Behavioral exposure for interoceptive tolerance (BE-FIT): A stage II randomized clinical trial protocol.

BACKGROUND: Exercise anxiety is a novel mechanism related to non-adherence to exercise and lifestyle physical activity. We developed a cognitive-behavioral treatment, Behavioral Exposure For Interoceptive Tolerance (BE-FIT), which is a manualized, values-based exposure intervention developed to target exercise anxiety that is delivered as a supplement to outpatient cardiac rehabilitation (CR). METHOD: We describe a Stage II randomized controlled trial (RCT) that is designed to test BE-FIT, compared to a Health Education Control (HEC) intervention on exercise and physical activity outcomes at end-of-treatment (EOT) and follow-ups (Weeks 12, 18, and 24), and evaluate mechanisms of change (i.e., reductions in exercise anxiety). Adults (N = 146) who are ≥40 years of age, cleared for outpatient exercise-based CR, low active and have elevated exercise anxiety will be recruited. The primary study hypothesis is that BE-FIT compared to HEC will result in higher levels of overall exercise and lifestyle physical activity at EOT and follow-ups. The second hypothesis is that BE-FIT vs HEC will produce greater reductions in exercise anxiety at EOT and Week 12. The third hypothesis is that reductions in exercise anxiety at EOT and Weeks 12 will mediate the effect of BE-FIT on activity outcomes at Weeks 18 and 24. DISCUSSION: We expect the results of this study will produce knowledge regarding BE-FIT's efficacy and mechanisms of action. Our goal is to better understand "how and why" the intervention is (or is not) effective and for whom, and increase collective knowledge and reproducibility of behavior change research.

Tumor Resection in Hepatic Carcinomas Restores Circulating T Regulatory Cells.

Background/Objectives: Cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) represent major primary liver cancers, affecting one of the most vital organs in the human body. T regulatory (Treg) cells play an important role in liver cancers through the immunosuppression of antitumor immune responses. The current study focuses on the characterization of circulating natural killer (NK) cells and T cell subsets, including Treg cells, in CCA and HCC patients, before and after surgical tumor resection, in order to understand the effect of tumor resection on the homeostasis of peripheral blood NK cells and T cells. Methods: Whole blood assays were performed to monitor immune alterations and the functional competence of circulating lymphocytes in a group of ten healthy individuals, eight CCA patients, and twenty HCC patients, before and one month after the surgical procedure, using flow cytometry, cell sorting, and qRT-PCR. Results: Before tumor resection, both HCC and CCA patients display increased percentages of CD8+ Treg cells and decreased frequencies of circulating CD4+ Treg cells. Notwithstanding, no functional impairment was detected on circulating CD4+ Treg cells, neither in CCA nor in HCC patients. Interestingly, the frequency of peripheral CD4+ Treg cells increased from 0.55% ± 0.49 and 0.71% ± 0.54 (in CCA and HCC, respectively) at T0 to 0.99% ± 0.91 and 1.17% ± 0.33 (in CCA and HCC, respectively) at T1, following tumor resection. Conclusions: Our results suggest mechanisms of immune modulation induced by tumor resection.

The adipose tissue melanocortin 3 receptor is targeted by ghrelin and leptin and may be a therapeutic target in obesity.

OBJECTIVE: Obesity is linked to perturbations in energy balance mechanisms, including ghrelin and leptin actions at the hypothalamic circuitry of neuropeptide Y (NPY) and melanocortin. However, information about the regulation of this system in the periphery is still scarce. Our objective was to study the regulation of the NPY/melanocortin system in the adipose tissue (AT) and evaluate its therapeutic potential for obesity and type 2 diabetes. METHODS: The expression of the NPY/melanocortin receptors' levels was assessed in the visceral AT of individuals with obesity and altered metabolism. Protein levels of these receptors were evaluated in cultured adipocytes incubated with ghrelin (30 and 100 ng/mL) and leptin (1 and 10 nM) and in the AT of an animal model with a mutation in the leptin receptor (ZSF1 rat), to understand their regulation by leptin and ghrelin. The vertical sleeve gastrectomy animal model was used to evaluate the putative therapeutic potential of the NPY/melanocortin system. RESULTS: In this study, we unravelled that leptin (1 nM and 10 nM) selectively reduced the levels of NPY5R and MC3R but no other NPYR/MCRs in cultured adipocytes. In turn, acylated ghrelin (100 ng/mL) significantly increased NPY1R, but the inhibition of its receptor also abrogates MC3R levels. However, in the Lepr-deficient ZSF1 rat, both NPY5R and MC3R levels were reduced, along with other NPYRs and MCRs, suggesting that leptin resistance negatively affects NPY and melanocortin signalling. In human adipose tissue, we found a downregulation of genes encoding the NPY and melanocortin receptors in the visceral AT of individuals with obesity and insulin resistance, being correlated with genes regulating metabolic activity. Additionally, diabetic obese rats submitted to vertical sleeve gastrectomy showed increased levels of NPY, melanocortin, ghrelin, and leptin receptors in the AT, including MC3R, suggesting it may constitute a therapeutic target in obesity. CONCLUSIONS: Our results suggest that the AT NPY/melanocortin system, particularly the MC3R, may be involved in the neuroendocrine regulation of adipocyte metabolism. Altogether, our work shows MC3R is under the control of the ghrelin/leptin duo, is reduced in patients with obesity and prediabetes, and may constitute a therapeutic target in obesity.

