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1.
BMJ Open ; 14(5): e081924, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38692715

ABSTRACT

OBJECTIVES: Adverse childhood experiences (ACEs) can affect individuals' resilience to stressors and their vulnerability to mental, physical and social harms. This study explored associations between ACEs, financial coping during the cost-of-living crisis and perceived impacts on health and well-being. DESIGN: National cross-sectional face-to-face survey. Recruitment used a random quota sample of households stratified by health region and deprivation quintile. SETTING: Households in Wales, UK. PARTICIPANTS: 1880 Welsh residents aged ≥18 years. MEASURES: Outcome variables were perceived inability to cope financially during the cost-of-living crisis; rising costs of living causing substantial distress and anxiety; and self-reported negative impact of rising costs of living on mental health, physical health, family relationships, local levels of antisocial behaviour and violence, and community support. Nine ACEs were measured retrospectively. Socioeconomic and demographic variables included low household income, economic inactivity, residential deprivation and activity limitation. RESULTS: The prevalence of all outcomes increased strongly with ACE count. Perceived inability to cope financially during the cost-of-living crisis increased from 14.0% with 0 ACEs to 51.5% with 4+ ACEs. Relationships with ACEs remained after controlling for socioeconomic and demographic factors. Those with 4+ ACEs (vs 0 ACEs) were over three times more likely to perceive they would be unable to cope financially and, correspondingly, almost three times more likely to report substantial distress and anxiety and over three times more likely to report negative impacts on mental health, physical health and family relationships. CONCLUSIONS: Socioeconomically deprived populations are recognised to be disproportionately impacted by rising costs of living. Our study identifies a history of ACEs as an additional vulnerability that can affect all socioeconomic groups. Definitions of vulnerability during crises and communications with services on who is most likely to be impacted should consider childhood adversity and history of trauma.


Subject(s)
Adaptation, Psychological , Adverse Childhood Experiences , Humans , Wales , Cross-Sectional Studies , Male , Female , Adverse Childhood Experiences/statistics & numerical data , Adverse Childhood Experiences/economics , Adult , Middle Aged , Adolescent , Young Adult , Aged , Mental Health , Surveys and Questionnaires , Anxiety/epidemiology , Anxiety/psychology , Financial Stress/psychology
2.
BMJ Case Rep ; 17(5)2024 May 21.
Article in English | MEDLINE | ID: mdl-38772869

ABSTRACT

Antiphospholipid antibody syndrome is an autoimmune condition with clinical manifestations of vascular thrombosis and adverse pregnancy outcomes including recurrent miscarriage, fetal loss, growth restriction and pre-eclampsia with persistent antiphospholipid antibodies on laboratory examination. Treatment is targeted at preventing recurrent thrombosis and improving pregnancy outcomes. Commonly, treatment includes aspirin and anticoagulation, however, newer immunomodulatory treatments may also improve outcomes. The case describes a patient with a history of multiple miscarriages and pregnancy losses, fetal growth restriction and pre-eclampsia, and pulmonary embolism. Because of her significant adverse pregnancy outcomes, she was treated with certolizumab with a successful delivery at 33 weeks and 6 days. She also developed acute pancreatitis in the postpartum period. This is a rare condition, affecting 1-14/10 000 births. The pancreatitis resolved with conservative management, and she had an uncomplicated interval cholecystectomy.


Subject(s)
Antiphospholipid Syndrome , Pancreatitis , Pregnancy Complications , Humans , Female , Pregnancy , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/drug therapy , Pancreatitis/immunology , Pancreatitis/complications , Pancreatitis/etiology , Pancreatitis/diagnosis , Adult , Peripartum Period , Pregnancy Outcome
3.
Adv Neonatal Care ; 24(1): E2-E10, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38181670

