Reticular Pseudodrusen in Age-Related Macular Degeneration

Historically, drusen, which are recognized as the hallmark of age-related macular degeneration (AMD), have been described in terms of size, margins, and texture, and several studies have emphasized the importance of large soft drusen particularly when combined with focal pigmentary irregularities in determining the risk of progression to neovascular AMD. However, recent developments in imaging over the past decade have revealed a further distinct phenotype strongly associated with the development of late AMD, namely, reticular pseudodrusen (RPD) or reticular drusen. Reticular pseudodrusen appear as yellowish interlacing networks in the fundus and, although visible on color photography, are better visualized using infrared imaging or spectral domain optical coherence tomography. Studies correlating spectral domain optical coherence tomography and confocal scanning laser ophthalmoscopy have shown that RPD are subretinal deposits located internal to the retinal pigment epithelium in contrast to traditional drusen, which are located external to the retinal pigment epithelium. As multiple longitudinal studies have revealed RPD are strong predictors for progression to both neovascular AMD and geographic atrophy, the interest in understanding the role that RPD play in the pathogenesis of AMD has grown. This review focuses on the current literature concerning RPD and considers what is currently known regarding their epidemiology, risk factors, appearance in both retinal imaging and histology, impact on visual function, relationship to other AMD lesions, and association with the development of late AMD.

Women’s Perceptions and Experiences of Fetal Macrosomia

Objective
to explore women's perceptions and experiences of pregnancy and childbirth following birth of a macrosomic infant (birth weight ≥4000 g).

Methods
a qualitative design utilising interviews conducted 13–19 weeks post partum in women's homes. The study was conducted in one Health and Social Care Trust in Northern Ireland between January and September 2010. Participants were identified from a larger cohort of women recruited to a prospective study exploring the impact of physical activity and nutrition on macrosomia. Eleven women who delivered macrosomic infants participated in this phase of the study.

Findings
four overarching themes emerged: preparation for delivery; physical and emotional impact of macrosomia; professional relations and perceptions of macrosomia. Findings highlighted the importance of communication with health professionals in relation to both prediction of macrosomia and decision making about childbirth, and offers further understanding into the physical and emotional impact of having a macrosomic infant on women. Furthermore, there was evidence that beliefs and perceptions relating to macrosomia may influence birth experiences and uptake of health promotion messages.

Key conclusions and implications for practice
this study provides important insight into women's experiences of macrosomia throughout the perinatal period and how they were influenced by previous birth experiences, professional relations and personal perceptions and beliefs about macrosomia. Pregnant women at risk of having a macrosomic infant may require extra support throughout the antenatal period continuing into the postnatal period. Support needs to be tailored to the woman's information needs, with time allocated to explore previous birth experiences, beliefs about macrosomia and options for childbirth.

Creating an eLearning Resource to Improve Knowledge and Understanding of Pregnancy in the Context of HIV Infection

Patient narratives have much to teach healthcare professionals about the experience of living with a chronic condition. While the biomedical narrative of HIV treatment is hugely encouraging, the narrative of living with HIV continues to be overshadowed by a persuasive perception of stigma. This paper presents how we sought to translate the evidence from a qualitative study of the perspectives of HIV affected pregnant women and expectant fathers on the care they received, from the pre conception to post natal period, into educational material for maternity care practice. Narrative scripts were written based on the original research interviews, with care taken to reflect the key themes from the research. We explore the way in which the qualitative findings bring to life patient and partner experiences and what it means for nurses, midwives and doctors to be prepared to care for couples affected by HIV. In so doing, we challenge the inequity between the dominance of biomedical knowledge over understanding the patient experience in the preparation of health professionals to care for HIV affected women and men who are having a baby or seeking to have a baby.

