Association between adverse childhood experiences and self-reported health-risk behaviors among cancer survivors: A population-based study.

AIMS: Existing evidence shows that people who report Adverse Childhood Experiences (ACEs) are more likely to exhibit health-risk behaviors. However, limited research on this topic pertains to oncology population. We aim to address this knowledge gap by estimating the prevalence of ACEs and investigating their association with self-reported health-risk behaviors among adult cancer survivors living in the U.S. METHODS: We conducted a secondary analysis using cross-sectional data from the 2021 Behavioral Risk Factor Surveillance System ACE module. We included 4,126 adults, aged ≥18 years, with a history of cancer. The outcome variable was self-reported health-risk behaviors, which included cigarette smoking, e-cigarette use, and binge alcohol drinking. Self-reported ACEs history was the primary independent variable, comprised of 11 questions regarding child abuse and dysfunctional households. We conducted descriptive statistics and multivariable logistic regression to describe the relationship between the ACE history and health-risk behaviors. RESULTS: Overall, 84.2% of cancer survivors self-reported as White, 58.4% were women, and 76.6% were aged 65+ years. Nearly two-thirds of the sample (63.2%) self-reported at least one ACE (prior to age 18) and 21.7% engaged in ≥1 health-risk-behaviors, such as cigarette smoking, binge alcohol drinking, or e-cigarette use. Experiencing ≥3 ACEs was associated with 145% increased odds of reporting at least one health-risk behavior (OR = 2.45, 95% CI [1.78-3.38]) when compared to those without a history of ACEs. Besides, survivors who were younger, divorced, less educated, and had low income had higher odds of reporting at least one health-risk behavior. CONCLUSIONS: Overall, a history of ACEs is associated with health-risk behaviors. These all can negatively impact cancer survivors' overall well-being. Early screening for ACE during oncologic visits can be a protective measure for preventing health-risk behaviors among cancer survivors.

The Impact of Military Trauma Exposures on Servicewomen's Pregnancy Outcomes: A Scoping Review.

INTRODUCTION: Active-duty servicewomen and veterans make up nearly 20% of the United States military and may experience trauma specific to military service. Military-specific trauma includes combat deployment and military sexual trauma, exposure to which may result in posttraumatic stress disorder (PTSD). The purpose of this scoping review is to examine the extent to which military trauma exposures impact the pregnancy outcomes of active-duty servicewomen and women veterans. METHODS: A systematic search of OVID MEDLINE, OVID Embase, and OVID PsycINFO from inception to September 25, 2023, identified studies examining associations between military trauma exposures and perinatal outcomes. Of the 614 studies identified, 464 were reviewed for relevance, with 16 meeting inclusion criteria. RESULTS: Of the 16 included studies, 14 found associations between military trauma exposure and adverse pregnancy outcomes including preterm birth, gestational diabetes, hypertensive disorders of pregnancy, low birth weight, and perinatal mood and anxiety disorders. The risks of adverse pregnancy outcomes increased with the severity of PTSD, the recency of combat deployment, and repetitive deployment. DISCUSSION: This scoping review strengthens the link between trauma exposures and adverse pregnancy outcomes for current and former military servicewomen. A gap in the literature persists regarding trauma exposure among active-duty servicewomen, which differs significantly from women veterans. As mental health conditions are the leading underlying cause of maternal mortality, standardized screening during the perinatal period for military-specific trauma exposures and PTSD is recommended for this population. Black servicewomen of junior enlisted rank carry disproportionate burdens of PTSD diagnosis and adverse pregnancy outcomes. Comprehensive prenatal and postpartum management may improve perinatal and neonatal outcomes for military servicewomen and provide an innovative approach to reducing existing racial disparities.

Perinatal mental health and pregnancy-associated mortality: opportunities for change.

