Communicating genetic information: a difficult challenge for future pediatricians

<p>Abstract</p> <p>Background</p> <p>The role of the pediatrician as genetic counselor is ideal because pediatricians have medical knowledge and experience with genetic disorders (e.g. Down syndrome). Moreover, pediatricians can provide comprehensive care in a medical home to patients with genetic disorders. However, changes in the curriculum of the pediatric resident are necessary to address the future challenges of effectively communicating genetic information to patients. The objective of this study was to explore these challenges and make recommendations for training to adequately prepare pediatricians for their future role as genetic counselors.</p> <p>Methods</p> <p>Three reviewers independently searched PubMed, OVID, and Medline databases to identify articles describing the challenges of communicating genetic information to patients, published from 1960 to December 2005. After the publications were identified and reviewed, four major areas of interest were identified in order to categorize the findings.</p> <p>Results</p> <p>Twenty-five publications were identified during the literature search. From the review, the following categories were selected to organize the findings: (1) Inherent difficulties of communicating and comprehending genetic information; (2) Comprehension of genetic information by pediatricians; (3) Genetics training in residency programs; and (4) The effect of genetic information on the future role of pediatricians and potential legal implications.</p> <p>Conclusion</p> <p>Pediatricians and residents lack essential knowledge of genetics and communication skills for effective counseling of patients. The review indicated that successful communication of genetic information involves a number of important skills and considerations. It is likely that these skills and considerations are universally required for the communication of most complex specialized medical information. In the past, communication skills have not been considered a priority. Today, these skills have become a demanding professional and even legal obligation. However, the challenges involved in communicating complex medical information cannot be successfully addressed with universal, one-size-fits-all recommendations. Residency training programs require changes to adequately prepare future pediatricians for the growing challenge of communicating genetic information. Four important skills should be considered in the training of residents to improve the communication of complex information to patients. These skills are (1) discriminating, (2) understanding, (3) simplifying, and (4) explaining information.</p

Characterization of the Single Stranded DNA Binding Protein SsbB Encoded in the Gonoccocal Genetic Island

Background: Most strains of Neisseria gonorrhoeae carry a Gonococcal Genetic Island which encodes a type IV secretion system involved in the secretion of ssDNA. We characterize the GGI-encoded ssDNA binding protein, SsbB. Close homologs of SsbB are located within a conserved genetic cluster found in genetic islands of different proteobacteria. This cluster encodes DNA-processing enzymes such as the ParA and ParB partitioning proteins, the TopB topoisomerase, and four conserved hypothetical proteins. The SsbB homologs found in these clusters form a family separated from other ssDNA binding proteins. Methodology/Principal Findings: In contrast to most other SSBs, SsbB did not complement the Escherichia coli ssb deletion mutant. Purified SsbB forms a stable tetramer. Electrophoretic mobility shift assays and fluorescence titration assays, as well as atomic force microscopy demonstrate that SsbB binds ssDNA specifically with high affinity. SsbB binds single-stranded DNA with minimal binding frames for one or two SsbB tetramers of 15 and 70 nucleotides. The binding mode was independent of increasing Mg 2+ or NaCl concentrations. No role of SsbB in ssDNA secretion or DNA uptake could be identified, but SsbB strongly stimulated Topoisomerase I activity

Impact of Circulating Cholesterol Levels on Growth and Intratumoral Androgen Concentration of Prostate Tumors

Prostate cancer (PCa) is the second most common cancer in men. Androgen deprivation therapy (ADT) leads to tumor involution and reduction of tumor burden. However, tumors eventually reemerge that have overcome the absence of gonadal androgens, termed castration resistant PCa (CRPC). Theories underlying the development of CRPC include androgen receptor (AR) mutation allowing for promiscuous activation by non-androgens, AR amplification and overexpression leading to hypersensitivity to low androgen levels, and/or tumoral uptake and conversion of adrenally derived androgens. More recently it has been proposed that prostate tumor cells synthesize their own androgens through de novo steroidogenesis, which involves the step-wise synthesis of androgens from cholesterol. Using the in vivo LNCaP PCa xenograft model, previous data from our group demonstrated that a hypercholesterolemia diet potentiates prostatic tumor growth via induction of angiogenesis. Using this same model we now demonstrate that circulating cholesterol levels are significantly associated with tumor size (R = 0.3957, p = 0.0049) and intratumoral levels of testosterone (R = 0.41, p = 0.0023) in LNCaP tumors grown in hormonally intact mice. We demonstrate tumoral expression of cholesterol uptake genes as well as the spectrum of steroidogenic enzymes necessary for androgen biosynthesis from cholesterol. Moreover, we show that circulating cholesterol levels are directly correlated with tumoral expression of CYP17A, the critical enzyme required for de novo synthesis of androgens from cholesterol (R = 0.4073, p = 0.025) Since hypercholesterolemia does not raise circulating androgen levels and the adrenal gland of the mouse synthesizes minimal androgens, this study provides evidence that hypercholesterolemia increases intratumoral de novo steroidogenesis. Our results are consistent with the hypothesis that cholesterol-fueled intratumoral androgen synthesis may accelerate the growth of prostate tumors, and suggest that treatment of CRPC may be optimized by inclusion of cholesterol reduction therapies in conjunction with therapies targeting androgen synthesis and the AR

