Improved Sensitivity for Molecular Detection of Bacterial and Candida Infections in Blood

The rapid identification of bacteria and fungi directly from the blood of patients with suspected bloodstream infections aids in diagnosis and guides treatment decisions. The development of an automated, rapid, and sensitive molecular technology capable of detecting the diverse agents of such infections at low titers has been challenging, due in part to the high background of genomic DNA in blood. PCR followed by electrospray ionization mass spectrometry (PCR/ESI-MS) allows for the rapid and accurate identification of microorganisms but with a sensitivity of about 50% compared to that of culture when using 1-ml whole-blood specimens. Here, we describe a new integrated specimen preparation technology that substantially improves the sensitivity of PCR/ESI-MS analysis. An efficient lysis method and automated DNA purification system were designed for processing 5 ml of whole blood. In addition, PCR amplification formulations were optimized to tolerate high levels of human DNA. An analysis of 331 specimens collected from patients with suspected bloodstream infections resulted in 35 PCR/ESI-MS-positive specimens (10.6%) compared to 18 positive by culture (5.4%). PCR/ESI-MS was 83% sensitive and 94% specific compared to culture. Replicate PCR/ESI-MS testing from a second aliquot of the PCR/ESI-MS-positive/culture-negative specimens corroborated the initial findings in most cases, resulting in increased sensitivity (91%) and specificity (99%) when confirmed detections were considered true positives. The integrated solution described here has the potential to provide rapid detection and identification of organisms responsible for bloodstream infections.     

RANK expression on breast cancer cells promotes skeletal metastasis

RANK ligand (RANKL), acting through its cognate receptor RANK, is a key factor for bone remodeling and metastasis by regulating the differentiation, survival and activation of osteoclasts. RANKL is also crucial for the development of mouse mammary glands during pregnancy and has been recently linked to the etiology of breast cancer via its direct activity on RANK-expressing normal or transformed breast epithelial cells, leading to increased mitogenesis, enhanced regenerative potential of mammary stem cells, and increased invasion and migration. We demonstrate that higher RANK expression in MDA-MB-231 breast cancer cells (MDA-231-RANK cells) is sufficient to confer a significantly greater metastatic growth rate in the bone compared with MDA-MB-231 cells which do not express high levels of RANK. Blockade of osteoclastic bone resorption, achieved with treatment by either RANKL inhibition or zoledronic acid, did reduce skeletal tumor progression of MDA-231-RANK cells suggesting that the vicious cycle contributes to metastatic growth. However, RANKL inhibition reduced skeletal growth of MDA-231-RANK tumors to a significantly greater extent than zoledronic acid, indicating that skeletal growth of RANK-positive tumors is also driven by direct RANKL effects. RANKL stimulated the expression of multiple genes associated with cell invasive behavior, including several matrix metalloproteinases and other genes previously defined as part of a bone metastasis gene signature. These data indicate that RANKL provokes breast cancer bone metastases via two distinct, but potentially overlapping mechanisms: stimulation of tumor-associated osteoclastogenesis and stimulation of RANK-expressing tumor cells.     

The Behavioral Intervention Technology Model: An Integrated Conceptual and Technological Framework for eHealth and mHealth Interventions

A growing number of investigators have commented on the lack of models to inform the design of behavioral intervention technologies (BITs). BITs, which include a subset of mHealth and eHealth interventions, employ a broad range of technologies, such as mobile phones, the Web, and sensors, to support users in changing behaviors and cognitions related to health, mental health, and wellness. We propose a model that conceptually defines BITs, from the clinical aim to the technological delivery framework. The BIT model defines both the conceptual and technological architecture of a BIT. Conceptually, a BIT model should answer the questions why, what, how (conceptual and technical), and when. While BITs generally have a larger treatment goal, such goals generally consist of smaller intervention aims (the "why") such as promotion or reduction of specific behaviors, and behavior change strategies (the conceptual "how"), such as education, goal setting, and monitoring. Behavior change strategies are instantiated with specific intervention components or “elements” (the "what"). The characteristics of intervention elements may be further defined or modified (the technical "how") to meet the needs, capabilities, and preferences of a user. Finally, many BITs require specification of a workflow that defines when an intervention component will be delivered. The BIT model includes a technological framework (BIT-Tech) that can integrate and implement the intervention elements, characteristics, and workflow to deliver the entire BIT to users over time. This implementation may be either predefined or include adaptive systems that can tailor the intervention based on data from the user and the user’s environment. The BIT model provides a step towards formalizing the translation of developer aims into intervention components, larger treatments, and methods of delivery in a manner that supports research and communication between investigators on how to design, develop, and deploy BITs.     

