We evaluated hormonal changes and problem-solving behaviors in 90 newlywed couples who were admitted to a hospital research unit for 24 hours. The subjects were selected on the basis of stringent mental and physical health criteria, and admissions were scheduled during the follicular phase of the woman's menstrual cycle. For frequent, unobtrusive endocrine sampling during the interaction tasks, a long polyethylene tube was attached to a heparin well, allowing nurses to draw blood samples at set intervals, out of subjects' sight. Five blood samples were obtained before, during, and after a 30-minute structured problem-solving or conflict task. The conflict session was recorded on videotapes that were later scored for problem-solving behaviors using the Marital Interaction Coding System (MICS). Marital conflict and MICS-coded hostile or negative behavior during conflict was closely linked to changes in serum hormonal levels across five of the six hormones we studied, in spite of the high marital satisfaction of our newlywed couples and the healthy lifestyles demanded by our exclusion criteria. Hostile behavior was associated with decreased levels of prolactin (PRL) and increases in epinephrine (EPI), norepinephrine (NEPI), ACTH, and growth hormone (GH), but not cortisol. These data suggest that the endocrine system may be an important mediator between personal relationships and health.
Personalized educational interventions have been shown to facilitate successful and inclusive statistics, mathematics, and data science (SMDS) in higher education through timely and targeted reduction of heterogeneous training disparities caused by years of cumulative, structural challenges in contemporary educational systems. However, the burden on the institutions and instructors to provide personalized training resources to large groups of students is also formidable, and often unsustainable. We present Individualized Pathways and Resources to Adaptive Control Theory-Inspired Scientific Education (iPRACTISE), a free, publicly available web app that serves as a tool to facilitate personalized trainings on SMDS and related topics through provision of personalized training recommendations as informed by computerized assessments and individuals' training preferences. We describe the resources available in iPRACTISE, and some proof-of-concept evaluation results from deploying iPRACTISE to supplement in-person and online classroom teaching in real-life settings. Strengths, practical difficulties, and potentials for future applications of iPRACTISE to crowdsource and sustain personalized SMDS education are discussed.
This study assesses the changes in the expression of histocompatibility antigen (HLA)-DR by mononuclear phagocytes from HIV-infected individuals. Overnight culture of monocytes resulted in an increase in HLA-DR expression by monocytes from uninfected individuals. In contrast, the expression of HLA-DR by monocytes from HIV-infected patients decreased spontaneously and was most pronounced in patients with clinical AIDS. We also found that Mycobacterium avium grew within monocytes from patients infected with HIV. The correlation between major histocompatibility complex (MHC) class II expression and Mycobacterial growth which has been reported in mice was not observed in monocytes from HIV-infected patients.
Syrus is courseware designed with the goal of helping students better understand logical sentences involving quantifiers. Syrus uses template-guided mutation of "seed" formulas to generate candidate practice problems, and third-party theorem-provers to automatically determine the truth value of each. It provides students with a virtually unlimited supply of unique and relevant practice problems and provides immediate feedback on each problem. Results of an empirical study of its efficacy are reported.
