Neighborhood × Serotonin Transporter Linked Polymorphic Region (5-HTTLPR) interactions for substance use from ages 10 to 24 years using a harmonized data set of African American children.

This study investigated the influences of neighborhood factors (residential stability and neighborhood disadvantage) and variants of the serotonin transporter linked polymorphic region (5-HTTLPR) genotype on the development of substance use among African American children aged 10-24 years. To accomplish this, a harmonized data set of five longitudinal studies was created via pooling overlapping age cohorts to establish a database with 2,689 children and 12,474 data points to span ages 10-24 years. A description of steps used in the development of the harmonized data set is provided, including how issues such as the measurement equivalence of constructs were addressed. A sequence of multilevel models was specified to evaluate Gene × Environment effects on growth of substance use across time. Findings indicated that residential instability was associated with higher levels and a steeper gradient of growth in substance use across time. The inclusion of the 5-HTTLPR genotype provided greater precision to the relationships in that higher residential instability, in conjunction with the risk variant of 5-HTTLPR (i.e., the short allele), was associated with the highest level and steepest gradient of growth in substance use across ages 10-24 years. The findings demonstrated how the creation of a harmonized data set increased statistical power to test Gene × Environment interactions for an under studied sample.

Machine Learning to Predict the Need for Postmastectomy Radiotherapy after Immediate Breast Reconstruction.

Background: Post mastectomy radiotherapy (PMRT) is an independent predictor of reconstructive complications. PMRT may alter the timing and type of reconstruction recommended. This study aimed to create a machine learning model to predict the probability of requiring PMRT after immediate breast reconstruction (IBR). Methods: In this retrospective study, breast cancer patients who underwent IBR from January 2017 to December 2020 were reviewed and data were collected on 81 preoperative characteristics. Primary outcome was recommendation for PMRT. Four algorithms were compared to maximize performance and clinical utility: logistic regression, elastic net (EN), logistic lasso, and random forest (RF). The cohort was split into a development dataset (75% of cohort for training-validation) and 25% used for the test set. Model performance was evaluated using area under the receiver operating characteristic curve (AUC), precision-recall curves, and calibration plots. Results: In a total of 800 patients, 325 (40.6%) patients were recommended to undergo PMRT. With the training-validation dataset (n = 600), model performance was logistic regression 0.73 AUC [95% confidence interval (CI) 0.65-0.80]; RF 0.77 AUC (95% CI, 0.74-0.81); EN 0.77 AUC (95% CI, 0.73-0.81); logistic lasso 0.76 AUC (95% CI, 0.72-0.80). Without significantly sacrificing performance, 81 predictive factors were reduced to 12 for prediction with the EN method. With the test dataset (n = 200), performance of the EN prediction model was confirmed [0.794 AUC (95% CI, 0.730-0.858)]. Conclusion: A parsimonious accurate machine learning model for predicting PMRT after IBR was developed, tested, and translated into a clinically applicable online calculator for providers and patients.

Clinical Application of Ureteroscope-Assisted Laparoscopic Surgery for Prostatic Utricle in Children.

Purpose: To investigate the use of ureteroscope-assisted laparoscopic surgery (UALS) in treating symptomatic prostatic utricle (PU) in children. Materials and Methods: Data on surgically treated cases of PU at the Department of Urology in Hunan Children's Hospital between September 2014 and September 2022 were retrospectively collected and analyzed. The diagnosis was confirmed by cystourethroscopy followed by ureteroscopy, and PU was excised by ureteroscope-assisted laparoscopy. Results: A total of 21 patients with PU were enrolled in this study. The median age of the patients at surgery was 8.1 (4.6-11.5) years. Karyotyping was available for 15 children: 13 (86.7%) were 46XY, 1 (6.7%) was 45X/46XY, and 1 (6.7%) was 45X/46XY/47XYY. The median length of the PU was 5.0 (4.1-7.1) cm. Nineteen patients underwent only ureteroscope-assisted laparoscopic excision, whereas 2 also had a perineal incision. All excisions were successfully performed. The median intraoperative blood loss was 25.0 (20.0-37.5) mL. The median hospital stay and follow-up durations were 18.0 (14.5-25.0) days and 24.0 (13.5-49.0) months, respectively. The patients reported no postoperative clinical symptoms. Conclusion: UALS allows for accurate patient positioning and thorough exposure of the anatomical structures, and it is a safe, effective, and minimally invasive treatment for PU in children.