Saturated Fats: A Perspective from Lactation and Milk Composition

For recommendations of specific targets for the absolute amount of saturated fat intake, we need to know what dietary intake is most appropriate? Changing agricultural production and processing to lower the relative quantities of macronutrients requires years to accomplish. Changes can have unintended consequences on diets and the health of subsets of the population. Hence, what are the appropriate absolute amounts of saturated fat in our diets? Is the scientific evidence consistent with an optimal intake of zero? If not, is it also possible that a finite intake of saturated fats is beneficial to overall health, at least to a subset of the population? Conclusive evidence from prospective human trials is not available, hence other sources of information must be considered. One approach is to examine the evolution of lactation, and the composition of milks that developed through millennia of natural selective pressure and natural selection processes. Mammalian milks, including human milk, contain 50% of their total fatty acids as saturated fatty acids. The biochemical formation of a single double bond converting a saturated to a monounsaturated fatty acid is a pathway that exists in all eukaryotic organisms and is active within the mammary gland. In the face of selective pressure, mammary lipid synthesis in all mammals continues to release a significant content of saturated fatty acids into milk. Is it possible that evolution of the mammary gland reveals benefits to saturated fatty acids that current recommendations do not consider

The relationship of tobacco and alcohol use with ageing self-perceptions in older people in Ireland.

Background: Health behaviour patterns in older groups, including tobacco and alcohol use, are key factors in chronic disease prevention. We explore ageing self-perceptions as motivating factors behind smoking and drinking alcohol in older adults, and the complex reasons why individuals engage harmfully in these behaviours. Methods: Cigarette and alcohol use was assessed in a large cross-sectional national sample aged 50 years and above from the Irish Longitudinal Study on Ageing (TILDA) (n = 6,576). The Brief Ageing Perceptions Questionnaire (BAPQ) assessed individual’s views of their own ageing across five domains. Study hypothesis that stronger beliefs on each of the BAPQ domains would be related to drinking and smoking was examined using multinomial logit models (MNLM). Regression parameter estimates for all variables were estimated relative risk ratios (RRR). Results: More women were non-drinkers (30 % vs. 20 %) and men displayed significantly higher alcohol use patterns. One in five older Irish adults was a current smoker (16.8 % of women, 17 % of men), and smoking and harmful drinking were strongly associated (P < .001). Some domains of ageing perceptions were significantly associated with harmful drinking and smoking. While the risk of being be harmful drinker decreased with stronger beliefs about the positive consequences of ageing (RRR 0.89), it increased with higher scores on both emotional representation and control positive domains. Greater awareness of ageing and stronger emotional reaction to ageing increased likelihood of smoking. A greater sense of control over the outcomes of ageing was associated with increased risk of both harmful drinking (RRR control positive 1.16) and smoking (RRR control and consequences negative 1.25). This suggests optimistic bias in relation to perceived health risk from smoking and harmful drinking as a potential adverse effect of perceptions of control. Risks of concurrent smoking and harmful drinking increased with chronic awareness of ageing (RRR 1.24), and negative emotional responses to it (RRR 1.21), and decreased with stronger perceptions of the positive consequences of ageing (RRR 0.85). Conclusions: The relationship between ageing perceptions, smoking and drinking is complex. Altering perceptions of ageing may be a useful intervention target aimed at facilitating engagement in preventative health behaviours in older people

Colorectal Cancer Screening: What Do Women From Diverse Ethnic Groups Want?

BACKGROUND: Little is known about factors associated with willingness to undergo colorectal cancer (CRC) screening for personal or public health benefit among women from diverse race/ethnic groups. OBJECTIVE: To evaluate factors associated with willingness to undergo CRC screening for personal and public health benefit among women from diverse race/ethnic groups. METHODS: We interviewed women aged 50 to 80 from four racial/ethnic groups from primary care clinics in 2003–2005. We asked about demographics, CRC screening knowledge and history, perceived risk of colon cancer, and about the outcomes of intention to be screened for personal benefit and for public health benefit. RESULTS: Of the 492 women who completed the interview, 32 % were White, 16 % were African American, 21 % were Latina and 32 % were Asian. Up-to-date screening was reported by 77 % of women, with similar numbers obtaining fecal occult blood test (FOBT) within 2 years or colonoscopy within 10 years. The majority of women were “likely or very likely” to get FOBT or colonoscopy after learning the benefits and risks. Multivariate models showed that compared to Whites, fewer Asians would undergo colonoscopy (OR = 0.28; 95 % CI: 0.12, 0.63), while more Latinas would undergo colonoscopy (OR = 6.14; 95 % CI: 1.77, 21.34) and obtain regular CRC screening (OR = 4.47; 95 % CI: 1.66, 12.04). The majority would obtain CRC screening even if they would not personally benefit; those who perceived themselves to be at higher than average cancer risk were more likely to participate in CRC screening for public health benefit (OR = 2.32; 95 % CI: 1.32, 4.09). CONCLUSIONS: The majority of women are willing to undergo screening for personal benefit. Asians were less likely, and Latinas more likely, to accept colonoscopy. Most are also willing to undergo screening for public health benefit. Self-perceived risk of CRC was the most consistent predictor of willingness and intention to be screened for either personal or public health benefi