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JAMA Network Open Jun 2024The US has the highest maternal mortality rate among developed countries. The Centers for Disease Control and Prevention deems nearly all of these deaths preventable,... (Observational Study)
Observational Study
IMPORTANCE
The US has the highest maternal mortality rate among developed countries. The Centers for Disease Control and Prevention deems nearly all of these deaths preventable, especially those attributable to mental health conditions. Coordination between US health care and social service systems could help further characterize circumstances and risks associated with perinatal suicide mortality.
OBJECTIVE
To examine contextual and individual precipitating circumstances and risks associated with perinatal suicide.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional observational study used a convergent mixed methods design to explore factors contributing to maternal suicides and deaths of undetermined intent (hereinafter, undetermined deaths) identified in National Violent Death Reporting System (NVDRS) data for January 1, 2003, to December 31, 2021. Analyses included decedents who were aged 10 to 50 years and pregnant or post partum at death (collectively, the perinatal group) and demographically matched female decedents who were not pregnant or recently pregnant (nonperinatal group) at death. Analyses were performed between December 2022 and December 2023.
EXPOSURES
Pregnancy status at death (perinatal or nonperinatal).
MAIN OUTCOMES AND MEASURES
The main outcomes included contributing circumstances associated with suicides and undetermined deaths cited in coroner, medical examiner, or law enforcement case narratives. The study examined quantitative differences between groups using a matched analysis and characterized key themes of salient suicide circumstances using qualitative content analysis.
RESULTS
This study included 1150 perinatal decedents identified in the NVDRS: 456 (39.6%) were pregnant at death, 203 (17.7%) were pregnant within 42 days of death, and 491 (42.7%) were pregnant within 43 to 365 days before death, yielding 694 postpartum decedents. The nonperinatal comparison group included 17 655 female decedents aged 10 to 50 years. The mean (SD) age was 29.1 (7.4) years for perinatal decedents and 35.8 (10.8) years for nonperinatal decedents. Compared with matched nonperinatal decedents, perinatal decedents had higher odds of the following identified contributing circumstances: intimate partner problems (IPPs) (odds ratio [OR], 1.45 [95% CI, 1.23-1.72]), recent argument (OR, 1.33 [95% CI, 1.09-1.61]), depressed mood (OR, 1.39 [95% CI, 1.19-1.63]), substance abuse or other abuse (OR, 1.21 [95% CI, 1.03-1.42]), physical health problems (OR, 1.37 [95% CI, 1.09-1.72]), and death of a family member or friend (OR, 1.47 [95% CI, 1.06-2.02]). The findings of the qualitative analysis emphasized the importance of mental health and identified 128 decedents (12.4%) with postpartum depression.
CONCLUSIONS AND RELEVANCE
This study provides insights into complex factors surrounding maternal suicide, and it highlights opportunities for further research to understand long-term consequences of perinatal mental health. These findings also underscore the need for targeted evidence-based interventions and effective policies targeting mental health, substance use, and IPPs to prevent maternal suicide and enhance maternal health outcomes.
Topics: Humans; Female; Pregnancy; Cross-Sectional Studies; Adult; Suicide; United States; Adolescent; Middle Aged; Young Adult; Child; Risk Factors; Maternal Mortality; Perinatal Mortality
PubMed: 38935375
DOI: 10.1001/jamanetworkopen.2024.18887 -
GeroScience Jun 2024Since most of the precipitating factors of delirium are not due to neurological disorders, neurological diagnostic tests (NDTs) may be of limited value. We hypothesized...
