Mobile toolbox (MTB) remote measures of executive function and processing speed: development and validation.

OBJECTIVE: The ability to remotely monitor cognitive skills is increasing with the ubiquity of smartphones. The Mobile Toolbox (MTB) is a new measurement system that includes measures assessing Executive Functioning (EF) and Processing Speed (PS): Arrow Matching, Shape-Color Sorting, and Number-Symbol Match. The purpose of this study was to assess their psychometric properties. METHOD: MTB measures were developed for smartphone administration based on constructs measured in the NIH Toolbox® (NIHTB). Psychometric properties of the resulting measures were evaluated in three studies with participants ages 18 to 90. In Study 1 (N = 92), participants completed MTB measures in the lab and were administered both equivalent NIH TB measures and other external measures of similar cognitive constructs. In Study 2 (N = 1,021), participants completed the equivalent NIHTB measures in the lab and then took the MTB measures on their own, remotely. In Study 3 (N = 168), participants completed MTB measures twice remotely, two weeks apart. RESULTS: All three measures exhibited very high internal consistency and strong test-retest reliability, as well as moderately high correlations with comparable NIHTB tests and moderate correlations with external measures of similar constructs. Phone operating system (iOS vs. Android) had a significant impact on performance for Arrow Matching and Shape-Color Sorting, but no impact on either validity or reliability. CONCLUSIONS: Results support the reliability and convergent validity of MTB EF and PS measures for use across the adult lifespan in remote, self-administered designs.

Comparison of Postoperative Complications Between Laparoscopic Myomectomy and Total Laparoscopic Hysterectomy.

STUDY OBJECTIVE: To compare postoperative complications of laparoscopic myomectomy (LM) with total laparoscopic hysterectomy (TLH). A secondary outcome examined whether complications differ by age. DESIGN: A retrospective cohort study. SETTING: A multicenter academic healthcare system. PATIENTS: Individuals > 18 years old undergoing LM from 2011 to 2021 or TLH for benign indications from 2020 to 2021. INTERVENTIONS: LM or TLH. MEASUREMENTS AND MAIN RESULTS: There were 1178 patients in the LM group and 1304 in the TLH group. Patients who underwent LM were younger, more often premenopausal, nonsmokers, with lower body mass index, lower preoperative hemoglobin, larger uterine size, and lower American Society of Anesthesiologists class. LM had longer operative times (154.1 ± 74.5 vs 145.9 ± 70.5 min, p <.0001), higher use of intraoperative hemostatic agents (25% vs 9.1%, p <.0001), and higher estimated blood loss (222.7 ± 313.0 vs 87.4 ± 145.9 mL, p <.0001) than TLH. Postoperatively, LM was associated with fewer surgical site infections (3.1% vs 5.8%, p <.0001), readmissions within 30 days (2.0% vs 5.6%, p <.0001), or emergency department visits within 90 days (10.9% vs 14.4%, p = .008). LM were more likely to be admitted 24 hours postoperatively (5.9% vs 3.4%, p = .0023) or receive a blood transfusion within 30 days (4.0% vs 1.0%, p <.0001). Variables associated with increased risk of postoperative complications were tobacco use, American Society of Anesthesiologists class > 3, preoperative anemia, estimated blood loss ≥ 150 mL, and specimen weight > 250 g. Logistic regression demonstrated that operative time ≥185 minutes was most strongly associated with 24-hour admission postoperatively (odds ratio [OR] = 12.95; 95% confidence interval [CI], 3.71-45.27). In individuals ≤ 37 years of age, the LM group was less likely than the TLH group to experience surgical site infection (OR, 0.30; 95% CI, 0.14-0.62) or present to the emergency department (OR, 0.40; 95% CI, 0.26-0.63). CONCLUSION: In this large cohort of patients, both LM and TLH had low rates of postoperative complications, but the complications differed for each approach. In appropriate surgical candidates, either approach may be offered based upon patients' goals.

Perioperative Complications of Laparoscopic versus Open Surgery for Pelvic Inflammatory Disease.

