An α-chain modification rivals the effect of fetal hemoglobin in retarding the rate of sickle cell fiber formation.

Adults with sickle cell disease bear a mutation in the ß-globin gene, leading to the expression of sickle hemoglobin (HbS; α2ßS2). Adults also possess the gene for γ-globin, which is a component of fetal hemoglobin (HbF, α2γ2); however, γ-chain expression normally ceases after birth. As HbF does not form the fibers that cause the disease, pharmacological and gene-modifying interventions have attempted to either reactivate expression of the γ chain or introduce a gene encoding a modified ß chain having γ-like character. Here, we show that a single-site modification on the α chain, αPro114Arg, retards fiber formation as effectively as HbF. Because this addition to the repertoire of anti-sickling approaches acts independently of other modifications, it could be coupled with other therapies to significantly enhance their effectiveness.

Entropy of Charge Inversion in DNA including One-Loop Fluctuations.

The entropy and charge distributions have been calculated for a simple model of polyelectrolytes attached to the surface of DNA using a field-theoretic method that includes fluctuations to the lowest one-loop order beyond mean-field theory. Experiments have revealed correlation-driven behavior of DNA in charged solutions, including charge inversion and condensation. In our model, the condensed polyelectrolytes are taken to be doubly charged dimers of length comparable to the distance between sites along the phosphate chains. Within this lattice gas model, each adsorption site is assumed to have either a vacancy or a positively charged dimer attached with the dimer oriented either parallel or perpendicular to the double-helix DNA chain. We find that the inclusion of the fluctuation terms decreases the entropy by ∼50% in the weak-binding regime. There, the bound dimer concentration is low because the dimers are repelled from the DNA molecule, which competes with the chemical potential driving them from the solution to the DNA surface. Surprisingly, this decrease in entropy due to correlations is so significant that it overcompensates for the entropy increase at the mean-field level, so that the total entropy is even lower than in the absence of interactions between lattice sites. As a bonus, we present a transparent exposition of the methods used that could be useful to students and others wishing to use this formulation to extend this calculation to more realistic models.

The Sickle-Cell Fiber Revisited.

Sickle cell disease is the consequence of a single point mutation on the surface of the ß chains of the hemoglobin molecule leading to the formation of rigid polymers that disrupt circulation. It has long been established that the polymers are comprised of seven pairs of double strands that are twisted replicas of the double strands found in crystals. Here, we review several newer developments that elaborate on that simple model and provide deeper insights into the process.

Factors in Early Adolescence Associated With a Mole-Prone Phenotype in Late Adolescence.

Importance: Nevi are important phenotypic risk factors for melanoma in adults. Few studies have examined the constitutional and behavioral factors associated with a mole-prone phenotype in adolescents. Objective: To identify host, behavioral, and dermoscopic factors in early adolescence (age, 14 years) that are associated with a mole-prone phenotype in late adolescence (age, 17 years). Design, Setting, and Participants: A prospective observational cohort study from the Study of Nevi in Children was conducted from January 1, 2009, to December 31, 2014, with a 2- to 3-year follow-up. A total of 569 students from the school system in Framingham, Massachusetts, were enrolled in the 8th or 9th grade (baseline; mean [SD] age, 14.4 [0.7] years). The overall retention rate was 73.3%, and 417 students were reassessed in the 11th grade. Main Outcome and Measures: Mole-prone phenotype in the 11th grade, defined as total nevus count of the back and 1 randomly selected leg in the top decile of the cohort or having any nevi greater than 5 mm in diameter. Results: Of the 417 students assessed at follow-up in the 11th grade (166 females and 251 males; mean [SD] age, 17.0 [0.4] years), 111 participants (26.6%) demonstrated a mole-prone phenotype: 69 students (62.2%) with 1 nevus greater than 5 mm in diameter, 23 students (20.7%) with total nevus count in the top decile, and 19 students (17.1%) with both characteristics. On multivariate analysis, baseline total nevus count (adjusted odds ratio, 9.08; 95% CI, 4.0-23.7; P < .001) and increased variability of nevus dermoscopic pattern (adjusted odds ratio, 4.24; 95% CI, 1.36-13.25; P = .01) were associated with a mole-prone phenotype. Conclusions and Relevance: This study found clinically recognizable factors associated with a mole-prone phenotype that may facilitate the identification of individuals at risk for melanoma. These findings could have implications for primary prevention strategies and help target at-risk adolescents for higher-intensity counseling about sun protection and skin self-examination.

