Service user experience of the Norfolk youth service

Purpose: There is an international drive to improve mental health services for young people. This study aims to investigate service user experience of a youth mental health service in Norfolk, UK. In addition to suggesting improvements to this service, recommendations are made for the development of youth mental health services in general. Design/methodology/approach: A mixed-methods approach was used. Quantitative data from satisfaction questionnaires were analysed using descriptive statistics and compared between two time points. A semi-structured interview was used to generate qualitative data. Thematic analysis was used to identify themes in the interview transcripts and triangulation was used to synthesise quantitative and qualitative data. Findings: Service users appeared satisfied with the service. Significant improvements in satisfaction were found between two time points. Qualitative analysis identified three main themes that were important to service users, including support, information and personhood. Practical implications: Recommendations for the development of youth mental health services are provided. Although these are based on findings from the Norfolk youth service, they are likely to apply to other mental health services for young people. Originality/value: Mental health care for young people requires significant improvement. The Norfolk youth service is one of the first services of its kind in the UK. The findings from this study might be helpful to consider in the development of youth mental health services across the world

The role of Yes-associated protein (YAP) in vertebrate development

Yes-associated protein 65 (YAP) contains multiple protein-protein interaction domains and functions as both a transcriptional co-activator and as a scaffolding protein within the cytoplasm or nucleus. Given that YAP binds to so many proteins that are critical for proper embryonic development and that this factor functions as a transcriptional co-activator, YAP likely plays an important role during early embryonic development. Given that YAP knockout mice struggled to progress normally through early development, in part because of nutritional deficiencies, we sought to better characterize a role for YAP during this time period by using embryos that develop externally: Xenopus laevis and Danio rerio. YAP morpholino (MO)-mediated loss-of-function resulted in a delay of mesoderm induction and severely impaired A-P axis elongation, phenotypes that were similar to YAP-/- mice. YAP gain-of-function experiments in Xenopus laevis expanded the progenitor populations in the neural plate and neural plate border zone, while concomitantly inhibiting differentiation markers for the neural crest, preplacodal ectoderm, hatching gland, epidermis, and somitic muscle. Regulation of gene expression is critically important in development and improper regulation of gene expression can lead to a variety of developmental defects, such as loss of conceptus, birth defects, and cancer. I found that yap expression is controlled by a TATA-less promoter, which includes a GC box where Sp1 binds and regulates yap transcription. I also found that adrenomedullin, a multifunctional peptide hormone known to act as a vasodilator, angiogenic factor, regulator of placental development, and tumor growth promoter, is a newly identified, putative target of YAP. These studies demonstrate that YAP is involved in the process of cell differentiation and the lack or overabundance of YAP protein disrupts the developmental time line of vertebrates with grievous consequences. Understanding the mechanistic details of these effects involve delineating the transcriptional control of YAP and its target genes. In the future, elucidating the linkage between YAP, the nuclear architecture, and transcriptional regulation will bolster our understanding of cell differentiation

Genetic lesions within the 3a gene of SARS-CoV

A series of frameshift mutations within the 3a gene has been observed in culture-derived severe acute respiratory syndrome coronavirus (SARS-CoV). We report here that viral RNA from clinical samples obtained from SARS-CoV infected patients also contains a heterogeneous population of wild-type and mutant 3a transcripts.Web of Scienc

Getting it Right: study protocol to determine the diagnostic accuracy of a culturally-specific measure to screen for depression in Aboriginal and/or Torres Strait Islander people

Abstract Introduction: A freely available, culturally valid depression screening tool is required for use by primary care services across Australia to screen for depression in Aboriginal and/or Torres Strait Islander populations. This is the protocol for a study aiming to determine the validity, sensitivity and specificity of the culturally adapted 9-item Patient Health Questionnaire (aPHQ-9). Methods and analysis: Cross sectional validation study. A total of 500 people who self-identify as Aboriginal and/or Torres Strait Islander, are ≥ 18 years of age, attending one of 10 primary health care services or service events across Australia and able to communicate sufficiently to answer study questions will be recruited. All participants will complete the aPHQ-9 and the criterion standard MINI International Neuropsychiatric Interview (MINI) 6.0.0. The primary outcome is criterion validity of the aPHQ-9. Process outcomes related to acceptability and feasibility of the aPHQ-9 will be analysed only if the measure is found to be valid. Ethics and dissemination: Lead ethical approval was obtained jointly from the University of Sydney Human Research Ethics Committee (project 2014/361) and the Aboriginal Health and Medical Research Council of New South Wales (project 1044/14). Results will be disseminated via the usual scientific forums including peer-reviewed publications and presentations at international conferences following presentation to, discussion with and approval by participating primary health care service staff and community. Study registration number: ACTRN1261400070568

The effect of a youth mental health service model on access to secondary mental healthcare for young people aged 14–25 years