Minorities Remain Underrepresented in HIV/AIDS Research Despite Access to Clinical Trials

Background and Objective: The reasons for minority underrepresentation in HIV/AIDS clinical trials remain unclear. We aimed to evaluate the knowledge, experience, and factors that influence minority participation in HIV/AIDS studies in the United States. Methods: An anonymous, bilingual, self-administered survey on study participation was given to HIV-infected adults attending AIDS Clinical Trials Group–affiliated clinics in the United States and Puerto Rico. Chi-square tests were used to evaluate differences by race, first language, and level of education. Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) for factors associated with being talked to about participation in a study. Results: We analyzed 2,175 complete surveys (221 in Spanish). Among respondents, 31% were White, 40% were Black/African American (AA), and 21% were Hispanic. The overall rate of previous participation in any HIV/AIDS study was 48%. Hispanics were less likely to know about studies compared to Whites and AAs (67% vs 74% and 76%, respectively; P .001). Compared to Whites, AAs and Hispanics were less likely to have been talked to about participating in a study (76% vs 67% and 67%, respectively; P .001). The OR for being talked to about participating in a study was 0.65 (95% CI, 0.52–0.81) for AAs and 0.65 (95% CI, 0.49–0.85) for Hispanics, compared to Whites. AAs and Hispanics were more likely to state that studies were not friendly to their race (17% and 10% vs 4%; P .001). Conclusions: Minorities continue to face barriers for HIV/AIDS trial participation, even when clinical research is available. Enrollment strategies should better target minorities to improve recruitment in HIV/AIDS research.     

Caloric beverage drinking patterns are differentially associated with diet quality and adiposity among Spanish girls and boys

The present study assesses the impact of beverage consumption pattern on diet quality and anthropometric proxy measures for abdominal adiposity in Spanish adolescents. Data were obtained from a representative national sample of 1,149 Spanish adolescents aged 10–18 years. Height, weight, and waist circumferences were measured. Dietary assessment was performed with a 24-h recall. Beverage patterns were identified by cluster analysis. Adherence to the Mediterranean diet was measured by the KIDMED index. Three beverage clusters were identified for boys—“whole milk” (62.5 %), “low-fat milk” (17.5 %) and “soft drinks” (20.1 %)—and for girls—^“whole milk” (57.8 %), “low-fat milk” (20.8 %) and juice (21.4 %), accounting for 8.3, 9.6, 13.9, 8.6, 11.5 and 12.9 % of total energy intake, respectively. Each unit of increase in the KIDMED index was associated with a 14.0 % higher (p?=?0.004) and 11.0 % lower (p?=?0.048) probability of membership in the “low-fat milk” and “soft drinks” cluster in girls and boys, respectively, compared with the “whole milk” cluster. Boys in the “soft drinks” cluster had a higher risk of 1-unit increase in BMI z score (29.0 %, p?=?0.040), 1-cm increase in waist circumference regressed on height and age (3.0 %, p?=?0.027) and 0.1-unit increase in waist/height ratio (21.4 %, p?=?0.031) compared with the “whole milk” cluster. Conclusion: A caloric beverage pattern dominated by intake of “soft drinks” is related to general and abdominal adiposity and diet quality in Spanish male adolescents.     

Pediatric neuroimaging using magnetic resonance imaging during non-sedated sleep

Background

Etiological studies of many neurological and psychiatric disorders are increasingly turning toward longitudinal investigations of infant brain development in order to discern predisposing structural and/or functional differences prior to the onset of overt clinical symptoms. While MRI provides a noninvasive window into the developing brain, MRI of infants and toddlers is challenging due to the modality’s extreme motion sensitivity and children’s difficulty in remaining still during image acquisition.

Objective

Here, we outline a broad research protocol for successful MRI of children under 4 years of age during natural, non-sedated sleep.

Materials and methods

All children were imaged during natural, non-sedated sleep. Active and passive measures to reduce acoustic noise were implemented to reduce the likelihood of the children waking up during acquisition. Foam cushions and vacuum immobilizers were used to limit intra-scan motion artifacts.

Results

More than 380 MRI datasets have been successfully acquired from 220 children younger than 4 years of age within the past 39 months. Implemented measures permitted children to remain asleep for the duration of the scan and allowed the data to be acquired with an overall 97% success rate.

Conclusion

The proposed method greatly advances current pediatric imaging techniques and may be readily implemented in other research and clinical settings to facilitate and further improve pediatric neuroimaging.