Perinatal mental health conditions have been associated with adverse pregnancy outcomes, including maternal death. This quality improvement project analyzed pregnancy-associated death among veterans with mental health conditions in order to identify opportunities to improve healthcare and reduce maternal deaths. Pregnancy-associated deaths among veterans using Veterans Health Administration (VHA) maternity care benefits between fiscal year 2011 and 2020 were identified from national VHA databases. Deaths among individuals with active mental health conditions underwent individual chart review using a standardized abstraction template adapted from the Centers for Disease Control and Prevention (CDC). Thirty-two pregnancy-associated deaths were identified among 39,720 paid deliveries with 81% (n = 26) occurring among individuals with an active perinatal mental health condition. In the perinatal mental health cohort, most deaths (n = 16, 62%) occurred in the late postpartum period and 42% (n = 11) were due to suicide, homicide, or overdose. Opportunities to improve care included addressing (1) racial disparities, (2) mental health effects of perinatal loss, (3) late postpartum vulnerability, (4) lack of psychotropic medication continuity, (5) mental health conditions in intimate partners, (6) child custody loss, (7) lack of patient education or stigmatizing patient education, and (8) missed opportunities for addressing reproductive health concerns in mental health contexts. Pregnancy-associated deaths related to active perinatal mental health conditions can be reduced. Mental healthcare clinicians, clinical teams, and healthcare systems have opportunities to improve care for individuals with perinatal mental health conditions.

Drug-Drug Interaction Between Cannabidiol, Cyclosporine, and Mycophenolate Mofetil: A Case Report.

Kidney transplantation remains the optimal therapy for many patients with end-stage kidney disease (ESKD). Chronic pain is one of the most common and distressing symptoms among patients with ESKD, and its treatment is a complex and challenging task to accomplish. The benefits of cannabidiol (CBD) in chronic pain treatment have been reported recently. Cannabidiol is metabolized by cytochrome P450, mainly CYP3A4 and CYP2C19, and can also undergo direct conjugation via UDP-glucuronosyltransferase enzymes, with a growing body of evidence suggesting it is also a potent inhibitor or inducer of these pathways. Cannabidiol was also found to be a potent inhibitor of carboxylesterases in vitro. Because cytochrome P450 enzymes and carboxylesterases are also responsible for the clearance and activation of immunosuppressants, respectively, drug-drug interactions are likely to occur. Here, we report a pharmacokinetic drug interaction between CBD and cyclosporine and mycophenolate mofetil in a patient with ESKD with a kidney transplantation. It is thus crucial to take into account these interactions and monitor drug levels to avoid drug toxicity or a lack of efficacy. This study is in accordance with the guidelines of the Declaration of Helsinki and the Declaration of Istanbul.

Prevalence and Correlates of Cannabis Use among U.S. Veterans during the Second Wave of the COVID-19 Pandemic.

INTRODUCTION: Military veterans are at increased risk of substance use disorders. Limited research is available about veterans' cannabis use (CU) during the coronavirus disease 2019 (COVID-19) pandemic. This study estimated the prevalence of past 30-day CU, investigated individual-level correlates of past 30-day CU, and evaluated the reasons (medical, recreational, or both) of past 30-day CU among U.S. Veterans during the second wave of the COVID-19 pandemic. MATERIALS AND METHODS: We used population-based, cross-sectional data from the 2021 Behavioral Risk Factor Surveillance System Survey Marijuana Use model. The sample included nationally representative military veterans aged 18+ years (n = 11,167). The outcome was past 30-day CU. Individual-level demographic, socioeconomic, behavioral, and clinical correlates were examined. Analyses were weighted to account for the survey's complex design with results generalizable to nearly 2.9 million veterans. We conducted weighted descriptive statistics, prevalence estimates, and multivariable logistic regression analyses. RESULTS: Out of 2.9 million veterans, 11.1% self-reported as non-Hispanic Black, 3.7% Hispanic, and 79.1% non-Hispanic White; 88.5% were men, and 72.8% were aged 50+ years. About 14.6% were current tobacco smokers, 4.7% were current e-cigarette users, 12.5% were binge alcohol drinkers, and 43.4% had three or more comorbid conditions. Overall, 8.5% reported CU in the past 30 days, of which 30.4% used it for medical reasons and 25.8% used it for nonmedical reasons. The prevalence of past 30-day CU decreased with age, education, and income level. Compared to their counterparts, the odds of past 30-day CU were greater among men, those living in urban areas, those with frequent mental distress, infrequent physical distress, and those who had at least one comorbid condition. Non-Hispanic Black veterans had 89% increased odds of past 30-day CU (adjusted odds ratio [AOR] =1.89, 95% confidence interval [CI], 1.19-3.0) compared with non-Hispanic White veterans. Current tobacco smokers had 3.54 (95% CI, 2.40-5.24) and former smokers had 1.78 (95% CI, 1.28-2.47) times higher odds of reporting past 30-day CU than never smokers. Current e-cigarette use (AOR = 3.37, 95% CI, 2.20-5.16) and binge drinking (AOR = 3.18, 95% CI, 2.29-4.41) were also statistically significantly associated with increased odds of past 30-day CU compared to no e-cigarette use and no binge drinking. CONCLUSIONS: CU is prevalent among veterans, and certain subgroups are at higher risk of CU. Thus, identifying high-risk subgroups of veterans and adequately educating them about CU's benefits, risks, and safety is crucial.

