Increasing Access to Mental Health Services: Videogame Players' Perspectives.

Young men's mental health is at the forefront of global public health concerns. Young males, who have a high incidence of mental health disorders, are a population that accesses services at lower rates than females and makes up the majority of videogame players. By considering the unique perspectives of digitally connected individuals on mental health service delivery, interventions may be designed to address their needs with a higher likelihood of success. This study investigated international male videogamers' perspectives on how their access to mental health services could be improved via an open-ended survey question. From a total of 2515 completed surveys, 761 responded to the qualitative question. Of these, the 71 responses that discussed access to and provision of mental healthcare services are reported in this article. Results suggest that digital mental health services were a promising way to reach this group. Anonymity and confidentiality were found to be important factors when considering online mental health services. Male videogame players identified a preference for both online and in-person services that are delivered synchronously, one-on-one with an expert practitioner, and readily available in settings that individuals find comfortable.

Can Isolated Discordant Atrioventricular Connections Survive Without Interatrial or Interventricular Shunt?

Clinical presentation of isolated discordant atrioventricular connections is akin to transposition of the great arteries. In the absence of a significant intracardiac shunt, profound cyanosis is expected at birth. We report one such 5-month-old infant who had only mild cyanosis. The left-sided tricuspid valve straddled the interventricular septum with a closed interventricular communication, a type of "Double Outlet Left Atrium with three atrioventricular valves," which provided the necessary "left to right" shunt while severe regurgitation through the straddling part and a patent ductus arteriosus provided the effective pulmonary blood flow.

Clinical outcomes of children and adolescents with sickle cell disease and COVID-19 infection: A year in review at a metropolitan tertiary pediatric hospital.

Background: COVID-19 was declared a global pandemic in March 2020. Early reports were primarily in adults, and sickle cell disease (SCD) was classified as a risk factor for severe COVID-19 disease. However, there are a limited number of primarily multi-center studies reporting on the clinical course of pediatric patients with SCD and COVID-19. Methods: We conducted an observational study of all patients with SCD diagnosed with COVID-19 at our institution between March 31, 2020, and February 12, 2021. Demographic and clinical characteristics of this group were collected by retrospective chart review. Results: A total of 55 patients were studied, including 38 children and 17 adolescents. Demographics, acute COVID-19 clinical presentation, respiratory support, laboratory findings, healthcare utilization, and SCD modifying therapies were comparable between the children and adolescents. Seventy-three percent (N = 40) of all patients required emergency department care or hospitalization. While 47% (N = 26) were hospitalized, only 5% (N = 3) of all patients required intensive care unit admission. Patients frequently had concurrent vaso-occlusive pain crisis (VOC) (N = 17, 43%) and acute chest syndrome (ACS) (N = 14, 35%). Those with ACS or an oxygen requirement had significantly higher white blood cell count, lower nadir hemoglobin, and higher D-dimers, supporting a pro-inflammatory and coagulopathic picture. Non-hospitalized patients were more likely to be on hydroxyurea than hospitalized patients (79 vs. 50%, p = 0.023). Conclusion: Children and adolescent patients with SCD and acute COVID-19 often present with ACS and VOC pain requiring hospital-level care. Hydroxyurea treatment appears to be protective. We observed no mortality despite variable morbidity.

Therapeutic targeting of tumour myeloid cells.

Myeloid cells are pivotal within the immunosuppressive tumour microenvironment. The accumulation of tumour-modified myeloid cells derived from monocytes or neutrophils - termed 'myeloid-derived suppressor cells' - and tumour-associated macrophages is associated with poor outcome and resistance to treatments such as chemotherapy and immune checkpoint inhibitors. Unfortunately, there has been little success in large-scale clinical trials of myeloid cell modulators, and only a few distinct strategies have been used to target suppressive myeloid cells clinically so far. Preclinical and translational studies have now elucidated specific functions for different myeloid cell subpopulations within the tumour microenvironment, revealing context-specific roles of different myeloid cell populations in disease progression and influencing response to therapy. To improve the success of myeloid cell-targeted therapies, it will be important to target tumour types and patient subsets in which myeloid cells represent the dominant driver of therapy resistance, as well as to determine the most efficacious treatment regimens and combination partners. This Review discusses what we can learn from work with the first generation of myeloid modulators and highlights recent developments in modelling context-specific roles for different myeloid cell subtypes, which can ultimately inform how to drive more successful clinical trials.