Since most of the precipitating factors of delirium are not due to neurological disorders, neurological diagnostic tests (NDTs) may be of limited value. We hypothesized that delirium has a high burden of NDTs with a low diagnostic yield. All patients admitted to the internal medicine wards of a single secondary teaching hospital between November 2019 and January 2020 were eligible. Within the first 48 h of their admission, they had a formal evaluation by a neuropsychologist to screen for presence of delirium. NDTs (brain MRI, brain CT, electroencephalography (EEG), and lumbar puncture) performed during the hospital stay were compared between patients with and without delirium using a logistic regression model stratified by a propensity score. The proportions of diagnostic yield (acute anomalies that changed the treatment management) provided by each type of examination were compared. Of 217 patients included, 19/32 patients (61%) with delirium had one or more NDTs, compared to 48/185 (26%) without delirium (adjusted OR 2.7; 95%CI 1.1-6.7; p = 0.027). The proportions of NDT results affecting management for patients with and without delirium were 13 and 20% for brain CT scans (p = 0.71), 29 and 38% for brain MRI (p = 0.99), and 20 and 10% for EEGs (p = 0.99), respectively. The higher proportion of NDTs performed on patients with delirium was associated with a low diagnostic yield, although not statistically different from those performed among inpatients without delirium. There is a need for restrictive, evidence-based guidelines to help with the work-up for patients with delirium.
PubMed: 38916662
DOI: 10.1007/s11357-024-01246-5 -
Journal of Cardiovascular Medicine... Jun 2024Spontaneous coronary artery dissection (SCAD) is a multifactorial process that involves predisposing factors and precipitating stressors. Genetic abnormality has been...
BACKGROUND
Spontaneous coronary artery dissection (SCAD) is a multifactorial process that involves predisposing factors and precipitating stressors. Genetic abnormality has been implicated to play a mechanistic role in the development of SCAD. This systematic review aims to summarize the current evidence concerning the link between SCAD and genetic abnormalities.
METHODS
We reviewed original studies published until May 2023 that reported SCAD patients with a genetic mutation by searching PubMed, Embase Ovid, and Google Scholar. Registries, cohort studies, and case reports were included if a definitive SCAD diagnosis was reported, and the genetic analysis was performed. Exclusion criteria included editorials, reviews, letters or commentaries, animal studies, meeting papers, and studies from which we were unable to extract data. Data were extracted from published reports.
RESULTS
A total of 595 studies were screened and 55 studies were identified. Among 116 SCAD patients with genetic abnormalities, 20% had mutations in the COL gene, 13.70% TLN1 gene, and 8.42% TSR1 gene. Mutations affecting the genes encoding COL and TLN1 were most frequently reported (20 and 13.7%, respectively). Interestingly, 15 genes of this collection were also reported in patients with thoracic aortic diseases as well. The genetic commonality between fibromuscular dysplasia (FMD) and SCAD was also included.
CONCLUSION
In this review, the inherited conditions and reported genes of undetermined significance from case reports associated with SCAD are collected. A brief description of the encoded protein and the clinical features associated with pathologic genes is provided. Current data suggested that the diagnostic yield of genetic studies for patients with SCAD would be low and routine genetic screening of such patients with no clinical features indicative of associated disorders remains debatable. This review can be used as a guide for clinicians to recognize inherited syndromic and nonsyndromic disorders associated with SCAD.
PubMed: 38916232
DOI: 10.2459/JCM.0000000000001634 -
Annals of Surgery Open : Perspectives... Jun 2024We sought to identify people who survived firearm suicide attempts to describe the acute stressors, substance use, and mental health conditions related to the attempt.
OBJECTIVE
We sought to identify people who survived firearm suicide attempts to describe the acute stressors, substance use, and mental health conditions related to the attempt.
BACKGROUND
Most firearm deaths in the United States are the result of suicide. Because firearm suicide attempts have a case fatality rate of approximately 90%, little is known about the precipitating factors that lead to firearm suicide attempts.
METHODS
We conducted a retrospective case series of patients admitted to a large hospital system between 2000 and 2019 who survived intentional, self-inflicted gunshot wounds to the head. Through the electronic medical record, we collected information about acute stressors, substance use, and mental health diagnoses before or at the time of the suicide attempt.
