Somatic Effects Research Articles

The effects of the paramedics’ field work on their mental status in Jeddah

ABSTRACT Background: Paramedics are continuously exposed to stressful events, making them liable to mental disorders. This study assesses the health of paramedics in Jeddah, focusing on their mental, emotional, and physical well-being. Methods: This cross-sectional study included fieldwork paramedics in Jeddah through an online survey distributed on social media. With a response rate of 86.09%, 192 complete responses were analyzed. Outcomes included mental health, mood and somatic effect, self-esteem, and sleep. Results: Most participants were males (83.85%), married (50%), non-heavy smokers (51.04%), and non-alcohol drinkers (51.04%). A significant number reported health-related work or daily life difficulties, with 62.5%–67.18% attributing these to physical and emotional issues, respectively. Over half rated their mental health as poor or somewhat poor, impacting their relationships significantly. Additionally, 70.31% frequently felt anger, and many faced limitations in physical activities. About 14.58% had a prior mental illness diagnosis, with nearly a quarter on medication, and 61.98% had recently sought psychiatric help. Sleep deprivation affected 61.98%, with 38.53% reporting poor sleep quality. Conclusions: The findings highlight the negative impact on paramedics’ mental health, showing a substantial diagnosis rate of mental disorders, activity limitations, negative mood, and relationship issues. Despite significant sleep problems, a positive aspect is their proactive psychiatric help-seeking behavior.

‘I think my body knew what it was before I did’: Affirming women’s embodied experiences as a conduit to knowing

This paper focuses on ignorance within the phenomenon of women who experience female ejaculation. Based on ethnographic research, I show how the experience of the phenomenon in the absence of propositional knowledge about it results in what I term ‘experiential ignorance.’ This type of ignorance is caused by the cultural positioning of propositional knowledge as the most valid and reliable form of knowledge about the body. Experiential ignorance can be manifested in many different ways, such as an inability to categorize and validate subjective bodily experiences, resulting in feelings of doubt, shame, and can even lead to somatic effects. Nevertheless, some women challenge this knowledge hierarchy by valuing their bodily sensations as legitimate sources of information. The paper concludes that reconceptualizing ignorance to include experiential dimensions reveals the power dynamics inherent in knowledge production and provides opportunities for women to reclaim authority over their bodies and pleasurable experiences. This framework has broader implications for understanding embodied knowledge and ignorance across diverse sociocultural contexts.

Chemometrics Evaluation of Lemongrass Essential Oils: Authenticity, Quality and Selection Of Bioactives against t. cruzi.

AbstractThe effectiveness of treatments against the parasite Trypanosoma cruzi, the causative agent of Chagas disease, is limited in the chronic phase of the disease. The essential oils of lemongrass (Cymbopogon citratus and Cymbopogon flexuosus) have shown activity against this parasite. This study aimed to use principal component analysis (PCA) to analyze the data of lemongrass essential oils submitted to gas chromatography with flame ionization detector (GC‐FID) and proton nuclear magnetic resonance (1H NMR) as well as partial least squares (PLS) regressions to correlate chemical variability with the results of biological assays. The PLS models highlighted geraniol, caryophyllene, and limonene as the main compounds responsible for antioxidant activity. Regarding cytotoxicity, the PLS models indicated that this activity is a cumulative effect of multiple compounds. For the trypanocidal effect, median lethal concentration (CL50) values ranged from 15.12 ± 3.96 to 110.10 ± 11.22 μg mL−1, resulting in selectivity index (SI) values of 2.99 to 22.55 times more selective for T. cruzi compared to host cells. PLS indicated that geraniol, neral and geranial were the main contributors to the trypanocidal effect, suggesting the potential for somatic or synergistic effects against trypomastigote forms.

Nocturnal Hypoglycemia in the Era of Continuous Glucose Monitoring.