MmCMS: mouse models' consensus molecular subtypes of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) primary tumours are molecularly classified into four consensus molecular subtypes (CMS1-4). Genetically engineered mouse models aim to faithfully mimic the complexity of human cancers and, when appropriately aligned, represent ideal pre-clinical systems to test new drug treatments. Despite its importance, dual-species classification has been limited by the lack of a reliable approach. Here we utilise, develop and test a set of options for human-to-mouse CMS classifications of CRC tissue. METHODS: Using transcriptional data from established collections of CRC tumours, including human (TCGA cohort; n = 577) and mouse (n = 57 across n = 8 genotypes) tumours with combinations of random forest and nearest template prediction algorithms, alongside gene ontology collections, we comprehensively assess the performance of a suite of new dual-species classifiers. RESULTS: We developed three approaches: MmCMS-A; a gene-level classifier, MmCMS-B; an ontology-level approach and MmCMS-C; a combined pathway system encompassing multiple biological and histological signalling cascades. Although all options could identify tumours associated with stromal-rich CMS4-like biology, MmCMS-A was unable to accurately classify the biology underpinning epithelial-like subtypes (CMS2/3) in mouse tumours. CONCLUSIONS: When applying human-based transcriptional classifiers to mouse tumour data, a pathway-level classifier, rather than an individual gene-level system, is optimal. Our R package enables researchers to select suitable mouse models of human CRC subtype for their experimental testing.

RAC1B function is essential for breast cancer stem cell maintenance and chemoresistance of breast tumor cells.

Breast cancer stem cells (BCSC) are presumed to be responsible for treatment resistance, tumor recurrence and metastasis of breast tumors. However, development of BCSC-targeting therapies has been held back by their heterogeneity and the lack of BCSC-selective molecular targets. Here, we demonstrate that RAC1B, the only known alternatively spliced variant of the small GTPase RAC1, is expressed in a subset of BCSCs in vivo and its function is required for the maintenance of BCSCs and their chemoresistance to doxorubicin. In human breast cancer cell line MCF7, RAC1B is required for BCSC plasticity and chemoresistance to doxorubicin in vitro and for tumor-initiating abilities in vivo. Unlike Rac1, Rac1b function is dispensable for normal mammary gland development and mammary epithelial stem cell (MaSC) activity. In contrast, loss of Rac1b function in a mouse model of breast cancer hampers the BCSC activity and increases their chemosensitivity to doxorubicin treatment. Collectively, our data suggest that RAC1B is a clinically relevant molecular target for the development of BCSC-targeting therapies that may improve the effectiveness of doxorubicin-mediated chemotherapy.

Speech-Language Pathologists' Views of Using Virtual Reality for Managing Cognitive-Communication Disorders Following Traumatic Brain Injury.

PURPOSE: Using virtual reality (VR) to support rehabilitation is an emerging area of research that may offer people with communication disorders a stable and safe communication environment to practice their communication skills. There are currently no VR applications that have been designed to assess or treat cognitive-communication disorders (CCDs) following traumatic brain injury (TBI). Therefore, this study aimed to explore the views of speech-language pathologists (SLPs) who work with people who have a TBI to generate ideas and considerations for using VR in rehabilitation for CCDs. VR researchers were included to provide expert advice about VR technology. METHOD: A total of 14 SLPs and three VR specialists participated in an online interview or focus group. Semistructured discussions explored participants' perspectives related to potential ideas for VR use and any perceived barriers and facilitators to VR implementation for managing CCDs following TBI. Data were video- and audio-recorded, transcribed, and analyzed qualitatively using thematic analysis. RESULTS: Three main themes were generated from thematic analysis: VR is a tool that could enhance clinical practice, the need to consider and navigate potential red flags, and solutions to pave the way forward. Suggestions to overcome perceived barriers to VR use were also provided. DISCUSSION: Participants expressed interest in using VR for rehabilitation of CCDs following TBI. However, potential barriers and risks to use should be considered prior to implementation. The findings offer guidance to support future research and development of VR in this field. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21669647.