Aims and method: The Norfolk Youth Service was created in 2012 in response to calls to redesign mental health services to better meet the needs of young people. The new service model transcends traditional boundaries by creating a single, ‘youth friendly’ service for young people aged 14–25 years. The aim of this study was to investigate the effect of the transition to this new model on patterns of referral, acceptance and service use. We analysed routinely collected data on young people aged 14–25 years referred for secondary mental healthcare in Norfolk before and after implementation of the youth mental health service. The number of referrals, their age and gender, proportion of referrals accepted and average number of service contacts per referral by age pre- and post-implementation were compared. Results: Referrals increased by 68% following implementation of the new service model, but the proportion of referrals accepted fell by 27 percentage points. Before implementation of the youth service, there was a clear discrepancy between the peak age of referral and the age of those seen by services. Following implementation, service contacts were more equitable across ages, with no marked discontinuity at age 18 years. Clinical implications: Our findings suggest that the transformation of services may have succeeded in reducing the ‘cliff edge’ in access to mental health services at the transition to adulthood. However, the sharp rise in referrals and reduction in the proportion of referrals accepted highlights the importance of considering possible unintended consequences of new service models. Declaration of interests: None

Cellular Characterization of SARS Coronavirus Nucleocapsid

The Severe and Acute Respiratory Syndrome coronavirus (SARS CoV) is a newly-emerged virus that caused an outbreak of atypical pneumonia in the winter of 2002-2003. Polyclonal antibodies raised against the nucleocapsid (N) of the SARS CoV showed the localization of N to the cytoplasm and the nucleolus in virus-infected and N-expressing Vero E6 cells. Like other coronavirus N proteins, the SARS N is probably a phosphoprotein. N protein expressed in mammalian cells is apparently able to “spread” to neighboring cells. For N to spread to neighboring cells, it must be exported out of the expressing cells. This is shown by the immunoprecipitation of N from the culture medium of a stable cell line expressing myc-N. Deletion studies showed that the 27 kD C-terminal domain of N (C1/2) is the minimal region of N that can spread to other cells. The nucleolar localization and spreading of N are artefacts of fixation, reminiscent of other protein-transduction domain (PTD)-containing proteinsWeb of Scienc

A Novel Severe Acute Respiratory Syndrome Coronavirus Protein, U274, is transported to the Cell Surface and undergoes Endocytosis

The severe acute respiratory syndrome coronavirus (SARS-CoV) genome contains open reading frames (ORFs) that encode for several genes that are homologous to proteins found in all known coronaviruses. These are the replicase gene 1a/1b and the four structural proteins, nucleocapsid (N), spike (S), membrane (M), and envelope (E), and these proteins are expected to be essential for the replication of the virus. In addition, this genome also contains nine other potential ORFs varying in length from 39 to 274 amino acids. The largest among these is the first ORF of the second longest subgenomic RNA, and this protein (termed U274 in the present study) consists of 274 amino acids and contains three putative transmembrane domains. Using antibody specific for the C terminus of U274, we show U274 to be expressed in SARS-CoV-infected Vero E6 cells and, in addition to the full-length protein, two other processed forms were also detected. By indirect immunofluorescence, U274 was localized to the perinuclear region, as well as to the plasma membrane, in both transfected and infected cells. Using an N terminus myc-tagged U274, the topology of U274 and its expression on the cell surface were confirmed. Deletion of a cytoplasmic domain of U274, which contains Yxx and diacidic motifs, abolished its transport to the cell surface. In addition, U274 expressed on the cell surface can internalize antibodies from the culture medium into the cells. Coimmunoprecipitation experiments also showed that U274 could interact specifically with the M, E, and S structural proteins, as well as with U122, another protein that is unique to SARS-CoV.Web of Scienc

Accelerated in vivo cardiac diffusion-tensor MRI using residual deep learning–based denoising in participants with obesity