Improving the Maternity Care Safety Net: Establishing Maternal Mortality Surveillance for Non-Obstetric Providers and Institutions.

The siloed nature of maternity care has been noted as a system-level factor negatively impacting maternal outcomes. Veterans Health Administration (VA) provides multi-specialty healthcare before, during, and after pregnancy but purchases obstetric care from community providers. VA providers may be unaware of perinatal complications, while community-based maternity care providers may be unaware of upstream factors affecting the pregnancy. To optimize maternal outcomes, the VA has initiated a system-level surveillance and review process designed to improve non-obstetric care for veterans experiencing a pregnancy. This quality improvement project aimed to describe the VA-based maternal mortality review process and to report maternal mortality (pregnancy-related death up to 42 days postpartum) and pregnancy-associated mortality (death from any cause up to 1 year postpartum) among veterans who use VA maternity care benefits. Pregnancies and pregnancy-associated deaths between fiscal year (FY) 2011-2020 were identified from national VA databases. All deaths underwent individual chart review and abstraction that focused on multi-specialty care received at the VA in the year prior to pregnancy until the time of death. Thirty-two pregnancy-associated deaths were confirmed among 39,720 pregnancies (PAMR = 80.6 per 100,000 live births). Fifty percent of deaths occurred among individuals who had experienced adverse social determinants of health. Mental health conditions affected 81%. Half (n = 16, 50%) of all deaths occurred in the late postpartum period (43-365 days postpartum) after maternity care had ended. More than half of these late postpartum deaths (n = 9, 56.2%) were related to suicide, homicide, or overdose. Integration of care delivered during the perinatal period (pregnancy through postpartum) from primary, mental health, emergency, and specialty care providers may be enhanced through a system-based approach to pregnancy-associated death surveillance and review. This quality improvement project has implications for all healthcare settings where coordination between obstetric and non-obstetric providers is needed.

Evaluation of OpenArray™ as a Genotyping Method for Forensic DNA Phenotyping and Human Identification.

A custom plate of OpenArray™ technology was evaluated to test 60 single-nucleotide polymorphisms (SNPs) validated for the prediction of eye color, hair color, and skin pigmentation, and for personal identification. The SNPs were selected from already validated subsets (Hirisplex-s, Precision ID Identity SNP Panel, and ForenSeq DNA Signature Prep Kit). The concordance rate and call rate for every SNP were calculated by analyzing 314 sequenced DNA samples. The sensitivity of the assay was assessed by preparing a dilution series of 10.0, 5.0, 1.0, and 0.5 ng. The OpenArray™ platform obtained an average call rate of 96.9% and a concordance rate near 99.8%. Sensitivity testing performed on serial dilutions demonstrated that a sample with 0.5 ng of total input DNA can be correctly typed. The profiles of the 19 SNPs selected for human identification reached a random match probability (RMP) of, on average, 10-8. An analysis of 21 examples of biological evidence from 8 individuals, that generated single short tandem repeat profiles during the routine workflow, demonstrated the applicability of this technology in real cases. Seventeen samples were correctly typed, revealing a call rate higher than 90%. Accordingly, the phenotype prediction revealed the same accuracy described in the corresponding validation data. Despite the reduced discrimination power of this system compared to STR based kits, the OpenArray™ System can be used to exclude suspects and prioritize samples for downstream analyses, providing well-established information about the prediction of eye color, hair color, and skin pigmentation. More studies will be needed for further validation of this technology and to consider the opportunity to implement this custom array with more SNPs to obtain a lower RMP and to include markers for studies of ancestry and lineage.

