Mental illness in parents of phenylketonuric children

1. (1) This paper presents the results of a field study designed to investigate the hypothesis that persons presumed heterozygous for phenylketonuria are more vulnerable to mental disorder than other persons. Three-hundred-and-thirty-one persons were interviewed, including 108 parents of phenylketonuric offspring, 102 parents with non-phenylketonuric mentally retarded offspring, and 121 parents of children with cystic fibrosis.2. (2) Information was collected by means of a standard interview schedule which inquired into mental health problems of the interviewees as well as their parents and siblings. Interviews were coded according to an explicit code. Mental Health was evaluated by a set of indices constructed by assigning numerical values to certain items in the code and summing related items. These indices served as operational definitions of mental illness.3. (3) Analysis of variance was used to evaluate data derived.4. (4) Decreasing social class appeared to be associated with increasing scores on the indices. In addition, men and women scored significantly differently on many of the indices. In general, differences due to sex and social class were in the direction which would have been expected if the indices had been measuring the problem areas we were trying to evaluate.5. (5) The parents of phenylketonuric children did not score differently from the other two groups, indicating that they were not more susceptible to mental health problems than the controls, at least as measured by our operational definitions.6. (6) Some of the problems associated with field studies of psychiatric disease are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33351/1/0000749.pd

The belief systems of protesting college students

A group of 29 college students who had been arrested or nominated as having participated in a street disturbance aimed at producing social change were interviewed. The interview schedule was highly similar to one which had been used to investigate attitudes toward violence in a random, representative sample of American men. The data collected from the arrestees are compared with data from college students in the national sample. This study shows that the arrestees are more likely to think that violence is necessary to produce social change than are college students generally, and are more likely to believe that existing social institutions are inadequate. As a group, the arrestees are more identified with white student demonstrators and black protestors than are college students generally. The arrestees are also likely to regard the police as untrusworthy, looking for trouble, and apt to dislike people like themselves. In addition to the negative attitudes toward the police held by the student arrestees, they are more likely to regard police actions as violence (and hence provocative) than are other college students. The arrestees are far more likely than other college students to cleave to humanistic values. However, most of the differences between the arrestees and other American college students could be predicted from a general model of the justification of violence, so that it appears that the student activists' beliefs differ not so much in kind from those of other Americans as they do in degree.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45278/1/10964_2005_Article_BF02214088.pd

Sex as a source of heterogeneity in a mental health survey

We have presented a series of constructs which were developed to measure the relative mental health of the members of three small populations. These constructs were highly concrete, and each of the 331 respondents investigated could be assigned a numerical rating without the use of clinical judgements of trained personnel. These constructs proved to be intercorrelated to a large degree. It was demonstrated that the size of the correlation between constructs was not always an accurate reflection of relationships within the population, so that certain relationships which were highly significant for men proved to be insignificant for women, and vice versa. The heterogeneous nature of the population could be shown to lead to two kinds of errors when data was looked at only for the population as a whole. (1) Loss or diminution of relationships which were true for one group but not the other; (2) errors in the interpretation of the significance of a relationship. It was pointed out that these errors probably represent general difficulties in the analysis of data from psychiatric studies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33353/1/0000751.pd

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Interprofessional Education in Introductory Pharmacy Practice Experiences at US Colleges and Schools of Pharmacy

Objective. To assess the extent to which US colleges and schools of pharmacy are incorporating interprofessional education into their introductory pharmacy practice experiences (IPPEs), and to identify barriers to implementation; characterize the format, structure, and assessment; and identify factors associated with incorporating interprofessional education in IPPEs

Targeted Chemotherapy overcomes drug resistance in melanoma

The emergence of drug resistance is a major obstacle for the success of targeted therapy in melanoma. Additionally, conventional chemotherapy has not been effective as drug-resistant cells escape lethal DNA damage effects by inducing growth arrest commonly referred to as cellular dormancy. We present a therapeutic strategy termed "targeted chemotherapy" by depleting protein phosphatase 2A (PP2A) or its inhibition using a small molecule inhibitor (1,10-phenanthroline-5,6-dione [phendione]) in drug-resistant melanoma. Targeted chemotherapy induces the DNA damage response without causing DNA breaks or allowing cellular dormancy. Phendione treatment reduces tumor growth of BRAFV600E-driven melanoma patient-derived xenografts (PDX) and diminishes growth of NRASQ61R-driven melanoma, a cancer with no effective therapy. Remarkably, phendione treatment inhibits the acquisition of resistance to BRAF inhibition in BRAFV600E PDX highlighting its effectiveness in combating the advent of drug resistance.status: accepte

Targeted chemotherapy overcomes drug resistance in melanoma

In this study, Yue et al. describe a therapeutic strategy termed “targeted chemotherapy” that involves depleting PP2A or inhibiting it using a small molecule inhibitor, phendione, in drug-resistant melanoma. The authors show phendione induces DNA damage response without causing DNA breaks or inducing cellular dormancy, therefore blocking tumor growth of BRAF mutant and NRAS mutant melanomas. The emergence of drug resistance is a major obstacle for the success of targeted therapy in melanoma. Additionally, conventional chemotherapy has not been effective as drug-resistant cells escape lethal DNA damage effects by inducing growth arrest commonly referred to as cellular dormancy. We present a therapeutic strategy termed “targeted chemotherapy” by depleting protein phosphatase 2A (PP2A) or its inhibition using a small molecule inhibitor (1,10-phenanthroline-5,6-dione [phendione]) in drug-resistant melanoma. Targeted chemotherapy induces the DNA damage response without causing DNA breaks or allowing cellular dormancy. Phendione treatment reduces tumor growth of BRAF V600E -driven melanoma patient-derived xenografts (PDX) and diminishes growth of NRAS Q61R -driven melanoma, a cancer with no effective therapy. Remarkably, phendione treatment inhibits the acquisition of resistance to BRAF inhibition in BRAF V600E PDX highlighting its effectiveness in combating the advent of drug resistance