Synthetic Cannabinoids (SCs) in Metaphors: a Metaphorical Analysis of User Experiences of Synthetic Cannabinoids in Two Countries

New psychoactive substances (NPS) remain a global public health and clinical challenge. Popular NPS include synthetic cannabinoids (SCs). A conceptual metaphorical analysis of user experiences of SCs was conducted in two European countries (Western and Central European). Metaphors are increasingly used to better understand drug user experiences and as medium to inform and guide clinical responses. Semi-structured interviews with 12 SC users were conducted in Hungary (n = 6) and Ireland (n = 6). Thematically segmented texts of SC usage (1) motivation, (2) effects, (3) consequences and (4) the setting were selected. A systematic analysis of conceptual metaphors was conducted on the selected texts. The conceptual target and source domains of the experiences of SC usage (motivation, effects, consequences) were analysed. Four conceptual source domains were found in all of the segmented and analysed narratives of psychological factors (motivations, effects, consequences): change in the vertical perception, perceiving that SC is everywhere, feeling disconnected, recognition of lack of control and identifying the SC as a destroying entity. The conceptual metaphors reflect how users perceive experiences of SC use, the discrepancy between the experience of embodiment and disembodiment. This study provides clinicians with an insight into the experiences of SC motivations, effects and consequences and can be used to inform and guide clinical and therapeutic responses in the support of those recovering from SC dependence.

     

Psychopharmaceutical Enhancers: Enhancing Identity?

The use of psychopharmaceuticals to enhance human mental functioning such as cognition and mood has raised a debate on questions regarding identity and authenticity. While some hold that psychopharmaceutical substances can help users to ‘become who they really are’ and thus strengthen their identity and authenticity, others believe that the substances will lead to inauthenticity, normalization, and socially-enforced adaptation of behaviour and personality. In light of this debate, we studied how persons who actually have experience with the use of psychopharmaceutical medication would view their ‘self’ or their authentic personal identity in relation to the use of medication. We have interviewed a number of adults diagnosed with ADHD and discussed their experiences with medication use in relation to their conceptions of self and identity. In the first part of this paper we illustrate that the concepts of identity and authenticity play an important and sometimes problematic role in experiences of ADHD adults. This shows that the question about identity and psychopharmacology is not merely an ‘academic’ issue, but one that influences everyday lives of real people. In order to answer the question whether psychopharmaceuticals threaten personal identity and authenticity, more than empirical research is needed. We also need to analyse the concepts of personal identity, authenticity and self: what do we mean when we are using statements as ‘a way of living that is uniquely our own’, ‘our true self’, or ‘who we really are’? In the second part of this paper we discuss two important philosophical views on personal identity, authenticity and self: the self-control view as elaborated by Frankfurt, and the self-expression view as proposed by Schechtman. We compare these with the experiences of our respondents to see which view can help us to understand the diverse and often conflicting experiences that people have with medication for ADHD. This will contribute to a better understanding of whether and in which cases personal identity and authenticity are threatened by psychopharmacology.     

Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal

Although several chemical structural classes of synthetic cannabinoids (SCs) were recently classified as Schedule I substances, rates of use and cases of serious toxic effects remain high. While case reports and media bring attention to severe SC toxicity, daily SC use resulting in dependence and withdrawal is a significant concern that is often overlooked when discussing the risks of these drugs. There is a rich literature on evidence-based approaches to treating substance use disorders associated with most abused drugs, yet little has been published regarding how to best treat symptoms related to SC dependence given its recency as an emerging clinically significant issue. This review provides a background of the pharmacology of SCs, recent findings of adverse effects associated with both acute intoxication and withdrawal as a consequence of daily use, and treatment approaches that have been implemented to address these issues, with an emphasis on pharmacotherapies for managing detoxification. In order to determine prevalence of use in cannabis smokers, a population at high risk for SC use, we obtained data on demographics of SC users, frequency of use, and adverse effects over a 3.5-year period (2012–2015) in the New York City metropolitan area, a region with a recent history of high SC use. While controlled studies on the physiological and behavioral effects of SCs are lacking, it is clear that risks associated with using these drugs pertain not only to the unpredictable and severe nature of acute intoxication but also to the effects of long-term, chronic use. Recent reports in the literature parallel findings from our survey, indicating that there is a subset of people who use SCs daily. Although withdrawal has not been systematically characterized and effective treatments have yet to be elucidated, some symptom relief has been reported with benzodiazepines and the atypical antipsychotic, quetiapine. Given the continued use and abuse of SCs, empirical studies characterizing (1) SCs acute effects, (2) withdrawal upon cessation of use, and (3) effective treatment strategies for SC use disorder are urgently needed.     

