Dynamics of nurses’ authority in the inpatient care of adolescent consumers with anorexia nervosa: A qualitative study of nursing perspectives

Nurses caring for adolescent consumers with anorexia nervosa in the inpatient setting are challenged in a unique way, in that they are caring for people with whom they do not have a mutually held concept of well‐being. Their efforts to ensure weight gain are frequently against the wishes of the consumer. This dissonance results in challenging interactions, where nursing care and authority may be undermined. This study investigated the dynamics of nurses’ authority within this context. Interviews with nurses (n = 10) were conducted and analysed through thematic analysis. Nurses reported that consumers, compelled by the psychopathology of anorexia nervosa, often sought to challenge or undermine their authority. Some nurses experienced the opposition and conflict as demoralizing, whereas others were able to maintain confidence in the therapeutic merit of their care. Younger, inexperienced nurses in this study were particularly vulnerable to interactions that mitigated their authority, due to their tendency to engage in friend‐like relationships. Nurses caring for adolescents with anorexia nervosa should be prepared to be confronted by interactions that overtly and surreptitiously undermine their capacity to exercise professional authority. It is important that nurses recognize the importance of maintaining their authority, and how it can be threatened in subtle and unexpected ways.     

Molecular analysis of the fragile X syndrome

Summary The molecular analysis of human X-linked disease has progressed rapidly over the last few years owing to advances in power of mapping techniques. Physical DNA maps covering more than 5 million base pairs have been constructed for several chromosomal regions. Many of these regions have now also been cloned into overlapping cosmid and YAC contigs facilitating the search for disease genes. The recent identification of the mutation in the fragile X syndrome is such an example of the power of YAC technology in the characterization of human genetic disease mutations.     

The epidural approach to the Meckel’s cave: a how I do it

Background

Meckel’s cave (MC) is a meningeal cleft lying in the middle fossa laterally to the cavernous sinus. Tumours that develop inside the MC may require a surgical resection. The authors describe the surgical technique of the intracranial epidural approach to the MC.

Methods

Based upon anatomical dissection showing the relevant surgical anatomy, and illustrated by the video of an operated case, the authors detail the surgical procedure. The key point is to shave the floor of the middle fossa and skeletonize the superior orbital fissure, rotundum and ovale foramen in order to delineate the plane of dural elevation and expose the lateral wall of the MC. The rules of exposure and resection of the tumour are then shown. Variations and limitations of the approach are discussed.

Conclusion

Conducted in a stepwise manner and following relevant landmarks, the epidural anterolateral approach offers a safe and reliable exposure to the diseases that develop within the MC.     

[18F]FPyZIDE: A versatile prosthetic reagent for the fluorine‐18 radiolabeling of biologics via copper‐catalyzed or strain‐promoted alkyne‐azide cycloadditions

Methods for the radiolabeling of biologics with fluorine‐18 have been of interest for several decades. A common approach consists in the preparation of a prosthetic reagent, a small molecule bearing a fluorine‐18 that is conjugated with the macromolecule to an appropriate function. Click chemistry, and more particularly cycloadditions, is an interesting approach to radiolabel molecules thanks to mild reaction conditions, high yields, low by‐products formation, and strong orthogonality. Moreover, the chemical functions involved in the cycloaddition reaction are stable in the drastic radiofluorination conditions, thus allowing a simple radiosynthetic route to prepare the prosthetic reagent. We report herein the radiosynthesis of ¹⁸F‐FPyZIDE, a pyridine‐based azide‐bearing prosthetic reagent. We exemplified its conjugation via copper‐catalyzed cycloaddition (CuAAC) and strain‐promoted cycloaddition (SPAAC) with several terminal alkyne or strained alkyne model compounds.     