A Novel Smad7 Genetic Variant Mapping on the Genomic Region Targeted by Mongersen Is Associated with Crohn's Disease.

BACKGROUND: Down-regulation of Smad7 with a specific Smad7 antisense (AS) oligonucleotide-containing oral drug (Mongersen) was effective in pre-clinical studies and initial clinical trials in Crohn's disease (CD) patients. A recent phase 3 trial was discontinued due to an apparent inefficacy of the drug, but factors contributing to the failure of this study remain unknown. Here, we analysed the frequency in CD of rs144204026 C/T single nucleotide polymorphism (SNP), which maps on the corresponding region targeted by the Smad7 AS contained in the Mongersen formulation and examined whether such a variant allele affects the ability of Smad7 AS to knockdown Smad7. METHODS: rs144204026 SNP frequency was evaluated in two independent Italian cohorts of Crohn's disease patients and normal controls. Genotyping was performed by allelic discrimination assay. Smad7 expression was evaluated in wild-type or heterozygous PBMCs treated with Smad7 AS. RESULTS: No TT genotype was seen in CD patients and controls. Heterozygous genotype was more frequent in CD patients of both cohort 1 (11/235, 4.68%) and cohort 2 (8/122, 6.56%) as compared to controls (6/363, 1.65%; p = 0.029 and p = 0.01 respectively). Overall, a statistically significant association was observed between the T variant allele and CD patients' susceptibility (p = 0.008; OR = 3.28, 95%CI: 1.3-8.3). Smad7 AS down-regulated Smad7 RNA independently of the presence of the variant allele. CONCLUSIONS: This is the first study to show an association between Smad7 rs144204026 SNP and CD patients. Data indicate that such a variant does not negatively influence the in vitro inhibitory effect of Smad7 AS on Smad7.

Comparative Analysis of ANDE 6C Rapid DNA Analysis System and Traditional Methods.

Rapid DNA analysis is an ultrafast and fully automated DNA-typing system, which can produce interpretable genetic profiles from biological samples within 90 minutes. This "swab in-profile out" method comprises DNA extraction, amplification by PCR multiplex, separation and detection of DNA fragments by capillary electrophoresis. The aim of study was the validation of the Accelerated Nuclear DNA Equipment (ANDE) 6C system as a typing method for reference samples according to the ISO/IEC 17025 standard. Here, we report the evaluation of the validity and reproducibility of results by the comparison of the genetic profiles generated by the ANDE 6C System with those generated by standard technologies. A quantity of 104 buccal swabs were analyzed both through the ANDE 6C technology and the traditional method (DNA extraction and quantification, amplification and separation by capillary electrophoresis). Positive typing was observed in 97% of cases for ANDE 6C technology with only three buccal swabs failing to reveal interpretable signals. Concordance was determined by comparing the allele calls generated by ANDE 6C and conventional technology. Comparison of 2800 genotypes revealed a concordance rate of 99.96%. These results met the ISO/IEC 17025 requirements, enabling us to receive the accreditation for this method. Finally, rapid technology has certainly reached a level of reliability which has made its use in laboratories of forensic genetics a reality.

Interpreting Mixture Profiles: Comparison between Precision ID GlobalFiler™ NGS STR Panel v2 and Traditional Methods.

