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Hospitalist involvement in family medicine residency training: A CERA study

Mon, 08/24/2015 - 3:25pm

BACKGROUND AND OBJECTIVES: Little is known about the impact of hospitalists on family medicine residencies. We surveyed family medicine residency directors to assess attitudes about hospitalists and their involvement in residency teaching.

METHODS: Questions were included in the 2012 Council of Academic Family Medicine Educational Research Alliance (CERA) survey of family medicine residency directors. Univariate statistics were used to describe programs, directors, and our questions on the use of hospitalists. Bivariate statistics were used to examine relationships between the use of hospitalists to teach and program characteristics.

RESULTS: Forty-one percent (n=175) of residency directors completed the hospitalist section of the CERA survey. Sixty-six percent of residency programs were community based/university affiliated. The majority of directors who have, or are planning to develop, a hospitalist service currently use an internal medicine service (92.5%), followed by family medicine (39.1%), pediatrics (35.4%), OB/laborists (18.0%), and combined services (8.7%). The majority of programs with a hospitalist training track (or plans to develop one) indicated that this was for a family medicine service. Sixty percent of programs that have a hospitalist service involve hospitalists in teaching. Twenty percent of directors reported that hospitalists serve as family medicine faculty, and 63% viewed them as "good educators." However, 85% reported no reduction in inpatient teaching by family medicine faculty despite using hospitalist teaching services.

CONCLUSIONS: Hospitalists have a significant educational role in family medicine resident training. Further research is needed to explore how hospitalists and family medicine faculty can collaborate to promote enhanced efficiency and effectiveness as residency teachers.

Weight loss motivations: a latent class analysis approach

Mon, 08/24/2015 - 3:25pm

OBJECTIVE: To identify subgroups of adults with respect to weight loss motivations and assess factors associated with subgroup membership.

METHOD: A cross-sectional survey among 414 overweight/ obese employees in 12 Massachusetts high schools was conducted. Latent class analysis (LCA) defined distinct weight loss motivation classes. Multinomial logistic regression assessed participant characteristics with class membership.

RESULTS: Three classes emerged: improving health; improving health and looking/feeling better; and improving health, looking/feeling, better and improving personal/social life. Compared to class 1, class 2 was more likely to be female and younger and class 3 was more likely to be female, younger, have children at home, and perceive themselves as very over-weight.

CONCLUSIONS: Findings can inform targeted weight loss interventions.

Explaining racial disparities in anticoagulation control: results from a study of patients at the Veterans Administration

Mon, 08/24/2015 - 3:25pm

Higher rates of stroke, major hemorrhage, and death among black patients receiving warfarin, compared with white patients, is likely related to poorer anticoagulation control. The research team investigated patient-level and site-level factors that might account for this group difference. A summary measure of anticoagulation control (percent time in therapeutic range [TTR]), patient characteristics, and site-level process of care measures were obtained for 9572 black and 88 481 white patients at the Veterans Health Administration. The research team studied disparity in TTR adjusting for patient and site characteristics. Mean unadjusted TTR for black patients was 6.5% lower than for white patients (P < .001). After accounting for the younger age of blacks, greater degrees of medication use, hospitalization, poverty, living in the South, and 11 other patient characteristics, only 2.0% of this racial disparity persisted. Process of care measures had minimal additional effect. These findings may inform efforts to reduce this racial disparity in achieving good anticoagulation control.