STUDY OBJECTIVE: To compare complications in patients undergoing laparoscopic vs open surgery for acute pelvic inflammatory disease (PID). DESIGN: We performed a retrospective cohort study of patients who underwent surgery for PID, using the American College of Surgeons National Surgical Quality Improvement Program database from 2010 to 2015. Propensity score matching was used to balance baseline characteristics and compare complications in patients who underwent laparoscopic vs open surgery. SETTING: Surgical management of acute PID. PATIENTS: Patients with a preoperative diagnosis of PID were identified using International Classification of Diseases, Ninth Revision, codes. We excluded patients with chronic PID, gynecologic malignancy, and those for whom the surgical route was unknown. INTERVENTIONS: Surgery for acute PID. MEASUREMENTS AND MAIN RESULTS: The study included 367 patients. The mean age was 43.0 ± 11.1 years, body mass index was 30.9 ± 11.2 kg/m2, and American Society of Anesthesiology class was 2 (interquartile range 2-3). Preoperative signs of sepsis were noted in 33.8% of the patients, and septic shock was present in 1.4%. Hysterectomy was performed in 67.6%, oophorectomy in 12.0%, and salpingectomy in 4.6%. Complications were experienced by 114 patients (31.1%), 11 (3.0%) of which were potentially life-threatening. Multivariate logistic regression identified the following to be independently associated with complications: laparoscopy (adjusted odds ratio [aOR] 0.48; 95% confidence interval [CI], 0.3-0.8; p <.01), operative time (aOR 1.01; 95% CI, 1.00-1.01; p <.01), appendectomy (aOR 2.36; 95% CI, 1.0-5.4; p = .04), elevated international normalized ratio (aOR 2.30; 95% CI, 1.3-4.2; p <.01), and low hematocrit level (aOR 2.53; 95% CI, 1.4-4.5; p <.01). Propensity scores were calculated and used to generate a matched cohort of patients who underwent laparoscopic vs open surgery; the groups were similar, with p <.05 for all covariates. After balancing confounding variables, a laparoscopic approach to surgery remained significantly associated with a lower risk of complications (coefficient -0.07; 95% CI, -0.11 to -0.02; p = .008). CONCLUSION: Laparoscopy was associated with lower complication rates than open surgery in this well-matched cohort of patients who underwent surgery for acute PID.

Genetics of gene expression and its effect on disease.

Common human diseases result from the interplay of many genes and environmental factors. Therefore, a more integrative biology approach is needed to unravel the complexity and causes of such diseases. To elucidate the complexity of common human diseases such as obesity, we have analysed the expression of 23,720 transcripts in large population-based blood and adipose tissue cohorts comprehensively assessed for various phenotypes, including traits related to clinical obesity. In contrast to the blood expression profiles, we observed a marked correlation between gene expression in adipose tissue and obesity-related traits. Genome-wide linkage and association mapping revealed a highly significant genetic component to gene expression traits, including a strong genetic effect of proximal (cis) signals, with 50% of the cis signals overlapping between the two tissues profiled. Here we demonstrate an extensive transcriptional network constructed from the human adipose data that exhibits significant overlap with similar network modules constructed from mouse adipose data. A core network module in humans and mice was identified that is enriched for genes involved in the inflammatory and immune response and has been found to be causally associated to obesity-related traits.

Young people's data governance preferences for their mental health data: MindKind Study findings from India, South Africa, and the United Kingdom.

Mobile devices offer a scalable opportunity to collect longitudinal data that facilitate advances in mental health treatment to address the burden of mental health conditions in young people. Sharing these data with the research community is critical to gaining maximal value from rich data of this nature. However, the highly personal nature of the data necessitates understanding the conditions under which young people are willing to share them. To answer this question, we developed the MindKind Study, a multinational, mixed methods study that solicits young people's preferences for how their data are governed and quantifies potential participants' willingness to join under different conditions. We employed a community-based participatory approach, involving young people as stakeholders and co-researchers. At sites in India, South Africa, and the UK, we enrolled 3575 participants ages 16-24 in the mobile app-mediated quantitative study and 143 participants in the public deliberation-based qualitative study. We found that while youth participants have strong preferences for data governance, these preferences did not translate into (un)willingness to join the smartphone-based study. Participants grappled with the risks and benefits of participation as well as their desire that the "right people" access their data. Throughout the study, we recognized young people's commitment to finding solutions and co-producing research architectures to allow for more open sharing of mental health data to accelerate and derive maximal benefit from research.

Am I Really Qualified To Be Here: Exploring The Impact Of Impostor Phenomenon On Training And Careers In OB/GYN Medical Education.

