Exploring neuroadaptive cellular pathways in chronic morphine exposure: An in-vitro analysis of cabergoline and Mdivi-1 co-treatment effects on the autophagy-apoptosis axis.

The complex impacts of prolonged morphine exposure continue to be a significant focus in the expanding area of addiction studies. This research investigates the effectiveness of a combined treatment using Cabergoline and Mdivi-1 to counteract the neuroadaptive changes caused by in vitro morphine treatment. The impact of Methadone, Cabergoline, and a combination of Cabergoline and Mdivi-1 on the cellular and molecular responses associated with Morphine-induced changes was studied in human Neuroblastoma (SK-N-MC) and Glioblastoma (U87-MG) cell lines that were exposed to prolong Morphine treatment. Cabergoline and Mdivi-1 combined treatment effectively influenced the molecular alterations associated with neuroadaptation in chronic morphine-exposed neural cells. This combination therapy normalized autophagy and reduced oxidative stress by enhancing total-antioxidant capacity, mitigating apoptosis, restoring BDNF expression, and balancing apoptotic elements. Our research outlines morphine's dual role in modulating mitochondrial dynamics via the dysregulation of the autophagy-apoptosis axis. This emphasizes the significant involvement of DRP1 activity in neurological adaptation processes, as well as disturbances in the dopaminergic pathway during in vitro chronic exposure to morphine in neural cells. This study proposes a novel approach by recommending the potential effectiveness of combining Cabergoline and Mdivi-1 to modulate the neuroadaptations caused by morphine. Additionally, we identified BDNF and PCNA in neural cells as potential neuroprotective markers for assessing the effectiveness of drugs against opioid toxicity, emphasizing the need for further validation. The study uncovers diverse effects observed in pretreated morphine glioblastoma cells under treatment with Cabergoline and methadone. This highlights the potential for new treatments in the DRD2 pathway and underscores the importance of investigating the interplay between autophagy and apoptosis to advance research in managing cancer-related pain. The study necessitates an in-depth investigation into the relationship between autophagy and apoptosis, with a specific emphasis on protein interactions and the dynamics of cell signaling.

COVID-19 pandemic and methanol poisoning outbreak in Iranian children and adolescents: A data linkage study.

BACKGROUND: During the first wave of COVID-19, many Iranians were poisoned by ingesting hand sanitizers and/or alcoholic beverages to avoid viral infection. To assess whether the COVID-19 pandemic resulted in an increased prevalence of accidental hand sanitizer/alcoholic beverage exposure in children and adolescents, we compared pediatric hospitalization rates during COVID-19 and the previous year. For poisoning admissions during COVID-19, we also evaluated the cause by age and clinical outcomes. METHODS: This retrospective data linkage study evaluated data from the Legal Medicine Organization (reporting mortalities) and hospitalization data from nine toxicology referral centers for alcohol-poisoned patients (age 0 to 18 years) for the study period (February 23 to June 22, 2020) and the pre-COVID-19 reference period (same dates in 2019). RESULTS: Hospitalization rates due to ethanol and methanol exposure were significantly higher in 2020 (n = 375) than 2019 (n = 202; OR [95% CI] 1.9 [1.6, 2.2], p < 0.001). During COVID-19, in patients ≤15 years, the odds of intoxication from hand sanitizers were significantly higher than from alcoholic beverages, while in 15- to 18-year-olds, alcoholic beverage exposure was 6.7 times more common (95% CI 2.8, 16.1, p < 0.001). Of 375 children/adolescents hospitalized for alcoholic beverage and hand sanitizer exposure in 2020, six did not survive. The odds of fatal outcome were seven times higher in 15- to 18-year-olds (OR (95% CI) 7.0 (2.4, 20.1); p < 0.001). CONCLUSION: The Iranian methanol poisoning outbreak during the first wave of COVID-19 was associated with significantly increased hospitalization rates among children and adolescents-including at least six pediatric in-hospital deaths from poisoning. Public awareness needs to be raised of the risks associated with ingesting alcoholic hand sanitizers.