Nocturnal hypoglycemia is a common acute complication of people with diabetes on insulin therapy. In particular, the inability to control glucose levels during sleep, the impact of external factors such as exercise, or alcohol and the influence of hormones are the main causes. Nocturnal hypoglycemia has several negative somatic, psychological, and social effects for people with diabetes, which are summarized in this article. With the advent of continuous glucose monitoring (CGM), it has been shown that the number of nocturnal hypoglycemic events was significantly underestimated when traditional blood glucose monitoring was used. The CGM can reduce the number of nocturnal hypoglycemia episodes with the help of alarms, trend arrows, and evaluation routines. In combination with CGM with an insulin pump and an algorithm, automatic glucose adjustment (AID) systems have their particular strength in nocturnal glucose regulation and the prevention of nocturnal hypoglycemia. Nevertheless, the problem of nocturnal hypoglycemia has not yet been solved completely with the technologies currently available. The CGM systems that use predictive models to warn of hypoglycemia, improved AID systems that recognize hypoglycemia patterns even better, and the increasing integration of artificial intelligence methods are promising approaches in the future to significantly minimize the risk of a side effect of insulin therapy that is burdensome for people with diabetes.

Long-term effects of doping with anabolic steroids during adolescence on physical and mental health.

Systematic doping programs like in the GDR were applied in adolescent competitive athletes to induce supramaximal athletic performance. The substances had adverse somatic and psychological effects. The psychological development of the young athletes was impaired and they suffered in adulthood from long-term effects and secondary diseases even years after the doping period. The study compared three groups: competitive athletes with doping(I), competitive athletes without doping(II) and persons with no sports activities(III). Somatic and psychological diseases were analyzed to identify the adverse effects of doping in the most vulnerable phase of development in adolescence. Participants were asked to supply a patient history and completed a questionnaire with standardized psychological tests. The doping cohort had a higher rate of somatic diseases, psychological disorders and social and professional difficulties. The differences were gender-specific with males more often having impaired liver function, depression, tumors and difficulties associated with the workplace . The doping group reported more emotional and physical neglect during childhood. They proved to be less optimistic but more pessimistic, to perceive less social support and to be more depressive. The study identified less extraversion and more neuroticism. Posttraumatic stress disorder (PTSD) occurred in a small number of participants in the doping group. Doping is associated with psychiatric variables. Predictors were the subscale identifying feelings of the Toronto alexithymia scale 20 (TAS-20), the sense of coherence and the Beck depression inventory 2 (BDI-II) and the Beck depression inventory (BDI). Physical and psychosocial effects imply correlation with the application of doping substances but might not only be due to the side effects of these substances but also caused by the system, which exerts great psychological pressure and stress during adolescence, ahighly vulnerable phase.

Peculiarities of adaptation of the cardiovascular system of combatants after exposure to combat stress and trauma

Abstract. Military operations are generally considered to be a pronounced psycho-traumatic situation due to specific factors that lead to persistent mental and somatic health disorders and a slowdown in the rate of further social adaptation of military personnel.
 Post-traumatic stress disorder (PTSD) is described as a set of complex somatic, cognitive, affective, and behavioral effects of psychological trauma.
 One of the essential features of combatants' PTSD is that after the end of the period of stay in the conditions of hostilities, a high incidence of chronic somatic diseases is manifested. There is a correlation in the neurotic symptoms (in all cases) of deterioration of the somatic condition, and exacerbation of somatic pathology aggravates mental disorders.
 The problem of morbidity and mortality from circulatory system diseases, blood poisoning and injuries is of particular relevance to combatants, as the onset of cardiovascular disease is closely related to the traumatic impact of wartime or PTSD. Particular attention to the medical and psychological consequences of the effects of extreme factors associated with combat on the body of military personnel is associated with both the prevalence of PTSD, which reaches 70-85%, and the duration of its symptoms.