Tanning and beauty: Mother and teenage daughters in discussion.

Tanning increases dramatically through the teenage years, but the family context of this health risk behavior is relatively unstudied. We conducted videotaped conversations between teenage girls (10th and 11th grade) and their mothers. We developed a coding system for discussion content and highlight findings including inadequate knowledge concerning the harms of tanning and positive views of outdoor tanning over indoor tanning, yet agreement that all tans are attractive. Many teens believed that indoor tanning is sometimes necessary to achieve the tanned look. These findings can usefully guide intervention development regarding the harms of all tanning, rather than indoor or outdoor tanning specifically.

Dermatoscopic imaging of skin lesions by high school students: a cross-sectional pilot study.

BACKGROUND: The ability of novices to perform imaging of skin lesions is not well studied. OBJECTIVES: To determine the ability of 12th grade high school students without formal training to take clinical and dermatoscopic images of skin lesions on patient-actors. PATIENTS/METHODS: Nineteen participants were divided into 11 gender-specific groups of 1-2 students. Groups were provided written instructions and assessed in their ability to (a) identify 8 pre-specified skin lesions, (b) take overview clinical images, and (c) take contact, polarized dermatoscopic images. Groups captured the same images twice using two different cameras [Nikon TM 1 J1 / VEOS HD1 and a VEOS DS3 (Canfield Scientific, Inc.)]. The sequence of camera use was determined using block randomization. If students made visibly poor skin contact during dermatoscopic imaging using their first camera, study investigators provided verbal instructions to place the second camera directly onto the skin. Students completed anonymous surveys before and after the imaging activity. RESULTS: Students were proficient at identifying the correct pre-specified skin lesions (86/88, 98%), capturing sufficient quality overview clinical images of the back and legs (41/42, 98%), and taking dermatoscopic images of the entire skin lesion (174/176, 99%). Regarding dermatoscopic image quality, 116 of 175 (66%) images were in focus. Out of focus images were attributed to poor skin contact. Groups that received feedback (n=4) were able to obtain a significantly higher proportion of in focus dermatoscopic images using their second camera compared to their first camera (16% to 72%, P<0.001). CONCLUSIONS: We identified several barriers that exist for participant-acquired dermatoscopic imaging. Instructions emphasizing the importance of skin contact are useful. Our results may help guide future patient-acquired teledermatoscopy efforts.

Clinical and dermoscopic stability and volatility of melanocytic nevi in a population-based cohort of children in Framingham school system.

Nevi are important risk markers of melanoma. The study aim was to describe changes in nevi of children using longitudinal data from a population-based cohort. Overview back photography and dermoscopic imaging of up to 4 index back nevi was performed at age 11 years (baseline) and repeated at age 14 years (follow-up). Of 443 children (39% females) imaged at baseline, 366 children (39% females) had repeated imaging 3 years later. At age 14, median back nevus counts increased by two; 75% of students (n=274) had at least one new back nevus and 28% (n=103) had at least one nevus that disappeared. Of 936 index nevi imaged dermoscopically at baseline and follow-up, 69% (645 nevi) had retained the same dermoscopic classification from baseline evaluation. Only 4% (n=13) of nevi assessed as globular at baseline were classified as reticular at follow-up, and just 3% (n=3) of baseline reticular nevi were classified as globular at follow-up. Of 9 (1%) index nevi that disappeared at follow-up, none showed halo or regression at baseline. In conclusion, the relative stability of dermoscopic pattern of individual nevi in the face of the overall volatility of nevi during adolescence suggests that specific dermoscopic patterns may represent distinct biological nevus subsets.

The CHEER study to reduce BMI in Elementary School students: a school-based, parent-directed study in Framingham, Massachusetts.