Trend of mortality rate due to traffic accidents in Iran from 2006 to 2020: A cross-sectional study.

Background: Traffic accidents are a common global cause of mortality and physical disability. This study aimed to investigate traffic accident-related mortality trends across provinces in Iran. Methods: In this study, information on all deaths caused by traffic accidents in Iran from 2006 to 2020 was collected from the Iranian Legal Medicine Organization, which collects annual data from all 31 Iranian provinces. The national and provincial demographics were assessed, and the trends in mortality rates were assessed over a 15-year span using joinpoint regression based on the log-linear model, with results expressed in terms of annual percentage change (APC). The analysis for the trend was performed using the Joinpoint Regression Program 4.9.0.1. Results: During the study period, 291,774 traffic accident-related deaths occurred in Iran, of which 78.6% were men and 21.4% were women. The mean age of the deceased was 37.75 ± 20.89 years. The mortality rate has dropped from 39/100,000 in 2006 to 18.3/100,000 in 2020. In total, the national mortality rate APC for 2006-2015 was -6.3% (P < 0.05) and for 2015-2020 was - 1.70% (P > 0.05). Conclusions: Despite the overall decreasing national trend in Iran's traffic accident-related mortality over the study period, the provincial variability was noted. Therefore, it seems necessary to design and conduct epidemiological studies in different areas and provinces, for a better and more accurate understanding of the factors affecting the occurrence of traffic accident-related deaths, resulting in more focused and measurable interventions.

Direct and Indirect Measures of Attention Indicating a Bias Toward Cues in Methamphetamine Users.

Introduction: This study aims to investigate the attentional bias toward drug-related stimuli along with subjective craving after encountering such stimuli in methamphetamine users. Studies of cue reactivity have confirmed a bias in attention and gaze toward drug-related stimuli for most substances; however, methamphetamine drugs are less studied through a direct measure, such as eye tracking. Methods: A total of 30 male subjects in the case group (methamphetamine users) and 36 subjects in the control group (no prior drug use) participated in this study. The participant's eye movement data were collected while they were viewing pairs of drug-related and non-drug images in a dot-probe paradigm. Craving was assessed via a self-report questionnaire on a scale of 0 to 10 before and after the psychophysical task. Results: The analysis of eye-movement data showed a meaningful gaze bias toward cue images (drug-related) in the case group. Additionally, the gaze duration on cue images was significantly higher in the case group, in contrast to the control group. The same effect was observed in analyzing the dot-probe task; that is, the mean reaction time to a probe that replaced a cue image was significantly lower. The mean of the first-fixation measure in the control group was not significantly higher than chance; however, the percentage of the first-fixation on cue images in the drug users was meaningfully biased. Reported craving was significantly greater after performing the task compared to before. Conclusion: Our results indicated an attentional bias toward drug-related cues in methamphetamine users as well as subjective craving after encountering such cues. Highlights: The gaze duration on cue images was significantly higher in methamphetamine users.The mean reaction time to a probe that replaced a cue image was significantly lower in methamphetamine users compared to the control group.The mean of the first-fixation measure in the case group was significantly better than chance.Craving was reported to be significantly greater after performing the task. Plain Language Summary: Substance users tend to focus on the stimuli associated with substances. This is known as attention bias. Attention bias leads to increased craving. Attention bias for various substances has been previously reported; however, methamphetamine attention bias has not been evaluated so far. In this study, we measured the attention bias toward stimuli related to methamphetamine in methamphetamine users and control subjects with direct (eye tracking) and indirect (dot probe paradigm) methods. In addition, we measured the number of cravings in the case group. Our results confirmed the bias in attention toward methamphetamine-related stimuli in the case group compared to the control group.

Formation and activity of NLRP3 inflammasome and histopathological changes in the lung of corpses with COVID-19.