Purpose: To develop and assess a residual deep learning algorithm to accelerate in vivo cardiac diffusion-tensor MRI (DT-MRI) by reducing the number of averages while preserving image quality and DT-MRI parameters. Materials and Methods: In this prospective study, a denoising convolutional neural network (DnCNN) for DT-MRI was developed; a total of 26 participants, including 20 without obesity (body mass index [BMI], 30 kg/m2; mean age, 28 years 6 3 [standard deviation]; 11 women) and six with obesity (BMI 30 kg/m2; mean age, 48 years 6 11; five women), were recruited from June 19, 2019, to July 29, 2020. DT-MRI data were constructed at four averages (4Av), two averages (2Av), and one average (1Av) without and with the application of the DnCNN (4AvDnCNN, 2AvDnCNN, 1AvDnCNN). All data were compared against the reference DT-MRI data constructed at eight averages (8Av). Image quality, characterized by using the signal-to-noise ratio (SNR) and structural similarity index (SSIM), and the DT-MRI parameters of mean diffusivity (MD), fractional anisotropy (FA), and helix angle transmurality (HAT) were quantified. Results: No differences were found in image quality or DT-MRI parameters between the accelerated 4AvDnCNN DT-MRI and the reference 8Av DT-MRI data for the SNR (29.1 6 2.7 vs 30.5 6 2.9), SSIM (0.97 6 0.01), MD (1.3 μm2/msec 6 0.1 vs 1.31 μm2/msec 6 0.11), FA (0.32 6 0.05 vs 0.30 6 0.04), or HAT (1.10°/% 6 0.13 vs 1.11°/% 6 0.09). The relationship of a higher MD and lower FA and HAT in individuals with obesity compared with individuals without obesity in reference 8Av DT-MRI measurements was retained in 4AvDnCNN and 2AvDnCNN DT-MRI measurements but was not retained in 4Av or 2Av DT-MRI measurements. Conclusion: Cardiac DT-MRI can be performed at an at least twofold-accelerated rate by using DnCNN to preserve image quality and DT-MRI parameter quantification

Enaminone Modulators of Extrasynaptic α4β3δ γ-Aminobutyric AcidA Receptors Reverse Electrographic Status Epilepticus in the Rat After Acute Organophosphorus Poisoning

Seizures induced by organophosphorus nerve agent exposure become refractory to treatment with benzodiazepines because these drugs engage synaptic γ-aminobutyric acid-A receptors (GABAARs) that rapidly internalize during status epilepticus (SE). Extrasynaptic GABAARs, such as those containing α4β3δ subunits, are a putative pharmacological target to comprehensively manage nerve agent-induced seizures since they do not internalize during SE and are continuously available for activation. Neurosteroids related to allopregnanolone have been tested as a possible replacement for benzodiazepines because they target both synaptic and extrasynaptic GABAARs receptors. A longer effective treatment window, extended treatment efficacy, and enhanced neuroprotection represent significant advantages of neurosteroids over benzodiazepines. However, neurosteroid use is limited by poor physicochemical properties arising from the intrinsic requirement of the pregnane steroid core structure for efficacy rendering drug formulation problematic. We tested a non-steroidal enaminone GABAAR modulator that interacts with both synaptic and extrasynaptic GABAARs on a binding site distinct from neurosteroids or benzodiazepines for efficacy to control electrographic SE induced by diisopropyl fluorophosphate or soman intoxication in rats. Animals were treated with standard antidotes, and experimental therapeutic treatment was given following 1 h (diisopropyl fluorophosphate model) or 20 min (soman model) after SE onset. We found that the enaminone 2-261 had an extended duration of seizure termination (>10 h) in the diisopropyl fluorophosphate intoxication model in the presence or absence of midazolam (MDZ). 2-261 also moderately potentiated MDZ in the soman-induced seizure model but had limited efficacy as a stand-alone anticonvulsant treatment due to slow onset of action. 2-261 significantly reduced neuronal death in brain areas associated with either diisopropyl fluorophosphate- or soman-induced SE. 2-261 represents an alternate chemical template from neurosteroids for enhancing extrasynaptic α4β3δ GABAAR activity to reverse SE from organophosphorous intoxication

Soil water improvements with the long-term use of a winter rye cover crop

AbstractThe Midwestern United States, a region that produces one-third of maize and one-quarter of soybean grain globally, is projected to experience increasing rainfall variability. One approach to mitigate climate impacts is to utilize crop and soil management practices that enhance soil water storage and reduce the risks of flooding as well as drought-induced crop water stress. While some research indicates that a winter cover crop in maize-soybean rotations increases soil water availability, producers continue to be concerned that water use by cover crops will reduce water for a following cash crop. We analyzed continuous in-field soil water measurements from 2008 to 2014 at a Central Iowa research site that has included a winter rye cover crop in a maize-soybean rotation for thirteen years. This period of study included years in the top third of the wettest on record (2008, 2010, 2014) as well as drier years in the bottom third (2012, 2013). We found the cover crop treatment to have significantly higher soil water storage at the 0–30cm depth from 2012 to 2014 when compared to the no cover crop treatment and in most years greater soil water content on individual days analyzed during the cash crop growing season. We further found that the cover crop significantly increased the field capacity water content by 10–11% and plant available water by 21–22%. Finally, in 2013 and 2014, we measured maize and soybean biomass every 2–3 weeks and did not see treatment differences in crop growth, leaf area or nitrogen uptake. Final crop yields were not statistically different between the cover and no cover crop treatment in any of the seven years of this analysis. This research indicates that the long-term use of a winter rye cover crop can improve soil water dynamics without sacrificing cash crop growth in maize-soybean crop rotations in the Midwestern United States