RESULTS
Thirty-four patients were included in the study cohort. Patients were predominantly White (74%) and male (88%), with a mean age of 44 (range, 14-82). Nineteen (56%) patients were acutely intoxicated with alcohol upon hospitalization and 17 (50%) patients had a positive urine drug screen. Acute stressors involving interpersonal relationships (53%), work/school (32%), and legal disputes (18%), among others, were documented in 82% of patients. Most patients (65%) had been diagnosed with depression before their index hospitalization. Most patients were discharged to an acute rehabilitation center (41%) or an inpatient psychiatric facility (41%).
CONCLUSIONS
Acute stress and alcohol intoxication were common in this cohort of patients who attempted suicide using firearms. These data offer an ability to learn from the experience of survivors of firearm suicide attempts, a rare population.
PubMed: 38911645
DOI: 10.1097/AS9.0000000000000418 -
Cureus May 2024Background Some studies suggest that the SARS-CoV-2 pandemic has contributed to diverting attention from other community-acquired infections (CAIs), leading to an...
Background Some studies suggest that the SARS-CoV-2 pandemic has contributed to diverting attention from other community-acquired infections (CAIs), leading to an increase in their incidence and severity. Our study aimed to describe and compare clinical features of CAI before and during the pandemic as a factor precipitating diabetes ketoacidosis (DKA). Methodology We included 250 patients who presented with DKA due to CAIs, other than SARS-CoV-2, divided into two distinct groups: 100 patients (G1) who consulted two years before the pandemic, and 150 patients (G2) who consulted during the SARS-CoV-2 pandemic. Cases in both groups were matched for age and type and duration of diabetes. Primary outcomes were a longer diagnosis delay and more severe DKA in G2 during the pandemic. Secondary outcomes included blood test results, duration of ketosis, duration of antibiotic therapy, and diabetes treatment. Results The diagnosis and treatment delays were longer for patients seeking medical care during the pandemic (p < 0.001). The duration of DKA was also significantly longer in the G2 group (p = 0.007). During the pandemic, patients' blood tests showed more anomalies with higher glycated hemoglobin (p = 0.02), C-reactive protein (p = 0.001), and lymphocytosis (p = 0.016). The duration of antibiotic therapy was also significantly longer in G2 (p = 0.01). Conclusions This study showed the impact of the COVID-19 pandemic on the management of diseases other than SARS-CoV-2. Indeed, several factors played a part in the increased incidence of CAIs, which were more severe than in the pre-pandemic period. These included fear of contagion, confinement, and physicians' preoccupation with the pandemic.
PubMed: 38910705
DOI: 10.7759/cureus.60967 -
Frontiers in Psychology 2024The ongoing international study on the mental health implications of climate change has prompted a deeper exploration of ecological emotions such as eco-anxiety,... (Review)
Review
The ongoing international study on the mental health implications of climate change has prompted a deeper exploration of ecological emotions such as eco-anxiety, eco-worry and eco-grief, which are associated with environmental degradation and the escalating climate crisis. Although psychological and mental health literature has mainly presented preliminary conceptual analyses, the understanding of ecological emotions remains unclear. This narrative review aims to clarify the definition, highlight precipitating factors, and outline the effects of ecological emotions on mental health, emphasizing the need for thorough research to shift the nonclinical intervention approach from merely promoting individual resilience to encouraging collective engagement. Our analysis of the literature reveals that the existing theoretical framework, which predominantly focuses on bolstering individual resilience, provides only temporary relief for acute symptoms without addressing the foundational social and environmental factors that trigger these ecological emotions. We conclude that it is crucial to overcome the limitations of Western anthropocentrism's human-to-human interaction approach and embrace the unity of humans and nature to effectively manage the increasing ecological emotions. This perspective draws insights from the holistic and collective wisdom of indigenous cultures and traditional Chinese philosophy, offering a potential pathway toward maintaining a sustainable emotional balance amid the worsening global ecological turmoil.
PubMed: 38903457
DOI: 10.3389/fpsyg.2024.1363418 -
Journal of Virology Jun 2024The 3' untranslated region (3'UTR) of the hepatitis C virus (HCV) RNA genome, which contains a highly conserved 3' region named the 3'X-tail, plays an essential role in...
