Personal Strategies to Reduce the Cardiovascular Impacts of Environmental Exposures.

Ubiquitous environmental exposures increase cardiovascular disease risk via diverse mechanisms. This review examines personal strategies to minimize this risk. With regard to fine particulate air pollution exposure, evidence exists to recommend the use of portable air cleaners and avoidance of outdoor activity during periods of poor air quality. Other evidence may support physical activity, dietary modification, omega-3 fatty acid supplementation, and indoor and in-vehicle air conditioning as viable strategies to minimize adverse health effects. There is currently insufficient data to recommend specific personal approaches to reduce the adverse cardiovascular effects of noise pollution. Public health advisories for periods of extreme heat or cold should be observed, with limited evidence supporting a warm ambient home temperature and physical activity as strategies to limit the cardiovascular harms of temperature extremes. Perfluoroalkyl and polyfluoroalkyl substance exposure can be reduced by avoiding contact with perfluoroalkyl and polyfluoroalkyl substance-containing materials; blood or plasma donation and cholestyramine may reduce total body stores of perfluoroalkyl and polyfluoroalkyl substances. However, the cardiovascular impact of these interventions has not been examined. Limited utilization of pesticides and safe handling during use should be encouraged. Finally, vasculotoxic metal exposure can be decreased by using portable air cleaners, home water filtration, and awareness of potential contaminants in ground spices. Chelation therapy reduces physiological stores of vasculotoxic metals and may be effective for the secondary prevention of cardiovascular disease.

Light exposure and its applications in human health.

Light exposure has been proven to have a significant impact on human health. As a result, researchers are increasingly exploring its potential benefits and drawbacks. With advancements in understanding light and the manufacturing of light sources, modern health lighting has become widely utilized in daily life and plays a critical role in the prevention and treatment of various illnesses. The use of light in healthcare is a global trend, with many countries actively promoting the development and application of relevant scientific research and medical technology. This field has gained worldwide attention and support from scientists and doctors alike. In this review, we examine the application of lighting in human health and recent breakthroughs in light exposure related to pathology, therapeutic strategies, molecular changes, and more. Finally, we also discuss potential future developments and areas of application.

Basic processes and clinical applications of mental imagery in worry: A systematic review.

BACKGROUND: In this systematic review, we aimed to synthesise existing research on the phenomenology of mental imagery among high worriers compared to healthy individuals, and to characterise the nature and effectiveness of existing imagery-related interventions in treatment of worry. METHODS: PsycInfo, CENTRAL, EMBASE, Medline, Medline Epub, and PubMed were searched for studies examining the relationship between worry/GAD and mental imagery, or interventions using imagery in treatment of worry/GAD. We assessed study quality and used qualitative narrative synthesis to comprehensively map study results. RESULTS: The search yielded 2589 abstracts that were assessed for eligibility independently by two authors. From this, 183 full texts were screened and 50 qualitatively synthesised. Twenty-seven reported an association between worry/GAD and an aspect of mental imagery. Here, overactive negative and worry imagery, and diminished positive future imagining, were associated with worry/GAD. Twenty-three studies reported an intervention. This literature suggested mixed findings regarding efficacy, including for imaginal exposure as an independent technique for GAD. CONCLUSIONS: Findings support dysfunctional negative imagining and diminished positive prospective imagery in GAD. General imagining abilities remain intact, which is promising for efforts to utilise imagery in treatment. Further research is warranted to develop innovative clinical applications of imagery in treatment of GAD.

The effects of an intensive outpatient treatment for PTSD.

