Z-Score Neurofeedback and Heart Rate Variability Training for Adults and Children with Symptoms of Attention-Deficit/Hyperactivity Disorder: A Retrospective Study.

ADHD is a common condition that causes suffering for those affected and economic loss for society at large. The current standard treatment for ADHD includes stimulant medications, which are not effective for all patients, may include side effects, and can be non-medically misused. Z-score neurofeedback (NFB) and heart rate variability (HRV) biofeedback are alternative treatment strategies that have been associated with Attention-Deficit/Hyperactivity Disorder (ADHD) symptom improvement. We utilized a retrospective pre-post study design to quantify the change in clients' ADHD symptoms after combined NFB + HRV treatment (which included simultaneous z-score training at four sites). We also assessed whether relevant physiological measures changed in accordance with the protocol, which would be consistent with effective NFB + HRV training. Adults (n = 39) and children (n = 100) with Borderline or Clinical ADHD classifications by the Achenbach System of Empirically Based Assessment (ASEBA) received 30 sessions of NFB + HRV training. Measures were compared before and after treatment for the ASEBA, the Integrated Visual and Auditory Continuous Performance Test (IVA), ADHD medication use, HRV and breathing parameters, and quantitative electroencephalogram (QEEG) parameters. Average ASEBA Attention-Deficit/Hyperactive Problems score improved after treatment for adults and children (p < 0.0001), with Cohen effect sizes (dz) of -1.21 and -1.17, respectively. 87.2% of adults and 80.0% of children experienced improvements of a magnitude greater than or equal to the Minimal Clinically Important Difference. After treatment, 70.8% of adults and 52.8% of children who began in the ASEBA Clinical range, and 80.0% of adults and 63.8% of children who began in the ASEBA Borderline range, were classified in the Normal range. IVA scores also improved after treatment. Changes in HRV and breathing pattern after treatment were consistent with the protocol. QEEG parameters after treatment were closer to the age-based normative mean, which is consistent with effective z-score NFB training.

Angiotensin II activates NF-κB through AT1A receptor recruitment of ß-arrestin in cultured rat vascular smooth muscle cells.

Activation of the angiotensin type 1A receptor (AT1AR) in rat aorta vascular smooth muscle cells (RASMC) results in increased synthesis of the proinflammatory enzyme cyclooxygenase-2 (COX-2). We previously showed that nuclear localization of internalized AT1AR results in activation of transcription of the gene for COX-2, i.e., prostaglandin-endoperoxide synthase-2. Others have suggested that ANG II stimulation of COX-2 protein synthesis is mediated by NF-κB. The purpose of the present study was to examine the interrelationship between AT1AR activation, ß-arrestin recruitment, and NF-κB activation in the ability of ANG II to increase COX-2 protein synthesis in RASMC. In the present study we utilized RASMC, inhibitors of the NF-κB pathway, ß-arrestin knockdown, radioligand binding, immunoblotting, and immunofluorescence to characterize the roles of AT1AR internalization, NF-κB activation, and ß-arrestin in ANG II-induced COX-2 synthesis. Ro-106-9920 or parthenolide, agents that inhibit the initial steps of NF-κB activation, blocked ANG II-induced p65 NF-κB nuclear localization, COX-2 protein expression, ß-arrestin recruitment, and AT1AR internalization without inhibiting ANG II-induced p42/44 ERK activation. Curcumin, an inhibitor of NF-κB-induced transcription, blocked ANG II-induced COX-2 protein expression without altering AT1AR internalization, ANG II-induced p65 NF-κB nuclear localization, or p42/44 ERK activation. Small interfering RNA-induced knockdown of ß-arrestin-1 and -2 inhibited ANG II-induced p65 NF-κB nuclear localization. In vascular smooth muscle cells, internalization of the activated AT1AR mediated by ß-arrestins activates the NF-κB pathway, producing nuclear localization of the transcription factor and initiation of COX-2 protein synthesis, thereby linking internalization of the receptor with the NF-κB pathway.