Extensive cell migration, axon regeneration, and improved function with polysialic acid-modified Schwann cells after spinal cord injury

Schwann cell (SC) implantation after spinal cord injury (SCI) promotes axonal regeneration, remyelination repair, and functional recovery. Reparative efficacy, however, may be limited because of the inability of SCs to migrate outward from the lesion-implant site. Altering SC cell surface properties by overexpressing polysialic acid (PSA) has been shown to promote SC migration. In this study, a SCI contusion model was used to evaluate the migration, supraspinal axon growth support, and functional recovery associated with polysialyltransferase (PST)-overexpressing SCs [PST-green fluorescent protein (GFP) SCs] or controls (GFP SCs). Compared with GFP SCs, which remained confined to the injection site at the injury center, PST-GFP SCs migrated across the lesion:host cord interface for distances of up to 4.4 mm within adjacent host tissue. In addition, with PST-GFP SCs, there was extensive serotonergic and corticospinal axon in-growth within the implants that was limited in the GFP SC controls. The enhanced migration of PST-GFP SCs was accompanied by significant growth of these axons caudal to lesion. Animals receiving PST-GFP SCs exhibited improved functional outcome, both in the open-field and on the gridwalk test, beyond the modest improvements provided by GFP SC controls. This study for the first time demonstrates that a lack of migration by SCs may hinder their reparative benefits and that cell surface overexpression of PSA enhances the ability of implanted SCs to associate with and support the growth of corticospinal axons. These results provide further promise that PSA-modified SCs will be a potent reparative approach for SCI. © 2012 Wiley Periodicals, Inc.     

Defining new frameworks for psychosocial intervention

The personal experiences of individuals with schizophrenia have been neglected in the psychiatric literature. Disappointingly, ideas about the impact of the illness on the experience of "self" have either been devalued or based primarily on the impressions of theorists rarely collaborating with individuals with the illness. Rather than making assumptions about the subjective experience of mental illness, we must enter a meaningful dialogue with our clients so that they can tell us about their situations using their own voices. This study presents life-history interviews with 15 individuals diagnosed with schizophrenia and describes the explanatory models they use to give coherence to their experiences of psychosis. The struggle for control emerges as a central theme with effects on the management of symptoms, self-image, feelings of social competence, and dealing with others' expectations. Respondents speak about the possibility of recovery from illness through engaging in a process of internal and external reorganization. These individuals echo the assertions in the literature generated by consumers and other investigators of subjective experience and advocate for recovery-based models of care including therapeutic discourse with clients.     