Introduction: Research has shown that combining different evidence-based PTSD treatments for patients with PTSD in an intensive inpatient format seems to be a promising approach to enhance efficiency and reduce generally high dropout rates.Objective: To assess the effectiveness of an intensive six-day outpatient trauma-focused treatment for patients with PTSD.Method: Data from 146 patients (89.7% female, mean age = 36.79, SD = 11.31) with PTSD due to multiple traumatization were included in the analyses. The treatment programme consisted of six days of treatment within two weeks, with two daily individual 90-minute trauma-focused sessions (prolonged exposure and eye movement desensitization and reprocessing), one hour of exercise, and one hour of psychoeducation. All participants experienced multiple traumas, and 85.6% reported one or more comorbid psychiatric disorders. PTSD symptoms and diagnoses were assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), and self-reported symptoms were assessed with the PTSD Checklist for DSM-5 (PCL-5).Results: A significant decline in PTSD symptoms (CAPS-5 and PCL-5) from pretreatment to one-month follow-up (Cohen's d = 1.13 and 1.59) was observed and retained at six-month follow-up (Cohen's d = 1.47 and 1.63). After one month, 52.4% of the patients no longer met the diagnostic criteria for PTSD (CAPS-5). The Reliable Change Index (RCI) shows that 73.9% of patients showed improvement on the CAPS-5 and 77.61% on the PCL-5. Additionally, 21.77% (CAPS-5) and 20.0% (PCL-5) showed no change, while 4.84% (CAPS-5) and 2.96% (PCL-5) showed symptom worsening.Discussion: The results show that an intensive outpatient trauma treatment programme, including two evidence-based trauma-focused treatments, exercise, and psychoeducation, is effective for patients suffering from PTSD as a result of multiple traumatization. Subsequent research should focus on more controlled studies comparing the treatment programme with other intensive trauma treatments and less frequent routine treatment.

Intensive outpatient trauma treatment is effective in treating PTSD.Six days of combining prolonged exposure, EMDR, exercise and psycho-education seems feasible and effective in treating PTSD.73.9% of the patients show improvement on the CAPS-5 and 77.61% show improvement on the PCL-5, symptom worsening was there in 4,84, respectively 2.96%.

Preeclampsia Onset, Days to Delivery, and Autism Spectrum Disorders in Offspring: Clinical Birth Cohort Study.

BACKGROUND: Maternal preeclampsia is associated with a risk of autism spectrum disorders (ASD) in offspring. However, it is unknown whether the increased ASD risk associated with preeclampsia is due to preeclampsia onset or clinical management of preeclampsia after onset, as clinical expectant management of preeclampsia allows pregnant women with this complication to remain pregnant for potentially weeks depending on the onset and severity. Identifying the risk associated with preeclampsia onset and exposure provides evidence to support the care of high-risk pregnancies and reduce adverse effects on offspring. OBJECTIVE: This study aimed to fill the knowledge gap by assessing the ASD risk in children associated with the gestational age of preeclampsia onset and the number of days from preeclampsia onset to delivery. METHODS: This retrospective population-based clinical cohort study included 364,588 mother-child pairs of singleton births between 2001 and 2014 in a large integrated health care system in Southern California. Maternal social demographic and pregnancy health data, as well as ASD diagnosis in children by the age of 5 years, were extracted from electronic medical records. Cox regression models were used to assess hazard ratios (HRs) of ASD risk in children associated with gestational age of the first occurrence of preeclampsia and the number of days from first occurrence to delivery. RESULTS: Preeclampsia occurred in 16,205 (4.4%) out of 364,588 pregnancies; among the 16,205 pregnancies, 2727 (16.8%) first occurred at <34 weeks gestation, 4466 (27.6%) first occurred between 34 and 37 weeks, and 9012 (55.6%) first occurred at ≥37 weeks. Median days from preeclampsia onset to delivery were 4 (IQR 2,16) days, 1 (IQR 1,3) day, and 1 (IQR 0,1) day for those first occurring at <34, 34-37, and ≥37 weeks, respectively. Early preeclampsia onset was associated with greater ASD risk (P=.003); HRs were 1.62 (95% CI 1.33-1.98), 1.43 (95% CI 1.20-1.69), and 1.23 (95% CI 1.08-1.41), respectively, for onset at <34, 34-37, and ≥37 weeks, relative to the unexposed group. Within the preeclampsia group, the number of days from preeclampsia onset to delivery was not associated with ASD risk in children; the HR was 0.995 (95% CI 0.986-1.004) after adjusting for gestational age of preeclampsia onset. CONCLUSIONS: Preeclampsia during pregnancy was associated with ASD risk in children, and the risk was greater with earlier onset. However, the number of days from first preeclampsia onset to delivery was not associated with ASD risk in children. Our study suggests that ASD risk in children associated with preeclampsia is not increased by expectant management of preeclampsia in standard clinical practice. Our results emphasize the need to identify effective approaches to preventing the onset of preeclampsia, especially during early pregnancy. Further research is needed to confirm if this finding applies across different populations and clinical settings.