Role of integrins in angiotensin II-induced proliferation of vascular smooth muscle cells.

Angiotensin II (AII) binds to G protein-coupled receptor AT(1) and stimulates extracellular signal-regulated kinase (ERK), leading to vascular smooth muscle cells (VSMC) proliferation. Proliferation of mammalian cells is tightly regulated by adhesion to the extracellular matrix, which occurs via integrins. To study cross-talk between G protein-coupled receptor- and integrin-induced signaling, we hypothesized that integrins are involved in AII-induced proliferation of VSMC. Using Oligo GEArray and quantitative RT-PCR, we established that messages for α(1)-, α(5)-, α(V)-, and ß(1)-integrins are predominant in VSMC. VSMC were cultured on plastic dishes or on plates coated with either extracellular matrix or poly-d-lysine (which promotes electrostatic cell attachment independent of integrins). AII significantly induced proliferation in VSMC grown on collagen I or fibronectin, and this effect was blocked by the ERK inhibitor PD-98059, suggesting that AII-induced proliferation requires ERK activity. VSMC grown on collagen I or on fibronectin demonstrated approximately three- and approximately sixfold increases in ERK phosphorylation after stimulation with 100 nM AII, respectively, whereas VSMC grown on poly-d-lysine demonstrated no significant ERK activation, supporting the importance of integrin-mediated adhesion. AII-induced ERK activation was reduced by >65% by synthetic peptides containing an RGD (arginine-glycine-aspartic acid) sequence that inhibit α(5)ß(1)-integrin, and by ∼60% by the KTS (lysine-threonine-serine)-containing peptides specific for integrin-α(1)ß(1). Furthermore, neutralizing antibody against ß(1)-integrin and silencing of α(1), α(5), and ß(1) expression by transfecting VSMC with short interfering RNAs resulted in decreased AII-induced ERK activation. This work demonstrates roles for specific integrins (most likely α(5)ß(1) and α(1)ß(1)) in AII-induced proliferation of VSMC.

Z-score neurofeedback, heart rate variability biofeedback, and brain coaching for older adults with memory concerns.

BACKGROUND: The three-month, multi-domain Memory Boot Camp program incorporates z-score neurofeedback (NFB), heart rate variability (HRV) biofeedback, and one-on-one coaching to teach memory skills and encourage behavior change in diet, sleep, physical fitness, and stress reduction. OBJECTIVE: This prospective trial evaluates the Memory Boot Camp program for adults ages 55 to 85 with symptoms of Mild Cognitive Impairment (MCI) and subjective memory complaints. METHODS: Participants were evaluated via the Montreal Cognitive Assessment (MoCA), NeuroTrax Global Cognitive Score, measures of anxiety, depression, sleep, quality of life, quantitative electroencephalography (QEEG), and HRV parameters at four timepoints: baseline, pre-program, post-program, and follow-up. The trial included a three-month waiting period between baseline and pre-program, such that each participant acted as their own control, and follow-up took place six months after completion of the program. RESULTS: Participants' MoCA scores and self-reported measures of anxiety, depression, sleep quality, and quality of life improved after treatment, and these changes were maintained at follow-up. Physiological changes in HRV parameters after treatment were not significant, however, breathing rate and QEEG parameters were improved at post-program and maintained at follow-up. Finally, participants' improvement in MoCA score over the treatment period was correlated with their improvement in two brain oscillation parameters targeted by the z-score NFB protocol: relative power of delta and relative power of theta. CONCLUSIONS: Trial results suggest that the Memory Boot Camp program is a promising treatment strategy for older adults with symptoms of MCI and subjective memory complaints.

COX-2 expression stimulated by Angiotensin II depends upon AT1 receptor internalization in vascular smooth muscle cells.