Burden of Childhood Cancer and the Social and Economic Challenges in Adulthood

Significant advancements in pediatric oncology have led to a continuously growing population of survivors. Although extensive research is being conducted on the short-, medium-, and long-term somatic effects, reports on psychosocial reintegration are often conflicting; therefore, there is an urgent need to synthesize the evidence to obtain the clearest understanding and the most comprehensive answer. To provide a comprehensive review and analysis of the socioeconomic attainment of childhood cancer survivors (CCSs) compared with their unaffected peers. A systematic review and meta-analysis was conducted using data obtained from a comprehensive search of MEDLINE (via PubMed), Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) databases on October 23, 2021; the search was updated until July 31, 2023. Eligible articles reported on educational attainment, employment, family formation, quality of life (QoL), or health-risk behavior-related outcomes of CCSs, and compared them with their unaffected peers. Study selection was performed in duplicate by 4 blinded independent coauthors. Data extraction was performed in duplicate by 4 independent authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Outcome measures were odds ratios (ORs) and mean differences with 95% CIs; data were pooled using a random-effects model. The search identified 43 913 articles, 280 of which were eligible for analysis, reporting data on a total of 389 502 survivors. CCSs were less likely to complete higher levels of education (OR, 0.69; 95% CI, 0.40-1.18), had higher odds of health-related unemployment (OR, 2.94; 95% CI, 1.90-4.57), and showed lower rates of marriage (OR, 0.72; 95% CI, 0.63-0.84) and parenthood (OR, 0.60; 95% CI, 0.49-0.74) compared with population-based controls. Study findings suggest that CCSs face several socioeconomic difficulties; as a result, the next goal of pediatric oncology should be to minimize adverse effects, as well as to provide lifelong survivorship support aimed at maximizing social reintegration.

Abstract 1252: AI-derived predictions improve identification of real-world cancer driver mutations

Abstract AI-based variant effect predictors (VEPs), such as AlphaMissense, which is based on the protein structure prediction method AlphaFold, have gained significant attention for their potential to predict pathogenic effects of mutations. However, the utility of these methods for identifying pathogenic mutations in cancer remains unknown. We sought to quantify the prevalence of variants of unknown significance (VUSs) across the pan-cancer, multi-institution AACR GENIE cohort (N=160,965 samples) and test the utility of VEPs (SIFT, PolyPhen, MutationAssessor, REVEL, CADD, and AlphaMissense), using publicly available mutation annotations from each method, for 1) Annotating known pathogenic somatic cancer variants across the GENIE cohort, using known benign single nucleotide polymorphisms as negative controls 2) Identifying VUSs associated with overall survival (OS) in two cohorts of patients with non-small cell cancer (NSCLC), the MSK-IMPACT NCSLC (N=8,690) and non-MSK AACR GENIE Biopharma Collaborative NSCLC (N=977) cohorts, and 3) Identifying VUSs associated with known genomic patterns of mutual exclusivity in the MSK-IMPACT NSCLC cohort. In the GENIE cohort, 79% of mutations identified were VUSs according to an FDA-recognized molecular knowledge database, with a wide range of VUS frequencies across genes. Among VEPs trained without prior human-annotated knowledge, CADD and AlphaMissense had the highest AUROCs (0.940, 95%CI 0.937-0.943 and 0.917, 95%CI 0.913-0.922 respectively) for predicting known cancer drivers, demonstrating the power of protein structure modeling or functional genomic data for enhancing cancer drivers prediction. All VEPs identified known driver mutations in tumor suppressor genes more accurately than oncogenes, highlighting the challenge in identifying gain-of-function mutations. We tested whether VUSs reclassified as pathogenic by VEPs are associated with prognosis using inverse probability of treatment-weighted Cox’s propensity hazard models controlling for tumor mutational burden, treatment history, and other factors. VUSs reclassified as pathogenic by AlphaMissense and other VEPs in KEAP1 and SMARCA4 correlated with worse OS, comparable to that of known oncogenic mutations in those genes. Patients with tumors containing VUSs annotated as benign had similar OS to patients without analogous driver mutations. Finally, VUSs reclassified as oncogenic by AlphaMissense in genes within the RTK/RAS and NRF2 pathways followed expected patterns of mutual exclusivity, further suggesting biological validity. Despite not being trained to predict somatic effects in cancer, AI-derived mutation annotations can broaden the subset of annotated pathogenic variants in cancer and contribute to a more complete understanding of cancer genetics. Real-world outcomes and alteration patterns are additional benchmarks to consider when assessing the utility of VEPs in cancer. Citation Format: Thinh N. Tran, Chris Fong, Karl Pichotta, Anisha Luthra, Ronglai Shen, Yuan Chen, Michele Waters, Susie Kim, Gregory Riely, Debyani Chakravarty, Nikolaus Schultz, Justin Jee. AI-derived predictions improve identification of real-world cancer driver mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1252.