Society of Behavioral Medicine (SBM) position statement: ban indoor tanning for minors

Mon, 08/24/2015 - 3:25pm

The Society of Behavioral Medicine (SBM), an interdisciplinary professional organization focused on the science of health behavior joins the American Academy of Dermatology, the American Academy of Pediatrics, and a host of other national and international organizations in support of a total ban on indoor tanning for minors under the age of 18. According to the International Agency for Research on Cancer, artificial sources of ultraviolet radiation are in the highest category of carcinogens, joining tobacco and asbestos. Strong evidence links indoor tanning to increased risk for melanoma with repeated exposure during childhood being associated with the greatest increase in risk. Several countries and five US states have passed legislation banning indoor tanning in minors. We strongly encourage the remaining US states to do the same in an effort to protect children and prevent new cases of melanoma. SBM also strongly encourages research that explores the use of tanning beds in the home. Home-based indoor tanning has the potential to be especially dangerous given the complete absence of safety regulations. Children are currently protected from exposure to health-harming substances like tobacco and lead; thus, legislation protecting them from artificial sources of ultraviolet radiation is yet another important step forward in improving public health.

Who benefits from diabetes self-management interventions? The influence of depression in the Latinos en Control trial

Mon, 08/24/2015 - 3:25pm

BACKGROUND: Depressive symptoms are common among adults with diabetes. Depression and social support may influence diabetes self-management.

PURPOSE: This study aimed to examine change in depressive symptoms and the role of depression and support on clinical and dietary outcomes among Latinos with type 2 diabetes participating in a diabetes self-management intervention.

METHODS: Participants (N = 252) were randomized to the intervention or usual care. Mixed effects models were used to examine interaction effects between intervention status and depressive symptoms (Centers for Epidemiologic Studies Depression (CES-D) score) and support for diabetes self-management behaviors at baseline. Outcomes were measured at baseline and 4 and 12 months and included dietary quality, physical activity, depressive symptoms, and hemoglobin A1c levels.

RESULTS: Intervention participants had lower CES-D scores at follow-up than control participants. An interaction effect between intervention status and CES-D scores predicted diet quality.

CONCLUSION: Latinos with depressive symptoms may derive the greatest benefits from diabetes self-management interventions. Additional research on support during diabetes self-management interventions is warranted.

The PROMIS Physical Function item bank was calibrated to a standardized metric and shown to improve measurement efficiency

Mon, 08/24/2015 - 3:25pm

OBJECTIVE: To document the development and psychometric evaluation of the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) item bank and static instruments.

STUDY DESIGN AND SETTING: The items were evaluated using qualitative and quantitative methods. A total of 16,065 adults answered item subsets (n > 2,200/item) on the Internet, with oversampling of the chronically ill. Classical test and item response theory methods were used to evaluate 149 PROMIS PF items plus 10 Short Form-36 and 20 Health Assessment Questionnaire-Disability Index items. A graded response model was used to estimate item parameters, which were normed to a mean of 50 (standard deviation [SD]=10) in a US general population sample.

RESULTS: The final bank consists of 124 PROMIS items covering upper, central, and lower extremity functions and instrumental activities of daily living. In simulations, a 10-item computerized adaptive test (CAT) eliminated floor and decreased ceiling effects, achieving higher measurement precision than any comparable length static tool across four SDs of the measurement range. Improved psychometric properties were transferred to the CAT's superior ability to identify differences between age and disease groups.

CONCLUSION: The item bank provides a common metric and can improve the measurement of PF by facilitating the standardization of patient-reported outcome measures and implementation of CATs for more efficient PF assessments over a larger range.

Patient-reported functional health and well-being outcomes with drug therapy: a systematic review of randomized trials using the SF-36 health survey

Mon, 08/24/2015 - 3:24pm

OBJECTIVES: To evaluate the responsiveness of the SF-36 Health Survey in drug trials and to determine how often clinically efficacious treatments produce meaningful functional health changes across medical conditions.

RESEARCH DESIGN: We conducted a systematic review of randomized, double-blind, placebo-controlled drug trials published from 1995 to 2011 that documented results for primary clinical endpoints and SF-36 outcomes. PubMed and a database of SF-36 publications were searched. We evaluated responsiveness as concordance (both statistically significant or both nonsignificant) between primary clinical and SF-36 outcomes. To determine how often SF-36 physical and mental component summary (PCS, MCS) score changes were of meaningful magnitude, mean net of placebo changes with treatment were compared against the developer's recommended 3-point threshold for a minimal important difference (MID) across groups of medical conditions.