The use of amino acids and their derivates to mitigate against pesticide-induced toxicity.

Exposure to pesticides induces oxidative stress and deleterious effects on various tissues in non-target organisms. Numerous models investigating pesticide exposure have demonstrated metabolic disturbances such as imbalances in amino acid levels within the organism. One potentially effective strategy to mitigate pesticide toxicity involves dietary intervention by supplementing exogenous amino acids and their derivates to augment the body's antioxidant capacity and mitigate pesticide-induced oxidative harm, whose mechanism including bolstering glutathione synthesis, regulating arginine-NO metabolism, mitochondria-related oxidative stress, and the open of ion channels, as well as enhancing intestinal microecology. Enhancing glutathione synthesis through supplementation of substrates N-acetylcysteine and glycine is regarded as a potent mechanism to achieve this. Selection of appropriate amino acids or their derivates for supplementation, and determining an appropriate dosage, are of the utmost importance for effective mitigation of pesticide-induced oxidative harm. More experimentation is required that involves large population samples to validate the efficacy of dietary intervention strategies, as well as to determine the effects of amino acids and their derivates on long-term and low-dose pesticide exposure. This review provides insights to guide future research aimed at preventing and alleviating pesticide toxicity through dietary intervention of amino acids and their derivates.

Subchronic Toxicity Evaluation of Idesia polycarpa Fruit Oil by 90-Day Oral Exposure in Wistar Rats.

Idesia polycarpa, belonging to the Flacourtiaceae family, is a tall deciduous tree, widely distributed in some Asian countries. It is famous for its high yield of fruit known as oil grape, which is rich of linoleic acid and linolenic acid, and so on. To provide evidences for its safe use as food, subchronic toxicity of I. polycarpa fruit oil and no observed adverse effect level were performed in male and female specific pathogen-free Wistar rats. Based on the Organization for Economic Co-operation and Development guidelines, the oil was orally administered to rats by gavage at 0, 1.0, 2.0, and 4.0mL/kg.bw/day for 90 days, followed by a 28-day recovery period. The results showed that no sign of oil-related toxicity, clinically or histologically, was observed in both male and female rats. Although there was a slight increase or decrease in some indicators such as hematology, serum chemistry, and so on, those changes were all within the normal ranges, and as presented in the 90-day study, the oil exhibited no toxic effect compared to the control rats. I. polycarpa might be a potential excellent and healthy vegetable oil resource.

Association and mediation analyses among multiple metal exposure, mineralocorticoid levels, and serum ion balance in residents of northwest China.

Toxic metals are vital risk factors affecting serum ion balance; however, the effect of their co-exposure on serum ions and the underlying mechanism remain unclear. We assessed the correlations of single metal and mixed metals with serum ion levels, and the mediating effects of mineralocorticoids by investigating toxic metal concentrations in the blood, as well as the levels of representative mineralocorticoids, such as deoxycorticosterone (DOC), and serum ions in 471 participants from the Dongdagou-Xinglong cohort. In the single-exposure model, sodium and chloride levels were positively correlated with arsenic, selenium, cadmium, and lead levels and negatively correlated with zinc levels, whereas potassium and iron levels and the anion gap were positively correlated with zinc levels and negatively correlated with selenium, cadmium and lead levels (all P < 0.05). Similar results were obtained in the mixed exposure models considering all metals, and the major contributions of cadmium, lead, arsenic, and selenium were highlighted. Significant dose-response relationships were detected between levels of serum DOC and toxic metals and serum ions. Mediation analysis showed that serum DOC partially mediated the relationship of metals (especially mixed metals) with serum iron and anion gap by 8.3% and 8.6%, respectively. These findings suggest that single and mixed metal exposure interferes with the homeostasis of serum mineralocorticoids, which is also related to altered serum ion levels. Furthermore, serum DOC may remarkably affect toxic metal-related serum ion disturbances, providing clues for further study of health risks associated with these toxic metals.

Skills training followed by either EMDR or narrative therapy for posttraumatic stress disorder in adult survivors of childhood abuse: a randomized controlled trial.