Involvement of ribosomal protein L17 and Y-box binding protein 1 in the assembly of hepatitis C virus potentially via their interaction with the 3' untranslated region of the viral genome.
UNLABELLED
The 3' untranslated region (3'UTR) of the hepatitis C virus (HCV) RNA genome, which contains a highly conserved 3' region named the 3'X-tail, plays an essential role in RNA replication and promotes viral IRES-dependent translation. Although our previous work has found a cis-acting element for genome encapsidation within 3'X, there is limited information on the involvement of the 3'UTR in particle formation. In this study, proteomic analyses identified host cell proteins that bind to the 3'UTR containing the 3'X region but not to the sequence lacking the 3'X. Further characterization showed that RNA-binding proteins, ribosomal protein L17 (RPL17), and Y-box binding protein 1 (YBX1) facilitate the efficient production of infectious HCV particles in the virus infection cells. Using small interfering RNA (siRNA)-mediated gene silencing in four assays that distinguish between the various stages of the HCV life cycle, RPL17 and YBX1 were found to be most important for particle assembly in the trans-packaging assay with replication-defective subgenomic RNA. assays showed that RPL17 and YBX1 bind to the 3'UTR RNA and deletion of the 3'X region attenuates their interaction. Knockdown of RPL17 or YBX1 resulted in reducing the amount of HCV RNA co-precipitating with the viral Core protein by RNA immunoprecipitation and increasing the relative distance in space between Core and double-stranded RNA by confocal imaging, suggesting that RPL17 and YBX1 potentially affect HCV RNA-Core interaction, leading to efficient nucleocapsid assembly. These host factors provide new clues to understanding the molecular mechanisms that regulate HCV particle formation.
IMPORTANCE
Although basic research on the HCV life cycle has progressed significantly over the past two decades, our understanding of the molecular mechanisms that regulate the process of particle formation, in particular encapsidation of the genome or nucleocapsid assembly, has been limited. We present here, for the first time, that two RNA-binding proteins, RPL17 and YBX1, bind to the 3'X in the 3'UTR of the HCV genome, which potentially acts as a packaging signal, and facilitates the viral particle assembly. Our study revealed that RPL17 and YBX1 exert a positive effect on the interaction between HCV RNA and Core protein, suggesting that the presence of both host factors modulate an RNA structure or conformation suitable for packaging the viral genome. These findings help us to elucidate not only the regulatory mechanism of the particle assembly of HCV but also the function of host RNA-binding proteins during viral infection.
PubMed: 38899899
DOI: 10.1128/jvi.00522-24 -
Acta Cirurgica Brasileira 2024Acute-on-chronic liver failure (ACLF) is a leading cause of death in cirrhotic patients. This study aims to describe the outcomes of in-patients with ACLF at a liver...
PURPOSE
Acute-on-chronic liver failure (ACLF) is a leading cause of death in cirrhotic patients. This study aims to describe the outcomes of in-patients with ACLF at a liver transplantation (LT) center in Brazil.
METHODS
Retrospective study analyzing patient data from 2017 to 2022. Re-transplant cases and patients without previous chronic liver disease were excluded. The ACLF diagnosis was based on the European Association for the Study of the Liver-Chronic Liver Failure criteria and assessments repeated on days 3 and 7 after the initial diagnosis.
RESULTS
Among 381 patients, 10.49% (n = 40) were diagnosed with ACLF. Bacterial infection was the most common precipitating factor (45%). Kidney failure occurred in 65% of the cases. The 28-day mortality rate was 35% and varied according to ACLF severity at diagnosis, from single organ failure (ACLF-1) at 22% to three organ failures (ACLF-3) at 60%. Eighteen patients (45%) were transplanted with a 100% 28-day survival rate. For ACLF-3 cases at diagnosis (n = 15), the 28-day and 1-year survival rates with a transplant (n = 4) were 100% and 80%, respectively, and without transplant (n = 11), 10 and 0%, respectively.
CONCLUSIONS
ACLF was associated with high mortality rates. LT was an effective therapeutic option, particularly for ACLF-3 cases.