ABSTRACT

BACKGROUND: Problematic feeding is common in infancy, particularly in infants with a history of premature birth or medical complexity. A concise, valid, and reliable measure of feeding that can be used across feeding methods is needed for clinical practice and research. PURPOSE: The purpose of this study was to create an assessment tool to evaluate symptoms of problematic feeding in infants that can be used across all feeding methods (breastfeeding, bottle-feeding, and mixed feeding), then test its psychometric properties and establish reference values. METHODS: Item response theory (IRT) was used to identify the most important items on the Neonatal Eating Assessment Tool (NeoEAT) related to symptoms of problematic feeding in infants (N = 1054) to create the Infant Eating Assessment Tool (InfantEAT). Reliability of the InfantEAT was tested using Cronbach's α and interitem correlations. Reference values of the InfantEAT were determined from a sample of healthy, full-term infants (n = 561). Percent agreement in identifying problematic feeding between the NeoEAT and the InfantEAT was calculated. RESULTS: The InfantEAT is comprised of 31 items in 9 subscales. The InfantEAT has evidence of acceptable reliability (α = 0.88). There was 74% agreement between the NeoEAT and the InfantEAT, with the InfantEAT being more sensitive to identifying problematic feeding. References values are presented for infants 0 to 2, 2 to 4, 4 to 6, and 6 to 7 months. IMPLICATIONS PRACTICE AND RESEARCH: The InfantEAT is a reliable and sensitive tool to evaluate symptoms of problematic feeding across feeding methods for infants younger than 7 months in both practice and research.


Subject(s)
Breast Feeding , Feeding Behavior , Infant , Infant, Newborn , Female , Humans , Psychometrics/methods , Reference Values , Reproducibility of Results , Surveys and Questionnaires
4.
Int J Cardiol Cardiovasc Risk Prev ; 19: 200226, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38093813

ABSTRACT

Technology-enabled home-based cardiac rehabilitation (HBCR) is an emerging alternative to traditional center-based cardiac rehabilitation (CBCR), but little is known about outcomes in women. We analyzed 753 diverse and medically complex women who participated in HBCR and CBCR within an integrated health system and found both groups had similar clinical outcomes. Results suggest HBCR is a viable alternative to CBCR among women, including women with multiple comorbidities.

5.
J Nurs Educ ; 62(12): 679-687, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38049305

ABSTRACT

BACKGROUND: Artificial intelligence (AI) has the potential to revolutionize nursing education. This study compared NCLEX-RN questions generated by AI and those created by nurse educators. METHOD: Faculty of accredited baccalaureate programs were invited to participate. Likert-scale items for grammar and clarity of the item stem and distractors were compared using Mann-Whitney U, and yes/no questions about clinical relevance and complex terminology were analyzed using chi-square. A one-sample binomial test with confidence intervals evaluated participants' question preference (AI-generated or educator-written). Qualitative responses identified themes across faculty. RESULTS: Item clarity, grammar, and difficulty were similar for AI and educator-created questions. Clinical relevance and use of complex terminology was similar for all question pairs. Of the four sets with preference for one item, three were generated by AI. CONCLUSION: AI can assist faculty with item generation to prepare nursing students for the NCLEX-RN examination. Faculty expertise is necessary to refine questions written using both methods. [J Nurs Educ. 2023;62(12):679-687.].


Subject(s)
Education, Nursing, Baccalaureate , Education, Nursing , Students, Nursing , Humans , Education, Nursing, Baccalaureate/methods , Artificial Intelligence , Educational Measurement/methods , Licensure, Nursing
6.
J Clin Med ; 12(21)2023 Oct 30.
Article in English | MEDLINE | ID: mdl-37959315

ABSTRACT

Borderline personality disorder (BPD) is highly prevalent in clinical perinatal mental health settings, although there are few systematic programmes to identify BPD at this time. Retrospective studies show compromised birth outcomes for women with this condition, and several authors have highlighted a significant range of problem outcomes for offspring identifiable from early infancy through the adult years, including the intergenerational transfer of mental health problems from mother to child. A literature review identifies the varying prevalence rates found in non-clinical and clinical settings and the paucity of published studies on the management of perinatal BPD, in particular focused both on the mother and mother-infant relationships. A case study is presented to show both the potential benefits of inpatient mother-baby unit protocols and of specialised longer-term group therapy. Many knowledge gaps can be identified for further clinical research that could potentially benefit families with perinatal BPD, including systematic identification of perinatal BPD and intensive programmes that not only could perhaps improve birth outcomes but also provide skills to mothers to help with their emotional regulation and potentially improve mother-infant relationships and longer-term offspring developmental pathways.