Forensic investigation for the identification of offenders, recognition of human remains, and verification of family relationships requires the analysis of particular types of highly informative DNA markers, which have high discriminatory power and are efficient for typing degraded samples. These markers, called STRs (Short Tandem Repeats), can be amplified by multiplex-PCR (Polymerase Chain Reaction) allowing attainment of a unique profile through which it is possible to distinguish one individual from another with a high statistical significance. The rapid and progressive evolution of analytical techniques and the advent of Next-Generation Sequencing (NGS) have completely revolutionized the DNA sequencing approach. This technology, widely used today in the diagnostic field, has the advantage of being able to process several samples in parallel, producing a huge volume of data in a short time. At this time, although default parameters of interpretation software are available, there is no general agreement on the interpretation rules of forensic data produced via NGS technology. Here we report a pilot study aimed for a comparison between NGS (Precision ID GlobalFiler™ NGS STR Panel v2, Thermo Fisher Scientific, Waltham, MA, USA) and traditional methods in their ability to identify major and minor contributors in DNA mixtures from saliva and urine samples. A quantity of six mixed samples were prepared for both saliva and urine samples from donors. A total of 12 mixtures were obtained in the ratios of 1:2; 1:4; 1:6; 1:8; 1:10; and 1:20 between minor and major contributors. Although the number of analyzed mixtures is limited, our results confirm that NGS technology offers a huge range of additional information on samples, but cannot ensure a higher sensitivity in respect to traditional methods. Finally, the Precision ID GlobalFiler™ NGS STR Panel v2 is a powerful method for kinship analyses and typing reference samples, but its use in biological evidence should be carefully considered on the basis of the characteristics of the evidence.

Uncovering genetic and non-genetic biomarkers specific for exudative age-related macular degeneration: significant association of twelve variants.

Age-related Macular Degeneration (AMD) represents one of the most sight-threatening diseases in developed countries that substantially impacts the patients' lifestyle by compromising everyday activities, such as reading and driving. In this context, understanding the prevalence, burden, and population-specific risk/protective factors of AMD is essential for adequate health care planning and provision. Our work aimed to characterize exudative AMD in Italian population and to identify the susceptibility/protective factors (genetic variants, age, sex, smoking and dietary habits) which are specific for the onset of disease. Our study involved a cohort of 1976 subjects, including 976 patients affected with exudative AMD and 1000 control subjects. In particular, the sample cohort has been subjected to a large genotyping analysis of 20 genetic variants which are known to be associated with AMD among European and Asiatic populations. This analysis revealed that 8 genetic variants (CFH, ARMS2, IL-8, TIMP3, SLC16A8, RAD51B, VEGFA and COL8A1) were significantly associated with AMD susceptibility. Successively, we performed a multivariate analysis, considering both genetic and non-genetic data available for our sample cohort. The multivariate analysis showed that age, smoking, dietary habits and sex, together with the genetic variants, were significantly associated with AMD in our population. Altogether, these data represent a starting point for the set-up of adequate preventive and personalized strategies aimed to decrease the burden of disease and improve the patients' quality of life.

KIF3A and IL-4 are disease-specific biomarkers for psoriatic arthritis susceptibility.

To date, the genes associated with Psoriatic Arthritis (PsA) are principally involved in inflammation, immune response and epidermal differentiation, without any information about the relationship between disease and bone metabolism genes. Our work was focused on 5q31 locus, which contains several genetic variants significantly associated with PsA. The study involved 1526 subjects (500 PsA, 426 PsV, 600 controls). The region was evaluated by selecting and genotyping the SNPs of interest by Real Time PCR and direct sequencing. The results were subjected to biostatistic and bioinformatic analysis. The case-control study highlighted a significant association between KIF3A/IL-4 and PsA, but not with PsV (Psoriasis Vulgaris) patients. In addition, the haplotype analysis revealed two haplotypes significantly associated with PsA susceptibility. The Linkage Disequilibrium (LD) study showed the presence of a specific block in high LD within 132,692,628-132,737,638 bp of 5q31, giving additional evidence of specific association of the 5q31 region in PsA patients. Moreover, KIF3A expression was assessed by immunohistochemistry assays which showed a marked and significant difference of KIF3A expression between pathological and normal tissues. Our analysis described KIF3A and IL-4 as novel susceptibility genes for PsA, suggesting a clear implication of bone metabolism genes in the disease etiopathogenesis.