Faculty Bibliography

First we just had to rule out any treatable medical conditions -- get the labs, head CT scan and chest X-ray. (According to a 2006 report, medication errors alone injure an estimated 1.5 million patients a year.)

Although bioinformatic analysis of the increasing numbers of diverse genome sequences and amount of functional data has provided insight into the evolution of signaling networks, bioinformatics approaches have limited application for understanding the evolution of highly divergent protein families. We used biochemical analyses to determine the in vitro properties of selected divergent components of the heterotrimeric guanine nucleotide-binding protein (G protein) signaling network to investigate signaling network evolution. In animals, G proteins are activated by cell-surface seven-transmembrane (7TM) receptors, which are named G protein-coupled receptors (GPCRs) and function as guanine nucleotide exchange factors (GEFs). In contrast, the plant G protein is intrinsically active, and a 7TM protein terminates G protein activity by functioning as a guanosine triphosphatase-activating protein (GAP). We showed that ancient regulation of the G protein active state is GPCR-independent and "self-activating," a property that is maintained in Bikonts, one of the two fundamental evolutionary clades containing eukaryotes, whereas G proteins of the other clade, the Unikonts, evolved from being GEF-independent to being GEF-dependent. Self-activating G proteins near the base of the Eukaryota are controlled by 7TM-GAPs, suggesting that the ancestral regulator of G protein activation was a GAP-functioning receptor, not a GEF-functioning GPCR. Our findings indicate that the GPCR paradigm describes a recently evolved network architecture found in a relatively small group of Eukaryota and suggest that the evolution of signaling network architecture is constrained by the availability of molecules that control the activation state of nexus proteins.

This report identifies human skeletal diseases associated with mutations in WNT1. In 10 family members with dominantly inherited, early-onset osteoporosis, we identified a heterozygous missense mutation in WNT1, c.652T-->G (p.Cys218Gly). In a separate family with 2 siblings affected by recessive osteogenesis imperfecta, we identified a homozygous nonsense mutation, c.884C-->A, p.Ser295*. In vitro, aberrant forms of the WNT1 protein showed impaired capacity to induce canonical WNT signaling, their target genes, and mineralization. In mice, Wnt1 was clearly expressed in bone marrow, especially in B-cell lineage and hematopoietic progenitors; lineage tracing identified the expression of the gene in a subset of osteocytes, suggesting the presence of altered cross-talk in WNT signaling between the hematopoietic and osteoblastic lineage cells in these diseases.

BACKGROUND: To increase knowledge of smoking-related health risks and provide smoking cessation information at the point of sale, in 2009, New York City required the posting of graphic point-of-sale tobacco health warnings in tobacco retailers. This study is the first to evaluate the impact of such a policy in the USA. METHODS: Cross-sectional street-intercept surveys conducted among adult current smokers and recent quitters before and after signage implementation assessed the awareness and impact of the signs. Approximately 10 street-intercept surveys were conducted at each of 50 tobacco retailers in New York City before and after policy implementation. A total of 1007 adults who were either current smokers or recent quitters were surveyed about the awareness and impact of tobacco health warning signs. Multivariate risk ratios (RR) were calculated to estimate awareness and impact of the signs. RESULTS: Most participants (86%) were current smokers, and the sample was 28% African-American, 32% Hispanic/Latino and 27% non-Hispanic white. Awareness of tobacco health warning signs more than doubled after the policy implementation (adjusted RR =2.01, 95% CI 1.74 to 2.33). Signage posting was associated with an 11% increase in the extent to which signs made respondents think about quitting smoking (adjusted RR =1.11, 95% CI 1.01 to 1.22). CONCLUSIONS: A policy requiring tobacco retailers to display graphic health warning signs increased awareness of health risks of smoking and stimulated thoughts about quitting smoking. Additional research aimed at evaluating the effect of tobacco control measures in the retail environment is necessary to provide further rationale for implementing these changes.

As doctors, they're fascinated by the relationship between physicians and patients. They're convinced that a deeper understanding of what's going on beneath the surface can benefit all parties involved. Here, Ofri shares the insider info one needs to get the best medical care--and the respect she deserves

The disproportionately high prevalence of hypertension and its associated mortality and morbidity in minority older adults is a major public health concern in the United States. Despite compelling evidence supporting the beneficial effects of therapeutic lifestyle changes on blood pressure reduction, these approaches remain largely untested among minority elders in community-based settings. The Counseling Older Adults to Control Hypertension trial is a two-arm randomized controlled trial of 250 African-American and Latino seniors, 60years and older with uncontrolled hypertension, who attend senior centers. The goal of the trial is to evaluate the effect of a therapeutic lifestyle intervention delivered via group classes and individual motivational interviewing sessions versus health education, on blood pressure reduction. The primary outcome is change in systolic and diastolic blood pressure from baseline to 12months. The secondary outcomes are blood pressure control at 12months; changes in levels of physical activity; body mass index; and number of daily servings of fruits and vegetables from baseline to 12months. The intervention group will receive 12 weekly group classes followed by individual motivational interviewing sessions. The health education group will receive an individual counseling session on healthy lifestyle changes and standard hypertension education materials. Findings from this study will provide needed information on the effectiveness of lifestyle interventions delivered in senior centers. Such information is crucial in order to develop implementation strategies for translation of evidence-based lifestyle interventions to senior centers, where many minority elders spend their time, making the centers a salient point of dissemination.