School-Based Suicide Prevention Efforts: The Impact of School Nurse Exclusivity on Moral Distress.

School nurses are well-positioned to assess, identify, and refer children and adolescents who are at risk of suicide. This multiple-case study examined the personal, behavioral, and environmental factors that influence the role of the school nurse in youth suicide prevention and intervention. Purposive sampling was used to recruit two school nurses who were identified as unique cases. Data from interviews, surveys, and documents generated a cross-case analysis. Findings indicate that school-level exclusive practices, such as a lack of communication and collaboration, greatly influence the role and reach of school nurses. Further, dilemmas arising from environmental barriers hinder school nurse capacity to promote student safety and affect moral distress levels. Leveraging data to demonstrate the pivotal role of school nurses to support mental health equity and reduce disparities in youth suicide is crucial to developing inclusive and responsive suicide prevention programs.

The Role of the School Nurse in Suicide Prevention: Implications for Equitable Care of Vulnerable Youth.

The rising rate of youth suicide in rural Eastern North Carolina reflects the national trend. Although school nurses have been regarded as the gateway professional for mental health services, their role in suicide prevention is not well understood. The purpose of this study was to explore school nursing practice regarding suicide prevention of school-aged children in one vulnerable region of the United States. Focus groups and surveys were collected from 35 school nurses in six school districts. Findings indicate that suicide protocols inclusive of the school nurse can facilitate their role in suicide prevention. Variation of school nursing practice existed between and within districts. These variations in school nursing practice highlight the need for school districts within the state and across the country to examine their policies and practices for mental health equity. Barriers such as higher caseloads, role disconnect, and lack of specialized training contributed to variations in practice.

Tools to enhance nursing students' confidence and skills in medication administration.

ABSTRACT: Nursing students experience high levels of stress and anxiety, which can be evident in tasks like administering medications in the clinical setting. This article shares tools to help decrease student stress during medication administration and foster a culture of safety.

Striatal Cholinergic Dysregulation after Neonatal Decrease in X-Linked Dystonia Parkinsonism-Related TAF1 Isoforms.

BACKGROUND: X-linked dystonia parkinsonism is a generalized, progressive dystonia followed by parkinsonism with onset in adulthood and accompanied by striatal neurodegeneration. Causative mutations are located in a noncoding region of the TATA-box binding protein-associated factor 1 (TAF1) gene and result in aberrant splicing. There are 2 major TAF1 isoforms that may be decreased in symptomatic patients, including the ubiquitously expressed canonical cTAF1 and the neuronal-specific nTAF1. OBJECTIVE: The objective of this study was to determine the behavioral and transcriptomic effects of decreased cTAF1 and/or nTAF1 in vivo. METHODS: We generated adeno-associated viral (AAV) vectors encoding microRNAs targeting Taf1 in a splice-isoform selective manner. We performed intracerebroventricular viral injections in newborn mice and rats and intrastriatal infusions in 3-week-old rats. The effects of Taf1 knockdown were assayed at 4 months of age with evaluation of motor function, histology, and RNA sequencing of the striatum, followed by its validation. RESULTS: We report motor deficits in all cohorts, more pronounced in animals injected at P0, in which we also identified transcriptomic alterations in multiple neuronal pathways, including the cholinergic synapse. In both species, we show a reduced number of striatal cholinergic interneurons and their marker mRNAs after Taf1 knockdown in the newborn. CONCLUSION: This study provides novel information regarding the requirement for TAF1 in the postnatal maintenance of striatal cholinergic neurons, the dysfunction of which is involved in other inherited forms of dystonia. © 2021 International Parkinson and Movement Disorder Society.

Consequences of the vaping epidemic on adolescents.

The prevalence of vaping has seen a dramatic increase in the last decade, especially among adolescent populations. This article discusses the background, prevalence, and associated risk factors of e-cigarettes.

Weight gain after adenotonsillectomy: a case control study.

OBJECTIVE: To study the association between adenotonsillectomy (T&A) and weight gain in children. STUDY DESIGN: Retrospective case-control series. SETTING: Tertiary academic children's medical center. SUBJECTS AND METHODS: A total of 154 children who underwent T&A at a tertiary care children's hospital between December 2010 and March 2011 were included. They were compared with 182 children with similar demographics who were seen in primary care clinics at the same institution (control group). Height and weight were compared at 6-month intervals over a 24-month period. Patients were divided into normal weight, overweight, and obese. A multilevel mixed-effects regression model was used for analysis. Significance was set at P ≤ .05. RESULTS: Children who underwent T&A gained more weight than controls at every interval. At 24 months, they gained an additional 2.6 kg (confidence interval [CI], 0.9-3.9) but were an additional 1.8 cm (CI, 0.1-3.5) taller. There was no difference in weight gain at 6 months for obese children. At 12, 18, and 24 months, the obese group outgained the control group. At 24 months, the obese T&A group had gained an average of 14.3 kg, while the control had gained 10.1 kg, for a difference of 4.2 kg (CI, 1.3-6.1) with no difference in height changes. There were no differences in weight or height changes for the normal-weight and overweight groups at the conclusion of the study. CONCLUSIONS: T&A leads to a significant increase in weight in obese but not normal-weight or overweight children. Efforts should be made to provide weight reduction counseling prior to T&A in obese children.