First-Gen Lens: Assessing Mental Health of First-Generation Students across Their First Year at College Using Mobile Sensing.

The transition from high school to college is a taxing time for young adults. New students arriving on campus navigate a myriad of challenges centered around adapting to new living situations, financial needs, academic pressures and social demands. First-year students need to gain new skills and strategies to cope with these new demands in order to make good decisions, ease their transition to independent living and ultimately succeed. In general, first-generation students are less prepared when they enter college in comparison to non-first-generation students. This presents additional challenges for first-generation students to overcome and be successful during their college years. We study first-year students through the lens of mobile phone sensing across their first year at college, including all academic terms and breaks. We collect longitudinal mobile sensing data for N=180 first-year college students, where 27 of the students are first-generation, representing 15% of the study cohort and representative of the number of first-generation students admitted each year at the study institution, Dartmouth College. We discuss risk factors, behavioral patterns and mental health of first-generation and non-first-generation students. We propose a deep learning model that accurately predicts the mental health of first-generation students by taking into account important distinguishing behavioral factors of first-generation students. Our study, which uses the StudentLife app, offers data-informed insights that could be used to identify struggling students and provide new forms of phone-based interventions with the goal of keeping students on track.

Predicting Brain Functional Connectivity Using Mobile Sensing.

Brain circuit functioning and connectivity between specific regions allow us to learn, remember, recognize and think as humans. In this paper, we ask the question if mobile sensing from phones can predict brain functional connectivity. We study the brain resting-state functional connectivity (RSFC) between the ventromedial prefrontal cortex (vmPFC) and the amygdala, which has been shown by neuroscientists to be associated with mental illness such as anxiety and depression. We discuss initial results and insights from the NeuroSence study, an exploratory study of 105 first year college students using neuroimaging and mobile sensing across one semester. We observe correlations between several behavioral features from students' mobile phones and connectivity between vmPFC and amygdala, including conversation duration (r=0.365, p<0.001), sleep onset time (r=0.299, p<0.001) and the number of phone unlocks (r=0.253, p=0.029). We use a support vector classifier and 10-fold cross validation and show that we can classify whether students have higher (i.e., stronger) or lower (i.e., weaker) vmPFC-amygdala RSFC purely based on mobile sensing data with an F1 score of 0.793. To the best of our knowledge, this is the first paper to report that resting-state brain functional connectivity can be predicted using passive sensing data from mobile phones.

Epithelial TGFß engages growth-factor signalling to circumvent apoptosis and drive intestinal tumourigenesis with aggressive features.

The pro-tumourigenic role of epithelial TGFß signalling in colorectal cancer (CRC) is controversial. Here, we identify a cohort of born to be bad early-stage (T1) colorectal tumours, with aggressive features and a propensity to disseminate early, that are characterised by high epithelial cell-intrinsic TGFß signalling. In the presence of concurrent Apc and Kras mutations, activation of epithelial TGFß signalling rampantly accelerates tumourigenesis and share transcriptional signatures with those of the born to be bad T1 human tumours and predicts recurrence in stage II CRC. Mechanistically, epithelial TGFß signalling induces a growth-promoting EGFR-signalling module that synergises with mutant APC and KRAS to drive MAPK signalling that re-sensitise tumour cells to MEK and/or EGFR inhibitors. Together, we identify epithelial TGFß signalling both as a determinant of early dissemination and a potential therapeutic vulnerability of CRC's with born to be bad traits.

The relationship between appraisals of auditory verbal hallucinations and real-time affect and social functioning.