Background: Individuals suffering from PTSD following childhood abuse represent a large subgroup of patients attending mental health services. The aim of phase-based treatment is to tailor treatment to the specific needs to childhood abuse survivors with PTSD with a Skills Training in Affective and Interpersonal Regulation (STAIR) phase, in which emotion dysregulation and interpersonal problems are targeted, and a trauma-focused phase.Objective: The purpose of this study was to compare STAIR + Eye Movement Desensitization and Reprocessing (EMDR) vs. STAIR + Narrative Therapy (NT) as treatments for PTSD following childhood-onset trauma in a routine clinical setting.Method: Sixty-eight adults were randomly assigned to STAIR/EMDR (8 STAIR-sessions followed by 12 EMDR-sessions) or STAIR/NT (8 STAIR-sessions followed by 12 NT-sessions). Assessments took place at pre-treatment, after each treatment phase and at 3 and 12 months post-intervention follow-up. Primary outcomes were interviewer-rated and self-reported symptom levels of PTSD. Secondary outcomes included symptom levels of depression and disturbances in emotion regulation and interpersonal skills.Results: Multilevel analyses in the intent-to-treat sample indicated that patients in both treatments improved substantially on PTSD symptom severity (CAPS: d = 0.81 to 1.29; PDS: d = 1.68 to 2.15), as well as on symptom levels of depression, anxiety, emotion regulation, dissociation and interpersonal skills. Effects increased or were maintained until 12-month follow-up. At mid-treatment, after STAIR, patients in both treatments improved moderately on PTSD symptom severity (PDS: d = 1.68 to 2.15), as well as on symptom levels of depression (BDI: d = .32 to .31). Symptoms of anxiety, emotion dysregulation, interpersonal problems and dissociation were not decreased after STAIR. There were no significant differences between the two conditions on any outcome.Conclusion: PTSD in adult survivors of childhood interpersonal trauma can effectively be treated by phase-based interventions using either EMDR or NT in the trauma-processing phase.Trial registration: ClinicalTrials.gov identifier: NCT01443182..

The study directly compares Skills Training in Affective and Interpersonal Regulation (STAIR) followed by either EMDR or Narrative Therapy in the trauma-processing phase in routine clinical setting.The brief phase-based treatment was found to be effective in reducing both symptoms of PTSD as well as emotion regulation and interpersonal problems in survivors of childhood abuse.Posttraumatic Stress Disorder in adult survivors of childhood interpersonal trauma can effectively be treated by phase-based interventions using either EMDR or Narrative Therapy in the trauma-processing phase.

Effect of docosahexaenoic acid and olive oil supplementation on pup weight in alcohol-exposed pregnant rats.

Background: Low birth weight has been observed in offspring of alcoholic mothers due likely to unresolved inflammation and oxidative injury. Dietary lipids play a role in inflammation and its resolution. The primary objective was to investigate the effect of DHA and olive oil on the birth weight of pups born to alcohol-exposed dams. Methods: Pregnant rats were randomized to the control or three treatment (alcohol) groups. From gestational days (GD) 8-19, the control group received daily olive oil and malto/dextrose, whereas groups 2 and 3 received olive oil and low-dose alcohol or high-dose alcohol, respectively. Group 4 received daily DHA and high-dose alcohol. The dam's blood was collected on GD 15 and 20 for cytokine analysis. Dams were sacrificed on GD 20. The mean birth weight of pups was compared by one-way ANOVA with post hoc Duncan's test. Results: There was a significant increase in the pups' mean birth weight in the high-dose alcohol/DHA and high-dose alcohol/olive oil. Higher pro-inflammatory cytokines (IL-1ß and IL-12p70) were noted in the alcohol-exposed dams. Conclusions: DHA and olive oil supplementation in alcohol-exposed pregnant rats significantly increased their pups' birth weight despite having high pro-inflammatory cytokines. The mechanism of this effect remains to be determined.

Novel Interventions on Comorbidities in Patients with Fetal Alcohol Spectrum Disorder (FASD): An Integrative Review.