Differential susceptibility to prevention: GABAergic, dopaminergic, and multilocus effects.

BACKGROUND: Randomized prevention trials provide a unique opportunity to test hypotheses about the interaction of genetic predispositions with contextual processes to create variations in phenotypes over time. METHODS: Using two longitudinal, randomized prevention trials, molecular genetic and alcohol use outcome data were gathered from more than 900 youths to determine whether prevention program participation would, across 2 years, moderate genetic risk for increased alcohol use conferred by the dopaminergic and GABAergic systems. RESULTS: We found that (a) variance in dopaminergic (DRD2, DRD4, ANKK1) and GABAergic (GABRG1, GABRA2) genes forecast increases in alcohol use across 2 years, and (b) youths at genetic risk who were assigned to the control condition displayed greater increases in alcohol use across 2 years than did youths at genetic risk who were assigned to the prevention condition or youths without genetic risk who were assigned to either condition. CONCLUSIONS: This study is unique in combining data from two large prevention trials to test hypotheses regarding genetic main effects and gene × prevention interactions. Focusing on gene systems purported to confer risk for alcohol use and abuse, the study demonstrated that participation in efficacious prevention programs can moderate genetic risk. The results also support the differential susceptibility hypothesis that some youths, for genetic reasons, are more susceptible than others to both positive and negative contextual influences.

Economic analysis of a multi-site prevention program: assessment of program costs and characterizing site-level variability.

Programmatic cost analyses of preventive interventions commonly have a number of methodological difficulties. To determine the mean total costs and properly characterize variability, one often has to deal with small sample sizes, skewed distributions, and especially missing data. Standard approaches for dealing with missing data such as multiple imputation may suffer from a small sample size, a lack of appropriate covariates, or too few details around the method used to handle the missing data. In this study, we estimate total programmatic costs for a prevention trial evaluating the Strong African American Families-Teen program. This intervention focuses on the prevention of substance abuse and risky sexual behavior. To account for missing data in the assessment of programmatic costs we compare multiple imputation to probabilistic sensitivity analysis. The latter approach uses collected cost data to create a distribution around each input parameter. We found that with the multiple imputation approach, the mean (95 % confidence interval) incremental difference was $2,149 ($397, $3,901). With the probabilistic sensitivity analysis approach, the incremental difference was $2,583 ($778, $4,346). Although the true cost of the program is unknown, probabilistic sensitivity analysis may be a more viable alternative for capturing variability in estimates of programmatic costs when dealing with missing data, particularly with small sample sizes and the lack of strong predictor variables. Further, the larger standard errors produced by the probabilistic sensitivity analysis method may signal its ability to capture more of the variability in the data, thus better informing policymakers on the potentially true cost of the intervention.

Elucidating Parenting Processes That Influence Adolescent Alcohol Use: A Qualitative Inquiry.

This study's purpose was to learn why some youth who participated in the Strong African American Families (SAAF) program increased alcohol use after 2 years whereas other youth did not. Using a sample of 28 African American caregiver-youth dyads, the authors collected qualitative data to explore these issues. Findings underscore the importance of caregivers' practicing vigilant monitoring to keep their adolescents from experimenting with alcohol. Recommendations for limiting access to alcohol and encouraging vigilant parenting are discussed.

The contribution of community and family contexts to African American young adults' romantic relationship health: a prospective analysis.