In addition to being a hallmark symptom of schizophrenia-spectrum disorders, auditory verbal hallucinations (AVH) are present in a range of psychiatric disorders as well as among individuals who are otherwise healthy. People who experience AVH are heterogeneous, and research has aimed to better understand what characteristics distinguish, among those who experience AVH, those who experience significant disruption and distress from those who do not. The cognitive model of AVH suggests that appraisals of voices determine the extent to which voices cause distress and social dysfunction. Previous work has relied largely on comparisons of "clinical" and "non-clinical" voice hearers, and few studies have been able to provide insight into the moment-to-moment relationships between appraisals and outcomes. The current study examines longitudinal data provided through ecological momentary assessment and passive sensors of 465 individuals who experience cross-diagnostic AVH. Results demonstrated associations of AVH appraisals to negative affect and social functioning. Above and beyond within-individual averages, when a participant reported increased appraisals of their voices as powerful and difficult to control, they were more likely to feel increased negative affect and reduced feelings of safety. AVH power appraisals were also associated with next-day number and duration of phone calls placed, and AVH controllability appraisals were associated with increased time near speech and reduced next-day time away from primary location. These results suggest that appraisals are state-like characteristics linked with day-to-day and moment-to-moment changes in impactful affective and behavioral outcomes; intervention approaches should aim to address these domains in real-time.

Total Wrist Fusion with an Intramedullary Device: A Single-Institution Series with a Minimum of One Year Follow-Up.

Objective The primary purpose of this study was to evaluate the functional and surgical outcomes of total wrist fusion (TWF) following the use of a locked intramedullary nail (IMN). Methods A single institution study was performed, which entailed in-person reexamination of 18 patients ( n = 19 wrists), out of 35 eligible patients, who underwent TWF with an IMN from 2010 to 2017. For each patient, demographic, preoperative diagnosis, physical examination, wrist radiograph, and outcome questionnaire data were obtained. The questionnaires included the visual analog scale (VAS), quick disabilities of the arm, shoulder, and hand (QuickDASH), and Mayo Wrist Score assessments. In addition, complication and reoperation data for all TWFs with an IMN during the 2010 to 2017 period (35 patients, n I = 38 wrists) were noted. Results In the 18 patients, age was 47.6 ± 13.9 years, 12 (63.2%) were female, and median follow-up was 150 weeks (range: 74-294). The VAS score was 0 ± 0 in 5 of 19 wrists with rheumatoid arthritis (RA) and 1.82 ± 2.78 in 14 of 19 wrists without RA. It was found that 21 of 38 wrists (55.3%) had an implant-related complication and 5 wrists (13%) underwent a reoperation due to the implant itself. Conclusions To date, no sufficient data are present demonstrating a clear advantage of an IMN over dorsal plating for TWF at intermediate-term follow-up. Surgeons should be knowledgeable of the several potential complications of this IMN prior to its use for TWF. Level of Evidence This is a Level IV, therapeutic study.

Chicken antibodies are highly suitable for particle enhanced turbidimetric assays.

Antibody-based assays are commonly used in clinical laboratories for analyzing plasma, serum and other samples for particular protein markers. Although such assays have been traditionally based on antibodies raised in mammals (e.g., mice, rabbits, goats), there are several advantages of using avian antibodies (IgY) raised in chickens, including production volumes, costs, and ethical/animal welfare considerations. A further disadvantage of using mammalian IgG in such assays is the potential for agglutination when exposed to rheumatoid factor (RF) in serum. However, when used in the free form the immune complexes formed with avian antibodies have been reported to have less ability than those formed with mammalian antibodies to cause the light scatter which are used for instrument measurement. In addition, when the amount of antigen exceeds the maximum precipitating point in relation to the amount of antibody, there is a rapid decline in the absorbance values of the immune complexes (antigen excess) when IgY is used. However, when avian antibodies are conjugated to a substrate and used in particle enhanced turbidimetric assays (PETIA), these problems are avoided. Here we investigated three clinical assays using chicken antibodies, one using free (unbound) IgY and two with IgY-based PETIA. The IgY PETIA demonstrated a strong scatter response, even at high antigen concentrations in contrast to the steep decline seen with free IgY antibodies. IgY PETIA reagents can provide test results with low coefficient of variation (<1% for duplicate samples). We also investigated the effect of RF on agglutination of mammalian antibodies (IgG from mouse, rabbit, sheep, and human) and chicken antibodies. Whereas agglutination was observed with all the mammalian antibodies in the presence of RF, this was not observed at all with chicken IgY. Our results support the growing body of evidence that chicken egg yolks can thus be a valuable source of antibodies for use in PETIA in clinical laboratories.