Sulfatase‐mediated manipulation of the astrocyte‐Schwann cell interface

Schwann cell (SC) transplantation following spinal cord injury (SCI) may have therapeutic potential. Functional recovery is limited however, due to poor SC interactions with host astrocytes and the induction of astrogliosis. Olfactory ensheathing cells (OECs) are closely related to SCs, but intermix more readily with astrocytes in culture and induce less astrogliosis. We previously demonstrated that OECs express higher levels of sulfatases, enzymes that remove 6‐O‐sulfate groups from heparan sulphate proteoglycans, than SCs and that RNAi knockdown of sulfatase prevented OEC‐astrocyte mixing in vitro. As human OECs are difficult to culture in large numbers we have genetically engineered SCs using lentiviral vectors to express sulfatase 1 and 2 (SC‐S1S2) and assessed their ability to interact with astrocytes. We demonstrate that SC‐S1S2s have increased integrin‐dependent motility in the presence of astrocytes via modulation of NRG and FGF receptor‐linked PI3K/AKT intracellular signaling and do not form boundaries with astrocytes in culture. SC‐astrocyte mixing is dependent on local NRG concentration and we propose that sulfatase enzymes influence the bioavailability of NRG ligand and thus influence SC behavior. We further demonstrate that injection of sulfatase expressing SCs into spinal cord white matter results in less glial reactivity than control SC injections comparable to that of OEC injections. Our data indicate that sulfatase‐mediated modification of the extracellular matrix can influence glial interactions with astrocytes, and that SCs engineered to express sulfatase may be more OEC‐like in character. This approach may be beneficial for cell transplant‐mediated spinal cord repair. GLIA 2016 GLIA 2017;65:19–33     

The effects of low intensity focused ultrasonic stimulation on dorsal root ganglion neurons and Schwann cells in vitro

Satisfactory treatment of peripheral nerve injury (PNI) faces difficulties owing to the intrinsic biological barriers in larger injuries and invasive surgical interventions. Injury gaps >3 cm have low chances of full motor and sensory recovery, and the unmet need for PNI repair techniques which increase the likelihood of functional recovery while limiting invasiveness motivate this work. Building upon prior work in ultrasound stimulation (US) of dorsal root ganglion (DRG) neurons, the effects of US on DRG neuron and Schwann cell (SC) cocultures were investigated to uncover the role of SCs in mediating the neuronal response to US in vitro. Acoustic intensity‐dependent alteration in selected neuromorphometrics of DRG neurons in coculture with SCs was observed in total outgrowth, primary neurites, and length compared to previously reported DRG monoculture in a calcium‐independent manner. SC viability and proliferation were not impacted by US. Conditioned medium studies suggest secreted factors from SCs subjected to US impact DRG neuron morphology. These findings advance the current understanding of mechanisms by which these cell types respond to US, which may lead to new noninvasive US therapies for treating PNI.     

Skeletal muscle satellite cells: Mediators of muscle growth during development and implications for developmental disorders

Satellite cells (SCs) are the muscle stem cells responsible for longitudinal and cross‐sectional postnatal growth and repair after injury and which provide new myonuclei when needed. We review their morphology and contribution to development and their role in sarcomere and myonuclear addition. SCs, similar to other tissue stem cells, cycle through different states, such as quiescence, activation, and self‐renewal, and thus we consider the signaling mechanisms involved in maintenance of these states. The role of the SC niche and their interactions with other cells, such as fibroblasts and the extracellular matrix, are all emerging as major factors that affect aging and disease. Interestingly, children with cerebral palsy appear to have a reduced SC number, which could play a role in their reduced muscular development and even in muscular contracture formation. Finally, we review the current information on SC dysfunction in children with muscular dystrophy and emerging therapies that target promotion of myogenesis and reduction of fibrosis. Muscle Nerve 50 : 723–732, 2014     

Schwann cell delivery of neurotrophic factors for peripheral nerve regeneration

Current treatments of injured peripheral nerves often fail to mediate satisfactory functional recovery. For axonal regeneration, neurotrophic factors (NTFs) play a crucial role. Multiple NTFs and other growth‐promoting factors are secreted, amongst others, by Schwann cells (SCs), which also provide cellular guidance for regenerating axons. Therefore, delivery of NTFs and transplantation of autologous or genetically modified SCs with therapeutic protein expression have been proposed. This article reviews polymer‐based and cellular approaches for NTF delivery, with a focus on SCs and strategies to modulate SC gene expression. Polymer‐based NTF delivery has mostly resided on nerve conduits (NC). While NC have generally provided prolonged NTF release, their therapeutic effect has remained significantly below that achieved with autologous nerve grafts. Several studies demonstrated enhanced nerve regeneration using NC seeded with SCs. The SCs have sometimes been modified genetically using non‐viral or viral vectors. Whereas non‐viral vectors produced poor transgene delivery, adenoviral vectors mediated high transgene transduction efficiency of SCs. Further improvements of safety and transgene expression of adenoviral vector may lead to rapid translation of pre‐clinical research to clinical trials.     