Accumulating evidence suggests that African American men and women experience unique challenges in developing and maintaining stable, satisfying romantic relationships. Extant studies have linked relationship quality among African American couples to contemporaneous risk factors such as economic hardship and racial discrimination. Little research, however, has examined the contextual and intrapersonal processes in late childhood and adolescence that influence romantic relationship health among African American adults. We investigated competence-promoting parenting practices and exposure to community-related stressors in late childhood, and negative relational schemas in adolescence, as predictors of young adult romantic relationship health. Participants were 318 African American young adults (59.4% female) who had provided data at four time points from ages 10-22 years. Structural equation modeling indicated that exposure to community-related stressors and low levels of competence-promoting parenting contributed to negative relational schemas, which were proximal predictors of young adult relationship health. Relational schemas mediated the associations of competence-promoting parenting practices and exposure to community stressors in late childhood with romantic relationship health during young adulthood. Results suggest that enhancing caregiving practices, limiting youths' exposure to community stressors, and modifying relational schemas are important processes to be targeted for interventions designed to enhance African American adults' romantic relationships.

Reply to Graziosi et al. Rationale in the Use of Adjuvant Chemotherapy in pT3N0M0 Gastric Cancer Resected Patients. Comment on "Chen et al. Prognostic Factors and the Role of Adjuvant Chemotherapy in Pathological Node-Negative T3 Gastric Cancer. J. Pers. Med. 2023, 13, 553".

We appreciate the authors very much for their interest in our article "Prognostic factors and the role of adjuvant chemotherapy in pathological node-negative T3 gastric cancer" [...].

Prognostic Factors and the Role of Adjuvant Chemotherapy in Pathological Node-Negative T3 Gastric Cancer.

The role of adjuvant chemotherapy in pathological T3N0M0 (pT3N0M0) gastric cancer (GC) remains unclear. The aim of this study was to analyze the prognostic factors of patients with pT3N0M0 GC and to clarify which ones could benefit from adjuvant chemotherapy. A total of 137 patients with pT3N0M0 GC were recruited between 1994 and 2020. Clinicopathological factors and adjuvant chemotherapy regimens were retrospectively collected. Prognostic factors of disease-free survival (DFS) and cancer-specific survival (CSS) were determined using univariate and multivariate analyses. The chemotherapy group was younger (p = 0.012), had had more lymph nodes retrieved (p = 0.042) and had higher percentages of vascular invasion (p = 0.021) or perineural invasion (p = 0.030) than the non-chemotherapy group. There were no significant differences in DFS (p = 0.222) and CSS (p = 0.126) between patients treated with or without adjuvant chemotherapy. Stump cancer, tumor size and perineural invasion were associated with higher rates of recurrence. Tumor size was an independent prognostic factor for DFS (hazard ratio, 4.55; confidence interval, 1.59-12.99; p = 0.005) and CSS (hazard ratio, 3.97; confidence interval, 1.38-11.43; p = 0.011). Tumor size independently influenced survival outcomes in pT3N0M0 patients who underwent radical surgery with and without adjuvant chemotherapy.

Perceived discrimination and longitudinal increases in adolescent substance use: gender differences and mediational pathways.

OBJECTIVES: This study was designed to test hypotheses about the prospective association of adolescents' perceptions of discrimination with increases in substance use and the processes that mediate this association. METHODS: African American youths residing in rural Georgia (n = 573; mean age = 16.0 years) provided longitudinal data on their experiences with discrimination, substance use, school engagement, and affiliations with substance-using peers. RESULTS: For male youths, perceived discrimination was significantly related to increases in substance use, and, as hypothesized, this association was mediated by the contributions of perceived discrimination to decreases in school engagement and increases in affiliations with substance-using peers. Analyses also indicated that discrimination influences substance use rather than vice versa. CONCLUSIONS: Results are consistent with the hypothesis that high levels of discrimination are linked to increases in substance use for African American male adolescents.

Life stress, the dopamine receptor gene, and emerging adult drug use trajectories: a longitudinal, multilevel, mediated moderation analysis.