Prenatal exposure to alcohol can cause Fetal Alcohol Spectrum Disorders (FASDs) after birth, encompassing a spectrum of physical, cognitive, and behavioral abnormalities. FASD represents a severe non-genetic disability avoidable through alcohol abstinence during pregnancy and when planning it. Clinical severity depends on alcohol impact, symptomatology, and resulting disabilities. FASD is a permanent disability with no recognized specific medical care. Conversely, secondary FASD-related disabilities can be symptomatically treated. This integrative review aims to provide information about the novel pharmacological treatments of FASD-associated comorbidities by selecting the last ten years of studies carried out on animals and humans. PRISMA guidelines were followed to search human/animal model studies of pharmacological interventions on FASD comorbidities, using different databases (PubMed, Cochrane, etc.). From 1348 articles, 44 met the criteria after full-text analysis. Firstly, all the reported studies point out that early diagnosis and tailored interventions are the principal tools to reduce FASD-related secondary disabilities, due to the fact that there is currently no approved pharmacological treatment for the tissue damage which produces FASD. Despite limitations in study designs and small sample sizes, these review results highlight how the treatment strategies of children with FASD have changed. In the past, studies focused on treating symptoms, but in the last years, researchers have turned their attention to the prevention targeting central nervous system embryogenesis. Novel treatments like choline and natural antioxidants and nutritional supplements are the most investigated treatments in humans with promising results. More follow-up studies need to be performed, to confirm and generalize reported efficacy to a wide sample size.

Melatonin protects oogenesis from hypobaric hypoxia-induced fertility damage in mice.

Environmental hypoxia adversely affects reproductive health in humans and animals at high altitudes. Therefore, how to alleviate the follicle development disorder caused by hypoxia exposure and to improve the competence of fertility in plateau non-habituated female animals are important problems to be solved urgently. In this study, a hypobaric hypoxic chamber was used for 4 weeks to simulate hypoxic conditions in female mice, and the effects of hypoxia on follicle development, proliferation and apoptosis of granulosa cells, reactive oxygen species (ROS) levels in MII oocyte and 2-cell rate were evaluated. At the same time, the alleviating effect of melatonin on hypoxic exposure-induced oogenesis damage was evaluated by feeding appropriate amounts of melatonin daily under hypoxia for 4 weeks. The results showed that hypoxia exposure significantly increased the proportion of antral follicles in the ovary, the number of proliferation and apoptosis granulosa cells in the follicle, and the level of ROS in MII oocytes, eventually led to the decline of oocyte quality. However, these defects were alleviated when melatonin was fed under hypoxia conditions. Together, these findings suggest that hypoxia exposure impaired follicular development and reduced oocyte quality, and that melatonin supplementation alleviated the fertility reduction induced by hypoxia exposure.

Combining cisplatin with Pinellia pedatisecta Schott lipid-soluble extract induces tumor immunogenic cell death in cervical cancer.

BACKGROUND: Pinellia pedatisecta Schott extract (PE) is extracted from Pinellia pedatisecta Schott (PPS), a traditional Chinese medicinal plant with the potential for direct anticancer effects or eliciting an anti-tumor response by activating the immune system. PURPOSE: To explore PE's ability and mechanism to reconstruct cisplatin's immunogenicity. METHODS: Cervical cancer cells were treated with cisplatin (CDDP) and/or PE. The exposure of calreticulin (CRT) on cell membrane was investigated by flow cytometry. The extracellular of ATP and HMGB1 was investigated by Western blot analysis, immunofluorescence and ELISA assay. Changes in immune profiles were using flow cytometry in vaccination and anti-tumor assays in vivo. Lastly, the mechanism of PE influenced the ROS/ERS pathway was examined by ROS assay kit, flow cytometry and Western blotting. RESULTS: PE treatment induced translocation of CRT from the endoplasmic reticulum to the cell membrane of tumor cells, concomitantly triggering immunogenic cell death (ICD). In terms of mechanisms, endoplasmic reticulum (ER) stress relievers could impede the ability of PE to induce immunogenicity. This indicates that PE is activated by ER stress, leading to subsequent induction of ICD. Upon analyzing RNA-seq data, it was observed that PE primarily induces programmed cell death in tumors by impeding upstream antioxidant mechanisms. Additionally, it transforms dying tumor cells into vaccines, activating a series of immune responses. CONCLUSIONS: This study observed for the first time that PE-induced CRT exposure on the membrane of cervical cancer cells compensates for the defect of nonimmunogenic cell death inducer CDDP thereby stimulating potent ICD. This ability restores the immunogenicity of CDDP through ER stress induced by the ROS signal. ROS played a role in PE's ability to induce ICD, leading to increased expression of ER stress-related proteins, including ATF3 and IRE-1α. PE exerted anti-cancer effects by increasing the ROS levels, and ROS/ERS signaling may be a potential avenue for cervical cancer treatment. Hence, the synergistic use of PE and CDDP holds potential for enhancing immunochemotherapy in cancer treatment.