Previously, we demonstrated that nuclear localization of the Angiotensin II AT1A receptor was associated with the activation of transcription for the COX-2 gene, PTGS-2. The hypothesis of the present study is that AT1AR internalization from the plasma membrane is a first step in the nuclear localization of the endogenous AT1AR of rat aortic vascular smooth muscle cells and the resultant increase of COX-2 protein expression. Angiotensin II produced both a time- and concentration-dependent increase in COX-2 protein expression in these cells. Treatment with sucrose or phenylarsine oxide, inhibitors of receptor internalization, significantly inhibited AT1AR internalization and abolished the increase in COX-2 protein produced by Angiotensin II without affecting COX-2 expression on its own. Sucrose pre-treatment of rat aortic vascular smooth muscle cells resulted in an increase in p42/44 and p38 activation, while phenylarsine oxide pre-treatment activated only p38 kinase without inhibiting activation of p42/44 produced by Angiotensin II. These results demonstrate that inhibiting the internalization of the AT1AR results in a loss of ability of Angiotensin II to increase the protein expression of COX-2, thus supporting previous work showing a relationship between AT1AR nuclear localization and activation of COX-2 gene expression. Surprisingly, in contrast to other studies, the data also indicates that activation of p42/44 and/or p38 does not correlate with the increased expression of COX-2.

Angiotensin II-induced cyclooxygenase 2 expression in rat aorta vascular smooth muscle cells does not require heterotrimeric G protein activation.

Angiotensin II (AngII) initiates cellular effects via its G protein-coupled angiotensin 1 (AT(1)) receptor (AT(1)R). Previously, we showed that AngII-induced expression of the prostanoid-producing enzyme cyclooxygenase 2 (COX-2) was dependent upon nuclear trafficking of activated AT(1)R. In the present study, mastoparan (an activator of G proteins), suramin (an inhibitor of G proteins), 1-[6-[[17beta-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122; a specific inhibitor of phospholipase C), and sarcosine(1)-Ile(4)-Ile(8)-AngII (SII-AngII; a G protein-independent AT(1)R agonist) were used to determine the involvement of G proteins and AT(1A)R trafficking in AngII-stimulated COX-2 protein expression in human embryonic kidney-293 cells stably expressing AT(1A)/green fluorescent protein receptors and cultured vascular smooth muscle cells, respectively. Mastoparan alone stimulated release of intracellular calcium and increased COX-2 expression. Preincubation with mastoparan inhibited AngII-induced calcium signaling without altering AngII-induced AT(1A)R trafficking, p42/44 extracellular signal-regulated kinase (ERK) activation, or COX-2 expression. Suramin or U73122 had no significant effect on their own; they did not inhibit AngII-induced AT(1A)R trafficking, p42/44 ERK activation, or COX-2 expression; but they did inhibit AngII-induced calcium responses. SII-AngII stimulated AT(1A)R trafficking and increased COX-2 protein expression without activating intracellular calcium release. These data suggest that G protein activation results in increased COX-2 protein expression, but AngII-induced COX-2 expression seems to occur independently of G protein activation.

Visual impairment following stroke: do stroke patients require vision assessment?

BACKGROUND: the types of visual impairment followings stroke are wide ranging and encompass low vision, eye movement and visual field abnormalities, and visual perceptual difficulties. OBJECTIVE: the purpose of this paper is to present a 1-year data set and identify the types of visual impairment occurring following stroke and their prevalence. METHODS: a multi-centre prospective observation study was undertaken in 14 acute trust hospitals. Stroke survivors with a suspected visual difficulty were recruited. Standardised screening/referral and investigation forms were employed to document data on visual impairment specifically assessment of visual acuity, ocular pathology, eye alignment and movement, visual perception (including inattention) and visual field defects. RESULTS: three hundred and twenty-three patients were recruited with a mean age of 69 years [standard deviation (SD) 15]. Sixty-eight per cent had eye alignment/movement impairment, 49% had visual field impairment, 26.5% had low vision and 20.5% had perceptual difficulties. CONCLUSIONS: of patients referred with a suspected visual difficulty, only 8% had normal vision status confirmed on examination. Ninety-two per cent had visual impairment of some form confirmed which is considerably higher than previous publications and probably relates to the prospective, standardised investigation offered by specialist orthoptists. However, under-ascertainment of visual problems cannot be ruled out.