Ethnocultural identification in psychotherapy

Ethnoculturally translocated individuals, members of minority groups, and patients in cross-cultural psychotherapy frequently experience disturbances of their ethnocultural identities. During psychotherapy these patients often attribute ethnocultural qualities to their therapists in a process called ethnocultural identification. This process may be used to foster a therapeutic identification in which the therapist reflects pieces of the patient's conflicted ethnocultural identity. Cases are presented here illustrating the use of ethnocultural identification as an auxiliary therapeutic tool to facilitate coping with changing cultural values and transitional experiences, and to promote the integration of the ethnocultural self into a consolidated sense of identity.     

Regulation of Schwann cell numbers in tellurium-induced neuropathy: apoptosis, supernumerary cells and internodal shortening

We have used an experimental model of tellurium(Te)-induced demyelinating neuropathy in the rat to study cellular mechanisms involved in regulating Schwann cell (SC) numbers during remyelination. Starting at postnatal day 21, weaned rats were fed a diet containing 1.1% elemental Te. Following 7 days of Te treatment and at several time points of post-tellurium treatment (PTe), the animals were processed for ultrastructural analysis, SC nuclei quantification and teased fibre preparations. It is well-established that Te induces a transient demyelinating/remyelinating sequence in sciatic nerves. The loss of the myelin sheath in this neuropathy produces active proliferation and overproduction of immature SCs. By electron microscopy analysis most mitotic SCs were located along demyelinated segments. Quantitative determination of SC nuclei per transverse section of sciatic nerve revealed a dramatic increase of SCs at 2 days PTe relative to control nerves. The number of SC nuclei then decreased progressively during the long-term period of recovery studied (330 days PTe). In Te-treated rats, SCs undergoing cell death were regularly found within the nerve fibre compartment, especially on demyelinated segments. Dying cells exhibited morphological features of apoptosis and appeared enclosed by lamellar processes of adjacent healthy SCs in extracellular compartments. Both healthy immature SCs and endoneurial macrophages were involved in the phagocytosis of apoptotic SCs. Particularly during remyelination, supernumerary endoneurial SCs were observed surrounding myelinated fibres. These cells progressively became atrophic with a morphological phenotype similar so that of “onion bulb” cells. On the other hand, teased fibre measurements revealed a remarkable permanent internodal shortening in remyelinated fibres from Te-treated sciatic nerves. These results indicate that a portion of redundant immature SCs are susceptible to elimination by apoptosis. However, other distinct biological mechanisms such as the persistence of supernumerary SCs in the endoneurium and the shortening of internodal lengths are also involved in regulating SC numbers during the remyelination stage. Received: 26 May 1997 / Revised: 12 September 1997 / Accepted: 1 October 1997     

Labeled Schwann cell transplantation: cell loss, host Schwann cell replacement, and strategies to enhance survival

Although transplanted Schwann cells (SCs) can promote axon regeneration and remyelination and improve recovery in models of spinal cord injury, little is known about their survival and how they interact with host tissue. Using labeled SCs from transgenic rats expressing human placental alkaline phosphatase (PLAP), SC survival in a spinal cord contusion lesion was assessed. Few PLAP SCs survived at 2 weeks after acute transplantation. They died early due to necrosis and apoptosis. Delaying transplantation until 7 days after injury improved survival. A second wave of cell death occurred after surviving cells had integrated into the spinal cord. Survival of PLAP SCs was enhanced by immunosuppression with cyclosporin; delayed transplantation in conjunction with immunosuppression resulted in the best survival. In all cases, transplantation of SCs resulted in extensive infiltration of endogenous p75+ cells into the injury site, suggesting that endogenous SCs may play an important role in the repair observed after SC transplantation.     