Environmental impact assessment due to the intake of uranium contained in surface waters in a semi-arid region in Brazil.

In Santa Quitéria City, part of the population uses surface water for potation. These waters do not undergo any treatment before consumption. As the region has a deposit of uranium, assessing water quality becomes important. In the present study, the uranium activity concentration (AC) in becquerels per liter was determined in water samples from six points. Univariate statistics showed differences between the soluble and the particulate fraction (soluble AC > particulate AC). The particulate fraction showed no variation in AC among the six points. On the other hand, the soluble fraction and the total fraction presented different ACs between them. The multivariate statistics allowed to separate the soluble from the particulate fraction of the points. The same tools applied to the total fraction made it possible to differentiate the sampling points, grouping them ((#1, #2); (#3, #4), and (#5, #6)). The maximum mean value of AC found was 0.177 Bq∙L-1, corresponding to 25% of the chemical toxicity limit (0.72 Bq∙L-1). The maximum mean dose rate, 2.25 µSv∙year-1, is lower than the considered negligible dose rate (> 10 µSv∙year-1). The excess lifetime cancer risk was 10-6, two orders of magnitude smaller than the threshold considered for taking action. The assessment parameters used in this work indicate that the risk due to the uranium intake by the local population is negligible.

Reduced body-image disturbance by body-image interventions is associated with neural-response changes in visual and social processing regions: a preliminary study.

Introduction: Body-image disturbance is a major factor in the development of eating disorders, especially among young women. There are two main components: perceptual disturbance, characterized by a discrepancy between perceived and actual body size, and affective disturbance, characterized by a discrepancy between perceived and ideal body size. Interventions targeting body-image disturbance ask individuals to describe their own body without using negative expressions when either viewing it in a mirror or imagining it. Despite the importance of reducing body-image disturbance, its neural mechanisms remain unclear. Here we investigated the changes in neural responses before and after an intervention. We hypothesized that neural responses correlated with the degree of body-image disturbance would also be related to its reduction, i.e., a reduction in perceptual and affective disturbances would be related to changes in attentional and socio-cognitive processing, respectively. Methods: Twenty-eight young adult women without known psychiatric disorders underwent a single 40-min intervention. Participants completed tasks before and after the intervention, in which they estimated their perceived and ideal body sizes using distorted silhouette images to measure body-image disturbance. We analyzed the behavioral and neural responses of participants during the tasks. Results: The intervention did not significantly reduce body-image disturbance. Analysis of individual differences showed distinct changes in neural responses for each type of disturbance. A decrease in perceptual disturbance was associated with bodily visuospatial processing: increased activation in the left superior parietal lobule, bilateral occipital gyri, and right cuneus. Reduced affective disturbance was associated with socio-cognitive processing; decreased activation in the right temporoparietal junction, and increased functional connectivity between the left extrastriate body area and the right precuneus. Discussion: We identified distinct neural mechanisms (bodily visuospatial and socio-cognitive processing) associated with the reduction in each component of body-image disturbance. Our results imply that different neural mechanisms are related to reduced perceptual disturbance and the expression thereof, whereas similar neural mechanisms are related to the reduction and expression of affective disturbance. Considering the small sample size of this study, our results should be regarded as preliminary.

The health risks of marine biotoxins associated with high seafood consumption: Looking beyond the single dose, single outcome paradigm with a view towards addressing the needs of coastal Indigenous populations in British Columbia.