The Hospital (Not So) Quiet Zone: Creating an Environment for Patient Satisfaction Through Noise Reduction Strategies.

PURPOSE: To determine whether using existing noise reduction strategies improves patients' overall satisfaction level during hospitalization on an adult outpatient cardiology unit and to assess whether noise reduction strategies were effective to decrease the ambient noise for both staff and patient environments. BACKGROUND: Excessive noise is a worldwide problem facing hospitals today. Noise has been proven to be detrimental to staff and patient well-being and hospital environment satisfaction levels. INTERVENTION: Staff noise perception online surveys, a poster presentation, and education of noise reduction strategies were completed. Two 6-week phases of pre- and postimplementation noise reduction strategies were initiated including closing of the doors, verbal and visual alarm reminders for staff, posting quiet signs, and limiting equipment through the unit. Patient telephone interviews regarding the noise environment during hospitalization in both phases and a follow-up staff noise perception online survey were completed. RESULTS: Staff surveys identified noise as an issue on the unit with staff communication (90%) being the main source. This correlated with patient surveys of five rooms closest to the desk considering the unit "noisy." Post-implementation patient surveys noted that strategies created in helping the unit become "quiet/mostly quiet." Closing patient doors was most effective in noise reduction, increasing patient unit satisfaction. CONCLUSION: The use of visual cues and staff education are effective in reducing noise levels. Decreased noise levels improved overall patient satisfaction with their hospital experience and created a less stressful work environment.

The use of antiembolic stockings. part 2: a clinical audit.

AIM: To audit current practice regarding selection and use of graduated elastic compression stockings (GECS) in the authors' Trust. Following a literature review it was important for the Trust that the authors audited current practice before the development and implementation of any new guidelines. BACKGROUND: A literature review enabled the authors to establish best practice principles for the use of GECS and develop guidelines for use across their Trust. However, feedback from various sources highlighted conflicting practices regarding the methods by which patients either did or did not receive stockings, and which lengths and brands were used. As the guidelines aimed to allow implementation of standardized change across the Trust, it was important to establish current practice with regard to GECS selection and use. Therefore, an audit tool was developed carried out on the use of GECS. METHODS: An audit tool was developed and implemented to establish the practices before the implementation of the guidelines. RESULTS: The audit demonstrated that there was no consistent policy within the surgical services directorate for the correct use of GECS. CONCLUSIONS: It is important that all healthcare providers have a local policy for GECS use, which makes it clear how an assessment for patients requiring GECS needs to be conducted and how that assessment is documented.

Graduated compression stockings to prevent deep vein thrombosis.

This article describes the correct use and length of graduated elastic compression stockings to prevent deep vein thrombosis (DVT) in general surgical patients. The authors aim to establish whether above or below knee stockings are more effective in the prevention of DVTs, discuss anti-embolic prophylaxis and offer advice on the appropriate management of patients.

Australian final year nursing students' and registered nurse supervisors' perceptions of a gerontology clinical learning experience: A preliminary appraisal.

Current international research suggests universities providing nursing education should focus on shifting students' attitudes towards valuing clinical learning derived from aged care settings, offering support and education for aged care facility staff supervising nursing students' learning in the aged care setting, and encouraging nursing graduates to consider pursuing careers in gerontology nursing. Against this international backdrop, one Australian School of Nursing designed a structured clinical learning experience to offer final year nursing students an opportunity to further their knowledge and understanding of the complexities of the role of the gerontology registered nurse. Additionally, this clinical learning experience included provision for nursing academics to offer support and expertise to the aged care facility staff around the role of supervising and assessing final year nursing students' clinical learning. The aim of this paper is to present fifteen final year nursing students' and nine registered nurse supervisors' evaluations of the gerontology clinical learning experience and the success of the learning experience towards meeting the project aims. Mostly participants reported positive experiences and agreed the experience illuminated the role of the gerontology registered nurse. Participants in this study also provided suggestions about the benefits and barriers of the clinical learning experience.