COVID-19 is a contagious disease that attacks many organs but the lungs are the main organs affected. The inflammasome activation results in the exacerbation of inflammatory response in infectious disease. The aim of this study is to investigate the formation and activity of the NLRP3 inflammasome complex and the histopathological changes caused by the coronavirus in the lung of deceased persons with COVID-19. In total, 10 corpses; 5 corpses with no history of any infectious diseases and COVID-19 and 5 corpses with the cause of death of COVID-19 were included in this study. Lung tissue samples were harvested during autopsy under safe conditions. Fresh tissues in each group were used to measure the genes expression and proteins level of NLRP3, ASC, Caspase-1, IL-1ß, IL-6 and TNF-α and a routine hematoxylin and eosin staining was performed for histological assessment. Data are represented as the means ± SD. Statistical significance difference was accepted at a p-value less than 5%. The NLRP3, ASC, Caspase-1, IL-1ß, IL-6 and TNF-α genes expression and proteins level were elevated in the lung of the COVID-19 group in comparison with the control group. Histological findings presented the increasing number of polymorphonuclear leukocytes, macrophages and also pulmonary fibrosis in the lungs of corpses with the cause of death of COVID-19. High expression of NLRP3 inflammasome components and its relation with the pathophysiology of the coronavirus-infected lung suggested that targeting the NLRP3 inflammasome could be helpful in achieving a more effective treatment in patients with COVID-19.

Exploring Change in Trend of Homicide Incidence Rate in Iran from 2006 to 2016: Applying Segmented Regression Model.

BACKGROUND: Murder is one of the public health problems. According to the WHO reports, murder is fourth leading cause of death among young people. The aim of this study was applying joint point regression model to study trend of homicide mortality in Iran, 2006-2016. STUDY DESIGN: A cross-sectional panel (pseudo-panel) study. METHODS: Homicide data during 2006 to 2016 were extracted from Iranian legal medicine organization. Trends of homicide incidence were summarized by annual percent change (APC) and average annual percent change (AAPC) using non-linear segmented regression model. RESULTS: Totally, 26918 homicide cases occurred during the period from 2006 to 2016. The highest and lowest frequency was related to the 15-29 yr (46.5%) and 0-4 yr (1.5%) age groups, respectively. The homicide incidence rate of the country in 2016 was 2.81 per 100,000. The four provinces of Sistan & Baluchistan, Khuzestan, Kerman and Ilam had the highest incidence rate in 2016, respectively. During the study period, the incidence rate of homicide in Iran and men have been significantly decreased (APC: -2.8% (95% CI: -3.9, -1.7) and -3.2% (95% CI: - 4.5, -1.8) respectively (P<0.001)). CONCLUSION: The pattern of homicide rate has a downward trend in the country. Moreover, the varying observed trends in some provinces can be due to the variability in mental, geographical, socio-economic and cultural conditions in each region.

Mortality and Years of Life Lost Due to Occupational Injury in Iran (2012-2016).

BACKGROUND: Occupational injury is a cause of premature mortality, mainly in low- and middle-income countries. Occupational injuries estimated to kill more than 300,000 workers worldwide every year. We estimated the years of life lost (YLL) of fatal unintentional occupational injuries in Iran for the five years of 2012-2016. STUDY DESIGN: A cross-sectional study. METHODS: To estimate the YLL, registered deaths due to occupational unintentional injury were identified from the Iranian Legal Medicine Organization. Estimated YLL was calculated according to Global Burden of Disease 2010 guideline. Population life expectancy in each corresponding years was retrieved from the national health database. All data collected entered into Excel software for calculations. RESULTS: In 2012-2016, fatal unintentional occupational injuries were the cause of 8,606 deaths in Iran, resulting in 4.6 prematurely lost life yr per 1000 males and 0.3 yr per 1000 females among workers, every year. 98.7% of the deaths occurred in males. Males from 15 to 19 yr of age and females from 10 to 14 yr of age showed the highest YLL rates. The rate of YLLs per 1,000 workers per year was 3.99 overall, 4.6 in males, and 0.4 in females. CONCLUSION: Premature mortality due to occupational injury is still a serious problem in the Iranian population. Our findings may be useful from a health policy perspective for designing and prioritizing interventions focused on the prevention of premature loss of life. Known prevention strategies need to be implemented widely to diminish avoidable injuries in the workplace.