People who consume high quantities of seafood are at a heightened risk for marine biotoxin exposure. Coastal Indigenous peoples may experience higher levels of risk than the general population due to their reliance on traditional marine foods. Most evidence on the health risks associated with biotoxins focus on a single exposure at one point in time. There is limited research on other types of exposures that may occur among those who regularly consume large quantities of seafood. The objective of this review is to assess what is known about the unique biotoxin exposure risks associated with the consumption patterns of many coastal Indigenous populations. These risks include [1]: repeated exposure to low doses of a single or multiple biotoxins [2]; repeated exposures to high doses of a single or multiple biotoxins; and [3] exposure to multiple biotoxins at a single point in time. We performed a literature search and collected 23 recent review articles on the human health effects of different biotoxins. Using a narrative framework synthesis approach, we collated what is known about the health effects of the exposure risks associated with the putative consumption patterns of coastal Indigenous populations. We found that the health effects of repeated low- or high-dose exposures and the chronic health effects of marine biotoxins are rarely studied or documented. There are gaps in our understanding of how risks differ by seafood species and preparation, cooking, and consumption practices. Together, these gaps contribute to a relatively poor understanding of how biotoxins impact the health of those who regularly consume large quantities of seafood. In the context of this uncertainty, we explore how known and potential risks associated with biotoxins can be mitigated, with special attention to coastal Indigenous populations routinely consuming seafood. Overall, we conclude that there is a need to move beyond the single-dose single-outcome model of exposure to better serve Indigenous communities and others who consume high quantities of seafood.

Mitoquinone mesylate as post-exposure prophylaxis against SARS-CoV-2 infection in humans: an exploratory single center pragmatic open label non-randomized pilot clinical trial with matched controls.

BACKGROUND: An ongoing important need exists to rapidly develop novel therapeutics for COVID-19 that will retain antiviral efficacy in the setting of rapidly evolving SARS-CoV-2 variants and potential future development of resistance of SARS-COV-2 to remdesivir and protease inhibitors. To date, there is no FDA-approved treatment for post-exposure prophylaxis against SAR-CoV-2. We have shown that the mitochondrial antioxidant mitoquinone/mitoquinol mesylate (Mito-MES), a dietary supplement, has antiviral activity against SARS-CoV-2 in vitro and in SARS-CoV-2 infected K18-hACE2 mice. METHODS: In this exploratory, pragmatic open label clinical trial (ClinicalTrials.gov identifier NCT05381454), we studied whether Mito-MES is an effective post-exposure prophylaxis treatment in people who had high-grade unmasked exposures to SARS-CoV-2 within 5 days prior to study entry. Participants were enrolled in real-world setting in Los Angeles, United States between May 1 and December 1, 2022 and were assigned to either mito-MES 20 mg daily for 14 days (n = 40) or no mito-MES (controls) (n = 40). The primary endpoint was development of SARS-CoV-2 infection based on 4 COVID-19 diagnostic tests [rapid antigen tests (RATs) or PCR] performed during the study period (14 days post exposure). FINDINGS: Out of 40 (23 females; 57.5%) study participants who took Mito-MES, 12 (30%) developed SARS-CoV-2 infection compared to 30 of the 40 controls (75%) (difference -45.0%, 95% confidence intervals (CI): -64.5%, -25.5%). Out of 40 (19 females; 47.5%) study participants in the control group, 30 (75.0%) had at least one positive COVID-19 diagnostic test and 23 (57.5%) were symptomatic. With regards to key secondary outcomes, among symptomatic SARS-CoV-2 infections, the median duration of viral symptoms was lower in the Mito-MES group (median 3.0, 95% CI 2.75, 3.25) compared to the control group (median 5.0, 95% CI 4.0, 7.0). None of the study participants was hospitalized or required oxygen therapy. Mito-MES was well tolerated and no serious side effect was reported in any study participant. INTERPRETATION: This work describes antiviral activity of mito-MES in humans. Mito-MES was well tolerated in our study population and attenuated transmission of SARS-CoV-2 infection. Given established safety of Mito-MES in humans, our results suggest that randomized control clinical trials of Mito-MES as post-exposure prophylaxis against SARS-CoV-2 infection are warranted. FUNDING: This work was supported in part by National Institutes of Health grant R01AG059501 (TK), National Institutes of Health grant R01AG059502 04S1 (TK), NIH/National Center for Advancing Translational Sciences (NCATS) UCLA CTSI Grant Number UL1TR001881 and California HIV/AIDS Research Program grant OS17-LA-002 (TK).

Risk factors associated with high-dose methotrexate induced toxicities.