RESULTS: Of 805 screened trials, 185 met eligibility criteria. Primary clinical and SF-36 outcomes were concordant in 151 trials (82%). Among clinically efficacious trials, 58% reported net mean SF-36 improvements > /=MID threshold; however, SF-36 changes were often modest (PCS IQR, 1.6-4.1; MCS IQR, 0.8-3.5). Variations in treatment impact were apparent across conditions. Clinically efficacious therapies for rheumatoid arthritis, psoriatic arthritis, and psoriasis consistently achieved the largest SF-36 improvements, with 87% exceeding MID, whereas no efficacious therapies for peripheral arterial disease or chronic obstructive pulmonary disease achieved MID threshold.

CONCLUSIONS: The SF-36 responds to treatment impact, distinguishing drug therapies that, on average, produce meaningful functional health benefits. Overall, just over half of clinically efficacious trials report meaningful functional health improvements, and results vary widely by medical condition.

ATM increases activation-induced cytidine deaminase activity at downstream S regions during class-switch recombination

Mon, 08/24/2015 - 3:24pm

Activation-induced cytidine deaminase (AID) initiates Ab class-switch recombination (CSR) in activated B cells resulting in exchanging the IgH C region and improved Ab effector function. During CSR, AID instigates DNA double-strand break (DSB) formation in switch (S) regions located upstream of C region genes. DSBs are necessary for CSR, but improper regulation of DSBs can lead to chromosomal translocations that can result in B cell lymphoma. The protein kinase ataxia telangiectasia mutated (ATM) is an important proximal regulator of the DNA damage response (DDR), and translocations involving S regions are increased in its absence. ATM phosphorylates H2AX, which recruits other DNA damage response (DDR) proteins, including mediator of DNA damage checkpoint 1 (Mdc1) and p53 binding protein 1 (53BP1), to sites of DNA damage. As these DDR proteins all function to promote repair and recombination of DSBs during CSR, we examined whether mouse splenic B cells deficient in these proteins would show alterations in S region DSBs when undergoing CSR. We find that in atm(-/-) cells Smu DSBs are increased, whereas DSBs in downstream Sgamma regions are decreased. We also find that mutations in the unrearranged Sgamma3 segment are reduced in atm(-/-) cells. Our data suggest that ATM increases AID targeting and activity at downstream acceptor S regions during CSR and that in atm(-/-) cells Smu DSBs accumulate as they lack a recombination partner.

The CAM-S: development and validation of a new scoring system for delirium severity in 2 cohorts

Mon, 08/24/2015 - 3:24pm

BACKGROUND: Quantifying the severity of delirium is essential to advancing clinical care by improved understanding of delirium effect, prognosis, pathophysiology, and response to treatment.

OBJECTIVE: To develop and validate a new delirium severity measure (CAM-S) based on the Confusion Assessment Method.

DESIGN: Validation analysis in 2 independent cohorts.

SETTING: Three academic medical centers.

PATIENTS: The first cohort included 300 patients aged 70 years or older scheduled for major surgery. The second included 919 medical patients aged 70 years or older.

MEASUREMENTS: A 4-item short form and a 10-item long form were developed. Association of the maximum CAM-S score during hospitalization with hospital and posthospital outcomes related to delirium was evaluated.

RESULTS: Representative results included adjusted mean length of stay, which increased across levels of short-form severity from 6.5 days (95% CI, 6.2 to 6.9 days) to 12.7 days (CI, 11.2 to 14.3 days) (P for trend and < 0.001) and across levels of long-form severity from 5.6 days (CI, 5.1 to 6.1 days) to 11.9 days (CI, 10.8 to 12.9 days) (P for trend andlt; 0.001). Representative results for the composite outcome of adjusted relative risk of death or nursing home residence at 90 days increased progressively across levels of short-form severity from 1.0 (referent) to 2.5 (CI, 1.9 to 3.3) (P for trend andlt; 0.001) and across levels of long-form severity from 1.0 (referent) to 2.5 (CI, 1.6 to 3.7) (P for trend and < 0.001).