The use of antiembolic stockings. Part 1: a literature review.

AIM: To determine, through literature review, the current best practice for selecting and using graduated elastic compression stockings (GECS). In particular, literature was sought to clarify which patients should be given GECS, and whether there were any underlying research recommendations as to which length of stocking should be worn. BACKGROUND: A procurement exercise identified that the clinical areas within the Surgical Services Directorate at each of the three hospital sites were spending significantly different amounts of money on the purchase of GECS and purchasing significantly different numbers per ward. Further analysis revealed that different hospital sites had different preferences for either knee-length or thigh-length stockings. Nurses and medical staff gave conflicting ideas for the correct use and type of stockings, which prompted the authors to access the literature to establish best guidelines. METHODS: A literature review was used to develop best practice guidelines for the use of GECS. RESULTS: There is good evidence from the literature demonstrating that the use of GECS in patients undergoing surgery can be effective in the prevention of deep vein thrombosis, used in conjunction with drug therapy, other prophylactic methods, or alone. CONCLUSIONS: There is strong evidence for the use of knee-length stockings instead of thigh-length stockings. It is critically important that patients are thoroughly assessed prior to the application of GECS.

High-Flow Nasal Cannula Utilization in Pediatric Critical Care.

BACKGROUND: High-flow nasal cannula (HFNC) is increasingly utilized in pediatrics, delivering humidified air and oxygen for respiratory conditions causing hypoxia and distress. In the neonatal ICU, it has been associated with better tolerance, lower complications, and lower cost. Few data exist regarding indications for use and the epidemiology of disease/pathology that warrants HFNC in the pediatric ICU. METHODS: This study is a retrospective cohort study of patients admitted to a tertiary children's hospital pediatric ICU and placed on HFNC from October 1, 2011 to October 31, 2013. Descriptive statistics were used to describe demographics and utilization data. t test comparisons were used for comparison data. RESULTS: Over the enrollment study period, 620 subjects with HFNC were managed, which represented 27% of total ICU admissions. The average age was 3.74 y (range 0-18.1 y), and subjects were 44% female and 65% African American. Reported primary indications for the utilization of HFNC were status asthmaticus (24%), status asthmaticus with pneumonia (17%), and bronchiolitis (16%). Of the subjects admitted with a primary diagnosis of status asthmaticus, 41% required management with terbutaline. Respiratory viral infections were detected by polymerase chain reaction in 334 subjects managed with HFNC (53.8%) and included 260 subjects testing positive for rhinovirus/enterovirus. When compared with all other respiratory viral illness, subjects with rhinovirus/enterovirus required a higher peak flow (14.9 L vs 13.1 L, P = .01); however, this was an older population, and peak oxygen concentration did not differ between the 2 groups (49.8% vs 47.1%, P = .25). HFNC was used as postextubation support in 16% of the subjects. Of the 63 subjects with congenital heart disease, 92% of the utilization was postextubation. CONCLUSIONS: HFNC was utilized in 27% of all pediatric ICU admissions for a wide range of indications. Development of protocols for the initiation, escalation, and weaning of HFNC would optimize the utilization.

Setting standards for planning off duty and audit of practice.

The off duty or rostering system is an important part of managing any ward or department. This article looks at the issues that need to be considered when drawing up and managing off duty. It recommends standards for off-duty planning and shares the results of an audit carried out against some of these standards in one NHS trust.