INTRODUCTION: High-dose methotrexate (HDMTX) therapy poses challenges in various neoplasms due to individualized pharmacokinetics and associated adverse effects. Our purpose is to identify early risk factors associated with HDMTX-induced toxicities, paving the way for personalized treatment. AREAS COVERED: A systematic review of PubMed and Cochrane databases was conducted for articles from inception to July 2023. Eligible studies included reviews, clinical trials, and real-world analyses. Irrelevant studies were excluded, and manual searches and citation reviews were performed. Factors such as MTX exposure, drug interactions, demographics, serum albumin, urine pH, serum calcium, and genetic polymorphisms affecting MTX transport (e.g. SLCO1B1), intracellular folate metabolism (MTHFR), cell development (ARID5B), metabolic pathways (UGT1A1, PNPLA3), as well as epigenetics were identified. EXPERT OPINION: This comprehensive review aids researchers and clinicians in early identification of HDMTX toxicity risk factors. By understanding the multifaceted risk factors associated with hematologic malignancies, personalized treatment approaches can be tailored to optimize therapeutic outcomes.

An overview of the ameliorative efficacy of Catharanthus roseus extract against Cd2+ toxicity: implications for human health and remediation strategies.

Rapid industrialization has led to an increase in cadmium pollution, a dangerously toxic heavy metal. Cadmium (Cd) is released into the environment through industrial processes and can contaminate air, water, and soil. This pollution poses a significant risk to human health and has become a pressing concern in many industrialized areas. Due to its extended half-life, it leads to a range of health problems, including hepato-nephritic toxicity, brain damage, and degenerative bone disorders. Intoxication alters various intracellular parameters, leading to inflammation, tissue injury, and oxidative stress within cells, which disrupts normal cellular functions and can eventually result in cell death. It has also been linked to the development of bone diseases such as osteoporosis. These adverse effects highlight the urgent need to address cadmium pollution and find effective solutions to mitigate its impact on human health. This article highlights the Cd-induced risks and the role of Catharanthus roseus (C. roseus) extract as a source of alternative medicine in alleviating the symptoms. Numerous herbal remedies often contain certain bioactive substances, such as polyphenols and alkaloids, which have the power to mitigate these adverse effects by acting as antioxidants and lowering oxidative cell damage. Research conducted in the field of alternative medicine has revealed its enormous potential to meet demands that may be effectively used in safeguarding humans and their environment. The point of this review is to investigate whether C. roseus extract, known for its bioactive substances, is being investigated for its potential to mitigate the harmful effects of cadmium on health. Further investigation is needed to fully understand its effectiveness. Moreover, it is important to explore the potential environmental benefits of using C. roseus extract to reduce the negative effects of Cd. This review conducted in the field of alternative medicine has revealed its enormous potential to meet demands that could have significant implications for both human health and environmental sustainability.

Self-guided imagery rescripting for worry images: A preliminary experimental investigation.

BACKGROUND: Mental images of feared events are overactive and intrusive in generalized anxiety disorder (GAD). Imagery rescripting involves integration of positive or neutral imagery and corrective information into images to facilitate emotional processing, reduce imagery intrusions, and re-structure underlying schema. Yet only one known study has applied the technique to treatment of worry. The present study aimed first to examine the relationship between trait worry and properties of future-oriented worry images, and second to examine the efficacy of a self-guided imagery rescripting intervention in improving individuals' response to their worries. METHODS: Participants recruited through Amazon Mechanical Turk (N = 365) identified their major worry and wrote the script of a worst-case scenario mental image. Participants were randomized to three conditions: re-writing the same worry image script (exposure), or writing scripts of either one or three positive alternative future-oriented images (rescripting conditions). RESULTS: In preliminary analyses, trait worry negatively predicted participants' ratings of worry images, including valence and ability to cope, and positively predicted distress, anticipated cost, and belief in their negative meaning. In experimental analyses, linear mixed-effects models revealed anxious response and cognitive appraisal of the threat were significantly lower among participants allocated to rescripting relative to exposure. There was no effect of rescripting type. CONCLUSIONS: This investigation demonstrated the impact of a future-oriented imagery rescripting task on anxiety and cognitive biases associated with real worries in an unselected sample. Results may contribute to the development of imagery rescripting interventions for GAD.