Abstract There is considerable evidence supporting the hypothesis that tomato carotenoids may contribute to prostate cancer prevention however the mechanisms remain uncertain. We propose that bioactive tomato components, such as lycopene, may impact testosterone signaling to inhibit prostate carcinogenesis. Four week-old C57/BL6 WT and TRAMP male mice were fed either control (AIN93G), 10% tomato powder or 0.25% lycopene beadlets. At eight weeks of age, mice were randomized among treatments: intact, castration, or castration + 2.5mg/kg testosterone repletion and animals sacrificed at 10 weeks of age. Prostate gene expression was quantified by Nanostring nCounter was used to quantify prostate gene expression with a 200 gene murine prostate carcinogenesis custom codeset and miRNA with codeset v1.1. Carotenoid analysis is by HPLC and proliferation (Ki67) by immunohistochemical evaluation. Feeding dietary tomato or lycopene increased serum lycopene, for example, in WT mice concentrations reached 335 +/- 33 nmol/L and 337 +/- 34 nmol/L in tomato and lycopene fed animals, respectively. As expected, the TRAMP genotype and testosterone stimulate proliferation with diet as a modulating factor. In the WT intact prostate, the tomato powder and lycopene diet decreased proliferation (p<0.009). The TRAMP genotype and endocrine status impacted the expression of multiple genes and miRNAs in several distinct patterns. For example, Birc5, Ki67, PCNA, BRCA1, ATM, Aurora kinase A / B, Cdc25c, Cyclin B2, cyclin E2, Fox M1,and miRs 15b, 16, 25, 200a, 200b, and 429 are increased in the TRAMP prostate, only when testosterone is present. Alternatively, TMPRSS2, CD31, CD34, Cox 2, nCad, Cyclin D1, Keratin 5, Shh, and p63, and miRs 145, 205, 328, and 423-5p are decreased in the TRAMP prostate in the presence of testosterone. Nkx3.1, miR 148a, and miR 375 are decreased upon castration whereas beta catenin, FGFR1 and TNF alpha are increased. Tomato and / or Lycopene modestly decreased expression of eCad, HIF 1 alpha, Paxillin, RxR alpha, Sca 1 and Vimentin and increased expression of CD133 and miR 22. These highly controlled in vivo studies document the strong interactions between genetic defects in the prostate, the hormonal environment, and diet in modulating early prostate carcinogenesis. Citation Format: Jennifer M. Thomas-Ahner, Lei Wan, Hsueh-Li Tan, Nancy E. Moran, Amy C. Elsen, Dennis K. Pearl, John W. Erdman, Steven K. Clinton. Tomato carotenoids and testosterone modulate mRNA and miRNA profiles during prostate carcinogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3701. doi:10.1158/1538-7445.AM2013-3701
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder that occurs in about 1 in 10,000 live births. SMA is caused by mutations in the survival motor neuron (SMN1) gene; homozygous deletion of exon 7 of the SMN1 gene has been observed in the majority of patients with SMA. A reliable and sensitive SMA diagnostic test is available that can identify this specific deletion in about 95% of the SMA affected patients. No specific therapy for SMA is currently available, although several promising therapies are being investigated. Early identification of affected infants before presentation of clinical symptoms may permit their enrollment in a clinical trial and the start of potential proactive treatment before the occurrence of irreversible neuronal loss and damage, usually within 3 to 6 months of delivery. The primary goal of population-based screening of newborn infants for SMA is to identify cases early, before symptoms occur, so that appropriate care can be provided. The purpose of population screening of potential parents is to identify at-risk couples, so that they can undergo genetic counseling and prenatal diagnosis, and can thus make an informed reproductive choice. At present, neither newborn screening nor carrier screening is considered standard of care. In this study, 2 pilot projects were performed addressing the clinical applicability of both population-based newborn screening and carrier screening. Newborn screening was performed on 40,103 anonymized blood spots, and 4 cases of SMA were correctly identified. Carrier screening was performed on 500 preconception or pregnant women, and 16 carriers were identified. A survey was sent to potential participants and responses were received from 392 patients of whom, 229 accepted prenatal carrier screening. After learning of their test results, the vast majority (98.7%) were glad they pursued screening. The findings of this study demonstrate that both population-based newborn screening and carrier screening for SMA is technically feasible and can provide an estimate of carrier frequency. The study also provides an assessment of the educational material used during genetic counseling that helps individuals to make an informed decision regarding carrier testing.
Replication of drug-resistant human immunodeficiency virus type 1 (HIV-1) in the presence of drug can lead to the failure of antiretroviral drug treatment. Drug failure is associated with the accumulation of drug resistance mutations. Previous studies have shown that 3'-azido-3'-deoxythymidine (AZT), (-)2',3'-dideoxy-3'-thiacytidine (3TC), and AZT-resistant HIV-1 reverse transcriptase (RT) can increase the virus in vivo mutation rate. In this study, the combined effects of drug-resistant RT and antiretroviral drugs on the HIV-1 mutant frequency were determined. In most cases, a multiplicative effect was observed with AZT-resistant or AZT/3TC dually resistant RT and several drugs (i.e., AZT, 3TC, hydroxyurea, and thymidine) and led to increases in the odds of recovering virus mutants to over 20 times that of the HIV-1 mutant frequency in the absence of drug or drug-resistance mutations. This observation indicates that HIV-1 can mutate at a significantly higher rate when drug-resistant virus replicates in the presence of drug. These increased mutant frequencies could have important implications for HIV-1 population dynamics and drug therapy regimens.