아동기 학대 경험이 신체화에 미치는 영향

Objectives The purpose of this study was to investigate the dual mediating effects of clarity on emotional awareness and maladaptive cognitive emotion regulation strategy between childhood abuse, somatization in adulthood.
 Methods The result of 291 adults between the ages of 20 and 59 were distrivuted to scales of childhood trauma, somatization, clarity on emotional awareness, and cognitive emotion regulation strategy. Descriptive statics, Pearson’s correlation analysis and dual mediation analysis analyzed data via SPSS 25.0, Process Macro 6 model.
 Results First, childhood abuse experience, somatization, and maladaptive cognitive emotion regulation strategy were positively correlated with each other, and these three variables were negatively correlated with clarity on emotional awareness. Second, in the relationship between childhood abuse experience and somatization, clarity on emotional awareness and maladaptive cognitive emotion regulation strategy showed a dual mediating effect. This means that the higher childhood abuse experience, the higher level of somatization in relationship, the clearer the emotional awareness as an emotional factor, and the less maladaptive cognitive emotion regulation strategy are adopted as a cognitive factor, the lower the somatization.
 Conclusions These findings indicate that it suggests factors for counseling psychological intervention in somatization due to childhood abuse experiences by revealing the dual mediating effect of clarity on emotional awareness and maladaptive cognitive emotion regulation strategy on the effects of childhood abuse experiences and adult somatization. Limitations and recommendations for future research are presented.

Analgesic effect of the ultrasound-guided thoracolumbar paravertebral block in patients undergoing robot-assisted laparoscopic nephrectomy: a randomized controlled trial.

Paravertebral block has similar effect as epidural anesthesia, and has good somatic and visceral analgesic effect. Paravertebral block is widely used in thoracic surgery, but rarely used in abdominal surgery. This study aimed to evaluate the analgesic effect of thoracolumbar paravertebral block in patients undergoing robot-assisted laparoscopic nephrectomy. One hundred patients undergoing elective robot-assisted laparoscopic nephrectomy were included in this study. Based on whether the thoracolumbar paravertebral block was performed, the patients were randomly divided into the thoracolumbar paravertebral block combined with general anesthesia group (TL-PVB group) and simple general anesthesia group (NO-PVB group). Oxycodone was administered for patient-controlled intravenous analgesia (PCIA). The primary outcomes included the amount of remifentanil used during surgery, the amount of oxycodone used in 24 and 48h after surgery. Secondary outcomes included the changes of heart rate (HR) and mean arterial pressure (MAP), time for the first analgesia administration, visual analog score (VAS) of pain during rest and movement, and time of postoperative recovery. Compared to the NO-PVB group, the amount of remifentanil used during surgery in patients with TL-PVB group was significantly reduced (1.78 ± 0.37mg vs. 3.09 ± 0.48 mg, p < 0.001), the amount of oxycodone used 24h after surgery was significantly reduced (8.70 ± 1.70mg vs. 13.79 ± 2.74 mg, p < 0.001), and the amount of oxycodone used 48h after surgery was remarkably reduced (21.83 ± 4.28mg vs. 27.27 ± 4.76 mg, p < 0.001). There were significant differences in the changes of HR and MAP between the two groups (p < 0.001). The first analgesic requirement time of TL-PVB group was significantly longer than that of NO-PVB group (468.56 ± 169.60min vs. 113.48 ± 37.26min, p < 0.001). The postoperative VAS during rest and movement of TL-PVB group were significantly lower than that of NO-PVB group (p < 0.01). Compared with NO-PVB group, patients in TL-PVB group needed shorter time to awaken from anesthesia, leave the operating room, anal exhaust, get out of bed, and had shorter length of postoperative hospital stay (p < 0.001). The incidence of postoperative adverse reactions were lower in the TL-PVB group than that in the NO-PVB group (p < 0.05). Ultrasound-guided thoracolumbar paravertebral block significantly reduces intraoperative and postoperative opioid consumption, and provides better analgesia in patients undergoing robot-assisted laparoscopic nephrectomy, which is a recommendable combined anesthesia technique. ChiCTR2200061326, 21/06/2022.

Mediating effect of coping dispositions on the association between trauma and gastrointestinal symptoms.