Engineered nanomedicine for myeloma and bone microenvironment targeting

Bone is a favorable microenvironment for tumor growth and a frequent destination for metastatic cancer cells. Targeting cancers within the bone marrow remains a crucial oncologic challenge due to issues of drug availability and microenvironment-induced resistance. Herein, we engineered bone-homing polymeric nanoparticles (NPs) for spatiotemporally controlled delivery of therapeutics to bone, which diminish off-target effects and increase local drug concentrations. The NPs consist of poly(d,l-lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), and bisphosphonate (or alendronate, a targeting ligand). The engineered NPs were formulated by blending varying ratios of the synthesized polymers: PLGA-b-PEG and alendronate-conjugated polymer PLGA-b-PEG-Ald, which ensured long circulation and targeting capabilities, respectively. The bone-binding ability of Ald-PEG-PLGA NPs was investigated by hydroxyapatite binding assays and ex vivo imaging of adherence to bone fragments. In vivo biodistribution of fluorescently labeled NPs showed higher retention, accumulation, and bone homing of targeted Ald-PEG-PLGA NPs, compared with nontargeted PEG-PLGA NPs. A library of bortezomib-loaded NPs (bone-targeted Ald-Bort-NPs and nontargeted Bort-NPs) were developed and screened for optimal physiochemical properties, drug loading, and release profiles. Ald-Bort-NPs were tested for efficacy in mouse models of multiple myeloma (MM). Results demonstrated significantly enhanced survival and decreased tumor burden in mice pretreated with Ald-Bort-NPs versus Ald-Empty-NPs (no drug) or the free drug. We also observed that bortezomib, as a pretreatment regimen, modified the bone microenvironment and enhanced bone strength and volume. Our findings suggest that NP-based anticancer therapies with bone-targeting specificity comprise a clinically relevant method of drug delivery that can inhibit tumor progression in MM.The incidence of bone metastasis is common in 60–80% of cancer patients (1). During bone metastasis, cancer cells induce a sequence of changes in the microenvironment such as secreting cytokines to increase the activity of osteoclasts via the parathyroid hormone-related protein (PTHrP), receptor activator of nuclear factor-κB ligand (RANKL), and interleukin-6 (IL-6), resulting in increased bone resorption and secretion of growth factors from the bone matrix (2). This creates a “vicious cycle” of bone metastasis, where bone marrow becomes packed with cancer cells that develop resistance to conventional chemotherapy, and leads to devastating consequences of bone fractures, pain, hypercalcaemia, and spinal cord and nerve compression syndromes (2, 3). Multiple myeloma (MM) is a plasma cell cancer that proliferates primarily in bone marrow and causes osteolytic lesions (1). Antiresorption agents, such as bisphosphonates, may alleviate bone pain, but they are ineffective at inducing bone healing or osteogenesis in MM patients (4).Bortezomib is a proteasome inhibitor that has shown marked antitumor effects in patients with MM. Proteasome inhibitors, such as bortezomib, are also effective at increasing bone formation, both preclinically and clinically (5–9). However, the major drawback of bortezomib use in early stages of MM development is its toxicity, specifically, peripheral neuropathy (5). Therefore, we aimed to develop a method to deliver bortezomib with decreased off-target side effects by using bone-specific, bortezomib-loaded nanoparticles (NPs). The NP system was based on biodegradable, biocompatible, and Food and Drug Administration (FDA)-approved components, which are both clinically and translationally relevant. NPs derived from poly(d,l-lactic-co-glycolic acid) (PLGA), a controlled release polymer system, are an excellent choice because their safety in the clinic is well established (10, 11). Polyethylene glycol (PEG)-functionalized PLGA NPs are especially desirable as PEGylated polymeric NPs have significantly reduced systemic clearance compared with similar particles without PEG (12, 13). A number of FDA-approved drugs in clinical practice use PEG for improved pharmaceutical properties such as enhanced circulation in vivo (12, 13). To target NPs to bone [rich in the mineral hydroxyapatite (HA)], the calcium ion-chelating molecules of bisphosphonates represent a promising class of ligands (14). Bisphosphonates, upon systemic administration, are found to deposit in bone tissue, preferentially at the high bone turnover sites, such as the metastatic bone lesions, with minimal nonspecific accumulation (14) and were used herein to deliver NPs to the bone.A few systems explored for MM treatment have been tested in vitro including the following: (i) snake venom and silica NPs (15); (ii) thymoquinone and PLGA-based particles (16); (iii) curcumin and poly(oxyethylene) cholesteryl ether (PEG-Chol) NPs (17), polyethylenimine-based NPs for RNAi in MM (18), paclitaxel-Fe₃O₄ NPs (19), and liposomes (20). However, none of the above-mentioned systems have aimed to manipulate the bone marrow microenvironment rather than the myeloma cells directly (21). To date, there are no reports of using bone-targeted, controlled release, polymeric NPs with stealth properties for MM therapy. In this study, we designed NPs bearing three main components: (i) a targeting element that can selectively bind to bone mineral; (ii) a layer of stealth (PEG) to minimize immune recognition and enhance circulation; and (iii) a biodegradable polymeric material, forming an inner core, that can deliver therapeutics and/or diagnostics in a controlled manner. In this study, the physicochemical properties of a range of NPs was investigated (including NP size, charge, targeting ligand density, drug loading, and drug release kinetics) and an optimal formulation with ideal properties and maximal drug encapsulation was used for in vivo efficacy studies. We fine-tuned the NP targeting ligand density to optimize its bone-binding ability and further investigated its application for targeting myeloma in the bone microenvironment. We believe our NP system has the potential to increase drug availability by improving pharmacokinetics and biodistribution that can provide bone microenvironment specificity, which may increase the therapeutic window and most certainly decrease the off-target effects (12, 13).     