LIMITATION: Data on clinical outcomes were measured in an older data set limited to patients aged 70 years or older.

CONCLUSION: The CAM-S provides a new delirium severity measure with strong psychometric properties and strong associations with important clinical outcomes.

PRIMARY FUNDING SOURCE: National Institute on Aging.

Preventive behaviors and knowledge of tick-borne illnesses: results of a survey from an endemic area

Mon, 08/24/2015 - 3:24pm

CONTEXT: Lyme disease (LD) is the most commonly reported vector-borne illness in the United States. With physically and economically burdensome effects, it is a concern of public health officials.

OBJECTIVES: To assess knowledge and preventive behaviors of individuals in the endemic area of Martha's Vineyard, Massachusetts, to better understand how sociodemographic data and knowledge correlate with preventive behaviors, and to update previous island studies.

DESIGN: A 30-item paper-based anonymous survey in either English or Portuguese based on language preference.

SETTING: The island of Martha's Vineyard and the ferry between island and mainland.

PARTICIPANTS: A total of 946 participants were recruited at 1 of 4 island locations. The majority of participants were traveling by ferry to and from Martha's Vineyard. To reach 2 populations potentially at high risk, that is, youths and outdoor workers, 3 additional venues included the island high school, an English-as-a-Second-Language class, and a local Brazilian church.

OUTCOME MEASURES: Four specific preventive behaviors as well as an overall composite prevention score.

RESULTS: Participants' knowledge of tick-borne illnesses was poor, and the frequency of practicing preventive behaviors was low; the most commonly reported behavior was checking one's skin for ticks (45%). Approximately one-third of respondents (37%) stated that they did not know the late symptoms of untreated LD, nor did they know early LD treatment options (49%). The 2 high-risk groups reported little participation in preventive measures. In multivariate analyses, only 4 characteristics-older age, confidence in telling deer tick from wood tick, seeing tick-borne illness as a serious threat, and certainty in ability to identify LD symptoms-attained significance associated with preventive behavior as an overall composite score.

CONCLUSIONS: Public health interventions focusing on accurately communicating risk, improving knowledge both of LD symptoms and of ticks that carry the disease, as well as teaching preventive behaviors may help reduce tick-borne illness rates.

Stratifying the risks of oral anticoagulation in patients with liver disease

Mon, 08/24/2015 - 3:24pm

BACKGROUND: Chronic liver disease presents a relative contraindication to warfarin therapy, but some patients with liver disease nevertheless require long-term anticoagulation. The goal is to identify which patients with liver disease might safely receive warfarin.

METHODS AND RESULTS: Among 102 134 patients who received warfarin from the Veterans Affairs from 2007 to 2008, International Classification of Diseases-Ninth Revision codes identified 1763 patients with chronic liver disease. Specific diagnoses and laboratory values (albumin, aspartate aminotransferase, alanine aminotransferase, creatinine, and cholesterol) were examined to identify risk of adverse outcomes, while controlling for available bleeding risk factors. Outcomes included percent time in therapeutic range, a measure of anticoagulation control, and major hemorrhagic events, by International Classification of Diseases-Ninth Revision codes. Patients with liver disease had lower mean time in therapeutic range (53.5%) when compared with patients without (61.7%; P < 0.001) and more hemorrhages (hazard ratio, 2.02; P < 0.001). Among patients with liver disease, serum albumin and creatinine levels were the strongest predictors of both outcomes. We created a 4-point score system: patients received 1 point each for albumin (2.5-3.49 g/dL) or creatinine (1.01-1.99 mg/dL), and 2 points each for albumin ( < 2.5 g/dL) or creatinine ( > /=2 mg/dL). This score predicted both anticoagulation control and hemorrhage. When compared with patients without liver disease, those with a score of zero had modestly lower time in therapeutic range (56.7%) and no increase in hemorrhages (hazard ratio, 1.16; P=0.59), whereas those with the worst score (4) had poor control (29.4%) and high hazard of hemorrhage (hazard ratio, 8.53; P < 0.001).