Psychosocial Aspects of Unwed Adolescent Pregnancy in Lusaka,Zambia

This article explores how professional carers cope with positive symptoms and disruptive behaviors of people diagnosed with schizophrenia who are living in care homes. Coping styles are seen as having a fundamental effect on stress levels and quality of life of both carers and users. The literature suggests that coping styles may influence symptom intensity of people diagnosed with schizophrenia. Until now, these coping strategies have not been analyzed in professional carers called monitors who work in care homes or supervised housing. In-depth interviews were conducted with ten expert carers working in care homes; they were asked about their experiences and interactions with users in a semistructured interview. The contents related to coping with symptoms and disruptive behaviors were selected on the basis of the grounded theory and studied from a qualitative perspective via an analysis of social positionings. Carers do not show any negative emotional burden when describing their experiences. Distraction coping strategies were used most to cope with positive symptoms. Neuromuscular relaxation and task coping strategies were also used. Interventions in the setting are considered essential for coping with violent behaviors. Carers use the majority of the strategies that are seen as most effective in the literature. The qualitative analysis of coping experiences is essential for the improvement and learning of the most effective caring behaviors.     

How Do People Perceive and Adapt to Any Consequences of Electro Convulsive Therapy on Their Daily Lives?

Great controversy surrounds the use of electroconvulsive therapy or ECT. However, it continues to be used internationally. While research on short term effects of ECT abound, there is limited knowledge about long term impacts of ECT on individuals, especially from the lived experience perspective. The aim of this qualitative study was to gain an in-depth understanding of longer-term lived experiences of ECT and how people navigate any impacts on their daily lives. Twenty-three people participated in semi-structured interviews. Data collection and analysis involved an iterative process. Data were coded into four categories: (1) My ECT experience included physical mechanics, decision making, clinic experiences, post ECT support and attitudes and support of others); (2) Direct impacts of ECT on me encompassed both cognitive and emotional impacts; (3) Impacts on my life comprised daily activities, relationships, ongoing health care; and My strategies incorporated fixing or working around the problem, reframing, using support networks, protecting myself and taking control. Insights gleaned through lived experiences have important implications for other service users, direct service providers and those striving for system reforms that embrace more recovery orientated and trauma informed practices.

     

A systematic evaluation of Schwann cell injection into acellular cold-preserved nerve grafts

Peripheral nerve regeneration after injury depends on environmental cues and trophic support. Schwann cells (SCs) secrete trophic factors that promote neuronal survival and help guide axons during regeneration. The addition of SCs to acellular nerve grafts is a promising strategy for enhancing peripheral nerve regeneration; however, inconsistencies in seeding parameters have led to varying results. The current work sought to establish a systematic approach to seeding SCs in cold-preserved acellular nerve grafts. Studies were undertaken to (1) determine the needle gauge for optimal cell survival and minimal epineurial disruption during injection, (2) track the seeded SCs using a commercially available dye, and (3) evaluate the seeding efficiency of SCs in nerve grafts. It was determined that seeding with a 27-gauge needle resulted in the highest viability of SCs with the least damage to the epineurium. In addition, Qtracker(?) dye, a commercially available quantum dot nanocrystal, was used to label SCs prior to transplantation, which allowed visualization of the seeded SCs in nerve grafts. Finally, stereological methods were used to evaluate the seeding efficiency of SCs in nerve grafts immediately after injection and following a 1- or 3-day in vitro incubation in SC growth media. Using a systematic approach, the best needle gauge and a suitable dye for SC visualization in acellular nerve grafts were identified. Seeding efficiency in these grafts was also determined. The findings will lead to improvements ability to assess injection of cells (including SCs) for use with acellular nerve grafts to promote nerve regeneration.     