7.
Cancer ; 129(23): 3820-3832, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37566341

ABSTRACT

BACKGROUND: The impact of survivorship care plans (SCPs) on the proximal and distal outcomes of adult and childhood cancer survivors, and parent proxies, is unclear. This study aimed to determine the relationship between SCP receipt and these outcomes. METHODS: A cross-sectional survey of adult and childhood cancer survivors (and parent proxies for survivors aged younger than 16 years) across Australia and New Zealand was conducted. Multivariate regression models were fitted to measure the impact of SCP receipt on proximal (unmet information needs and propensity to engage with, and attend, cancer-related follow-up care) and distal outcomes (quality of life and satisfaction with cancer-related follow-up care) with control for cancer history and sociodemographic factors. RESULTS: Of 1123 respondents, 499 were adult cancer survivors and 624 were childhood cancer survivors (including 222 parent proxies). We found that SCP receipt was predictive of greater attendance at, and awareness of, cancer-related follow-up care (adult: odds ratio [OR], 2.46; 95% CI, 1.18-5.12; OR, 2.38; 95% CI, 1.07-5.29; child/parent: OR, 2.61; 95% CI, 1.63-4.17; OR, 1.63; 95% CI, 1.06-2.50; respectively). SCP receipt also predicted fewer unmet information needs related to "follow-up care required" and "possible late effects" (adult: OR, 0.44; 95% CI, 0.20-0.96; OR, 0.29; 95% CI, 0.13-0.64; child/parent: OR, 0.46; 95% CI, 0.30-0.72; OR, 0.57; 95% CI, 0.38-0.85; respectively). In terms of distal outcomes, SCP receipt predicted a better global quality of life for adult cancer survivors (ß, 0.08; 95% CI, -0.01-7.93), proxy-reported health-related quality of life (ß, 0.15; 95% CI, 0.44-7.12), and satisfaction with follow-up care for childhood cancer survivors (OR, 2.93; 95% CI, 1.64-5.23). CONCLUSIONS: Previous studies have shown little impact of SCPs on distal end points. Results suggest that SCPs may be beneficial to cancer survivors' proximal and distal outcomes.


Subject(s)
Aftercare , Neoplasms , Adult , Child , Humans , Aged , Survivorship , Quality of Life , Cross-Sectional Studies , Neoplasms/therapy , Personal Satisfaction , Patient Care Planning
8.
Drug Alcohol Depend Rep ; 8: 100182, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37600151

ABSTRACT

Aims: Benzofurans are used recreationally, due their ability to cause psychostimulant and/or entactogenic effects, but unfortunately produce substantial adverse effects, including death. Three benzofurans 5-(2-aminopropyl)-2,3-dihydrobenzofuran (5-APDB), 5-(2-aminopropyl)-2,3-dihydrobenzofuran (5-MAPB) and 6-(2-aminopropyl) benzofuran (6-APB) were tested to determine their behavioral effects in comparison with 2,3-methylenedioxymethamphetamine (MDMA), cocaine, and methamphetamine. Methods: Locomotor activity was tested in groups of 8 male Swiss-Webster mice in an open-field task to screen for locomotor stimulant or depressant effects and to identify behaviorally active doses and times of peak effect. Discriminative stimulus effects were tested in groups of 6 male Sprague-Dawley rats trained to discriminate MDMA (1.5 mg/kg), cocaine (10 mg/kg), or methamphetamine (1 mg/kg) from saline using a FR 10 for food in a two-lever operant task. Results: In the locomotor activity test, MDMA (ED50 = 8.34 mg/kg) produced peak stimulant effects 60 to 80 min following injection. 5-MAPB (ED50 = 0.92 mg/kg) produced modest stimulant effects 50 to 80 min after injection, whereas 6-APB (ED50 = 1.96 mg/kg) produced a robust stimulant effect 20 to 50 min after injection. 5-APDB produced an early depressant phase (ED50 = 3.38 mg/kg) followed by a modest stimulant phase (ED50 = 2.57 mg/kg) 20 to 50 min after injection. In the drug discrimination tests, 5-APDB (ED50 = 1.02 mg/kg), 5-MAPB (ED50 = 1.00 mg/kg) and 6-APB (ED50 = 0.32 mg/kg) fully substituted in MDMA-trained rats, whereas only 5-MAPB fully substituted for cocaine, and no compounds fully substituted for methamphetamine. Conclusions: The synthetic benzofuran compound 5-APDB and 5-MAPB produced weak locomotor effects, whereas 6-APB produced robust locomotor stimulant effects. All compounds were more potent than MDMA. All three compounds fully substituted in MDMA-trained rats suggesting similar subjective effects. Taken together, these results suggest that these benzofuran compounds may have abuse liability as substitutes for MDMA.