OBJECTIVE: Individuals with Impostor Phenomenon (IP) believe they have achieved success by fooling others into thinking they are intelligent/capable and fear they will be discovered. This fear has been shown to cause psychological distress and may affect OB/GYN training. The objective of this study was to investigate the prevalence of IP and correlation with anxiety among OB/GYN trainees and faculty. DESIGN/SETTING: An anonymous cross-sectional survey including a demographic questioner, Clance Impostor Scale, and Generalized Anxiety Disorder 2-items screening tool was distributed to 200 attendees at the 2019 American College of Obstetricians and Gynecologists Annual Meeting. PARTICIPANTS: Eighty-nine medical students, 38 residents, 3 fellows, and 9 attendings completed the survey for a response rate of 72%. RESULTS: The average participant experienced frequent feelings of IP with the mean score of 65 ± 18. Nine (8%) experienced few feelings of IP, 27 (24%) had moderate IP feelings, 55 (50%) had frequent IP feelings, and 20 (18%) had intense IP feeling. There was no difference between IP score and trainee/faculty gender, race, or region of country. The degree of IP was significantly associated with level of medical training with more experienced physicians scoring lower than trainees (F = 6.07, p = 0.001). Finally, an association was found between anxiety and IP; individuals with a positive GAD-2 screen had significantly more feelings of IP compared to individuals with a negative GAD-2 screen (t = 4/79, p < 0.001). CONCLUSION: This study suggests that IP is likely prevalent among OB/GYN trainees and correlate with anxiety. Further discussion is needed regarding the impact of IP on medical education training and career advancement in the field of OB/GYN and other surgical specialties.

Self-reported racial/ethnic discrimination and bronchodilator response in African American youth with asthma.

IMPORTANCE: Asthma is a multifactorial disease composed of endotypes with varying risk profiles and outcomes. African Americans experience a high burden of asthma and of psychosocial stress, including racial discrimination. It is unknown which endotypes of asthma are vulnerable to racial/ethnic discrimination. OBJECTIVE: We examined the association between self-reported racial/ethnic discrimination and bronchodilator response (BDR) among African American youth with asthma ages 8 to 21 years (n = 576) and whether this association varies with tumor necrosis factor alpha (TNF-α) level. MATERIALS AND METHODS: Self-reported racial/ethnic discrimination was assessed by a modified Experiences of Discrimination questionnaire as none or any. Using spirometry, BDR was specified as the mean percentage change in forced expiratory volume in one second before and after albuterol administration. TNF-α was specified as high/low levels based on our study population mean. Linear regression was used to examine the association between self-reported racial/ethnic discrimination and BDR adjusted for selected characteristics. An interaction term between TNF-α levels and self-reported racial/ethnic discrimination was tested in the final model. RESULTS: Almost half of participants (48.8%) reported racial/ethnic discrimination. The mean percent BDR was higher among participants reporting racial/ethnic discrimination than among those who did not (10.8 versus 8.9, p = 0.006). After adjustment, participants reporting racial/ethnic discrimination had a 1.7 (95% CI: 0.36-3.03) higher BDR mean than those not reporting racial/ethnic discrimination. However, we found heterogeneity of this association according to TNF-α levels (p-interaction = 0.040): Among individuals with TNF-α high level only, we observed a 2.78 higher BDR mean among those reporting racial/ethnic discrimination compared with those not reporting racial/ethnic discrimination (95%CI: 0.79-4.77). CONCLUSIONS: We found BDR to be increased in participants reporting racial/ethnic discrimination and this association was limited to African American youth with TNF-α high asthma, an endotype thought to be resistant to traditional asthma medications. These results support screening for racial/ethnic discrimination in those with asthma as it may reclassify disease pathogenesis.

PAF antagonist treatment reduces pro-inflammatory cytokine mRNA after spinal cord injury.

Platelet-activating factor (PAF) is a pro-inflammatory molecule which contributes to secondary damage after spinal cord injury (SCI). To test if PAF contributes to cytokine induction following SCI, female Long-Evans rats were pretreated with the PAF antagonist WEB 2170 prior to receiving a contusion injury at spinal cord level T10 using the NYU impactor. RNase protection assay (RPA) analysis revealed that IL-1alpha mRNA peaked at I h post-injury while IL-1beta and IL-6 mRNA levels were higher and peaked at 6 h.TNF-alpha mRNA was almost undetectable. All mRNA levels approached baseline by 24 h. Treatment with WEB 2170 (1 mg/kg, i.p.) 15 min prior to injury significantly decreased mRNA levels for all three cytokines at 6 h post-injury, but not at I h post-injury. These results demonstrate a role for PAF in proinflammatory cytokine induction after SCI.

Multi-tissue coexpression networks reveal unexpected subnetworks associated with disease.

BACKGROUND: Obesity is a particularly complex disease that at least partially involves genetic and environmental perturbations to gene-networks connecting the hypothalamus and several metabolic tissues, resulting in an energy imbalance at the systems level. RESULTS: To provide an inter-tissue view of obesity with respect to molecular states that are associated with physiological states, we developed a framework for constructing tissue-to-tissue coexpression networks between genes in the hypothalamus, liver or adipose tissue. These networks have a scale-free architecture and are strikingly independent of gene-gene coexpression networks that are constructed from more standard analyses of single tissues. This is the first systematic effort to study inter-tissue relationships and highlights genes in the hypothalamus that act as information relays in the control of peripheral tissues in obese mice. The subnetworks identified as specific to tissue-to-tissue interactions are enriched in genes that have obesity-relevant biological functions such as circadian rhythm, energy balance, stress response, or immune response. CONCLUSIONS: Tissue-to-tissue networks enable the identification of disease-specific genes that respond to changes induced by different tissues and they also provide unique details regarding candidate genes for obesity that are identified in genome-wide association studies. Identifying such genes from single tissue analyses would be difficult or impossible.

