Gelation by histidine-derived ureas

A series of l-histidine-derived monoureas are described which exhibit versatile organogelation peroperties when the substituent directly attached to the urea is an aliphatic group. Arylureas exhibit a tendency to bind chloride anion

A revised edition of the readiness to change questionnaire (treatment version)

The UK Alcohol Treatment Trial provided an opportunity to examine the factor structure of the Readiness to Change Questionnaire-Treatment Version (RCQ[TV]) in a large sample (N = 742) of individuals in treatment for alcohol problems who were given the RCQ[TV] at baseline, 3-months and 12-months follow-up. Confirmatory factor analysis of the previously reported factor structure (5 items for each of Precontemplation, Contemplation and Action scales) resulted in a relatively poor fit to the data. Removal of one item from each of the scales resulted in a 12-item instrument for which goodness-of-fit indices were improved, without loss of internal consistency of the three scales, on all three measurement occasions. Inspection of relationships between stage allocation by the new instrument and negative alcohol outcome expectancies provided evidence of improved construct validity for the revised edition of the RCQ[TV]. There was also a strong relationship between stage allocation at 3-months follow-up and outcome of treatment at 12 months. The revised edition of the RCQ[TV] offers researchers and clinicians a shorter and improved measurement of stage of change in the alcohol treatment population

Disparities in routine breast cancer screening for medicaid managed care members with a work-limiting disability

Objective: Examine disparities in routine mammography for women who qualify for Medicaid, because of a work-limiting disability. Methods: Individual-level data were obtained for women enrolled in Massachusetts Medicaid Managed Care plans who met the 2007 Healthcare Effectiveness Data and Information Set (HEDIS) criteria for the breast cancer screening measure (n=35,171). Disability status was determined from Medicaid eligibility records. Mammography screening was modeled using multivariate logistic regression. Separate models for women with and without a disability were also estimated. Results: Although unadjusted breast cancer screening rates were roughly equal for women with and without disability, after adjusting for confounders disability status had a significant negative association with screening mammography (OR=0.74; p Conclusion: Nationwide, rates of routine mammography for Medicaid managed care plans averaged below 50% in 2006. Given that a majority of eligible women served by Medicaid have disabilities, and studies have shown that women with disabilities are more likely to be diagnosed with late stage disease, a focus on improving rates of screening for women with disabilities is overdue

The role of DNA methylation in directing the functional organization of the cancer epigenome

The holistic role of DNA methylation in the organization of the cancer epigenome is not well understood. Here we perform a comprehensive, high-resolution analysis of chromatin structure to compare the landscapes of HCT116 colon cancer cells and a DNA methylation-deficient derivative. The NOMe-seq accessibility assay unexpectedly revealed symmetrical and transcription-independent nucleosomal phasing across active, poised, and inactive genomic elements. DNA methylation abolished this phasing primarily at enhancers and CpG island (CGI) promoters, with little effect on insulators and non-CGI promoters. Abolishment of DNA methylation led to the context-specific reestablishment of the poised and active states of normal colon cells, which were marked in methylation-deficient cells by distinct H3K27 modifications and the presence of either well-phased nucleosomes or nucleosome-depleted regions, respectively. At higher-order genomic scales, we found that long, H3K9me3-marked domains had lower accessibility, consistent with a more compact chromatin structure. Taken together, our results demonstrate the nuanced and context-dependent role of DNA methylation in the functional, multiscale organization of cancer epigenomes.Charles Heidelberger Memorial Fellowshi

Safety and physiological effects of two different doses of elosulfase alfa in patients with morquio a syndrome: A randomized, double-blind, pilot study.

The primary treatment outcomes of a phase 2, randomized, double-blind, pilot study evaluating safety, physiological, and pharmacological effects of elosulfase alfa in patients with Morquio A syndrome are herewith presented. Patients aged ≥7 years and able to walk ≥200 m in the 6-min walk test (6MWT) were randomized to elosulfase alfa 2.0 or 4.0 mg/kg/week for 27 weeks. The primary objective was to evaluate the safety of both doses. Secondary objectives were to evaluate effects on endurance (6MWT and 3-min stair climb test [3MSCT]), exercise capacity (cardio-pulmonary exercise test [CPET]), respiratory function, muscle strength, cardiac function, pain, and urine keratan sulfate (uKS) levels, and to determine pharmacokinetic parameters. Twenty-five patients were enrolled (15 randomized to 2.0 mg/kg/week and 10 to 4.0 mg/kg/week). No new or unexpected safety signals were observed. After 24 weeks, there were no improvements versus baseline in the 6MWT, yet numerical improvements were seen in the 3MSCT with 4.0 mg/kg/week. uKS and pharmacokinetic data suggested no linear relationship over the 2.0-4.0 mg/kg dose range. Overall, an abnormal exercise capacity (evaluated in 10 and 5 patients in the 2.0 and 4.0 mg/kg/week groups, respectively), impaired muscle strength, and considerable pain were observed at baseline, and there were trends towards improvements in all domains after treatment. In conclusion, preliminary data of this small study in a Morquio A population with relatively good endurance confirmed the acceptable safety profile of elosulfase alfa and showed a trend of increased exercise capacity and muscle strength and decreased pain

Designer Receptors Enhance Memory in a Mouse Model of Down Syndrome

Designer receptors exclusively activated by designer drugs (DREADDs) are novel and powerful tools to investigate discrete neuronal populations in the brain. We have used DREADDs to stimulate degenerating neurons in a Down syndrome (DS) model, Ts65Dn mice. Individuals with DS develop Alzheimer\u27s disease (AD) neuropathology and have elevated risk for dementia starting in their 30s and 40s. Individuals with DS often exhibit working memory deficits coupled with degeneration of the locus coeruleus (LC) norepinephrine (NE) neurons. It is thought that LC degeneration precedes other AD-related neuronal loss, and LC noradrenergic integrity is important for executive function, working memory, and attention. Previous studies have shown that LC-enhancing drugs can slow the progression of AD pathology, including amyloid aggregation, oxidative stress, and inflammation. We have shown that LC degeneration in Ts65Dn mice leads to exaggerated memory loss and neuronal degeneration. We used a DREADD, hM3Dq, administered via adeno-associated virus into the LC under a synthetic promoter, PRSx8, to selectively stimulate LC neurons by exogenous administration of the inert DREADD ligand clozapine-N-oxide. DREADD stimulation of LC-NE enhanced performance in a novel object recognition task and reduced hyperactivity in Ts65Dn mice, without significant behavioral effects in controls. To confirm that the noradrenergic transmitter system was responsible for the enhanced memory function, the NE prodrug l-threo-dihydroxyphenylserine was administered in Ts65Dn and normosomic littermate control mice, and produced similar behavioral results. Thus, NE stimulation may prevent memory loss in Ts65Dn mice, and may hold promise for treatment in individuals with DS and dementia

Households’ aspirations for rural development through agriculture

In sub-Saharan Africa, rural households are the focus of many development efforts and the transformation of smallholder agriculture is one entry point for this process. Understanding farming households’ technology choices remains one of the most critical aspects of agricultural research in rural areas. However, many technologies that are known to be effective and potentially highly beneficial have remained widely unused. One reason is that predicting farmers’ decisions concerning agricultural technologies using conventional economic theories is flawed. In this article, we suggest that human aspirations have a much greater influence on technology choices than hitherto believed. We further argue that a better understanding of aspirations will improve the targeting of technology development by researchers. We propose distributed ethnography to empirically test the influence of human aspirations on technology choice. From such insight, we anticipate better research priority setting as well as more effective rural development strategies in general