Accuracy of determination of free light chains (Kappa and Lambda) in plasma and serum by Swedish laboratories as monitored by external quality assessment.

BACKGROUND: Free light chain (FLC) measurements are important in diagnosing monoclonal gammopathies. As FLC are heterogeneous, different reagents and instruments for measuring FLC concentrations may give diverging results that affect assessment of patients with monoclonal gammopathies. Here we investigated agreement between different FLC methods using data from the Swedish external quality assurance (EQA) programme. METHODS: The two main FLC assays, N Latex FLC (Siemens) and Serum Freelite (The Binding Site), using four nephelometric or turbidimetric instrument platforms, were compared. Results from 27 EQA rounds distributed to 11-16 Swedish hospital laboratories during 2015-2020 were investigated. RESULTS: The kappa (κ) FLC measurements deviated significantly over time, but when only nephelometry was used, deviation from the mean was lower (median ranges: -5% to 13 %). The CV was significantly higher for the Freelite assay (mean CV = 8.7) than for the N latex assay (mean CV = 5.7) (p < 0.0001). The coefficient of determination between all combinations of reagents and instrument platforms used was generally good (r2 = 0.76-0.87), and the correlation slope acceptable (0.81-1.2). For lambda (λ) FLC measurements, no concordance between combinations of instruments and reagents is apparent, deviating between -40 % to + 48 % from the mean. The CV was significantly higher for the combination with nephelometry and the Freelite assay (CV mean = 13.9 %) than nephelometry and the N latex assay (CV mean = 9.9 %) (p <0.001). The coefficient of determination varied between combinations of reagents and instrument platforms (r2 = 0.59-0.89) and the slope ranged between 0.48 and 1.5. Significant differences between the two reagents used were sometimes noted. CONCLUSIONS: Imprecision in λFLC affects the κFLC/λFLC ratio. This may be important in clinical assessment of patients, especially differentiating between monoclonal and polyclonal gammopathies.

Consensus definition of essential, optimal, and suggested components of a pediatric sickle cell disease center.

Sickle cell disease (SCD) requires coordinated, specialized medical care for optimal outcomes. There are no United States (US) guidelines that define a pediatric comprehensive SCD program. We report a modified Delphi consensus-seeking process to determine essential, optimal, and suggested elements of a comprehensive pediatric SCD center. Nineteen pediatric SCD specialists participated from the US. Consensus was predefined as 2/3 agreement on each element's categorization. Twenty-six elements were considered essential (required for guideline-based SCD care), 10 were optimal (recommended but not required), and five were suggested. This work lays the foundation for a formal recognition process of pediatric comprehensive SCD centers.

Healthy plant-based diets and their short-term effects on weight loss, nutrient intake and serum cholesterol levels.