Small RNAs from plants, bacteria and fungi within the order Hypocreales are ubiquitous in human plasma

Background

The human microbiome plays a significant role in maintaining normal physiology. Changes in its composition have been associated with bowel disease, metabolic disorders and atherosclerosis. Sequences of microbial origin have been observed within small RNA sequencing data obtained from blood samples. The aim of this study was to characterise the microbiome from which these sequences are derived.

Abundant non-human small RNA sequences were identified in plasma and plasma exosomal samples. Assembly of these short sequences into longer contigs was the pivotal novel step in ascertaining their origin by BLAST searches. Most reads mapped to rRNA sequences. The taxonomic profiles of the microbes detected were very consistent between individuals but distinct from microbiomes reported at other sites. The majority of bacterial reads were from the phylum Proteobacteria, whilst for 5 of 6 individuals over 90% of the more abundant fungal reads were from the phylum Ascomycota; of these over 90% were from the order Hypocreales. Many contigs were from plants, presumably of dietary origin.  In addition, extremely abundant small RNAs derived from human Y RNAs were detected.

A characteristic profile of a subset of the human microbiome can be obtained by sequencing small RNAs present in the blood. The source and functions of these molecules remain to be determined, but the specific profiles are likely to reflect health status. The potential to provide biomarkers of diet and for the diagnosis and prognosis of human disease is immense.

Repeated measures of body mass index and C-reactive protein in relation to all-cause mortality and cardiovascular disease: Results from the consortium on health and ageing network of cohorts in Europe and the United States (CHANCES)

Obesity has been linked with elevated levels of C-reactive protein (CRP), and both have been associated with increased risk of mortality and cardiovascular disease (CVD). Previous studies have used a single ‘baseline’ measurement and such analyses cannot account for possible changes in these which may lead to a biased estimation of risk. Using four cohorts from CHANCES which had repeated measures in participants 50 years and older, multivariate time-dependent Cox proportional hazards was used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) to examine the relationship between body mass index (BMI) and CRP with all-cause mortality and CVD. Being overweight (≥25–<30 kg/m2) or moderately obese (≥30–<35) tended to be associated with a lower risk of mortality compared to normal (≥18.5–<25): ESTHER, HR (95 % CI) 0.69 (0.58–0.82) and 0.78 (0.63–0.97); Rotterdam, 0.86 (0.79–0.94) and 0.80 (0.72–0.89). A similar relationship was found, but only for overweight in Glostrup, HR (95 % CI) 0.88 (0.76–1.02); and moderately obese in Tromsø, HR (95 % CI) 0.79 (0.62–1.01). Associations were not evident between repeated measures of BMI and CVD. Conversely, increasing CRP concentrations, measured on more than one occasion, were associated with an increasing risk of mortality and CVD. Being overweight or moderately obese is associated with a lower risk of mortality, while CRP, independent of BMI, is positively associated with mortality and CVD risk. If inflammation links CRP and BMI, they may participate in distinct/independent pathways. Accounting for independent changes in risk factors over time may be crucial for unveiling their effects on mortality and disease morbidity.

Positioning Clinical Nurse Specialists and Nurse Practitioners as Change Champions to Implement a Pain Protocol in Long-Term Care

Pain management for older adults in long-term care (LTC) has been recognized as a problem internationally. The purpose of this study was to explore the role of a clinical nurse specialist (CNS) and nurse practitioner (NP) as change champions during the implementation of an evidence-based pain protocol in LTC. In this exploratory, multiple-case design study, we collected data from two LTC homes in Ontario, Canada. Three data sources were used: participant observation of an NP and a CNS for 18 hours each over a 3-week period; CNS and NP diaries recording strategies, barriers, and facilitators to the implementation process; and interviews with members of the interdisciplinary team to explore perceptions about the NP and CNS role in implementing the pain protocol. Data were analyzed using thematic content analysis. The NP and CNS used a variety of effective strategies to promote pain management changes in practice including educational outreach with team members, reminders to nursing staff to highlight the pain protocol and educate about practice changes, chart audits and feedback to the nursing staff, interdisciplinary working group meetings, ad hoc meetings with nursing staff, and resident assessment using advanced skills. The CNS and NP are ideal champions to implement pain management protocols and likely other quality improvement initiatives.