Trend of years of life lost due to suicide in Iran (2006-2015).

OBJECTIVES: Suicide is a major global public health problem and much burden in the societies. This study aims to calculate the years of life lost (YLL) due to suicide and investigate its trend in Iran. METHODS: Information on deaths due to suicide in Iran was extracted from Iran Legal Medicine Organization. The years of life lost was calculated in each year according to gender and age-groups. To examine the trend for different years, joinpoint regression was used. RESULTS: The 35,297 deaths due to suicide were recorded in 2006-2015. The total YLL in the 10-year period was 34.52 per 1000 persons in males, 13.61 per 1000 persons in females and 23.35 per 1000 persons in both sexes. Hanging comprised the largest YLL of suicide. The annual percent change of YLL rate was 3.3%. CONCLUSIONS: The results revealed that male shows an increasing trend in YLL specifically among youth and adult, while there is no improvement in females. There is a national need to implement an effective health policy intervention in Iran.

Epidemiological Study of Mortality Rate from Alcohol and Illicit Drug Abuse in Iran.

BACKGROUND: The estimate of mortality associated with illicit opiate use provides useful information to those directing and monitoring local, national and international policies and programs. This study investigated the epidemiology of mortality due to the illegal consumption of narcotics and psychotropic substances in the Iran to provide evidence-based public health data for useful programs and actions aimed at preventing drug-related mortality. STUDY DESIGN: A cross-sectional study. METHODS: The information regarding all cases of psychotropic positive was collected from Legal Medicine Organization, occurred on Mar 2015 to Feb 2016. Demographic and epidemiological data were extracted from recorded documents. Data were then analyzed in Stata software. RESULTS: Overall, 2306 died cases from opioid or psychotropic abuse were evaluated. The mean age of the subjects was 36.07±12.61 yr, they were mostly single male, and 88.64% of them had Iranian nationality. The mortality rate from opiate and psychotropic abuse in the whole country was 38.22 per 1000000 population. The most common location of death was at home or in another private residence. History of overdose, suicide, hospitalization in psychiatric hospital, staying in prison and substance abuse in the family observed in some people who died from drug abuse. CONCLUSIONS: Mortality rate from substance abuse is more among unmarried young men aged 30-39 yr with low education level also in self-employed. We suggest policies to prevent this person accessing and using drug.

Characterizing Mortality from Substance Abuse in Iran: An Epidemiological Study during March 2014 to February 2015.

BACKGROUND: Drug abuse is a severe and chronic disorder that leaves morbidity, disability and premature mortality in the society. The study of death due to substance abuse provides useful information for local, national and international administrators. Thus, by identifying the factors that have an impact on overdose-related mortality we can provide suitable intervention for vulnerable groups. The aim of this study was an investigation of mortality rate caused by consumption of narcotic and psychoactive substances in Iran. METHODS: In this cross-sectional study, demographic and epidemiological data about all people whose cause of death was substance abuse in March 2014 to February 2015 were collected from Legal Medicine Organization (LMO). Finally, the information that was extracted from two checklists was analyzed by descriptive statistics. FINDINGS: In this study, 2986 cases died from substances abuse were evaluated. Most deaths have befallen in unmarried young men with mean age of 36.9 ± 12.3, in the private locations. The mortality rate of drug abuse in the whole country was 38.4 per 1000000 population. The proportion of mortality was higher in Iranian nationality and in people who had a diploma and less education. History of overdose, suicide, hospitalization in a psychiatric hospital, staying in prison and substance abuse in the family were investigated in the study population. CONCLUSION: The present study revealed that mortality rate from substance abuse is more among unmarried young men aged 30-39 years with low education level and also in the self-employed group. We suggest that policies should be taken to prevent these people from accessing and using the drug.