9.
J Cannabis Res ; 5(1): 17, 2023 Jun 07.
Article in English | MEDLINE | ID: mdl-37280709

ABSTRACT

BACKGROUND: The reintroduction of Cannabis sativa L. in the form of hemp (< 0.3% THC by dry weight) into the US agricultural sector has been complex and remains confounded by its association with cannabis (> 0.3% THC by dry weight). This has been further exacerbated by inconsistent hemp regulations in the US since the 2014 Farm Bill's reintroduction. METHODS: A content analysis was performed to analyze the terms and definitions presented by state and tribal hemp production plans, the USDA Hemp producer license, and the 2014 state pilot plans. A total of 69 hemp production plans were analyzed. RESULTS: Results suggest significant discrepancies between hemp production plans, which have been exacerbated by extending the 2014 Farm Bill language into the 2018 Farm Bill timeframe. CONCLUSIONS: Findings from this study point to areas in need of uniformity and consistency as the regulatory framework is modified and provides a starting point for change for federal policymakers. The results may also be useful to companies attempting to market products across state boundaries. Suggestions for how to mitigate these inconsistencies are provided based on the content analysis findings.

10.
Acta Neuropathol ; 145(5): 651-666, 2023 05.
Article in English | MEDLINE | ID: mdl-37014508

ABSTRACT

Group 4 tumours (MBGrp4) represent the majority of non-WNT/non-SHH medulloblastomas. Their clinical course is poorly predicted by current risk-factors. MBGrp4 molecular substructures have been identified (e.g. subgroups/cytogenetics/mutations), however their inter-relationships and potential to improve clinical sub-classification and risk-stratification remain undefined. We comprehensively characterised the paediatric MBGrp4 molecular landscape and determined its utility to improve clinical management. A clinically-annotated discovery cohort (n = 362 MBGrp4) was assembled from UK-CCLG institutions and SIOP-UKCCSG-PNET3, HIT-SIOP-PNET4 and PNET HR + 5 clinical trials. Molecular profiling was undertaken, integrating driver mutations, second-generation non-WNT/non-SHH subgroups (1-8) and whole-chromosome aberrations (WCAs). Survival models were derived for patients ≥ 3 years of age who received contemporary multi-modal therapies (n = 323). We first independently derived and validated a favourable-risk WCA group (WCA-FR) characterised by ≥ 2 features from chromosome 7 gain, 8 loss, and 11 loss. Remaining patients were high-risk (WCA-HR). Subgroups 6 and 7 were enriched for WCA-FR (p < 0·0001) and aneuploidy. Subgroup 8 was defined by predominantly balanced genomes with isolated isochromosome 17q (p < 0·0001). While no mutations were associated with outcome and overall mutational burden was low, WCA-HR harboured recurrent chromatin remodelling mutations (p = 0·007). Integration of methylation and WCA groups improved risk-stratification models and outperformed established prognostication schemes. Our MBGrp4 risk-stratification scheme defines: favourable-risk (non-metastatic disease and (i) subgroup 7 or (ii) WCA-FR (21% of patients, 5-year PFS 97%)), very-high-risk (metastatic disease with WCA-HR (36%, 5-year PFS 49%)) and high-risk (remaining patients; 43%, 5-year PFS 67%). These findings validated in an independent MBGrp4 cohort (n = 668). Importantly, our findings demonstrate that previously established disease-wide risk-features (i.e. LCA histology and MYC(N) amplification) have little prognostic relevance in MBGrp4 disease. Novel validated survival models, integrating clinical features, methylation and WCA groups, improve outcome prediction and re-define risk-status for ~ 80% of MBGrp4. Our MBGrp4 favourable-risk group has MBWNT-like excellent outcomes, thereby doubling the proportion of medulloblastoma patients who could benefit from therapy de-escalation approaches, aimed at reducing treatment induced late-effects while sustaining survival outcomes. Novel approaches are urgently required for the very-high-risk patients.