Avoidance and Rumination as Predictors of Substance Use, Mental Health, and Pain Outcomes Among People Living With HIV.

Pain, substance use, and mental health conditions are common among people living with HIV (PLWH), and avoidance and rumination may influence the co-occurrence of these conditions. The present study examined longitudinal associations between avoidance/rumination and pain outcomes, anxiety, anger, and substance use among PLWH. Participants (N = 187) with chronic pain and depressive symptoms completed self-report assessments over a 1-year period. Greater avoidance/rumination was positively associated with mental health outcomes (anxiety, anger), pain interference, and alcohol use across participants after controlling for depression severity. At time points with greater avoidance/rumination than average, participants also reported increased pain severity and interference, anxiety and anger symptoms, and alcohol use. No associations were found between avoidance/rumination and cannabis use. Results suggest a mechanistic effect of avoidance/rumination, such that increases in avoidance/rumination correspond with poorer health outcomes among PLWH over time. Targeting avoidance/rumination through intervention approaches may be beneficial for addressing comorbid health conditions among PLWH. Additional research is necessary to investigate this possibility and further characterize the effects of avoidance/rumination on health outcomes for PLWH.

Design and rationale for a randomized clinical trial testing the efficacy of a lifestyle physical activity intervention for people with HIV and engaged in unhealthy drinking.

BACKGROUND: Among people living with HIV (PLWH), unhealthy drinking presents an increased risk for negative outcomes. Physical inactivity and sedentariness raise additional health risks. Despite evidence that physical activity (PA) is associated with improved physical and mental functioning and reduced alcohol cravings, there have been no PA studies conducted with PLWH engaged in unhealthy drinking. We describe a study protocol of a remote lifestyle physical activity (LPA) intervention to increase PA and reduce alcohol consumption among PLWH. METHODS: Using online advertisements, 220 low-active PLWH engaged in unhealthy drinking will be recruited and randomized nationwide. After providing informed consent and completing a baseline interview, participants will receive a Fitbit. Participants will complete 15 days of ecologic momentary assessment through a phone application and up to 15 days of Fitbit wear time. Following this period, participants will be randomly assigned to a Fitbit-only control condition or a LPA and Fitbit intervention condition. Health counselors meet with control participants once (and have 6 subsequent brief check ins on Fibit use) and with intervention participants 7 times for PA counseling over a 12-week period. Follow-up assessments will be conducted at 3- and 6-months post-randomization. We hypothesize that individuals in the LPA and Fitbit condition will have lower rates of alcohol consumption and higher rates of PA at 6-month follow-up. CONCLUSION: The randomized controlled trial described in this paper investigates remote methods to influence multimorbidity among PLWH using a LPA approach for increasing PA and reducing alcohol consumption.

Steroidal epoxides as anticancer agents in lung, prostate and breast cancers: The case of 1,2-epoxysteroids.