Fiber-modified adenovirus for central nervous system Parkinson's disease gene therapy.

Gene-based therapies for neurological diseases continue to develop briskly. As disease mechanisms are elucidated, flexible gene delivery platforms incorporating transcriptional regulatory elements, therapeutic genes and targeted delivery are required for the safety and efficacy of these approaches. Adenovirus serotype 5 (Ad5)-based vectors can carry large genetic payloads to provide this flexibility, but do not transduce neuronal cells efficiently. To address this, we have developed a tropism-modified Ad5 vector with neuron-selective targeting properties for evaluation in models of Parkinson disease therapy. A panel of tropism-modified Ad5 vectors was screened for enhanced gene delivery in a neuroblastoma cell line model system. We used these observations to design and construct an unbiased Ad vector platform, consisting of an unmodified Ad5 and a tropism-modified Ad5 vector containing the fiber knob domain from canine Ad serotype 2 (Ad5-CGW-CK2). Delivery to the substantia nigra or striatum showed that this vector produced a neuronally-restricted pattern of gene expression. Many of the transduced neurons were from regions with afferent projections to the injection site, implicating that the vector binds the presynaptic terminal resulting in presynaptic transduction. We show that Ad5-CGW-CK2 can selectively transduce neurons in the brain and hypothesize that this modular platform is potentially adaptable to clinical use.

Alcohol use: from childhood through adolescence.

Alcohol use is often overlooked and more importantly unsuspected in young children 3-11 years of age. Alcohol use in preteens is commonly overlooked when there is growing evidence to suggest that the age at which one begins drinking can be predictive of future problem drinking and other substance abuse. There is a need for health care professionals and elementary school educators to be aware of the real and growing problem of alcohol use from childhood through adolescence. It is sometimes difficult to recognize because many of the effects of alcohol mimic routine presentations seen in children. This article focuses on the significance, contributing factors, effects on the body, comorbidities, and social and psychological effects of alcohol use on children through adolescence. It also examines diagnostic screening for alcohol use in adolescence and the detrimental role of the nurse in assisting with identifying and preventing the problem of alcohol use in childhood through adolescence.

Transduction of brain dopamine neurons by adenoviral vectors is modulated by CAR expression: rationale for tropism modified vectors in PD gene therapy.

BACKGROUND: Gene-based therapy is a new paradigm for the treatment of Parkinson disease (PD) and offers considerable promise for precise targeting and flexibility to impact multiple pathobiological processes for which small molecule agents are not available. Some success has been achieved utilizing adeno-associated virus for this approach, but it is likely that the characteristics of this vector system will ultimately create barriers to progress in clinical therapy. Adenovirus (Ad) vector overcomes limitations in payload size and targeting. The cellular tropism of Ad serotype 5 (Ad5)-based vectors is regulated by the Ad attachment protein binding to its primary cellular receptor, the coxsackie and adenovirus receptor (CAR). Many clinically relevant tissues are refractory to Ad5 infection due to negligible CAR levels but can be targeted by tropism-modified, CAR-independent forms of Ad. Our objective was to evaluate the role of CAR protein in transduction of dopamine (DA) neurons in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Ad5 was delivered to the substantia nigra (SN) in wild type (wt) and CAR transgenic animals. Cellular tropism was assessed by immunohistochemistry (IHC) in the SN and striatal terminals. CAR expression was assessed by western blot and IHC. We found in wt animals, Ad5 results in robust transgene expression in astrocytes and other non-neuronal cells but poor infection of DA neurons. In contrast, in transgenic animals, Ad5 infects SNc neurons resulting in expression of transduced protein in their striatal terminals. Western blot showed low CAR expression in the ventral midbrain of wt animals compared to transgenic animals. Interestingly, hCAR protein localizes with markers of post-synaptic structures, suggesting synapses are the point of entry into dopaminergic neurons in transgenic animals. CONCLUSIONS/SIGNIFICANCE: These findings demonstrate that CAR deficiency limits infection of wild type DA neurons by Ad5 and provide a rationale for the development of tropism-modified, CAR-independent Ad-vectors for use in gene therapy of human PD.