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are two gastrointestinal (GI) conditions known to be exacerbated by traumatic life experiences. One way in which these experiences might influence individuals' susceptibility to GI pathology, is by reducing their ability to deal with adversities effectively and predisposing them to passive coping styles that leave them vulnerable to the somatic effects of trauma. To validate this hypothesis, the present cross-sectional study assessed the mediating effect of coping dispositions on the association between trauma and GI disease activity in an adult sample of 189 bowel patients (94 IBD, 95 IBS) and 92 controls. Results confirmed that GI patients exhibit significantly more cumulative trauma, pervasive feelings of uncontrollability and passive coping strategies than controls. Moreover, the use of passive coping styles was positively associated with the accumulation of trauma and the expression of GI symptoms. Using hierarchical regression and mediation analyses, we found support for the sequential model postulating passive coping styles as (partial) mediators of trauma-induced (GI) disease manifestations. Specifically, out of all coping styles associated with cumulative trauma, behavioural disengagement most powerfully mediated the effect of trauma on GI symptom severity, accounting for 12% (IBD) to 14% (IBS) of its total effect. A somewhat smaller mediating role was observed for social support coping, the reduced reliance on which explained 7% (IBS) to 10% (IBD) of trauma's total effect. Finally, neuroticism acted as a channel through which past traumatization affected subjects' proneness to behavioural disengagement and, consequently, their GI disease activity.

A Retrospective Study: Reduction of Anxiety Through Music Therapy During Hospitalization

Abstract This retrospective review of 56 charts of adult hospital patients examined verbal anxiety ratings (VAR) of premusic therapy- and post-music therapy sessions to report on the preliminary efficacy of live music interventions on anxiety. Due to the high rate of anxiety associated with hospitalization and its negative somatic and psychological effects, it is important that anxiety is assessed and treated by qualified professionals. Nonpharmacological approaches such as music therapy help to address the root of anxiety by providing a relaxation cue to patients’ parasympathetic nervous system and also address patients’ psychological concerns. This retrospective analysis explores the real-world evidence of music therapy for the treatment of hospital-associated anxiety symptoms through a review of all music therapy sessions with a charted verbal anxiety rating (VAR) ≥3 documented in the electronic health record. Paired samples t-test showed that music therapy sessions resulted in a statistically significant reduction in pre- and post-verbal anxiety rating; t(60) = 9.806, p &amp;lt; .001. This study demonstrates that music therapy is a feasible treatment modality for assessing and ameliorating self-reported anxiety symptoms in hospitalized adults.

Sexual dysfunction, activity and interest changes in the antenatal and postnatal period

Most women are unprepared for the changes in their sexual health and functioning that occur during pregnancy and after childbirth. The aim of our study is to provide a comprehensive summary, based on international publications and currently available Hungarian research, of how normative changes during pregnancy, which have somatic and psychological effects, affect the sexual functioning of individuals and couples. We will review the characteristics of sexual health during pregnancy, focusing on how the sexual activity and interest of expectant mothers change in each trimester as pregnancy progresses, what the typical sexual dysfunctions are and how couples' sexual habits and positional choices change, what the typical concerns and beliefs are that distract couples from having sex. Among the postpartum effects, our study will focus on how sexual functioning is affected by the mode of delivery, perineal trauma and episiotomy. It will also look at the effects of breastfeeding and hormonal changes on sexual life. Recommendations for prevention and intervention of reproductive sexual problems will be made. Orv Hetil. 2023; 164(46): 1807-1816.

Graded brain fMRI response to somatic and visual acupuncture stimulation.

Increased stimulation can enhance acupuncture clinical response; however, the impact of acupuncture stimulation as "dosage" has rarely been studied. Furthermore, acupuncture can include both somatic and visual components. We assessed both somatic and visual acupuncture dosage effects on sensory ratings and brain response. Twenty-four healthy participants received somatic (needle inserted, manually stimulated) and visual (needle video, no manual stimulation) acupuncture over the leg at three different dosage levels (control, low-dose, and high-dose) during functional magnetic resonance imaging (fMRI). Participants reported the perceived deqi sensation for each acupuncture dose level. Blood-oxygen-level dependent imaging data were analyzed by general linear model and multivariate pattern analysis. For both somatic and visual acupuncture, reported deqi sensation increased with increased dosage of acupuncture stimulation. Brain fMRI analysis demonstrated that higher dosage of somatic acupuncture produced greater brain responses in sensorimotor processing areas, including anterior and posterior insula and secondary somatosensory cortex. For visual acupuncture, higher dosage of stimulation produced greater brain responses in visual-processing areas, including the middle temporal visual areas (V5/MT+) and occipital cortex. Psychophysical and psychophysiological responses to both somatic and visual acupuncture were graded in response to higher doses. Our findings suggest that acupuncture response may be enhanced by the dosage of needling-specific and nonspecific components, represented by different neural mechanisms.