Cancer continues to be a serious threat to human health worldwide. Lung, prostate and triple-negative breast cancers are amongst the most incident and deadliest cancers. Steroidal compounds are one of the most diversified therapeutic classes of compounds and they were proven to be efficient against several types of cancer. The epoxide function has been frequently associated with anticancer activity, particularly the 1,2-epoxide function. For this reason, three 1,2-epoxysteroid derivatives previously synthesised (EP1, EP2 and EP3) and one synthesised for the first time (oxysteride) were evaluated against H1299 (lung), PC3 (prostate) and HCC1806 (triple-negative breast) cancer cell lines. A human non-tumour cell line, MRC-5 (normal lung cell line) was also used. EP2 was the most active compound in all cell lines with IC50 values of 2.50, 3.67 and 1.95 µM, followed by EP3 with IC50 values of 12.65, 15.10 and 14.16 µM in H1299, PC3 and HCC1806 cells, respectively. Additional studies demonstrated that EP2 and EP3 induced cell death by apoptosis at lower doses and apoptosis/necrosis at higher doses, proving that their effects were dose-dependent. Both compounds also exerted their cytotoxicity by ROS production and by inducing double-strand breaks. Furthermore, EP2 and EP3 proved to be much less toxic against a normal lung cell line, MRC5, indicating that both compounds might be selective, and they also demonstrated suitable in silico ADME and toxicity parameters. Finally, none of the compounds induced haemoglobin release. Altogether, these results point out the extreme relevance of both compounds, especially EP2, in the potential treatment of these types of cancer.

A lifestyle physical activity intervention for women in alcohol treatment: A pilot randomized controlled trial.

INTRODUCTION: Compared to men, women with alcohol use disorder (AUD) are more likely to drink to manage stress and negative affect. Given women's risk for poor drinking outcomes, it is critical to develop and test interventions that target these affective factors. Physical activity improves negative affect and has emerged as a promising adjunct to AUD treatment and, thus, may be especially valuable for women. METHODS: Fifty women with AUD (49.9 ± 12.0 years of age) participated in either a 12-week telephone-delivered lifestyle physical activity plus Fitbit (LPA + Fitbit) or a health education contact (HEC) control intervention following a partial hospital addictions treatment program. The study examined changes in drinking behaviors, mental health outcomes, and physical activity engagement post-intervention using both conventional test statistics and standard effect sizes. RESULTS: Higher rates of continuous abstinence during the 12-week period were observed in the LPA + Fitbit condition (55.6 %) than in the HEC condition (33.6 %); odds ratio = 2.97. However, among women who drank any alcohol during the 12-weeks, slightly higher rates of heavy drinking and drinks/day were observed among women in the LPA + Fitbit condition. Significant differences for improved mental health outcomes (including depression, anxiety, negative affect, positive affect, perceived stress, and behavioral activation) and increased self-reported physical activity were consistently observed among participants in the LPA + Fitbit condition, relative to HEC. CONCLUSIONS: The LPA + Fitbit program had a positive impact on alcohol abstinence, mental health, and physical activity in adult women receiving treatment for AUD. Future research should continue to investigate the optimal implementation strategies, duration, and intensity of LPA interventions in the context of a fully-powered RCT.

Predictors of damage accrual and its impact on health-related quality of life of thrombotic antiphospholipid syndrome: Independent validation of the damage index for antiphospholipid syndrome (DIAPS).

OBJECTIVES: We aim to independently assess the validity of the damage index for antiphospholipid syndrome (DIAPS) in thrombotic antiphospholipid syndrome (APS) patients by exploring the prevalence and risk factors of organ damage and evaluating its impact on health-related quality of life (HR-QoL). METHODS: Cross-sectional study including all thrombotic APS patients (Sydney criteria) attending a Portuguese tertiary centre. Damage was assessed using the DIAPS, and HR-QoL using the 3- and 5-level EuroQol HR-QoL (EQ-D5-3L and 5L), and Visual Analogue Scale (VAS) applied via a phone questionnaire. Spearman's correlation between DIAPS and the HR-QoL scales was performed. Risk factors for damage accrual and HR-QoL impairment were explored using univariate and multivariate logistic regression. RESULTS: Among the 108 patients (female, 65.7%; white, 90.7%; primary APS, 75.9%; median disease duration, 6 years), damage (DIAPS≥1) developed in 48.2% of patients (mean ± SD DIAPS, 3.08 ± 1.83). DIAPS's neuropsychiatric domain was the most affected (24.2%), followed by the peripheral vascular domain (20.3%). No clinical, demographic nor laboratory parameters were significantly associated with damage. Regarding HR-QoL, pain/discomfort, anxiety/depression and usual activities domains were the most frequently impaired in both scales. DIAPS's domains correlated similarly with the EQ-5D-3L and 5L scales' individual domains. Female sex, medical disorders, secondary APS and type of presenting thrombosis (arterial) increased the risk of HR-QoL impairment. Total DIAPS was associated with higher odds of mobility, self-care and pain/discomfort impairment in both EQ-5D-3L and 5L scales but lost its independent risk in multivariable analysis. CONCLUSION: This external validation of DIAPS reinforces the ability of the score to correlate with HR-QoL while also highlighting risk factors for HR-QoL impairment other than damage accrual.