This study was designed to examine the prospective relations of life stress and genetic status with increases in drug use. African Americans (N = 399) in rural Georgia (Wave 1 mean age = 17 years) provided three waves of data across 27.5 months and a saliva sample from which the dopamine receptor D4 (DRD4) gene was genotyped. Multilevel growth curve modeling analysis indicated that emerging adults manifested the highest escalations in drug use when they reported high life stress and carried an allele of DRD4 with 7 or more repeats (7 + R allele). In addition, emerging adults who reported high life stress and carried the 7 + R allele evinced the largest increases in two proximal risk factors for drug use: affiliations with drug-using companions and drug use vulnerability cognitions. Furthermore, when the Gene × Environment interaction effects on the increases in affiliations with drug-using companions and vulnerability cognitions were entered into the model forecasting drug use, the Life Stress × DRD4 Status interaction on drug use became nonsignificant in the presence of the risk mechanisms. This finding provides an example of "second generation" Gene × Environment interaction research in which the interaction's effects on proximal risk mechanisms account for its effects on outcomes.

The strong African American families-teen trial: rationale, design, engagement processes, and family-specific effects.

This study addresses two limitations in the literature on family-centered intervention programs for adolescents: ruling out nonspecific factors that may explain program effects and engaging parents into prevention programs. The Rural African American Families Health project is a randomized, attention-controlled trial evaluating the efficacy of the Strong African American Families-Teen (SAAF-T) program, a family-centered risk-reduction intervention for rural African American adolescents. Rural African American families (n = 502) with a 10th-grade student were assigned randomly to receive SAAF-T or a similarly structured, family-centered program that focused on health and nutrition. Families participated in audio computer-assisted self-interviews at baseline and 6-month follow-up. Program implementation procedures yielded a design with equivalent doses, five sessions of family-centered intervention programming for families in each condition. Of eligible families screened for participation, 76% attended four or five sessions of the program. Consistent with our primary hypotheses, SAAF-T youth, compared to attention-control youth, demonstrated higher levels of protective family management skills, a finding that cannot be attributed to nonspecific factors such as aggregating families in a structured, interactive setting.

[Transfection of iNOS suppresses the growth of androgen-independent prostate cancer DU145 cells].

OBJECTIVE: To observe the effect of the inducible nitric oxide synthase (iNOS) gene on androgen-independent prostate cancer DU145 cells in vitro. METHODS: The iNOS gene was transfected into androgen-independent prostate cancer DU145 cells. The positive cells were selected as the transfected group for amplification, and an empty vector (EV) group and a control group were also set. The mRNA transcription of iNOS was analyzed by RT-PCR. The morphological changes of the cells were observed, the effect of iNOS transfection on the cell growth determined using the MTB method, and the apoptosis of DU145 cells detected by flow cytometry, followed by analysis of the effect of NOS inhibitors on the transfected cells. RESULTS: DU145 cells transfected with iNOS secreted significantly more nitric oxide ([272.50 +/- 15.82] micromol/L) than those of the EV and control groups ([122.00 +/- 18.93] micromol/L and [121.00 +/- 6.98] micromol/L) (P < 0.05). The rate of cell apoptosis was markedly enhanced in the transfected group as compared with the EV and control groups ([42.78 +/- 2.01]% vs [30.65 +/- 1.46]% and [28.96 +/- 1.50]%, P < 0.05). MTP test indicated a slower growth of the DU145 cells in the former than in the latter two (P < 0.05). NOS inhibitors enhanced their growth, but with no significance (P > 0.05). CONCLUSION: DU145 cells transfected with iNOS could secrete high-concentration nitric oxide, induce cell apoptosis, and suppress cell proliferation, which may provide a potentially effective gene therapy for advanced androgen-independent prostate cancer.

Clinical Efficacy of Laparoscopic Orchiopexy With the Modified Prentiss Maneuver for Non-palpable Testis Near the Internal Ring.