Design of clinical trials of gene therapy in Parkinson disease.

No current therapy for Parkinson disease has been shown to slow or reverse the progressive course of the disease. As a departure from traditional treatments, gene therapy approaches provide a new hope for realizing this long-sought goal; but before they can be widely employed for use in patients, they must first be submitted to the rigorous safety and efficacy standards of the clinical trial. Some of the challenges of gene therapy clinical trial design are similar to those in studies of conventional pharmacological agents and include addressing the heterogeneity of the disease, the need for clinical and surrogate endpoints, and the issue of distinguishing "symptomatic" from "neuroprotective" effects. Gene therapy trials also raise the issues of the risks of viral therapy, issues of dose-response, the need for sham surgery, and the long duration of risks and benefits. We conclude that the most feasible designs are for those treatments that are expected to produce a rapid improvement in directly observable symptoms. Trials of agents which are expected to produce only a slowing of progression and not a reversal of the disease course are likely to take much longer and will require the development of methods to assess quality of life and other non-motor aspects of the disease.

Quantitative 1H magnetic resonance spectroscopic imaging determines therapeutic immunization efficacy in an animal model of Parkinson's disease.

Nigrostriatal degeneration, the pathological hallmark of Parkinson's disease (PD), is mirrored by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication. MPTP-treated animals show the common behavioral, motor, and pathological features of human disease. We demonstrated previously that adoptive transfer of Copaxone (Cop-1) immune cells protected the nigrostriatal dopaminergic pathway in MPTP-intoxicated mice. Herein, we evaluated this protection by quantitative proton magnetic resonance spectroscopic imaging (1H MRSI). 1H MRSI performed in MPTP-treated mice demonstrated that N-acetyl aspartate (NAA) was significantly diminished in the substantia nigra pars compacta (SNpc) and striatum, regions most affected in human disease. When the same regions were coregistered with immunohistochemical stains for tyrosine hydroxylase, numbers of neuronal bodies and termini were similarly diminished. MPTP-intoxicated animals that received Cop-1 immune cells showed NAA levels, in the SNpc and striatum, nearly equivalent to PBS-treated animals. Moreover, adoptive transfer of immune cells from ovalbumin-immunized to MPTP-treated mice failed to alter NAA levels or protect dopaminergic neurons and their projections. These results demonstrate that 1H MRSI can evaluate dopaminergic degeneration and its protection by Cop-1 immunization strategies. Most importantly, the results provide a monitoring system to assess therapeutic outcomes for PD.

Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease.

Degeneration of the nigrostriatal dopaminergic pathway, the hallmark of Parkinson's disease, can be recapitulated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice. Herein, we demonstrate that adoptive transfer of copolymer-1 immune cells to MPTP recipient mice leads to T cell accumulation within the substantia nigra pars compacta, suppression of microglial activation, and increased local expression of astrocyte-associated glial cell line-derived neurotrophic factor. This immunization strategy resulted in significant protection of nigrostriatal neurons against MPTP-induced neurodegeneration that was abrogated by depletion of donor T cells. Such vaccine treatment strategies may provide benefit for Parkinson's disease.

Advances in neuroimaging for HIV-1 associated neurological dysfunction: clues to the diagnosis, pathogenesis and therapeutic monitoring.

Persons with advanced human immunodeficiency virus type one (HIV-1) infection seek medical advice for a wide range of neurological disorders including, but not limited to, peripheral neuropathy, toxoplasmosis, cryptococcal meningitis, cytomegalovirus retinitis progressive multifocal leukoencephalopathy, lymphoma and dementia. The diagnosis of HIV-1-associated dementia (HAD) induced as a direct consequence of HIV infection of the brain comes commonly by exclusion. Diagnostic decisions can often be clouded by concomitant depression, motor impairments, and lethargy that follow debilitating immune suppression and weight loss. Indeed, cognitive, motor and behavior abnormalities underlie a variety of neurological dysfunctions associated with advanced HIV-1 infection. Thus, even combinations of clinical, laboratory and neuroimaging tests [for example, magnetic resonance imaging (MRI), computed tomography (CT), single photon emission computed tomography (SPECT) and positron emission tomography (PET)] often fail to provide conclusive diagnostic information. Nonetheless, the recent development of quantitative MR spectroscopic imaging has improved diagnostic possibilities for HAD. We are pleased to discuss these developments as well as taking a forward look into what will soon be made available to improve neuroimaging diagnostic precision. New MR and SPECT testing are being developed in our laboratories and elsewhere both for animal model systems and in humans with HIV-1 disease. Such tests can facilitate dynamic measures of HIV-1 neuropathogenesis providing information for disease events that even 2 years ago were unattainable.