Subject(s)
Cerebellar Neoplasms , Medulloblastoma , Child , Humans , Medulloblastoma/pathology , Risk Factors , Mutation/genetics , Chromosome Aberrations , Cerebellar Neoplasms/pathology , Prognosis
11.
Nat Commun ; 14(1): 1221, 2023 03 03.
Article in English | MEDLINE | ID: mdl-36869047

ABSTRACT

Medulloblastoma, the most common malignant pediatric brain tumor, often harbors MYC amplifications. Compared to high-grade gliomas, MYC-amplified medulloblastomas often show increased photoreceptor activity and arise in the presence of a functional ARF/p53 suppressor pathway. Here, we generate an immunocompetent transgenic mouse model with regulatable MYC that develop clonal tumors that molecularly resemble photoreceptor-positive Group 3 medulloblastoma. Compared to MYCN-expressing brain tumors driven from the same promoter, pronounced ARF silencing is present in our MYC-expressing model and in human medulloblastoma. While partial Arf suppression causes increased malignancy in MYCN-expressing tumors, complete Arf depletion promotes photoreceptor-negative high-grade glioma formation. Computational models and clinical data further identify drugs targeting MYC-driven tumors with a suppressed but functional ARF pathway. We show that the HSP90 inhibitor, Onalespib, significantly targets MYC-driven but not MYCN-driven tumors in an ARF-dependent manner. The treatment increases cell death in synergy with cisplatin and demonstrates potential for targeting MYC-driven medulloblastoma.


Subject(s)
Brain Neoplasms , Cerebellar Neoplasms , Glioma , Medulloblastoma , Proto-Oncogene Proteins c-myc , Animals , Child , Humans , Mice , Mice, Transgenic , N-Myc Proto-Oncogene Protein
12.
Sci Rep ; 13(1): 2671, 2023 02 15.
Article in English | MEDLINE | ID: mdl-36792613

ABSTRACT

Each year, bovine respiratory disease (BRD) results in significant economic loss in the cattle sector, and novel metabolic profiling for early diagnosis represents a promising tool for developing effective measures for disease management. Here, 1H-nuclear magnetic resonance (1H-NMR) spectra were used to characterize metabolites from blood plasma collected from male dairy calves (n = 10) intentionally infected with two of the main BRD causal agents, bovine respiratory syncytial virus (BRSV) and Mannheimia haemolytica (MH), to generate a well-defined metabolomic profile under controlled conditions. In response to infection, 46 metabolites (BRSV = 32, MH = 33) changed in concentration compared to the uninfected state. Fuel substrates and products exhibited a particularly strong effect, reflecting imbalances that occur during the immune response. Furthermore, 1H-NMR spectra from samples from the uninfected and infected stages were discriminated with an accuracy, sensitivity, and specificity ≥ 95% using chemometrics to model the changes associated with disease, suggesting that metabolic profiles can be used for further development, understanding, and validation of novel diagnostic tools.


Subject(s)
Cattle Diseases , Mannheimia haemolytica , Respiration Disorders , Respiratory Syncytial Virus Infections , Respiratory Tract Diseases , Animals , Cattle , Male , Respiratory Tract Diseases/veterinary , Magnetic Resonance Spectroscopy , Metabolomics , Plasma , Respiratory Syncytial Virus Infections/diagnosis , Respiratory Syncytial Virus Infections/veterinary
13.
Clin Pediatr (Phila) ; 62(2): 136-142, 2023 02.
Article in English | MEDLINE | ID: mdl-35945826

ABSTRACT

Treatment of tongue-tie in infants suggests improvements for breastfeeding mothers, including reduced nipple pain and improved latching onto the breast. The effects of frenotomy on infant feeding and gastrointestinal dysfunction remain controversial, with insufficient evidence on the relationship between tongue-tie and disorders of the gastrointestinal tract. The purpose of this study was to compare symptoms of gastrointestinal (GI) distress and gastroesophageal reflux (GER) prior to and 2 weeks following frenotomy in infants with tongue-tie. Parents were surveyed prior to frenotomy and 2 weeks post procedure, using the Gastrointestinal and Gastroesophageal Reflux (GIGER) Scale for Infants and Toddlers. Eighty-four participants completed surveys at both time points, with significant improvements in GI and GER symptoms 2 weeks after frenotomy. Younger infants and those with more severe tongue-tie had the greatest improvements in GI and GER symptoms. Infants with tongue-tie and symptoms of GI tract distress may experience improvement in symptoms after frenotomy.