BD PuraMatrix peptide hydrogel as a culture system for human fetal Schwann cells in spinal cord regeneration

BD PuraMatrix peptide hydrogel, a three‐dimensional cell culture model of nanofiber scaffold derived from the self‐assembling peptide RADA16, has been applied to regenerative tissue repair in order to develop novel nanomedicine systems. In this study with PuraMatrix, self‐assembling nanofiber scaffold (SAPNS) and Schwann cells (SCs) were isolated from human fetal sciatic nerves, cultured within SAPNS, and then transplanted into the spinal cord after injury (SCI) in rats. First, the peptide nanofiber scaffold was evaluated via scanning electron microscopy and atomic force microscopy. With phase‐contrast microscopy, the appearance of representative human fetal SCs encapsulated in PuraMatrix on days 3, 5, and 7 in 12‐well plates was revealed. The Schwann cells in PuraMatrix were cultured for 2 days, and the SCs had active proliferative potential. Spinal cord injury was induced by placing a 35‐g weight on the dura of T9–T10 segments for 15 min, followed by in vivo treatment with SAPNS and human fetal SCs (100,000 cells/10 μl/injection) grafted into spinal cord 7 days after SCI. After treatment, the recovery of motor function was assessed periodically using the Basso, Beattie, and Bresnahan scoring system. Eight weeks after grafting, animals were perfusion fixed, and the survival of implanted cells was analyzed with antibody recognizing SCs. Immunohistochemical analysis of grafted lumber segments at 8 weeks after grafting revealed reduced asterogliosis and considerably increased infiltration of endogenous S100⁺ cells into the injury site, suggesting that PuraMatrix may play an important role in the repair observed after SAPNS and human fetal SC transplantation. © 2012 Wiley Periodicals, Inc.     

Professional competencies for promoting recovery in mental illness

This study explored professional caregiving from the perspective of people diagnosed with schizophrenia to develop proposed professional competencies for promoting recovery. We conducted semi-structured qualitative interviews with 40 people diagnosed with schizophrenia to explore their experiences of caregiving. Interview segments related to professional caregiving were analyzed to derive categories and themes that described aspects of caregiving that clients believed contributed to their recovery. The proposed competencies derived from the interviews overlap with hypothesized competencies identified in the literature, but also suggest other areas of skill and attitude that relate to promoting recovery, including use of time, talk, and teamwork. The significance participants attach to time and talk suggests that services play an important role in recovery by creating the space for service users and service providers to engage in recovery-promoting practices.     

Differential in vitro modulation of Schwann cell proliferation by Mycobacterium leprae and macrophages in the murine strains, Swiss white and C57Bl/6

The special susceptibility of Schwann cells (SCs) to parasitization by M. leprae and of macrophages to M. leprae-induced defects implicates them in leprous nerve pathogenesis. SC proliferation is an important prerequisite for peripheral nerve regeneration and is regulated by a number of secretory factors. Several of these factors are secreted by SCs themselves as well as by the macrophages which are recruited at the site of lesion to assist in regeneration. SC proliferation, as indicated by 3H-thymidine incorporation, was therefore studied in response to M. leprae infection and in the presence of macrophages in order to determine the role of SC in leprous neuropathy. Cells derived from two strains of mice, Swiss White (SW) and C57Bl/6 were used, as macrophages from these strains have been shown to differ in their response to M. leprae; such differences are similar to those observed in macrophages from lepromatous and tuberculoid leprosy patients, respectively. Infection with M. leprae for a duration of 9 days resulted in reduced proliferation of SCs from SW strain, while SCs from C57Bl/6 remained unaffected. However, in the presence of macrophages, SCs from both strains not only showed enhanced proliferation, but SW SCs also overcame the M. leprae-induced suppression of their proliferation. Altered SC proliferation, therefore, can be implicated as a factor in leprous nerve pathogenesis. The strain variation observed in the response of SCs indicate different nerve damage mechanisms in lepromatous and tuberculoid patients.