Intermittent Catheter Reimbursement in the United States: The Experience of Nine Stakeholders Through the Lens of Actor-Network Theory

A narrow interpretation of “medical necessity” can result in poorer health as well as a more restricted life for people with disabilities. We examined the impact of US policy on reimbursement of intermittent catheters (ICs) on the lives of people with neurogenic bladder (NB) who require catheters to urinate. We conducted in-depth, longitudinal interviews with nine stakeholders. Actor-Network Theory was used to describe interactions among human agents, IC products, and policies in the reimbursement arena. Restrictions on the type and quantities of ICs reimbursed emerged as the most potent inhibitor to health and wellbeing among consumers with NB. IC suppliers, due to the large number of other stakeholders with whom they interact in the reimbursement process, emerged as strong enablers of preferred IC use among people with NB. Lack of an impartial central clearinghouse on IC products and coverage impeded consumers’ ability to make informed decisions

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

hREV3 is essential for error-prone translesion synthesis past UV or benzo[a]pyrene diol epoxide-induced DNA lesions in human fibroblasts

In S. cerevisiae, the REV3 gene, encoding the catalytic subunit of polymerase zeta, is involved in translesion synthesis and required for the production of mutations induced by ultraviolet radiation (UV) photoproducts and other DNA fork-blocking lesions, and for the majority of spontaneous mutations. To determine whether hREV3, the human homolog of yeast REV3, is similarly involved in error-prone translesion synthesis past UV photoproducts and other lesions that block DNA replication, an hREV3 antisense construct under the control of the TetP promoter was transfected into an infinite life span human fibroblast cell strain that expresses a high level of tTAk, the activator of that promoter. Three transfectant strains expressing high levels of hREV3 antisense RNA were identified and compared with their parental cell strain for sensitivity to the cytotoxic and mutagenic effects of UV. The three hREV3 antisense-expressing cell strains were not more sensitive than the parental strain to the cytotoxic effect of UV, but the frequency of mutants induced by UV in their HPRT gene was significantly reduced, i.e. to 14% that of the parent. Two of these hREV3 antisense-expressing cell strains were compared with the parental strain for sensitivity to (+/-)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene (BPDE). They were not more sensitive than the parent strain to the cytotoxic effect of BPDE, but the frequency of mutants induced was significantly reduced, i.e. in one strain, to 17% that of the parent, and in the other, to 24%. DNA sequencing showed that the kinds of mutations induced by BPDE in the parental and the derivative strains did not differ and were similar to those found previously with finite life span human fibroblasts. The data strongly support the hypothesis that hRev3 plays a critical role in the induction of mutations by UV or BPDE. Because the level of hRev3 protein in human fibroblasts is below the level of antibody detection, it was not possible to demonstrate that the decrease in mutagenesis reflected decreased hRev3 protein. However, the conclusion is supported by the fact that in a similar study with a strain expressing a high level of antisense hREV1, a very similar result was obtained, i.e. UV or BPDE mutagenesis was virtually eliminated

Oligonucleotide microarray analysis of strain- and gender-associated gene expression in the human blood fluke, Schistosoma japonicum

Schistosomiasis is a chronic and debilitating disease caused by blood flukes (digenetic trematodes) of the genus Schistosoma. Schistosomiasis japonica, a zoonosis caused by Schistosoma japonicum, is endemic to the Philippines and China. We utilised a 22,575 feature custom oligonucleotide DNA microarray designed from public domain databases of schistosome-expressed sequence tags to explore differential gene expression between the Philippine (SJP) and Chinese (SJC) strains of S. japonicum, and between male and female S. japonicum. We found that 593, 664 and 426 probes were differentially expressed between the two geographical strains when we compared mix sexed adults, male worms and female worms. Additionally, the study revealed that 1163 male- and 1016 female-associated probes were differentially expressed in SJP whereas 1047 male- and 897 female-associated probes were differentially expressed in SJC. The study greatly expands previously published data of strain and gender-associated differential expression in S. japonicum. Further, these new data provide a stepping stone for understanding the complexities of the biology, sexual differentiation, maturation, and development of human schistosomes, signaling new approaches for identifying novel intervention and diagnostic targets against schistosomiasis

Oligonucleotide microarray analysis of strain- and gender-associated gene expression in the human blood fluke, Schistosoma japonicum

Schistosomiasis is a chronic and debilitating disease caused by blood flukes (digenetic trematodes) of the genus Schistosoma. Schistosomiasis japonica, a zoonosis caused by Schistosoma japonicum, is endemic to the Philippines and China. We utilised a 22,575 feature custom oligonucleotide DNA microarray designed from public domain databases of schistosome-expressed sequence tags to explore differential gene expression between the Philippine (SJP) and Chinese (SJC) strains of S. japonicum, and between male and female S. japonicum. We found that 593, 664 and 426 probes were differentially expressed between the two geographical strains when we compared mix sexed adults, male worms and female worms. Additionally, the study revealed that 1163 male- and 1016 female-associated probes were differentially expressed in SJP whereas 1047 male- and 897 female-associated probes were differentially expressed in SJC. The study greatly expands previously published data of strain and gender-associated differential expression in S. japonicum. Further, these new data provide a stepping stone for understanding the complexities of the biology, sexual differentiation, maturation, and development of human schistosomes, signaling new approaches for identifying novel intervention and diagnostic targets against schistosomiasis

Establishing a Baseline Measure of School Wellness-Related Policies Implemented in a Nationally Representative Sample of School Districts

The Child Nutrition and WIC Reauthorization Act of 2004 required school districts to establish a local school wellness policy by the first day of the 2006-2007 school year. To provide a baseline measure of the extent to which wellness-related policies were implemented in school districts nationwide in 2006, this study analyzed data from the 2006 School Health Policies and Programs Study (SHPPS). SHPPS used a cross-sectional design to measure policies and practices among a nationally representative sample of 538 public school districts. The authors applied a standardized wellness policy coding system to the data by matching each element to relevant questions from SHPPS and calculated the percentage of school districts meeting each element in the coding system. Statistical analyses included calculation of 95% confidence intervals for percentages and mean number of elements met in each area. In 2006, none of the districts met all elements included in the coding system for local wellness policies. In addition, the percentage of districts meeting each element varied widely. On average, districts met the greatest number of elements in the area of nutrition education, and the least number of elements in the area of physical activity. By applying a coding system for district policies to an existing dataset, this study used a novel approach to determine areas of strength and weakness in the implementation of local school wellness-related policies in 2006