Meat juice as a feasible alternative sample for tuberculosis surveillance in large game.

In hunted animals, quality of blood samples may often be compromised. Alternative samples, such as meat juice, may offer an advantage to perform serological tests. This study evaluates if meat juice is a feasible alternative sample to perform the Tuberculosis ELISA test in hunted large game. Between 2017 and 2022, 175 samples were collected from 97 animals (14 red deer + 83 wild boar) in Portugal and Spain. Cohen's kappa coefficient was calculated at 0.71, pointing out a good agreement using 156 paired samples. The sensitivity of the ELISA test with serum was 37.6%, considering Tuberculosis-like lesions (TBL) detected during the initial examination (26 TBL+/ELISA+ in a total of 78 serum samples). Using meat juice as matrix, the sensitivity increased to 37.5% (33 TBL+/ELISA+ in 97 meat juice samples). According to the agreement score and sensitivity being so close between the two matrices tested, meat juice could be a feasible alternative matrix.

Sweet taste preference as a moderator of links between internalizing symptoms and alcohol craving.

OBJECTIVE: Strong positive links exist between mood, alcohol craving, and sweet taste preference. Research suggests a substitution effect of alcohol with sweets. During alcohol abstinence, individuals have increased craving for alcohol and sweets, in association with anxiety and depression symptoms. Thus, the present study examined the moderating role of sweet taste preference on links between anxiety and depression symptoms and alcohol craving. METHOD: Participants were individuals (N = 91) with alcohol use disorder (AUD) enrolled in a partial hospitalization program. Participants completed baseline assessments of anxiety and depression symptoms, alcohol use and craving, and sweet taste preference. RESULTS: We found significant correlations between symptoms of depression, anxiety, alcohol craving, and sweet taste preference. Sweet taste preference moderated links between both depression and anxiety symptoms with alcohol craving. CONCLUSIONS: For those low and moderate in sweet taste preference, internalizing symptoms appeared positively linked with alcohol craving. For those high in sweet taste preference, alcohol craving remained elevated regardless of anxiety symptoms, but appeared to decrease with heightened depressive symptoms. Should future research replicate this finding using controlled research designs that demonstrate temporality and causality, tailored early AUD interventions may be justified based on individuals' levels of sweet taste preference.

The impact of antiphospholipid antibodies/antiphospholipid syndrome on systemic lupus erythematosus.

aPLs are a major determinant of the increased cardiovascular risk in patients with SLE. They adversely affect clinical manifestations, damage accrual and prognosis. Apart from the antibodies included in the 2006 revised classification criteria for APS, other non-classical aPLs might help in identifying SLE patients at increased risk of thrombotic events. The best studied are IgA anti-ß2-glycoprotein I, anti-domain I ß2-glycoprotein I and aPS-PT. Major organ involvement includes kidney and neuropsychiatric systems. aPL/APS severely impacts pregnancy outcomes. Due to increased thrombotic risk, these patients require aggressive cardiovascular risk factor control. Primary prophylaxis is based on low-dose aspirin in high-risk patients. Warfarin is the gold-standard drug for secondary prophylaxis.

Do changes in mood and anxiety mediate exercise-induced reductions in alcohol cravings? An exploratory study.