Topics: Humans; Retrospective Studies; Acute-On-Chronic Liver Failure; Brazil; Male; Female; Middle Aged; Liver Transplantation; Adult; Aged; Survival Rate; Liver Cirrhosis; Severity of Illness Index; Treatment Outcome
PubMed: 38896629
DOI: 10.1590/acb392624 -
Metabolic Brain Disease Jun 2024Oxidative stress from generation of increased reactive oxygen species or has been reported to play an important role in dementia. Oxidative stress due to free radicals...
Oxidative stress from generation of increased reactive oxygen species or has been reported to play an important role in dementia. Oxidative stress due to free radicals of oxygen or reactive oxygen species could be precipitating factors in the etiology of dementia. Apomorphine has been reported to have neuroprotective effects. To monitor memory enhancing and neuroprotective effects of apomorphine, we determined the antioxidant enzymes activities, lipid peroxidation, acetylcholine esterase (AChE) activity in brain and plasma, following repetitive administration of apomorphine in rat model of dementia. Biogenic amine levels were also monitored in hippocampus. Repeated administration of scopolamine was taken as an animal model of dementia. Decreased glutathione peroxidase, superoxide dismutase and catalase activities were observed in these animal models of dementia. While increased lipid peroxidation was also observed in the brain and plasma samples. The results showed significant effects of apomorphine. The activities of antioxidant enzymes displayed increased activities in both brain and plasma. Glutathione peroxidase and catalase activities were found to be significantly higher in brain and plasma of apomorphine treated rats. Superoxide dismutase (SOD) was significantly decreased in plasma of scopolamine injected rats; and a decreased tendency (non-significant) of SOD in brain was also observed. AChE activity in brain and plasma was significantly decreased in scopolamine treated rats. Learning and memory of rats in the present study was assessed by Morris Water Maze (MWM). Short-term memory and long-term memory was impaired significantly in scopolamine treated rats, which was prevented by apomorphine. Moreover, a marked decrease in biogenic amines was also found in the brain of scopolamine treated rats and was reverted in apomorphine treated rats. Results showed that scopolamine-treatment induced memory impairment and induced oxidative stress in rats as compared to saline-treated controls. These impairments were significantly restored by apomorphine administration. In conclusion, our data suggests that apomorphine at the dose of 1 mg/kg could be a potential therapeutic agent to treat dementia and related disorders.
PubMed: 38896206
DOI: 10.1007/s11011-024-01372-1 -
BioRxiv : the Preprint Server For... Jun 2024DNA double-strand breaks (DSBs) present a critical threat to genomic integrity, often precipitating genomic instability and oncogenesis. Repair of DSBs predominantly...
DNA double-strand breaks (DSBs) present a critical threat to genomic integrity, often precipitating genomic instability and oncogenesis. Repair of DSBs predominantly occurs through homologous recombination (HR) and non-homologous end joining (NHEJ). In HR-deficient cells, DNA polymerase theta (Polθ) becomes critical for DSB repair via microhomology-mediated end joining (MMEJ), also termed theta-mediated end joining (TMEJ). Thus, Polθ is synthetically lethal with BRCA1/2 and other HR factors, underscoring its potential as a therapeutic target in HR-deficient cancers. However, the molecular mechanisms governing Polθ-mediated MMEJ remain poorly understood. Here we present a series of cryo-electron microscopy structures of the Polθ helicase domain (Polθ-hel) in complex with DNA containing 3'-overhang. The structures reveal the sequential conformations adopted by Polθ-hel during the critical phases of DNA binding, microhomology searching, and microhomology annealing. The stepwise conformational changes within the Polθ-hel subdomains and its functional dimeric state are pivotal for aligning the 3'-overhangs, facilitating the microhomology search and subsequent annealing necessary for DSB repair via MMEJ. Our findings illustrate the essential molecular switches within Polθ-hel that orchestrate the MMEJ process in DSB repair, laying the groundwork for the development of targeted therapies against the Polθ-hel.
PubMed: 38895274
DOI: 10.1101/2024.06.07.597860