Thermosensitive hydrogels of poly(methyl vinyl ether-co-maleic anhydride) - Pluronic (R) F127 copolymers for controlled protein release

Thermosensitive hydrogels are of a great interest due to their many biomedical and pharmaceutical applications. In this study, we synthesized a new series of random poly (methyl vinyl ether-co-maleic anhydride) (Gantrez (R) AN, GZ) and Pluronic (R) F127 (PF127) copolymers (GZ-PF127), that formed thermosensitive hydrogels whose gelation temperature and mechanical properties could be controlled by the molar ratio of GZ and PF127 polymers and the copolymer concentration in water. Gelation temperatures tended to decrease when the GZm/PF127 ratio increased. Thus, at a fixed GZm/PF127 value, sol-gel temperatures decreased at higher copolymer concentrations. Moreover, these hydrogels controlled the release of proteins such as bovine serum albumin (BSA) and recombinant recombinant kinetoplastid membrane protein of Leishmania (rKMP-11) more than the PF127 system. Toxicity studies carried out in J774.2 macrophages showed that cell viability was higher than 80%. Finally, histopathological analysis revealed that subcutaneous administration of low volumes of these hydrogels elicited a tolerable inflammatory response that could be useful to induce immune responses against the protein cargo in the development of vaccine adjuvants.

A mixed methods study of the work patterns of full-time nurse practitioners in nursing homes

Aims and objectives: The aim of this study was to explore the integration of the nurse practitioner role in Canadian nursing homes to enable its full potential to be realised for resident and family care. The objective was to determine nurse practitioners' patterns of work activities. 

Background: Nurse practitioners were introduced in Canadian nursing homes a decade ago on a pilot basis. In recent years, government and nursing home sector interest in the role has grown along with the need for data to inform planning efforts. 

Design: The study used a sequential mixed methods design using a national survey followed by case studies. 

Methods: A national survey of nurse practitioners included demographic items and the EverCare Nurse Practitioner Role and Activity Scale. Following the survey, case studies were conducted in four nursing homes. Data were collected using individual and focus group interviews, document reviews and field notes. 

Results: Twenty-three of a target population of 26 nurse practitioners responded to the survey, two-thirds of whom provided services in nursing homes with one site and the remainder in nursing homes with as many as four sites. On average, nurse practitioners performed activities in communicator, clinician, care manager/coordinator and coach/educator subscales at least three to four times per week and activities in the collaborator subscale once a week. Of the 43 activities, nurse practitioners performed daily, most were in the clinician and communicator subscales. Case study interviews involved 150 participants. Findings complemented those of the survey and identified additional leadership activities. 

Conclusion: Nurse practitioners undertake a range of primary health care and advanced practice activities which they adapt to meet the unique needs of nursing homes. Relevance to clinical practice: Knowledge of work patterns enables nursing homes to implement the full range of nurse practitioner roles and activities to enhance resident and family care.

Rapid quantification of microRNAs in plasma using a fast real time PCR system

The ability to rapidly detect circulating small RNAs, in particular microRNAs (miRNAs), would further increase their already established potential as biomarkers in a range of conditions. One rate-limiting factor is the time taken to perform quantitative real time PCR amplification. We therefore evaluated the ability of a novel thermal cycler to perform this step in less than 10 minutes. Quantitative PCR was performed on an xxpress® thermal cycler (BJS Biotechnologies, Perivale, UK), which employs a resistive heating system and forced air cooling to achieve thermal ramp rates of 10 °C/s, and a conventional peltier-controlled LightCycler 480 system (Roche, Basel, Switzerland) ramping at 4.8 °C/s. The threshold cycle (Ct) for detection of 18S rDNA from a standard genomic DNA sample was significantly more variable across the block (F-test, p=2.4x10-25) for the xxpress (20.01±0.47SD) than the LightCycler (19.87±0.04SD). RNA was extracted from human plasma, reverse transcribed and a panel of miRNAs amplified and detected using SYBR green (Kapa Biosystems, Wilmington, Ma, USA). The sensitivity of both systems was broadly comparable and both detected a panel of miRNAs reliably and indicated similar relative abundances. The xxpress thermal cycler facilitates rapid qPCR detection of small RNAs and brings point-of care diagnostics based upon circulating miRNAs a step closer to reality.