Objective: To compare the clinical efficacy and safety of laparoscopic orchiopexy with the modified Prentiss maneuver (LOMPM) and laparoscopic trans-inguinal orchiopexy (LTIO) for the treatment of non-palpable testis (NPT) <1 cm from the internal ring. Methods: Children with unilateral NPT who underwent laparoscopic orchiopexy at our center between February 2018 and January 2021 were retrospectively analyzed. According to the surgical method, they were divided into LOMPM and LTIO groups. The operation time, postoperative pain degree, postoperative complications and follow-up results were compared between the two groups. Results: A total of 98 patients were included in this study, including 41 cases in the LOMPM group and 57 cases in the LTIO group. All patients underwent successful surgery. The LOMPM group was superior to the LTIO group in terms of postoperative testicular position (lower scrotm: 90.2 vs. 71.9%, P = 0.026). There were no significant differences in operation time, postoperative pain score, and complications between the two groups. Preoperative testicular volume, postoperative testicular volume, and testicular growth rate in the LOMPM group were comparable to those in the LTIO group. There were no testicular atrophy, inguinal hernia and hydrocele in both groups after operation. Conclusions: LOMPM was comparable in safety to LTIO, but LOMPM had a good post-operative testicular position, and was suitable for the treatment of NPT near the internal ring.

Prognostic Significance of Perineural Invasion in Patients with Stage II/III Gastric Cancer Undergoing Radical Surgery.

The prognostic significance of perineural invasion in patients with gastric cancer (GC) is controversial. This study aimed to determine the prognostic value of perineural invasion in patients with stage II/III GC undergoing radical surgery. A total of 1913 patients with stage II/III GC who underwent curative resection between 1994 and 2015 were recruited. Clinicopathological factors, tumor recurrence patterns, disease-free survival, and cancer-specific survival were compared in terms of perineural invasion. The prognostic factors of disease-free survival and cancer-specific survival were determined using univariate and multivariate analyses. Perineural invasion was found in 57.1% of the patients. Age of <65 years, female sex, large tumor size, upper tumor location, total gastrectomy, advanced tumor invasion depth and nodal involvement, greater metastatic to examined lymph node ratio, undifferentiated tumor, and presence of lymphatic or vascular invasion were significantly associated with perineural invasion. The patients with perineural invasion had higher locoregional/peritoneal recurrence rates than those without. Perineural invasion was independently associated with disease-free survival and cancer-specific survival. In conclusion, perineural invasion positivity is associated with aggressive tumor behaviors and higher locoregional/peritoneal recurrence rates in patients with stage II/III GC undergoing curative surgery. It is an independent unfavorable prognostic factor of disease recurrence and cancer-specific survival.

A novel scoring system using easily assessible predictors of return of spontaneous circulation and mortality in traumatic out-of-hospital cardiac arrest patients: A retrospective cohort study.

BACKGROUND: An accident event may necessitate triage of multiple cases of traumatic out-of-hospital cardiac arrest (TOHCA). However, factors for prioritizing treatment among multiple TOHCA patients have not been established. This study aims to use easily assessible predictors of TOHCA outcomes to develop a triage scoring system. METHODS: Patients with TOHCA brought to our hospital by emergency medical services (EMS) were included for analysis to identify independent risk factors for poor outcomes. A scoring system was developed and validated internally and externally. RESULTS: Of the 401 included patients, 86 (21.4%) had return of spontaneous circulation (ROSC) after cardiopulmonary resuscitation (CPR) for 30 min (81 patients, 94.2%) or 45 min (86 patients, 100%). The emergency department (ED) mortality rate was 89.3% and overall in-hospital mortality rate was 99%. Univariate and multivariate analyses identified body temperature <33 °C (OR, 4.65; 95% CI, 1.37-15.86), obvious chest injury (OR, 2.11; 95% CI, 1.03-4.34), and presumable etiology of out-of-hospital cardiac arrest (OR, 1.73; 95% CI, 1.01-2.98) as significant independent risk factors for non-ROSC. The TOHCA score, calculated as 1 point per risk factor, correlated significantly with the rate of non-ROSC and ED mortality (TOHCA score 0, 1, 2, 3: non-ROSC rate, 63.0%, 80.4%, 90.8%, 100%, respectively; ED mortality rate, 79.5%, 91.5%, 96.1%, and 100% respectively). The results of internal and external validations show a similar trend in both non-ROSC and mortality in the ED with increasing score. CONCLUSIONS: Termination of CPR for TOHCA after 45 min is reasonable; a 30-min resuscitation is acceptable in case of insufficient medical staff or resources. The TOHCA score may be able to be used with caution for triage.

