Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals.

We propose a framework for modeling sequence motifs based on the maximum entropy principle (MEP). We recommend approximating short sequence motif distributions with the maximum entropy distribution (MED) consistent with low-order marginal constraints estimated from available data, which may include dependencies between nonadjacent as well as adjacent positions. Many maximum entropy models (MEMs) are specified by simply changing the set of constraints. Such models can be utilized to discriminate between signals and decoys. Classification performance using different MEMs gives insight into the relative importance of dependencies between different positions. We apply our framework to large datasets of RNA splicing signals. Our best models out-perform previous probabilistic models in the discrimination of human 5' (donor) and 3' (acceptor) splice sites from decoys. Finally, we discuss mechanistically motivated ways of comparing models.     

Pigment changes in human skin after cryotherapy

We have investigated the changes in pigmentation and melanocyte distribution in human skin after a standardized freeze injury. All lesions developed hypopigmentation with a peripheral rim of hyperpigmentation. Abnormalities in pigmentation persisted for at least 6 months. Hyperpigmentation was predominantly an epidermal phenomenon. After brief freezes, hypopigmentation persisted despite the presence of functional melanocytes. After prolonged freezes, the consistent finding was an absence of melanosomes in keratinocytes, although melanocytes were present. We conclude that prolonged changes in skin color are frequent after brief freezes and that hypopigmentation is not synonymous with an absence of melanocytes. This suggests that hypopigmentation after the cryosurgical treatment of malignant melanocytic tumors may not equate with cure.     

Cytokeratin provides a specific marker for human arachnoid cells grown in vitro

Cells from cranial and spinal arachnoid membranes of humans were grown in culture. Their growth characteristics, morphology and details of their cytoskeletal composition are described. Arachnoid membranes, obtained at autopsy, were finely minced and incubated in tissue culture medium. Monolayers of cells of homogeneous morphology grew from these tissue fragments. The cells were flat and polygonal. They divided slowly to form non-overlapping monolayers of low cell density. Electron microscopic examination of cultured arachnoid cells revealed numerous desmosome-like tight junctions and abundant intermediate filaments (tonofilaments). Both morphological features are characteristic of arachnoid cells in situ, but not of cells in the fibroblast-rich dura mater. Immunofluorescence microscopy with monoclonal antibodies demonstrated cytokeratin in the cytoplasm of primary cultures of arachnoid cells. Thus we demonstrated that these cultured cells retained certain of the specific differentiated properties of arachnoid cells in situ and that they are not fibroblasts (which lack tight junctions and cytokeratins). To our knowledge, there have been no previous reports of in vitro growth of arachnoid cells. This in vitro model should be useful in studying the response of arachnoid cells to a variety of substances thought to be involved in the chronic inflammatory condition of the meninges known as arachnoiditis.     

Some comments on the aerobiology of fungus spores

While exposure/symptom relationships are relatively well-defined for pollen allergens, such relationships have not been clearly established for airborne fungus spores due to a lack of clearly defined seasonal patterns, prevalence of world-wide cosmopolitan fungi, and serious problems with sampling and identification. Ascospores and basidiospores have been least studied with respect to aerobiology, although both are clearly allergenic. Preliminary data on allergenicity and diurnal and seasonal prevalence patterns for selected ascospore and basidiospore types are presented.     

Field survey of circadian rhythm in PEF of electronics workers suffering from colophony-induced asthma

Twenty-two British electronics workers suffering from occupationally-induced asthma due to their exposure to colophony fumes self-recorded their peak expiratory flow (PEF) every 1-2 hr throughout the waking span for at least two weeks, both during work and vacation periods. Data were analyzed by a two-step procedure using the statistical techniques of Single and Population Mean Cosinor analyses. The objective endpoints of mesor (24-hr mean), amplitude (measure of 24-hr rhythmic variation) and acrophase (peak time along the scale of 24 hr) for the time-spans of the work-week (Monday-Friday), weekend after work (Saturday-Sunday) and vacation weekdays and vacation weekends were compared. The PEF data of four workers who participated in the study for nearly one year also were evaluated for seasonal variation. A statistically significant difference (P less than 0.04) was detected in the PEF amplitude between work and vacation weeks; the difference in the PEF mesor and acrophase between work-weekdays and work-weekends achieved near or statistical significance (P = 0.07 and 0.05, respectively). The at-work amplitude was higher and the acrophase earlier timed. There was no statistically significant difference between work-week and weekend-after-work PEF mesors. Winter PEF mesors were significantly lower than summer ones in the four subjects self-measuring their bronchial patency over the year. Overall, the findings indicate that data obtained through employee surveys, using lightweight portable and inexpensive PEF Wright meters and analyzed by statistical analyses used in the field of biological rhythm research, yield objective evidence of occupationally associated decrements in pulmonary function resulting from colophony fume exposure.     

A Home-Based Educational Intervention Improves Patient Activation Measures and Diabetes Health Indicators among Zuni Indians

Introduction

One in three people will be diagnosed with diabetes by 2050, and the proportion will likely be higher among Native Americans. Diabetes control is currently suboptimal in underserved populations despite a plethora of new therapies. Patient empowerment is a key determinant of diabetes control, but such empowerment can be difficult to achieve due to resource limitation and cultural, language and health literacy barriers. We describe a home-based educational intervention using Community Health Representatives (CHRs), leading to improvement in Patient Activation Measures scores and clinical indicators of diabetes control.

Methods

Sixty participants with type 2 diabetes (T2D) completed a baseline evaluation including physical exam, Point of Care (POC) testing, and the Patient Activation Measure (PAM) survey. Participants then underwent a one hour group didactic session led by Community Health Representatives (CHRs) who subsequently carried out monthly home-based educational interventions to encourage healthy lifestyles, including diet, exercise, and alcohol and cigarette avoidance until follow up at 6 months, when clinical phenotyping and the PAM survey were repeated.

Results

PAM scores were increased by at least one level in 35 (58%) participants, while 24 participants who started at higher baseline score did not change. Six months after intervention, mean levels of A1C decreased by 0.7 ± 1.2%; fasting blood glucose decreased by 24.0 ± 38.0 mg/dl; BMI decreased by 1.5 ± 2.1 kg/m2; total cholesterol decreased by 12.0± 28.0 mg/dl; and triglycerides decreased by 52.0 ± 71.0 mg/dl. All of these changes were statistically significant (p<0.05).

Conclusion

This six month, CHR led and community-oriented educational intervention helps inform standards of practice for the management of diabetes, engages diabetic populations in their own care, and reduces health disparities for the underserved population of Zuni Indians.

Trial Registration

ClinicalTrials.gov NCT02339311