Childhood obesity may be lessened by parent-focused interventions. A pilot parent-directed trial with 46 parents of overweight and obese elementary school students was conducted at two ethnically diverse public schools in Framingham, Massachusetts. Parents were randomly assigned to either the Materials Group, which received mailed educational materials, or the Materials plus Personal Encounters Group, which received educational materials through interactions with community health workers (CHWs). Parents completed baseline and post-intervention surveys; children's body mass index (BMI) percentiles were measured at baseline and post-intervention. There were no differences in the reduction of children's BMI between groups. However, the mean BMI percentile for all children dropped from 94.1 to 90.6 (p = .005), while there was no change in BMI among a nonrandomized contemporaneous control group. Findings are limited by the lack of a true control group and small sample size. Results from this school nurse and CHW outreach program to parents are encouraging.

Study of Nevi in Children (SONIC): baseline findings and predictors of nevus count.

The authors report baseline findings and predictors of nevus count (log total nevi) at the completion of year 1 (2004) of the first known population-based, prospective study of nevi in a US cohort of children. Overall, 64% (n = 443/691) of grade 5 students and their parents in Framingham, Massachusetts, completed surveys and underwent digital photography. Total nevus count was associated with skin and hair color and tendency to burn, as measured by a sun sensitivity index. In multivariate analyses, male gender (rate ratio (RR) = 1.38, 95% confidence interval (CI): 1.22, 1.55; P < 0.0001), spending 5-6 weekly hours outdoors between 10 AM and 4 PM (RR = 1.13, 95% CI: 1.00, 1.28; P = 0.051), getting a painful sunburn once (RR = 1.24, 95% CI: 0.98, 1.57; P = 0.073) and at least twice (RR = 1.34, 95% CI: 0.99, 1.82; P = 0.061), and wearing a shirt at the beach or pool rarely (RR = 1.29, 95% CI: 1.08, 1.54; P = 0.005), sometimes (RR = 1.26, 95% CI: 1.01, 1.57; P = 0.041), and often and always (RR = 1.32, 95% CI: 1.13, 1.54; P = 0.001) were associated with increased number of nevi. Identifying factors that predict the development of nevi will improve primary prevention efforts during early life.

Study of health outcomes in school children: key challenges and lessons learned from the Framingham Schools' Natural History of Nevi Study.

BACKGROUND: We describe the planning, recruitment, key challenges, and lessons learned in the development of a study of the evolution of nevi (moles) among children in a school setting. METHODS: This population-based study of digital photography and dermoscopy of the child's back (overview, close-up, and dermoscopic images) and genetic specimens took place among fifth graders in the Framingham, Massachusetts School System. Schoolchildren and their parents completed baseline surveys on sun protection practices, sunburns, and past ultraviolet exposures, including summer and vacation experiences. RESULTS: Prestudy outreach was conducted with children, parents, nurses, administrators, and pediatricians. Of the 691 Framingham families with a fifth grader (aged 10-11), 443 consented to complete surveys and undergo digital photography and dermoscopy during the school's routine scoliosis testing. Of the 443 families providing consent, 369 agreed to genetic testing. We identified key factors to consider when implementing school-based studies: (a) pilot studies to demonstrate feasibility, (b) inclusion of school administration and parents, (c) grassroots approach with multiple contacts, and (d) embedding research studies within preexisting school health services. CONCLUSIONS: Launching an observational study within the school environment required an academic/school collaboration across numerous disciplines including dermatology, epidemiology, genetics, medical photography, school health, community health education, and most notably, the need for the presence of a full-time study nurse in the school. A large school system proved to be an excellent resource to conduct this first prospective study on the evolution of moles in US schoolchildren. The key challenges and lessons learned may be applicable to other investigators launching school-based initiatives.

Lattice-gas model of DNA charge inversion by a positively charged polyelectrolyte.

The model of DNA charge inversion by Nguyen and Shklovskii [T. T. Nguyen and B. I. Shklovskii, Phys. Rev. Lett. 89, 018101 (2002)] is extended. A single double-helix strand of DNA is represented by a lattice of negative charges at the positions of the protruding oxygens of the phosphates along the DNA backbone, and the adsorbed polyelectrolyte molecules are represented by charged dimers. A lattice-gas model is used in which dimers adsorbing either parallel or perpendicular to the lattice are treated as separate species, and the model allows for vacancies between adsorbed species. The mean field theory used is formulated as a saddle-point approximation of the exact functional integral representation of the grand canonical partition function, opening the way for the inclusion of the effects of charge fluctuation corrections.