Subject(s)
Ankyloglossia , Gastroesophageal Reflux , Female , Infant , Humans , Lingual Frenum/surgery , Breast Feeding , Ankyloglossia/surgery , Parents
15.
J Pediatr Hematol Oncol ; 45(3): e415-e418, 2023 04 01.
Article in English | MEDLINE | ID: mdl-35622992

ABSTRACT

Central nervous system germ cell tumors (CNS-GCTs) comprise 4% of all pediatric CNS tumors, with one third being nongerminomatous GCT (CNS-NG-GCT) type. The majority of these tumors arise in the intracranial compartment with 20% having drop metastases in the spine. We present a rare case of a 2-year-old boy with a primary intradural-extramedullary NG-GCT arising from the lumbosacral spine with a trifecta of unfavorable features, that is, young age, alpha-feto protein >1000 ng/mL, and disseminated disease within the cranium. Owing to his young age, he was treated with chemotherapy alone, avoiding radiation. His tumor marker (alpha-feto protein) declined from 8468 to 10 k-U/L over 8 weeks, and he remained in remission at the last follow-up. This atypical presentation of an intradural-extramedullary tumor with cranial dissemination in a childhood NG-GCT has yet to be described in the literature. Here we use this opportunity to highlight the treatment strategies and challenges in this unique clinical case.


Subject(s)
Brain Neoplasms , Central Nervous System Neoplasms , Neoplasms, Germ Cell and Embryonal , Testicular Neoplasms , Male , Humans , Child, Preschool , Child , Neoplasms, Germ Cell and Embryonal/therapy , Central Nervous System Neoplasms/therapy , Biomarkers, Tumor/metabolism , Brain Neoplasms/therapy , Brain Neoplasms/pathology
16.
MCN Am J Matern Child Nurs ; 48(1): 17-23, 2023.
Article in English | MEDLINE | ID: mdl-36103597

ABSTRACT

PURPOSE: The aims of this study were to describe maternal and infant symptoms relative to tongue- and lip-tie severity and describe changes in symptoms and feeding efficiency from pre- to post-frenotomy. STUDY DESIGN AND METHODS: A one-group pre- and post-intervention study design was used. Data from a dental practice were collected from medical records of infants less than 1 year old who underwent a frenotomy procedure for tongue- and/or lip-tie. Infant and maternal symptoms were compared with severity of tongue- and lip-tie using binary logistic regression. Wilcoxon Signed Rank test compared pain scores and feeding duration pre- and post-frenotomy. Linear regression compared total number of symptoms reported pre-frenotomy with tongue- and lip-tie severity. RESULTS: N = 121 dyads were included. More severe classifications of tongue- and lip-tie were significantly associated with certain infant and maternal symptoms pre-frenotomy. Improvements were noted in all reported infant symptoms post-frenotomy. Feeding duration times significantly decreased post-frenotomy. CLINICAL IMPLICATIONS: Infants and mothers experience problematic symptoms with feeding associated with tongue- and lip-tie. Nurses are the primary care providers during postpartum and should be alert to signs and symptoms that may suggest oral restrictions. Early evaluation and involvement of feeding experts may improve the breastfeeding experience of the dyad.


Subject(s)
Ankyloglossia , Lingual Frenum , Infant , Female , Humans , Lingual Frenum/surgery , Ankyloglossia/surgery , Breast Feeding , Lip/surgery , Treatment Outcome , Tongue , Mothers
17.
Neuropsychol Rehabil ; : 1-21, 2022 Dec 29.
Article in English | MEDLINE | ID: mdl-36580420

ABSTRACT

OBJECTIVES: The growing population of survivors of childhood brain tumors present the challenge of long-term quality of survival. The domains most affected by tumor and treatment are those implicated in development of typical intellectual functions: attention, working memory, and processing speed, with consequent effects upon function and quality of life. In this paper we present service evaluation data on the 12-month effect upon processing speed, visual and auditory attentional domains in 29 patients receiving methylphenidate aged 5-16 years (Mean=10.6). METHODS: Patients received immediate-release methylphenidate and were converted to modified-release as appropriate. Mean optimal dose of immediate-release methylphenidate was 0.34 mg/kg per dose (range 0.2-0.67). RESULTS: Patients showed a significant positive impact of methylphenidate on attention in all tests of selective visual attention from the Test of Everyday Attention for Children 2. A significant improvement was also shown on response time. Significant change was not found on psychometric measures of sustained auditory or visual attention, or selective auditory attention. Ratings of Health-Related Quality of Life showed a positive benefit of methylphenidate at 12 months. Side effects were minimal and not statistically significant. CONCLUSIONS: Survivors of childhood brain tumor with attentional and processing speed deficit show clinical benefit from methylphenidate.