CONCLUSIONS: Patients with liver disease receiving warfarin have poorer anticoagulation control and more hemorrhages. A simple 4-point scoring system using albumin and creatinine identifies those at risk for poor outcomes.

Cigarette smoking and gestational diabetes mellitus in Hispanic woman

Mon, 08/24/2015 - 3:24pm

AIMS: Hispanic women are at increased risk of gestational diabetes mellitus (GDM) as compared to non-Hispanic white women. While smoking has been associated with increased risk of type 2 diabetes, studies of smoking and GDM are sparse and conflicting. Therefore, we evaluated the relationship between cigarette smoking and GDM in Hispanic women.

METHODS: We conducted a pooled analysis of two Hispanic datasets based in Massachusetts: the UMass Medical Health Care dataset and the Proyecto Buena Salud dataset. A total of 3029 Hispanic prenatal care patients with singleton gestations were included. Cigarette smoking prior to and during pregnancy was collected via self-report. Diagnosis of GDM was abstracted from medical records and confirmed by study obstetricians.

RESULTS: One-fifth of participants (20.4%) reported smoking prior to pregnancy, and 11.0% reported smoking in pregnancy. A total of 143 women (4.7%) were diagnosed with GDM. We did not observe an association between pre-pregnancy cigarette smoking and odds of GDM (multivariable OR=0.77, 95% CI 0.47, 1.25). In contrast, smoking during pregnancy was associated with a 54% reduction in odds of GDM (OR=0.46, 95% CI 0.22, 0.95). However, this association was no longer statistically significant after adjustment for age, parity, and study site (OR=0.47, 95% CI 0.23, 1.00).

CONCLUSIONS: In this population of Hispanic pregnant women, we did not observe statistically significant associations between pre-pregnancy smoking and odds of GDM. A reduction in odds of GDM among those who smoked during pregnancy was no longer apparent after adjustment for important diabetes risk factors.

Linkage of a de-identified United States rheumatoid arthritis registry with administrative data to facilitate comparative effectiveness research

Mon, 08/24/2015 - 3:24pm

OBJECTIVE: Linkages between registries and administrative data may provide a valuable resource for comparative effectiveness research. However, personal identifiers that uniquely identify individuals are not always available. Here we describe methods to link a de-identified arthritis registry and US Medicare data. The linked data set was also used to evaluate the generalizability of the registry to the US Medicare population.

METHODS: Rheumatoid arthritis (RA) patients participating in the Consortium of Rheumatology Researchers of North America (CORRONA) registry were linked to Medicare data restricted to rheumatology claims or claims for RA. Deterministic linkage was performed using age, sex, provider identification number, and geographic location of the CORRONA site. We then searched for visit dates in Medicare matching visit dates in CORRONA, requiring > /=1 exact matching date. Linkage accuracy was quantified as a positive predictive value in a subcohort (n = 1,581) with more precise identifiers.

RESULTS: CORRONA participants with self-reported Medicare (n = 11,001) were initially matched to 30,943 Medicare beneficiaries treated by CORRONA physicians. A total of 8,431 CORRONA participants matched on > /=1 visit; 5,317 matched uniquely on all visits. The number of patients who linked and linkage accuracy (from the subcohort) were high for patients with > 2 visits (n = 3,458, 98% accuracy), exactly 2 visits (n = 822, 96% accuracy), and 1 visit (n = 1,037, 79% accuracy) that matched exactly on calendar date. Demographics and comorbidity profiles of registry participants were similar to nonparticipants, except participants were more likely to take disease-modifying antirheumatic drugs and biologic agents.