OBJECTIVE: Exercise is increasingly used as adjunct treatment for alcohol use disorder (AUD). Evidence suggests that moderate-to-high-intensity exercise can ameliorate cravings. We explored the potential mediating effects of changes in mood states in the relationship between exercise intensity and alcohol cravings. METHOD: Secondary analyses of a nested single-arm trial within a randomized controlled trial (FitForChange). In total, 117 sedentary adults (68.4% female, M = 52 ± 12 years) with clinician diagnosed (Diagnostic and Statistical Manual of Mental Disorders, fifth edition) AUD and indications of craving (Desire for Alcohol Questionnaire) completed a 12-min submaximal cardiorespiratory fitness test on a cycle ergometer. Assessments of craving, mood states (POMS), and state anxiety (STAI-Y1) were taken immediately before, after, and 30 min after exercise. Ratings of perceived exertion (RPE) were included as indirect measures of exercise intensity. The med4way command in Stata was used to explore mediating and interaction effects of improvements in total mood disturbance (TMD) and state anxiety. RESULTS: Improvements in mood and anxiety did not mediate the effect of higher exercise intensity on reductions in alcohol craving. A significant reference interaction was found between "hard" (or greater) exertion and anxiety improvements (ß = -1.06, 95% CI [-1.50, -0.61]). Participants whose anxiety reduced during exercise had two times higher odds of reduced cravings when exercising at a higher intensity than participants whose anxiety worsened (OR = 2.04, 95% CI [1.12, 3.72]). CONCLUSIONS: Reductions in anxiety may partly explain the positive effect of higher exercise intensity on alcohol cravings. The findings are preliminary and require replication in future studies. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Chronic Pain and Cannabis Use Frequency, Intensity, and Severity in Young Adults.

BACKGROUND: Cannabis use is common among young adults and is associated with many physical and mental health problems. Persons with chronic pain may be particularly susceptible to using cannabis at high rates, including for analgesic purposes, thus exposing themselves to greater risk of cannabis-related problems. However, little research has examined connections between chronic pain and cannabis use in the young adult population. MATERIALS AND METHODS: Participants were young adults from the community who were recruited for a larger health behaviors study. The present sample included 403 persons from this larger sample who reported cannabis use in the past 90 days. Participants completed measures of demographic characteristics, cannabis and alcohol use, and chronic pain. RESULTS: This young adult sample reported using cannabis on an average of 47.1 of the past 90 days, and 20.1% reported chronic pain. Chronic pain was associated with greater cannabis use frequency (IRR = 1.35, 95%CI 1.15; 1.57, p < 0.001), intensity (IRR = 1.61, 95%CI 1.18; 2.21, p = 0.003), and negative consequences (IRR = 1.23, 95%CI 1.02; 1.48, p < 0.030). DISCUSSION: In this sample of young adults who use cannabis, chronic pain was significantly associated with frequent, intense cannabis use, as well as more cannabis-related negative consequences. These findings suggest that chronic pain may be a marker for a particularly high-risk pattern of cannabis use in this age group, thus identifying an especially vulnerable subset of young adults who may require heightened research and clinical attention.

Circulating Cell-Free Mitochondrial DNA and Depressive Symptoms Among Low-Active Adults Who Smoke.

OBJECTIVES: Mitochondrial dysfunction is implicated in the pathophysiology of psychiatric disorders. Levels of circulating cell-free mitochondrial DNA (cf-mtDNA) are observed to be altered in depression. However, the few studies that have measured cf-mtDNA in depression have reported conflicting findings. This study examined cf-mtDNA and depressive symptoms in low-active adults who smoke. METHODS: Participants were adults 18 to 65 years old ( N = 109; 76% female) with low baseline physical activity and depressive symptoms recruited for a smoking cessation study. Self-report measures assessed depression severity, positive and negative affect, and behavioral activation. Blood was collected and analyzed for cf-mtDNA. Relationships between depressive symptoms and cf-mtDNA were examined with correlations and linear regression. RESULTS: Levels of cf-mtDNA were associated with categorically defined depression (Center for Epidemiologic Studies Depression Scale score >15), lower positive affect, and decreased behavioral activation ( p < .05). Relationships remained significant after adjustment for age, sex, and nicotine dependence. In a linear regression model including all depressive symptom measures as predictors, Center for Epidemiologic Studies Depression Scale group and lower positive affect remained significant. CONCLUSIONS: This work suggests that mitochondrial changes are associated with depressive symptoms in low-active adults who smoke. Higher levels of cf-mtDNA in association with depression and with lower positive affect and decreased behavioral activation are consistent with a possible role for mitochondrial function in depressive symptoms.

Evaluation of intervention components to maximize yoga practice among people with chronic pain taking opioid agonist therapy: A factorial experiment using the multiphase optimization strategy framework.