Traumatic events and their relative PTSD burden in Northern Ireland: a consideration of the impact of the ‘Troubles’

Purpose

Over a 30-year period in its recent history, daily life in Northern Ireland (NI) was characterised by civil violence, colloquially termed as the ‘Troubles’. The current report examines exposure to 29 traumatic event types and the associated conditional prevalence of post-traumatic stress disorder (PTSD) among the Northern Ireland population, with a focus on the impact of traumatic events that were characteristic of the NI ‘Troubles’.

Method

Results presented are based on analysis of data from the Northern Ireland Study of Health and Stress (NISHS). The NISHS is a representative epidemiological study of mental health among the NI adult population (N = 4,340) and part of the World Mental Health Survey Initiative.

Results

Perpetration of violence, physical assault by a spouse or partner and private events were the event types associated with the highest conditional prevalence of PTSD. Despite this elevated risk, collectively these events accounted for just 16.8 % of the overall public burden of PTSD, given their low prevalence among the general population. Events that were characteristic of civil conflict, including unexpected death of a loved one, witnessing death or a dead body or someone seriously injured and being mugged or threatened with a weapon accounted for the highest proportion of the overall public health burden of PTSD (18.6, 9.4 and 7.8 %, respectively). These findings are a feature of the higher prevalence of these events among the general population coupled with their moderate to above average risk of PTSD.

Conclusions

Despite the formal end to conflict in NI in 1999, a substantial proportion of the adult population continue to suffer the adverse mental health effects of chronic trauma exposure. Given rates of recovery of PTSD in the absence of evidence-based treatments, it is likely that the legacy of mental ill health associated with conflict, if not adequately addressed, will endure for many years.     

Reference data for arm muscle and arm adipose tissue areas in Mexican Americans from the Hispanic Health and Nutrition Examination survey (HHANES 1982–1984): Comparisons with whites and blacks from NHANES II (1976–1980)

Data for arm muscle area (AMA) and arm adipose tissue area (AATA) from 3695 Mexican American children 6 months to 18 years of age included in HHANES (1982–1984) were used to obtain age-and gender-specific means and selected percentiles. These statistics were compared with those for non-Hispanic white and non-Hispanic black children from NHANES II (1976–1980). In comparison with non-Hispanic white and non-Hispanic black children, the Mexican American children tended to have smaller means and percentile values for AMA but larger values for AATA. There was considerable sexual dimorphism in AMA and AATA. Within each population, boys tended to have larger means and percentile values for AMA than girls, and girls tended to have larger values for AATA than boys. Within each population of boys, there was a prepubescent gain in AATA, followed by a midpubescent loss, and then an increase near the middle of the second decade. This “fat wave” pattern was not noticeable in girls. Population differences in age- and gender-specific mean values for AMA and AATA were small. Few statistically significant differences were observed; these were no more common than would occur by chance. Therefore, population-specific reference data for AMA and AATA may not be needed for the clinical evaluation of Mexican Americans, non-Hispanic blacks, and non-Hispanic whites. © 1996 Wiley-Liss, Inc.