas-station attendants exposed to air benzene (Study 2); and truck drivers exposed to traffic-derived elemental carbon (Study 3). We measured methylation by bisulfite-PCR-pyrosequencing in 10 differentially‒evolved repetitive element subfamilies. Results High-exposure groups exhibited subfamily-specific methylation differences compared to low-exposure groups: L1PA2 showed lower DNA methylation in steel workers ( P =0.04) and gas station attendants ( P =0.03); L1Ta showed lower DNA methylation in steel workers ( P =0.02); Alu Yb8 showed higher DNA methylation in truck drivers ( P =0.05). Within each study, dose–response analyses showed subfamily-specific correlations of methylation with exposure levels. Interaction models showed that the effects of the exposures on DNA methylation were dependent on the subfamily evolutionary age, with stronger effects on older LINEs from PM 10 (p‒interaction=0.003) and benzene (p‒interaction=0.04), and on younger Alu s from PM 10 (p-interaction=0.02). Conclusions The evolutionary age of repetitive element subfamilies determines differential susceptibility of DNA methylation to airborne pollutants.

Even the most sophisticated emergency care system is ineffective if bystanders fail to recognize a serious injury or do not know how to call for help. In LMICs when road traffic crashes occur, emergency response and services are fairly good in main cities, but only few systems are in place in the rural areas. In Colombia, a study done by local research groups stated that an average of two hours or more is the norm and in some areas it can be as high as eight to fourteen hours.We sought to empower communities in rural areas of Colombia which have poor resources and have limited enforcement of road safety measures, such as control of speed, or protection for road users. Children usually walk to school or are brought by motorcycle. Our empowerment is done through education, training and provision of basic emergency equipment.In cities, a number of private service providers and volunteer firefighter teams fill gaps in provision of emergency response. These volunteers are especially significant in small towns with poor resourcesCommunity volunteer empowerment model need to be translated and scaled up in rural areas where emergency response is very limited. There is a national interest in developing organized emergency care systems in line with SDG commitments. Looking to the future, 7,000 km of new roads are planned before 2020 in Colombia, increasing the need for targeted road safety intervention.