BACKGROUND: Chronic pain affects up to half of individuals taking opioid agonist therapy (OAT; i.e., methadone and buprenorphine) for opioid use disorder (OUD), and yoga-based interventions may be useful for decreasing pain-related disability. Whereas more yoga practice (i.e., higher "dosage") may improve pain-related outcomes, it can be challenging for people with chronic pain taking OAT to attend class regularly and sustain a regular personal yoga practice. Therefore, we plan to optimize a yoga-based intervention (YBI) package in order to support class attendance and personal practice, thus maximizing the yoga dose received. STUDY DESIGN: Using the Multiphase Optimization Strategy (MOST) framework, we will conduct a factorial experiment to examine four intervention components that may be added to a weekly yoga class as part of a YBI. Components include: 1) personal practice videos featuring study yoga teachers, 2) two private sessions with a yoga teacher, 3) daily text messages to inspire personal practice, and 4) monetary incentives for class attendance. The primary outcome will be minutes per week engaged in yoga (including class attendance and personal practice). We plan to enroll 192 adults with chronic pain who are taking OAT for OUD in this 2x2x2x2 factorial experiment. CONCLUSION: Results of the study will guide development of an optimized yoga-based intervention package that maximizes dosage of yoga received. The final treatment package can be tested in a multisite efficacy trial of yoga to reduce pain interference in daily functioning in people with chronic pain who are taking OAT. TRIAL REGISTRATION: Pre-registration of the study was completed on ClinicalTrials.gov (identifier: NCT04641221).

Methodological approach for an integrated female-specific study of anxiety and smoking comorbidity.

Two primary ovarian hormones that fluctuate across the female menstrual cycle-estradiol and progesterone-have been independently linked in separate literatures to nicotine reinforcement and anxiety psychopathology. We identify existing methodological limitations in these literatures, describe an example protocol that was developed to address such limitations, highlight case examples, and offer insights on the resulting advantages and challenges. This protocol was an observational, prospective, within-subjects study of female cigarette smokers who were followed over the course of a complete menstrual cycle. Non-treatment seeking, female cigarette smokers (N = 50), between the ages of 18-40 who have a normal menstrual cycle (25-35 days in length) were recruited from the community. Females with anxiety or mood psychopathology represented 38.0% of the sample. Salivary progesterone and estradiol were assessed each morning via at-home saliva collection methods. Self-reported within-day momentary ratings of anxiety and nicotine reinforcement were collected using ecological momentary assessment (EMA) via a mobile app. Protocol compliance was >85%. Within- and between-subjects heterogeneity was observed in the progesterone and estradiol, anxiety, and nicotine craving measures, especially in the context of anxiety psychopathology. We aimed to integrate the anxiety and nicotine dependence literatures and advance the empirical study of the role of ovarian hormones. This protocol reflects an intensive, yet feasible approach to collecting daily-level naturalistic data related to estradiol, progesterone, anxiety, and nicotine reinforcement.

Impact of Different Treatment Regimens and Timeframes in the Plasmatic Metabolic Profiling of Patients with Lung Adenocarcinoma.

In recent years, the treatment of advanced non-small cell lung cancer (NSCLC) has suffered a variety of alterations. Chemotherapy (CTX), immunotherapy (IT) and tyrosine kinase inhibitors (TKI) have shown remarkable results. However, not all patients with NSCLC respond to these drug treatments or receive durable benefits. In this framework, metabolomics has been applied to improve the diagnosis, treatment, and prognosis of lung cancer and particularly lung adenocarcinoma (AdC). In our study, metabolomics was used to analyze plasma samples from 18 patients with AdC treated with CTX or IT via 1H-NMR spectroscopy. Relevant clinical information was gathered, and several biochemical parameters were also evaluated throughout the treatments. During the follow-up of patients undergoing CTX or IT, imaging control is recommended in order to assess the effectiveness of the therapy. This evaluation is usually performed every three treatments. Based on this procedure, all the samples were collected before the beginning of the treatment and after three and six treatments. The identified and quantified metabolites in the analyzed plasma samples were the following: isoleucine, valine, alanine, acetate, lactate, glucose, tyrosine, and formate. Multivariate/univariate statistical analyses were performed. Our data are in accordance with previous published results, suggesting that the plasma glucose levels of patients under CTX become higher throughout the course of treatment, which we hypothesize could be related to the tumor response to the therapy. It was also found that alanine levels become lower during treatment with CTX regimens, a fact that could be associated with frailty. NMR spectra of long responders' profiles also showed similar results. Based on the results of the study, metabolomics can represent a potential option for future studies, in order to facilitate patient selection and the monitoring of therapy efficacy in treated patients with AdC. Further studies are needed to improve the prospective identification of predictive markers, particularly glucose and alanine levels, as well as confer guidance to NSCLC treatment and patient stratification, thus avoiding ineffective therapeutic strategies.