A novel mutation in the lysyl hydroxylase 1 gene causes decreased lysyl hydroxylase activity in an Ehlers-Danlos VIA patient.

The clinical diagnosis of a patient with the phenotype of Ehlers-Danlos syndrome type VI was confirmed biochemically by the severely diminished level of lysyl hydroxylase (LH) activity in the patient's skin fibroblasts. A novel homozygous mutation, a single base change of T(1360)-->G in exon 13 of the LH1 gene, predicted to result in W446G, was identified in the patient's full-length cDNA. This was confirmed in genomic DNA from both the patient and her parents, who were heterozygous for the mutation. This mutation was introduced into an LH1-pAcGP67 baculoviral construct and expressed, in parallel with normal LH1, in an insect cell system. The loss of LH activity in the mutated recombinant construct confirmed the pathogenicity of this mutation. Although not in the major catalytic site, this mutation occurs in a highly conserved region of the LH1 gene and may contribute to loss of activity by interfering with normal folding of the enzyme.

Tissue-specific expression and regulation of the alternatively-spliced forms of lysyl hydroxylase 2 (LH2) in human kidney cells and skin fibroblasts.

Lysyl hydroxylases 1, 2, and 3 catalyse the hydroxylation of specific lysines in collagen. A small percentage of these hydroxylysine residues are precursors for the cross-link formation essential for the tensile strength of collagen. Lysyl hydroxylase 2 (LH2) exists as two alternatively-spliced forms; the long transcript (the major ubiquitously-expressed form) includes a 63 bp exon (13A) that is spliced out in the short form (expressed, together with the long form, in human kidney, spleen, liver, and placenta). This study shows that this alternative splicing event can be regulated by both cell density and cycloheximide (CHX). Although only the long form of LH2 is detected in untreated confluent human skin fibroblasts, after 24 h treatment with CHX the short LH2 transcript is also expressed. In kidney cells, in which both LH2 transcripts are equally expressed, the long LH2 transcript is significantly decreased after 24 h CHX treatment, whereas expression of the short transcript is slightly increased. This suggests that, in kidney cells, the splicing mechanism for the inclusion of exon 13A in LH2 requires a newly-synthesized protein factor that is suppressed by CHX, whereas, in skin fibroblasts in which levels of LH2 (long) are unaffected, CHX appears to suppress a factor that inhibits exclusion of exon 13A, thereby promoting expression of LH2 (short). As these alternate transcripts of LH2 may have specificity for hydroxylation of lysines in either telopeptide or helical collagen domains, their relative expression determines the type of cross-links formed, thereby affecting collagen strength. Therefore, any perturbation of the regulation of LH2 splicing could influence the stability of the extracellular matrix and contribute to specific connective tissue disorders.

An Ehlers-Danlos syndrome type VIA patient with cystic malformations of the meninges.

We have characterized a patient with the phenotype of Ehlers-Danlos syndrome type VIA (EDS VIA: kyphoscoliotic form), accompanied by the unique feature of cystic malformations of the meninges, to be homozygous for a large duplication of 8.9 kb in the lysyl hydroxylase 1 (LH1) gene that is the cause of severely decreased levels of LH activity in her skin fibroblasts. Electrophoresis of full length cDNA for LH1, prepared from the patient's fibroblasts and amplified by PCR, showed an abnormally large DNA fragment indicative of a duplication mutation; this mutation was confirmed in genomic DNA by PCR using duplication-specific primers and sequence analysis of the duplication junction. The homozygosity of this mutation was confirmed by analysis of DNA from the unaffected parents which showed them to be carriers of this duplication. This seven exon duplication is the most common mutation in the LH1 gene in patients with EDS VIA and occurs via a homologous recombination of Alu sequences in introns 9 and 16. Using the data from this study and other recent reports, we have updated the allele frequency for this mutation, based on 19 duplicated alleles out of a total of 104 genetically independent alleles from 53 EDS VIA families, to be 18.3%.