The Severity of Postoperative Pancreatic Fistula Predicts 30-Day Unplanned Hospital Visit and Readmission after Pancreaticoduodenectomy: A Single-Center Retrospective Cohort Study.

BACKGROUND: Unplanned hospital visits (UHV) and readmissions after pancreaticoduodenectomy (PD) impact patients' postoperative recovery and are associated with increased financial burden and morbidity. The aim of this study is to identify predictive factors related to these events and target the potentially preventable UHV and readmissions. METHODS: We enrolled 518 patients in this study. Characteristics were compared between patients with or without UHV and readmissions. RESULTS: The unplanned visit and readmission rate was 23.4% and 15.8%, respectively. Postoperative pancreatic fistula (POPF) grade B or C, the presence of postoperative biliary drainage, and reoperation were found to be predictive factors for UHV, whereas POPF grade B or C and the presence of postoperative biliary drainage were independently associated with hospital readmission. The most common reason for readmission was an infection, followed by failure to thrive. The overall mortality rate in the readmission group was 4.9%. CONCLUSIONS: UHV and readmissions remain common among patients undergoing PD. Patients with grade B or C POPF assessed during index hospitalization harbor an approximately two-fold increased risk of subsequent unplanned visits or readmissions compared to those with no POPF or biochemical leak. Proper preventive strategies should be adopted for high-risk patients in this population to maintain the continuum of healthcare and improve quality.

Perceived discrimination, serotonin transporter linked polymorphic region status, and the development of conduct problems.

This study examined the prospective relations of adolescents' perceptions of discrimination and their genetic status with increases in conduct problems. Participants were 461 African American youths residing in rural Georgia (Wave 1 mean age = 15.5 years) who provided three waves of data and a saliva sample from which a polymorphism in the SCL6A4 (serotonin transporter [5-HTT]) gene polymorphism known as the 5-HTT linked promoter region (5-HTTLPR) was genotyped. Data analyses using growth curve modeling indicated that perceived discrimination was significantly related to the slope of conduct problems. As hypothesized, interactions between perceived discrimination and genetic status emerged for male but not female youths. Compared with those carrying two copies of the long allele variant of 5-HTTLPR, male youths carrying one or two copies of its short allele variant evinced higher rates of conduct problems over time when they perceived high levels of racial discrimination. These findings are consistent with resilience and differential susceptibility propositions stating that genes can both foster sensitivity to adverse events and confer protection from those events.

Natural mentoring processes deter externalizing problems among rural African American emerging adults: a prospective analysis.

A 3-wave model linking natural mentoring relationships to externalizing behavior was tested with 345 rural African American emerging adults in their final year of high school. Structural equation models were executed linking multi-informant reports of mentor-emerging adult relationship quality with youths' externalizing behavior 18 months later. Consistent with our primary hypotheses, emerging adults whose relationships with their natural mentors were characterized by instrumental and emotional support and affectively positive interactions reported lower levels of anger, rule-breaking behavior, and aggression. These effects emerged independent of the influences of family support and youth gender. Two intrapersonal processes, a future orientation and self-regulation, emerged as mediators of the influence of natural mentoring relationships. The influence of natural mentors was most pronounced for emerging adults experiencing high levels of life stress.

Contextual stress and health risk behaviors among African American adolescents.

This study examined the longitudinal association between contextual stress and health risk behaviors and the role of protective factors in a community epidemiologically-defined sample of urban African American adolescents (N = 500; 46.4% female). Structural equation modeling was used to create a latent variable measuring contextual stress (community violence, neighborhood disorder, and experiences with racial discrimination). Contextual stress in 8th grade was associated with aggressive behavior and substance use 2 years later for boys. For girls, contextual stress predicted later substance use, but not aggressive behavior. High academic competence and self-worth reduced the impact of contextual stress on substance use for boys. Implications for intervention and directions for future research on health risk behaviors among African American adolescents are discussed.