Publications

The intrinsic antiretroviral factor APOBEC3G (A3G) is highly active against HIV-1 and other retroviruses. In different cell types, A3G is expressed in high-molecular-mass (HMM) RNA- protein complexes or low-molecular-mass (LMM) forms displaying different biological activities. In resting CD4 T cells, a LMM form of A3G potently restricts HIV-1 infection soon after virion entry. However, when T cells are activated, LMM A3G is recruited into HMM complexes that include Staufen-containing RNA granules. These complexes are probably nucleated by the induced expression of Alu/hY retroelement RNAs that accompany T-cell activation. HMM A3G sequesters these retroelement RNAs away from the nuclear long interspersed nuclear element-derived enzymes required for Alu/hY retrotransposition. Human immunodeficiency virus (HIV) exploits this 'window of opportunity' provided by the loss of LMM A3G in activated CD4 T cells to productively infect these cells. During HIV virion formation, newly synthesized LMM A3G is preferentially encapsidated but only under conditions where Vif is absent and thus not able to target A3G for proteasome-mediated degradation. Together, these findings highlight the discrete functions of the different forms of A3G. LMM A3G opposes the external threat posed by exogenous retroviruses, while HMM A3G complexes oppose the internal threat posed by the retrotransposition of select types of retroelements.

The extent to which common variants contribute to common phenotypes and disease in humans has important consequences for the future of medical genomics. Two reports have recently clarified this issue for one of the most pressing public health concerns, obesity. These large and comprehensive genome-wide association studies find that common variants within at least 11 genes are associated with obesity. Interestingly, most of these genes are highly expressed in the central nervous system, further highlighting its role in the pathogenesis of obesity. However, the individual and combined effects of these variants explain only a small fraction of the inherited variability in obesity, suggesting that rare variants may contribute significantly to the genetic predisposition for this condition.

Latinos account for 15% of the US population, a proportion projected to grow to 30% by the year 2050. Although there is tremendous diversity within this community, commonalities of language, beliefs, attitudes, and behaviors unite Latinos, making them more similar than different. Differences by national origin, although important, are attenuated when immigrants come to the United States, dominated by an English-language, Anglo-centric culture. For non-Latino and non-Spanish-speaking clinicians, communication barriers and cultural misunderstandings can impede the care of dying Latino patients and their families. We present the case of a young, pregnant, Spanish-speaking woman from Central America diagnosed with a fatal leukemia. As illustrated by this case, Latino immigrants face a number of external challenges to optimal end-of-life care: (1) geographic distance as well as political and economic realities often separate patients from their valued families; (2) undocumented immigrants are frequently uninsured and fear of deportation may create a barrier to accessing health services; (3) language and literacy barriers; and (4) concerns about discrimination. Other Latino issues that may be more pronounced in end-of-life settings include cultural themes and religious and spiritual influences. We recommend that professional interpreters must be used for discussions about goals of care with Spanish-speaking patients and families or when negotiating conflict between the patient, family, and the health care team. Concrete suggestions are provided for clinicians in working with interpreters, eliciting culturally based attitudes and beliefs, and implementing universal strategies for clear health communication.

BACKGROUND

Doctor-patient communication is an important marker of health-care quality. Little is known about the extent to which medical comorbidities, disease severity and depressive symptoms influence perceptions of doctor-patient communication in patients with chronic disease.

METHODS

In a cross-sectional study of 703 outpatients with chronic coronary disease, we evaluated the extent to which patient reports of doctor-patient communication were influenced by medical comorbidities, disease severity and depressive symptoms. We assessed patient reports of doctor-patient communication using the Explanations of Condition and Responsiveness to Patient Preferences subscales from the "Interpersonal Processes of Care" instrument. Poor doctor-patient communication was defined as a score of <4 (range 1 to 5) on either subscale. All patients completed the nine-item Patient Health Questionnaire (PHQ) for measurement of depressive symptoms and underwent an extensive evaluation of medical comorbidities and cardiac function.

RESULTS

In univariate analyses, the following patient characteristics were associated with poor reported doctor-patient communication on one or both subscales: female sex, white or Asian race and depressive symptoms. After adjusting for demographic factors, medical comorbidities and disease severity, each standard deviation (5.4-point) increase in depressive symptom score was associated with a 50% greater odds of poor reported explanations of condition (OR 1.5, 95% CI, 1.2-1.8; p < 0.001) and a 30% greater odds of poor reported responsiveness to patient preferences (OR 1.3, 95% CI, 1.1-1.5; p = 0.01). In contrast, objective measures of disease severity (left ventricular ejection fraction, exercise capacity, inducible ischemia) and medical comorbidities (hypertension, diabetes, myocardial infarction) were not associated with reports of doctor-patient communication.

CONCLUSIONS

In outpatients with chronic coronary heart disease, depressive symptoms are associated with perceived deficits in doctor-patient communication, while medical comorbidities and disease severity are not. These findings suggest that patient reports of doctor-patient communication may partly reflect the psychological state of the patient.