Risk of Second Tumors in Retinoblastoma Survivors after Ionizing Radiation: A Review.

Retinoblastoma (RB) is the most common ocular neoplasm in children, whose development depends on two mutational events that occur in both alleles of the retinoblastoma susceptibility gene (RB1). Regarding the nature of these mutational events, RB can be classified as hereditary if the first event is a germline mutation and the second one is a somatic mutation in retina cells or nonhereditary if both mutational events occur in somatic cells. Although the rate of survival of RB is significantly elevated, the incidence of second malignant neoplasms (SMNs) is a concern, since SMNs are the main cause of death in these patients. Effectively, RB patients present a higher risk of SMN incidence compared to other oncology patients. Furthermore, evidence confirms that hereditary RB survivors are at a higher risk for SMNs than nonhereditary RB survivors. Over the decades, some studies have been performed to better understand this subject, evaluating the risk of the development of SMNs in RB patients. Furthermore, this risk seems to increase with the use of ionizing radiation in some therapeutic approaches commonly used in the treatment of RB. This review aims to clarify the effect of ionizing radiation in RB patients and to understand the association between the risk of SMN incidence in patients that underwent radiation therapy, especially in hereditary RB individuals.

Coronary Artery Calcium Identified on Non-Gated Chest CT Scans: A Wasted Opportunity for Preventive Cardiological Care.

BACKGROUND: Coronary artery calcium (CAC) evaluated on dedicated cardiac computed tomography (CT) is an independent predictor of cardiovascular events. This study aimed to evaluate the correlation between CAC detected on non-gated standard chest CT and coronary lesions on coronary angiography (CAG) and determine its impact on prognosis. METHODS: Consecutive patients who underwent CAG due to acute coronary syndrome and had prior non-contrasted non-gated chest CT were included and retrospectively evaluated. Coronary artery calcium was evaluated by quantitative (Agatston score) and qualitative (visual assessment) assessment. RESULTS: A total of 114 patients were included in this study. The mean time difference between chest CT and CAG was 23 months. Coronary artery calcium was visually classified as mild, moderate, and severe in 31%, 33%, and 16% of patients, respectively. Moderate or severe CAC was an independent predictor of significant lesions on CAG (OR 22; 95% CI 8-61; p<0.001) and all-cause mortality (OR 4; 95% CI 2-9; p=0.001). Quantitative CAC evaluation accurately predicted significant lesions on CAG (AUC 0.81; p<0.001). While significant CAC was identified in 80% of chest CTs, formal reporting was 25%. CONCLUSION: Coronary artery calcium evaluation with chest CT was feasible and strongly associated with severity of coronary disease on CAG and mortality. Although the identification of CAC on chest CT represents a unique opportunity for cardiovascular risk stratification for preventive care, CAC underreporting is frequent.

Impact of COVID-19's Economic Burden on Alcohol-Related Problems: An Indirect Effect of Depression, Stress, and Anxiety.

The COVID-19 pandemic resulted in global monumental upheaval. Many people were displaced from their jobs and sources of income. COVID-19 was also linked to increased mental health difficulties and increased alcohol consumption and problems. The current study aims to identify the indirect effect of depression, stress, and anxiety on the relations between the economic burden of COVID-19 and alcohol problems. Participants (N = 344) were recruited via Amazon's Mechanical Turk (MTurk). Participants completed a questionnaire about substance use, mood, and the economic burden of COVID-19. Eligible participants were 18 years or older, consumed alcohol or cannabis within the past week, and verified through Amazon. Results indicated significant indirect effects of depression, stress, and anxiety on the association between the economic burden of COVID-19 and alcohol problems regardless of use. Findings revealed large effect sizes, suggesting that mental health symptomatology may have a large impact on the association between COVID-19's economic burden and alcohol-related problems. Findings suggest mental health difficulties indirectly effect the association between COVID-19's economic burden and alcohol-related problems. Intervention efforts targeting mental health may be beneficial in reducing alcohol problems among individuals experiencing distress due to large-scale public health impact, such as the COVID-19 pandemic.