Aptamer micelles targeting fractalkine-expressing cancer cells in vitro and in vivo

In this work we hypothesized that the chemokine fractalkine can serve as a cancer molecular target. We engineered aptamer micelles functionalized with an outer poly(ethylene glycol) (PEG) corona, and investigated the extent and efficacy of using them as a targeting tool against fractalkine-expressing colon adenocarcinoma cells. In vitro cell binding results showed that aptamer micelles bound and internalized to fractalkine-expressing cancer cells with the majority of the micelles found free in the cytoplasm. Minimal surface binding was observed by healthy cells. Even though partial PEGylation did not prevent serum adsorption, micelles were highly resistant to endonuclease and exonuclease degradation. In vivo biodistribution studies and confocal studies demonstrated that even though both aptamer and control micelles showed tumor accumulation, only the aptamer micelles internalized into fractalkine-expressing cancer cells, thus demonstrating the potential of the approach and showing that fractalkine may serve as a specific target for nanoparticle delivery to cancer cells.     

Ethnicity,length of residence,and prospective trends in body mass index in a national sample of Australian adults (2006–2014)

Purpose

Increasing global migration, high obesity in developed countries, and ethnic health inequalities are compelling reasons to monitor immigrant obesity trends. Longitudinal studies of ethnicity, length of residence, and adiposity in contexts outside of the United States are lacking.

Associations between history of chronic lung disease and non–small cell lung carcinoma in Maryland: variations by sex and race

Purpose

Lung cancer is a multifactorial malignancy for which some risk factors, such as chronic lung diseases, their interactions with smoking, and how they differ by race and sex, are not fully understood. We investigated the associations between chronic inflammatory lung disease and non–small cell lung carcinoma (NSCLC) and how sex and race may affect such associations.

The free healthcare initiative in Sierra Leone: Evaluating a health system reform, 2010‐2015

This article presents the findings of a theory‐based evaluation of the Sierra Leone Free Health Care Initiative (FHCI), using mixed methods. Analytical approaches included time‐series analysis of national survey data to examine mortality and morbidity trends, as well as modelling of impact using the Lives Saved Tool and expenditure trend analysis. We find that the FHCI responded to a clear need in Sierra Leone, was well designed to bring about needed changes in the health system to deliver services to the target beneficiaries, and did indeed bring funds and momentum to produce important systemic reforms. However, its ambition was also a risk, and weaknesses in implementation have been evident in a number of core areas, such as drugs supply. We conclude that the FHCI was one important factor contributing to improvements in coverage and equity of coverage of essential services for mothers and children. Modelled cost‐effectiveness is high—in the region of US$ 420 to US$ 444 per life year saved. The findings suggest that even—or perhaps especially—in a weak health system, a reform‐like fee removal, if tackled in a systematic way, can bring about important health system gains that benefit vulnerable groups in particular.     

Sensorimotor integration in Complex Regional Pain Syndrome: a transcranial magnetic stimulation study

There is evidence that patients with Complex Regional Pain Syndrome (CRPS) have altered central sensorimotor processing. Sensory input can influence motor output either through indirect pathways or through direct connections from the sensory to motor cortex. The purpose of this study was to investigate sensorimotor interaction via direct connections in patients with CRPS and to compare the results with normal subjects'. Direct short-latency sensory-motor interaction was evaluated in eight patients with CRPS1 affecting a hand. Modulation of EMG responses to transcranial magnetic stimulation (TMS) induced by concomitant median nerve stimulation was measured, the so-called, short-latency afferent inhibition (SAI). Results were compared with eight normal subjects who were age and sex matched with the patients. As expected, all the normal subjects' EMG responses to TMS with median nerve stimulation were smaller than responses to TMS alone. In seven of the eight CRPS patients EMG responses to TMS were suppressed when paired with median nerve stimulation. Only one CRPS patient's results showed no suppression of EMG responses. These results suggest that the disease mechanisms of CRPS1 do not typically affect the direct neural circuit between sensory and motor cortex and that normal sensorimotor interaction is occurring via this route.     

Competencies and skills for remote and rural maternity care: a review of the literature

AIM: This paper reports a review of the literature on skills, competencies and continuing professional development necessary for sustainable remote and rural maternity care. BACKGROUND: There is a general sense that maternity care providers in rural areas need specific skills and competencies. However, how these differ from generic skills and competencies is often unclear. METHODS: Approaches used to access the research studies included a comprehensive search in relevant electronic databases using relevant keywords (e.g. 'remote', 'midwifery', 'obstetrics', 'nurse-midwives', education', 'hospitals', 'skills', 'competencies', etc.). Experts were approached for (un-)published literature, and books and journals known to the authors were also used. Key journals were hand searched and references were followed up. The original search was conducted in 2004 and updated in 2006. FINDINGS: Little published literature exists on professional education, training or continuous professional development in maternity care in remote and rural settings. Although we found a large literature on competency, little was specific to competencies for rural practice or for maternity care. 'Hands-on' skills courses such as Advanced Life Support in Obstetrics and the Neonatal Resuscitation Programme increase confidence in practice, but no published evidence of effectiveness of such courses exists. CONCLUSION: Educators need to be aware of the barriers facing rural practitioners, and there is potential for increasing distant learning facilitated by videoconferencing or Internet access. They should also consider other assessment methods than portfolios. More research is needed on the levels of skills and competencies required for maternity care professionals practising in remote and rural areas.     

An approach to shortening the timeframe between the emergence of new compounds on the drugs market and the availability of reference standards: The microscale syntheses of nitrazolam and clonazolam for use as reference materials,utilizing polymer‐supported reagents

Nitrazolam and clonazolam are 2 designer benzodiazepines available from Internet retailers. There is growing evidence suggesting that such compounds have the potential to cause severe adverse events. Information about tolerability in humans is scarce but typically, low doses can be difficult to administer for users when handling bulk material. Variability of the active ingredient in tablet formulations can also be of a concern. Customs, toxicology and forensic laboratories are increasingly encountering designer benzodiazepines, both in tablet and powdered form. The unavailability of reference standards can impact on the ability to identify these compounds. Therefore, the need arises for exploring in‐house approaches to the preparation of new psychoactive substances (NPS) that can be carried out in a timely manner. The present study was triggered when samples of clonazolam were received in powdered and tablet form at a time when reference material for this drug was commercially unavailable. Therefore, microscale syntheses of clonazolam and its deschloro analog nitrazolam were developed utilizing polymer‐supported reagents starting from 2‐amino‐2'‐chloro‐5‐nitrobenzophenone (clonazolam) and 2‐amino‐5‐nitrobenzophenone (nitrazolam). The final reaction step forming the 1,2,4‐triazole ring moiety was performed within a gas chromatography–mass spectrometry (GC–MS) injector. A comparison with a preparative scale synthesis of both benzodiazepine derivatives showed that microscale synthesis might be an attractive option for a forensic laboratory in terms of time and cost savings when compared with traditional methods of synthesis and when qualitative identifications are needed to direct forensic casework. The reaction by‐product profiles for both the micro and the preparative scale syntheses are also presented.