PRONOSTIC DES PATIENTS HOSPITALISES POUR COVID-19 AU CENTRE DE TRAITEMENT DES EPIDEMIES (CTE) DE L’HOPITAL REGIONAL DE THIES DU 1ER MAI 2020 AU 15 SEPTEMBRE 2020

SummaryIntroduction: Since the beginning of March 2020, Senegal has been confronted with the COVID-19 pandemic, and its first case was recorded on 2 March of the same year. In the Thiès region, studies have focused mainly on the management of confirmed cases of COVID-19, but few have addressed the evolutionary aspect. We therefore took upon us to assess the prognosis of patients after hospitalisation in order to evaluate possible somatic or psychological effects linked to COVID-19.Methodology : This was a prospective study from May 1st to September 15th 2020 (i.e. the first wave of the covid-19 pandemic), descriptive with analytical aims. The population represented confirmed cases of COVID-19 hospitalised at the CTE of the Thiès regional hospital. This was an item-based tele-evaluation approach, and data were collected using a structured survey form and by telephone call, then analysed using SPSS Statistics version 25 software.Results : At the end of data collection, 97 patients were identified according to the established criteria. The majority of patients came from Thiès (40%), followed by Tivaouane (14%, 24.1 km from the CTE) and Pout (12%, 16.1 km from the CTE). The mean age of the patients was 49.63 +/- 17.7 years, ranging from 7 to 79 years, and 55% were male.Twenty-seven percent were asymptomatic. For those who were symptomatic, the most frequent symptoms were fever (37%), headache (34%) and cough (33%), followed by agueusia (22%), asthenia (21%) and difficulty breathing (11%).Anaemia was noted in 16% of patients, leucopenia in 3%, thrombocytosis and thrombocytopenia in 3%.COVID-19 pneumopathy (ground-glass appearance) was noted in 7%.No patient experienced any psychological effects during this study. However, one patient had persistent dyspnoea.In our work, fifty-four percent (54%) of patients were not followed up after their recovery from COVID-19. However, 22% of patients were monitored for hypertension and 16% for diabetes. The majority of patients (91%) were «satisfied», or even «very satisfied» (4%), with their care at the CTE.Conclusion : Patients admitted at the Thiès CTE during the first wave of the COVID pandemic were predominantly male. They were followed up systematically on a case-by-case basis unless they had comorbidities such as hypertension or diabetes. The majority of these patients were very satisfied with their care at the CTE. Overall, the outcome was favourable, but one case of persistent respiratory distress was noted, possibly associated with a «long COVID» Keywords: COVID-19, CTE, effects

SAT284 Is Stress Vulnerability In CAH Related To Epinephrine Deficiency And CYP21A2 Genotype?