Healthy plant-based diets (hPBD) are being promoted to reduce the risks of cardiovascular and associated diseases. This study investigates short-term adherence to a hPBD to examine whether these dietary changes impact weight and cardiovascular risk factors. A simple, uncontrolled, before and after design was used. Twenty women (mean BMI 31 ± 4 kg/m2 ) participated in a 6-week hPBD intervention. Participants completed a 3-week reset, eliminating all refined sugar, heavily processed foods, artificial sweeteners, alcohol, meat, fish, dairy and oil from their diets, which could then be reintroduced into their diet if the participant chose to do so. Participants had 1-h, weekly group support sessions. A weight loss of 4.4 kg, SD = 1.8 kg (n = 17, t = 10.2, p < 0.001) was observed after 6 weeks following the hPBD. BMI reduced from 31 to 29 kg/m2 (mean reduction = 1.38, SD = 0.76, n = 17, t = 7.49, p < 0.001). Reductions for waist circumference (mean reduction = 4.4 cm, SD = 5.22 cm, n = 8, t = 2.55, p = 0.034), LDL cholesterol (mean reduction = 0.600 mmol/L, SD = 0.828, n = 17, t = 2.81, p = 0.014) and total cholesterol (mean = 0.525 mmol/L, SD = 0.969, n = 17, t = 2.24, p = 0.040) were also observed. Body fat % was not significantly reduced (mean reduction = 2.3, SD = 6.6, n = 17, t = 1.49, p = 0.154). Dietary data were obtained from 17 participants at week 3 and from six participants at week 6. Energy intake at week 3 decreased compared with baseline (mean reduction = 1068 kcal/day, SD = 585 kcal, n = 17, t = 7.07, p < 0.001) and at week 6 (mean reduction = 715 kcal, SD = 645 kcal, n = 6, t = 2.72, p = 0.042). Protein, saturated fat and cholesterol intakes were also lower at weeks 3 and 6 compared with baseline. Fibre intake increased significantly from baseline to week 6 (mean increase = 11.3 g/day, SD = 8.9, n = 6, t = 3.11, p = 0.027) whilst sugar intake decreased from baseline to week 3 (mean reduction = 26.0 g/day, SD = 22.3, n = 17, t = 4.52, p < 0.001), but the reduction at week 6 was not significant. These results suggest that motivated participants can learn to adopt new dietary patterns for a few weeks at least with some support. This study demonstrated positive effects of a hPBD on weight reduction, cholesterol and BMI over a short time period, although the short- and long-term adherence to this diet requires further research.

Amino acid signature during sickle cell pain crisis shows significant alterations related to nitric oxide and energy metabolism.

Nitric oxide depletion secondary to arginase induced arginine deficiency has been shown to be important in the pathophysiology of vaso-occlusion in sickle cell pain crisis. Our objective of this study was to perform a comprehensive amino acid evaluation during sickle cell pain crisis. In a total of 58 subjects (29 in steady-state sickle cell disease and 29 with sickle cell pain crisis), the amino acids related to nitric oxide pathway was significantly decreased during sickle cell pain crisis compared to steady-state sickle cell disease: arginine (p = 0.001), citrulline (p = 0.012), and ornithine (p = 0.03). In addition, the amino acids related to energy metabolism was significantly decreased during a pain crisis: asparagine (p < 0.001), serine (p = 0.002), histidine (p = 0.017), alanine (p = 0.004), tyrosine (p = 0.012), methionine (p = 0.007), cystine (p = 0.016), isoleucine (p = 0.016) and lysine (p = 0.006). The amino acid related to oxidative stress were significantly higher during a sickle cell pain crisis (glutamic acid (p < 0.001). Furthermore, multivariate analysis with partial least squares-discriminant analysis (PLS-DA) showed that deficiencies of the amino acids arginine, asparagine, citrulline, methionine and alanine were the most important related to sickle cell pain crisis.

Online Group Counseling for Young People Through a Customized Social Networking Platform: Phase 2 of Kids Helpline Circles.

There is a growing need for high-quality evidence to support the efficacy of online counseling and peer support via social networking sites (SNSs) as an intervention to reduce mental health symptoms in young people. This article presents Phase 2 of Kids Helpline (KHL) Circles, which used mixed methods to assess the acceptability, safety, user experience, and mental health benefits of a purpose-built, counselor-facilitated SNS. Young people aged 13-25 years (n = 552) were recruited to participate in one of six 8-week "Circles." Of those, 154 participants completed study surveys at three timepoints (baseline, midpoint, endpoint). Significant reductions in depression, anxiety, stress, and general distress symptoms were reported at the midpoint of the intervention, with further significant reductions in depression and stress symptoms by the endpoint. More than half said that their mental health improved as a direct result of KHL Circles, and most felt less mental health stigma and would be more willing to seek help for mental health issues in the future. These results contribute to increasing the evidence base for SNS interventions to reduce mental health symptoms. Adjustments are necessary for the ongoing evolution of this service to ensure it is user-centered and scientifically rigorous.