CONCLUSION: Linkage between a national, de-identified outpatient arthritis registry and Medicare data on multiple nonunique identifiers appears feasible and valid.

A group-randomized trial of shared decision making for non-steroidal anti-inflammatory drug risk awareness: primary results and lessons learned

Mon, 08/24/2015 - 3:24pm

RATIONALE, AIMS AND OBJECTIVES: Frequent use and serious adverse effects related to non-steroidal anti-inflammatory drugs (NSAIDs) underscore the need to raise patient awareness about potential risks. Partial success of patient- or provider-based interventions has recently led to interest in combined approaches focusing on both patient and physician. This research tested a shared decision-making intervention for increasing patient-reported awareness of NSAID risk.

METHODS: A group randomized trial was performed in Alabama from 2005 to 2007. Intervention group doctor practices received continuing medical education (CME) about NSAIDs and patient activation tools promoting risk assessment and communication during visits. Comparison group doctor practices received only CME. Cross-sectional data were collected before and after the intervention. Generalized linear latent and mixed models with logistic link tested relationships among the intervention, study phase, intervention by study phase interaction and patient-reported awareness of risks with either prescription or over-the-counter (OTC) NSAIDs.

RESULTS: Three hundred and forty-seven patients at baseline and 355 patients at follow-up participated in this study. The intervention [adjusted odds ratio (AOR)=0.74, P=0.248], follow-up study phase (AOR=1.31, P=0.300) and intervention by study phase interaction (AOR=0.98, P=0.942) were not significantly associated with patient-reported awareness of any prescription NSAID risk. Follow-up study phase was associated with increased odds of reporting any OTC NSAID risk awareness (AOR=2.99, P < 0.001), but the patient activation intervention and intervention by study phase interaction were not significantly associated with patient-reported awareness of any OTC NSAID risk (AOR=0.98, P=0.929; AOR=0.87, P=0.693, respectively).

CONCLUSIONS: Our point-of-care intervention encouraging shared decision making did not increase NSAID risk awareness.

Differential expression of APE1 and APE2 in germinal centers promotes error-prone repair and A:T mutations during somatic hypermutation

Mon, 08/24/2015 - 3:24pm

Somatic hypermutation (SHM) of antibody variable region genes is initiated in germinal center B cells during an immune response by activation-induced cytidine deaminase (AID), which converts cytosines to uracils. During accurate repair in nonmutating cells, uracil is excised by uracil DNA glycosylase (UNG), leaving abasic sites that are incised by AP endonuclease (APE) to create single-strand breaks, and the correct nucleotide is reinserted by DNA polymerase beta. During SHM, for unknown reasons, repair is error prone. There are two APE homologs in mammals and, surprisingly, APE1, in contrast to its high expression in both resting and in vitro-activated splenic B cells, is expressed at very low levels in mouse germinal center B cells where SHM occurs, and APE1 haploinsufficiency has very little effect on SHM. In contrast, the less efficient homolog, APE2, is highly expressed and contributes not only to the frequency of mutations, but also to the generation of mutations at A:T base pair (bp), insertions, and deletions. In the absence of both UNG and APE2, mutations at A:T bp are dramatically reduced. Single-strand breaks generated by APE2 could provide entry points for exonuclease recruited by the mismatch repair proteins Msh2-Msh6, and the known association of APE2 with proliferating cell nuclear antigen could recruit translesion polymerases to create mutations at AID-induced lesions and also at A:T bp. Our data provide new insight into error-prone repair of AID-induced lesions, which we propose is facilitated by down-regulation of APE1 and up-regulation of APE2 expression in germinal center B cells.

Tweeting it off: characteristics of adults who tweet about a weight loss attempt

Mon, 08/24/2015 - 3:24pm

OBJECTIVE: The purpose of this study was to describe adults who use Twitter during a weight loss attempt and to compare the positive and negative social influences they experience from their offline friends, online friends, and family members.