Concomitant osmotic and chaotropicity-induced stresses in Aspergillus wentii: compatible solutes determine the biotic window

Whereas osmotic stress response induced by solutes has been well-characterized in fungi, less is known about the other activities of environmentally ubiquitous substances. The latest methodologies to define, identify and quantify chaotropicity, i.e. substance-induced destabilization of macromolecular systems, now enable new insights into microbial stress biology (Cray et al. in Curr Opin Biotechnol 33:228–259, 2015a, doi:10.​1016/​j.​copbio.​2015.​02.​010; Ball and Hallsworth in Phys Chem Chem Phys 17:8297–8305, 2015, doi:10.​1039/​C4CP04564E; Cray et al. in Environ Microbiol 15:287–296, 2013a, doi:10.​1111/​1462-2920.​12018). We used Aspergillus wentii, a paradigm for extreme solute-tolerant fungal xerophiles, alongside yeast cell and enzyme models (Saccharomyces cerevisiae and glucose-6-phosphate dehydrogenase) and an agar-gelation assay, to determine growth-rate inhibition, intracellular compatible solutes, cell turgor, inhibition of enzyme activity, substrate water activity, and stressor chaotropicity for 12 chemically diverse solutes. These stressors were found to be: (i) osmotically active (and typically macromolecule-stabilizing kosmotropes), including NaCl and sorbitol; (ii) weakly to moderately chaotropic and non-osmotic, these were ethanol, urea, ethylene glycol; (iii) highly chaotropic and osmotically active, i.e. NH4NO3, MgCl2, guanidine hydrochloride, and CaCl2; or (iv) inhibitory due primarily to low water activity, i.e. glycerol. At ≤0.974 water activity, Aspergillus cultured on osmotically active stressors accumulated low-M r polyols to ≥100 mg g dry weight−1. Lower-M r polyols (i.e. glycerol, erythritol and arabitol) were shown to be more effective for osmotic adjustment; for higher-M r polyols such as mannitol, and the disaccharide trehalose, water-activity values for saturated solutions are too high to be effective; i.e. 0.978 and 0.970 (25 ºC). The highly chaotropic, osmotically active substances exhibited a stressful level of chaotropicity at physiologically relevant concentrations (20.0–85.7 kJ kg−1). We hypothesized that the kosmotropicity of compatible solutes can neutralize chaotropicity, and tested this via in-vitro agar-gelation assays for the model chaotropes urea, NH4NO3, phenol and MgCl2. Of the kosmotropic compatible solutes, the most-effective protectants were trimethylamine oxide and betaine; but proline, dimethyl sulfoxide, sorbitol, and trehalose were also effective, depending on the chaotrope. Glycerol, by contrast (a chaotropic compatible solute used as a negative control) was relatively ineffective. The kosmotropic activity of compatible solutes is discussed as one mechanism by which these substances can mitigate the activities of chaotropic stressors in vivo. Collectively, these data demonstrate that some substances concomitantly induce chaotropicity-mediated and osmotic stresses, and that compatible solutes ultimately define the biotic window for fungal growth and metabolism. The findings have implications for the validity of ecophysiological classifications such as ‘halophile’ and ‘polyextremophile’; potential contamination of life-support systems used for space exploration; and control of mycotoxigenic fungi in the food-supply chain.