18.
Cancer Res ; 82(24): 4586-4603, 2022 12 16.
Article in English | MEDLINE | ID: mdl-36219398

ABSTRACT

Relapse is the leading cause of death in patients with medulloblastoma, the most common malignant pediatric brain tumor. A better understanding of the mechanisms underlying recurrence could lead to more effective therapies for targeting tumor relapses. Here, we observed that SOX9, a transcription factor and stem cell/glial fate marker, is limited to rare, quiescent cells in high-risk medulloblastoma with MYC amplification. In paired primary-recurrent patient samples, SOX9-positive cells accumulated in medulloblastoma relapses. SOX9 expression anti-correlated with MYC expression in murine and human medulloblastoma cells. However, SOX9-positive cells were plastic and could give rise to a MYC high state. To follow relapse at the single-cell level, an inducible dual Tet model of medulloblastoma was developed, in which MYC expression was redirected in vivo from treatment-sensitive bulk cells to dormant SOX9-positive cells using doxycycline treatment. SOX9 was essential for relapse initiation and depended on suppression of MYC activity to promote therapy resistance, epithelial-mesenchymal transition, and immune escape. p53 and DNA repair pathways were downregulated in recurrent tumors, whereas MGMT was upregulated. Recurrent tumor cells were found to be sensitive to treatment with an MGMT inhibitor and doxorubicin. These findings suggest that recurrence-specific targeting coupled with DNA repair inhibition comprises a potential therapeutic strategy in patients affected by medulloblastoma relapse. SIGNIFICANCE: SOX9 facilitates therapy escape and recurrence in medulloblastoma via temporal inhibition of MYC/MYCN genes, revealing a strategy to specifically target SOX9-positive cells to prevent tumor relapse.


Subject(s)
Brain Neoplasms , Cerebellar Neoplasms , Medulloblastoma , Animals , Humans , Mice , Cerebellar Neoplasms/pathology , Medulloblastoma/pathology , Neoplasm Recurrence, Local/genetics , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , SOX9 Transcription Factor/genetics , SOX9 Transcription Factor/metabolism , Transcription Factors/metabolism
19.
Nurs Educ Perspect ; 43(5): 315-317, 2022.
Article in English | MEDLINE | ID: mdl-35947141

ABSTRACT

ABSTRACT: Using servant leadership as a framework, leaders within a school of nursing guided faculty during the COVID-19 pandemic and called them to address social injustice in the summer of 2020. A model was developed to sustain growth and build resilience of students, faculty, and staff. Influenced by external and internal drivers that stimulated the need for change, strategies were implemented based on core principles of servant leadership. Outcomes emerged in three categories: collaborative strengths demonstrated by students, faculty, and staff; performance of the community to be intentional about change; and transformative practices leading to enhancement of internal and external partnerships.


Subject(s)
COVID-19 , Pandemics , Faculty , Humans , Leadership
20.
Cell Rep ; 40(5): 111162, 2022 08 02.
Article in English | MEDLINE | ID: mdl-35926460

ABSTRACT

Medulloblastoma is currently subclassified into distinct DNA methylation subgroups/subtypes with particular clinico-molecular features. Using RNA sequencing (RNA-seq) in large, well-annotated cohorts of medulloblastoma, we show that transcriptionally group 3 and group 4 medulloblastomas exist as intermediates on a bipolar continuum between archetypal group 3 and group 4 entities. Continuum position is prognostic, reflecting a propensity for specific DNA copy-number changes, and specific switches in isoform/enhancer usage and RNA editing. Examining single-cell RNA-seq (scRNA-seq) profiles, we show that intratumoral transcriptional heterogeneity along the continuum is limited in a subtype-dependent manner. By integrating with a human scRNA-seq reference atlas, we show that this continuum is mirrored by an equivalent continuum of transcriptional cell types in early fetal cerebellar development. We identify distinct developmental niches for all four major subgroups and link each to a common developmental antecedent. Our findings show a transcriptional continuum arising from oncogenic disruption of highly specific fetal cerebellar cell types, linked to almost every aspect of group 3/group 4 molecular biology and clinico-pathology.


Subject(s)
Cerebellar Neoplasms , Medulloblastoma , Cerebellar Neoplasms/genetics , Cerebellar Neoplasms/pathology , DNA Methylation/genetics , Humans , Medulloblastoma/genetics , Medulloblastoma/pathology
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