MATERIALS AND METHODS: Participants (N=100, 80% female, mean age=37.65, SD=8.42) were recruited from Twitter. They completed a brief survey about their experiences discussing their weight loss attempt with their online and offline friends and provided responses to open-ended questions on the benefits and drawbacks of discussing weight on Twitter, Facebook, and weight-specific social networks.

RESULTS: Participants rated their connections on Twitter and weight loss-specific social networks to be significantly greater sources of positive social influence for their weight loss (F(3)=3.47; p < 0.001) and significantly lesser sources of negative social influence (F(3)=40.39 and F(3)=33.68 (both p < 0.001)) than their offline friends, family, and Facebook friends. Greater positive social influence from Twitter and Facebook friends was associated with greater weight loss in participants' most recent weight loss attempt (r=0.30, r=0.32; p < 0.01). The most commonly reported benefits of tweeting about weight loss include social support, information, and accountability. The most common drawbacks reported are that interactions were too brief and lacked personal connection.

DISCUSSION: People who discuss their weight loss on Twitter report more social support and less negativity from their Twitter friends than their Facebook friends and in-person relationships.

CONCLUSIONS: Online social networks should be explored as a tool for connecting patients who lack weight loss social support from their in-person relationships.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

An integrated approach in a case of facioscapulohumeral dystrophy

Mon, 08/24/2015 - 10:45am

BACKGROUND: Muscle fatigue, weakness and atrophy are basilar clinical features that accompany facioscapulohumeral dystrophy (FSHD) the third most common muscular dystrophy.No therapy is available for FSHD.

CASE PRESENTATION: We describe the effects of 6mo exercise therapy and nutritional supplementation in a 43-year-old woman severely affected by FSHD.

CONCLUSION: A mixed exercise program combined with nutritional supplementation can be safely used with beneficial effects in selected patients with FSHD.

PLAAC: a web and command-line application to identify proteins with prion-like amino acid composition

Mon, 08/24/2015 - 10:45am

Prions are self-templating protein aggregates that stably perpetuate distinct biological states and are of keen interest to researchers in both evolutionary and biomedical science. The best understood prions are from yeast and have a prion-forming domain with strongly biased amino acid composition, most notably enriched for Q or N. PLAAC is a web application that scans protein sequences for domains with P: rion- L: ike A: mino A: cid C: omposition. Users can upload sequence files, or paste sequences directly into a textbox. PLAAC ranks the input sequences by several summary scores and allows scores along sequences to be visualized. Text output files can be downloaded for further analyses, and visualizations saved in PDF and PNG formats.

AVAILABILITY AND IMPLEMENTATION: The Ruby-based web framework and the command-line software (implemented in Java, with visualization routines in R) are available at under the MIT license. All software can be run under OS X, Windows and Unix.

Gene therapy for the nervous system: challenges and new strategies

Mon, 08/24/2015 - 10:45am

Current clinical treatments for central nervous system (CNS) diseases, such as Parkinson's disease and glioblastoma do not halt disease progression and have significant treatment morbidities. Gene therapy has the potential to "permanently" correct disease by bringing in a normal gene to correct a mutant gene deficiency, knocking down mRNA of mutant alleles, and inducing cell-death in cancer cells using transgenes encoding apoptosis-inducing proteins. Promising results in clinical trials of eye disease (Leber's congenital aumorosis) and Parkinson's disease have shown that gene-based neurotherapeutics have great potential. The recent development of genome editing technology, such as zinc finger nucleases, TALENS, and CRISPR, has made the ultimate goal of gene correction a step closer. This review summarizes the challenges faced by gene-based neurotherapeutics and the current and recent strategies designed to overcome these barriers. We have chosen the following challenges to focus on in this review: (1) delivery vehicles (both virus and nonviral), (2) use of promoters for vector-mediated gene expression in CNS, and (3) delivery across the blood-brain barrier. The final section (4) focuses on promising pre-clinical/clinical studies of neurotherapeutics.