Abstract Disclosure: A. Nordenstrom: None. K. Ekbom: None. R. Said: None. A. Strandqvist: None. H. Lönnberg: None. M. Lindberg: None. N. Bertman: None. A.L. Hirschberg: None. H. Falhammar: None. A. Rickenlund: None. Introduction: Primary adrenal insufficiency due to CYP21A2 deficiency results in epinephrine deficiency.The lack of a sufficient increase in epinephrine during high intensity exercise has been described, and increased hydrocortisone doses cannot compensate and normalize glucose response. Clinically patients with CAH seem vulnerable to stress. A possible role of epinephrine deficiency for stress vulnerability has not been studied previously. Research question: Do patients with CAH show increased stress sensitivity, depression and anxiety compared to healthy controls? Is stress sensitivity related to the severity of CAH, e.g. CYP21A2 genotype? Can vulnerability to different types of stress be correlated to the individual’s capacity to produce epinephrine? Methodology: 26 patients, aged 18-52 years, (13 F, 13 M) and 14 sex-matched controls. Plasma metanephrines (metabolites of catecholamines) were measured at start and at the peak of physical exertion on a maximum work test using ergometer cycle. All participants answered validated questionnaires regarding perceived stress (PSS), depression and anxiety (HADS), signs of fatigue syndrome (KEDS).Plasma metanephrine (metabolite of epinephrine) was correlated to CYP21A2 genotype. The results of the psychological questionnaires were correlated to the metanephrine levels and to the CYP21A2 genotype. Results: Patients with CAH had lower metanephrine levels than controls and it was related to CYP21A2 genotype. The few included patients with null genotype had virtually no metanephrin and lower levels than individuals with I2G genotype which has not been shown before.The patients scored higher on anxiety and stress and for risk of fatigue syndromed than controls. However, the men with null genotype did not report increased anxiety and depression compared to controls. Men with I2G genotype had lower scores than I172N genotype.There was a clear sex difference in that women had higher scores than men and women with severe genotypes, null and I2G, had more signs of depression and anxiety. There were no differences for perceived stress. Interpretation/Conclusions: Over all the results for the patients on the questionnaires showed a similar pattern with increasing signs of stress vulnerability with milder genotype and increasing, but deficient, metanephrine levels. An interesting finding was that a total epinephrine deficiency, as in null genotype, with less somatic effects of stress (increased heart rate etc), may be beneficial for some aspects of perceived stress tolerance. However, it may put these patients at increased risk of fatigue or burn out syndrome. The psychological effects of the virilization due to CAH per se may partly overshadow the effects of the epinephrine deficiency in women with CAH. Larger studies are needed to be able to study what role the capacity to produce epinephrine, has for the psychological stress vulnerability in CAH. Presentation: Saturday, June 17, 2023

Somatic mutation effects diffused over microRNA dysregulation.

As an important player in transcriptome regulation, microRNAs may effectively diffuse somatic mutation impacts to broad cellular processes and ultimately manifest disease and dictate prognosis. Previous studies that tried to correlate mutation with gene expression dysregulation neglected to adjust for the disparate multitudes of false positives associated with unequal sample sizes and uneven class balancing scenarios. To properly address this issue, we developed a statistical framework to rigorously assess the extent of mutation impact on microRNAs in relation to a permutation-based null distribution of a matching sample structure. Carrying out the framework in a pan-cancer study, we ascertained 9008 protein-coding genes with statistically significant mutation impacts on miRNAs. Of these, the collective miRNA expression for 83 genes showed significant prognostic power in nine cancer types. For example, in lower-grade glioma, 10 genes' mutations broadly impacted miRNAs, all of which showed prognostic value with the corresponding miRNA expression. Our framework was further validated with functional analysis and augmented with rich features including the ability to analyze miRNA isoforms; aggregative prognostic analysis; advanced annotations such as mutation type, regulator alteration, somatic motif, and disease association; and instructive visualization such as mutation OncoPrint, Ideogram, and interactive mRNA-miRNA network. The data underlying this article are available in MutMix, at http://innovebioinfo.com/Database/TmiEx/MutMix.php.

Quality of life of adolescent and adult survivors of childhood cancer in Europe-A systematic review.

Advances in diagnostics and treatment of childhood cancer during the past few decades have substantially increased survival, resulting in a growing population of survivors of childhood cancer. Somatic and mental late effects of the cancer and the treatment may impact the quality of life (QoL). Previous reviews of QoL in survivors of childhood cancer have shown contradictory findings across studies and the majority of studies included have been based on data from North America and may not be directly comparable to a European setting. The aim of our study was to critically evaluate and summarise the latest evidence on the QoL of childhood cancer survivors in Europe and to identify survivors at particular risk. The eligible studies were published between 2008 and 2022, conducted in Europe and included participants who had survived at least 5 years after diagnosis of a childhood cancer. The main outcome of interest was QoL of survivors which was measured with validated qualitative and quantitative QoL questionnaires. A systematic literature search conducted in PubMed, EMBASE, PsycINFO and CINALH resulted in inclusion of 36 articles with a total of 14 342 survivors of childhood cancer. The majority of included studies found that childhood cancer survivors reported poorer QoL than comparisons. Female gender, treatment with haematopoietic stem cell transplantation and a brain tumour diagnosis were associated with lower QoL. With a growing population of childhood cancer survivors with many years ahead of them, targeted interventions and optimal follow-up care are important to improve the QoL of survivors.