Integrating QTL and high-density SNP analyses in mice to identify Insig2 as a susceptibility gene for plasma cholesterol levels.

The use of inbred strains of mice to dissect the genetic complexity of common diseases offers a viable alternative to human studies, given the control over experimental parameters that can be exercised. Central to efforts to map susceptibility loci for common diseases in mice is a comprehensive map of DNA variation among the common inbred strains of mice. Here we present one of the most comprehensive high-density, single nucleotide polymorphism (SNP) maps of mice constructed to date. This map consists of 10,350 SNPs genotyped in 62 strains of inbred mice. We demonstrate the utility of these data via a novel integrative genomics approach to mapping susceptibility loci for complex traits. By integrating in silico quantitative trait locus (QTL) mapping with progressive QTL mapping strategies in segregating mouse populations that leverage large-scale mapping of the genetic determinants of gene expression traits, we not only facilitate identification of candidate quantitative trait genes, but also protect against spurious associations that can arise in genetic association studies due to allelic association among unlinked markers. Application of this approach to our high-density SNP map and two previously described F2 crosses between strains C57BL/6J (B6) and DBA/2J and between B6 ApoE(-/-) and C3H/HeJ ApoE(-/-) results in the identification of Insig2 as a strong candidate susceptibility gene for total plasma cholesterol levels.

Platelet-activating factor induces cell death in cultured astrocytes and oligodendrocytes: involvement of caspase-3.

The biologically active lipid metabolite, platelet-activating factor (PAF), is thought to contribute to inflammatory processes and tissue damage in a variety of central nervous system (CNS) injuries. In previous studies, we found that after contusion spinal cord injury, treatment with a PAF antagonist led to significantly increased white matter tissue sparing as well as decreased mRNA levels for pro-inflammatory cytokines. Some studies suggest that PAF can also have toxic effects on neurons in vitro. Few studies, however, have examined the effects of PAF on glial cells of the CNS. In the present study, the potential for PAF to act as a toxin to cultured astrocytes was examined. Also investigated were the effects of PAF on oligodendrocytes at two different stages of development. Treatment with 0.02-2 microM PAF for 72 h resulted in significant levels of cell death in both cell types (P < 0.05), an effect that was blocked by the PAF receptor antagonists, WEB 2170 and BN 52021. To investigate PAF-induced glial cell death further, we looked for activation of the enzyme, caspase-3, which can be indicative of apoptosis. Immunocytochemistry demonstrated that PAF at all concentrations caused activation of caspase-3 at 24, 48, and 72 h after treatment in both cell types. Caspase-3-dependent cell death was further confirmed using knockout mice (-/-) deficient in the caspase-3 gene. Toxicity was lost when astrocytes (-/-) were exposed to 0.02-2 microM PAF (P < 0.01). Oligodendrocytes (-/-) were not susceptible to toxicity at 2 microM PAF (P < 0.001). The results demonstrate that the pro-inflammatory molecule, PAF, induces cell death in cultured CNS glial cells and that this effect is, in part, dependent on caspase-3 activation.

CD4+ T cells mediate murine syngeneic graft-versus-host disease-associated colitis.

Syngeneic graft-vs-host disease (SGVHD) develops following lethal irradiation, reconstitution with syngeneic bone marrow, and treatment with a 21-day course of the immunosuppressive agent cyclosporin A (CsA). Following cessation of CsA, this inducible disease is characterized by weight loss, diarrhea, and development of inflammation in the colon and liver. Although nonspecific effector cells and Th1 cytokines have been shown to participate in disease induction, the role of T cells has not been fully elucidated. Initial studies demonstrated significant increases in CD4+ T cells, but not other T cell populations in the colons of diseased animals relative to transplant control animals. To demonstrate a functional linkage between increases in colonic CD4+ T cells and disease induction, in vivo T cell depletion studies were performed. Beginning on the day of bone marrow transplantation, groups of control and CsA-treated animals were treated with mAb against either CD4 or CD8 for 21 days. Treatment with anti-CD4, but not anti-CD8, eliminated clinical symptoms and colon pathology. Interestingly, neither anti-CD4 nor anti-CD8 therapy affected the development of liver pathology associated with SGVHD. These findings demonstrated that CD4+ T cells initiate development of the intestinal inflammation associated with murine SGVHD.