Knowledge level of medical students about ionising radiation used for diagnostic purpose in radiology: a survey study.

People exposed to ionising radiation may develop harmful somatic and genetic effects in their anatomical structures. Technological advancements, particularly in radiological devices, research and examinations result in a significant increase in the number of radiological investigations. This large number of radiological examinations increased the number of patients affected by ionising radiation. This study aims to evaluate the medical students' knowledge of ionising radiation and, examine the level of knowledge of medical students on the awareness and safety of ionising radiation exposure, emphasises the importance of radiation curricula internship programmes. This study is a survey application. The chi-square test is used. As a result, the intern's knowledge of ionising radiation increased significantly after the internship in a radiology unit. Although it has been significantly increased, it is still insufficient. This gap can be filled by incorporating radiology unit internship programmes into the curriculum of medical faculty education programmes.

Abstract 5227: Cross-trait genome-wide association meta-analyses of clonal hematopoiesis and solid tumor risk

Abstract Clonal hematopoiesis (CH) is an age-related phenomenon where hematopoietic stem cells and their progeny acquire specific somatic mutations in a small, well-defined set of leukemogenic genes conferring them with fitness advantage leading to clonal proliferation. Mosaic chromosomal alterations (mCAs) are somatic structural variants that are manifestations of genomic instability and a sign of CH when they occur in blood. The recent availability of large-scale cohorts with blood exome sequence and genotype data has powered genome-wide association studies (GWAS) investigating the germline genetic contribution to CH and mCA risk. However, phenotypes of somatic mutation acquisition in driver genes, clonal selection and expansion, and chromosomal mosaicism are processes that are not confined to blood and contribute to neoplastic transformation across tissue types. GWAS of solid tumor susceptibility have so far identified hundreds of germline variants associated with cancer risk and it is likely that a subset of these variants contributes to solid tumor risk by affecting these somatic phenotypes in the corresponding tissues of origin and that some of the variants exert these somatic effects across tissues. We aimed to identify this subset of solid tumor risk variants by undertaking fixed effects inverse-variance weighted meta-analyses combining breast, prostate, ovarian, and endometrial cancer GWAS (total n = 237,483 cases/317,006 controls; no UK Biobank samples included) with UK Biobank-based CH (10,203 “cases”/173,918 controls) and mCA (66,011 “cases”/378,188 controls) risk GWAS in pairs where each pair involved one solid tumor type and one of either CH or mCA (for example, breast cancer and mCA constituted a pair). These analyses collectively identified 61 independent (r2&amp;lt;0.05) lead variants at combined cross-trait genome-wide significance (P&amp;lt;5 × 10−8) across 22 genomic loci where each lead variant was associated with each trait individually at P&amp;lt;10−3, had the same direction of allelic effect across traits, and little evidence of heterogeneity in effect (I2&amp;lt;40%). New loci (&amp;gt;1 Mb away from previously reported risk loci for a given trait) counts were: 14 new loci in the context of mCA risk, 6 new loci for CH risk, 2 for breast cancer risk, and one each for prostate, ovarian, and endometrial cancer risks. In silico functional annotation of these loci suggested lead variant-target genes that could be assigned to the discrete pathways of mitotic spindle assembly (INCENP, CENPN, ZWILCH, MAD1L1), p53 signaling (TP53, MDM4, SPI1), DNA damage repair (ATM, RAD51C, CHEK2, USP28, PARP8), and myeloid oncogenesis (WT1, HOXA9, L3MBTL3). Our novel approach combining the latest and largest blood somatic genomic trait GWAS with large-scale solid tumor risk GWAS thus yielded clear mechanistic insights into the shared inherited genetic basis of solid tumor risk and somatic genomic traits. Citation Format: Victoria Gray, George Richenberg, Pedro Quirós, Matthew Freedman, Paul Pharoah, Simon Gayther, Michelle Jones, George Vassiliou, Kate Lawrenson, Siddhartha Kar. Cross-trait genome-wide association meta-analyses of clonal hematopoiesis and solid tumor risk. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5227.