Imaging Features of Primary Intracranial Sarcoma with DICER1 Mutation: A Multicenter Case Series.

Primary intracranial sarcoma, DICER1-mutant, is a rare, recently described entity in the fifth edition of the WHO Classification of CNS Tumors. Given the entity's rarity and recent description, imaging data on primary intracranial sarcoma, DICER1-mutant, remains scarce. In this multicenter case series, we present detailed multimodality imaging features of primary intracranial sarcoma, DICER1-mutant, with emphasis on the appearance of the entity on MR imaging. In total, 8 patients were included. In all 8 patients, the lesion demonstrated blood products on T1WI. In 7 patients, susceptibility-weighted imaging was obtained and demonstrated blood products. Primary intracranial sarcoma, DICER1-mutant, is a CNS neoplasm that primarily affects pediatric and young adult patients. In the present case series, we explore potential imaging findings that are helpful in suggesting this diagnosis. In younger patients, the presence of a cortical lesion with intralesional blood products on SWI and T1-weighted MR imaging, with or without extra-axial blood products, should prompt the inclusion of this entity in the differential diagnosis.

The ion-gas-neutral interactions with surfaces-2 (IGNIS-2) facility for the study of plasma-material interactions.

The Ion-Gas-Neutral Interactions with Surfaces-2 (IGNIS-2) surface science facility has been designed at the Pennsylvania State University with the specific purpose of enabling experiments to study plasma-material interactions. This in situ surface modification and characterization facility consists of multiple reconfigurable substations that are connected through a central transfer chamber. This fully connected vacuum system ensures that the physical and chemical properties of samples are not altered between surface modification and analysis. The modification techniques in IGNIS-2 include a low-energy (<300 eV), high-flux (up to 1016 cm-2 s-1) broad-beam ion source, a liquid metal dropper, a lithium injection system, an RF sputter source, and an evaporator. Its characterization techniques include charged particle-based techniques, such as low-energy ion scattering (enabled by two <5 keV ion sources) and x-ray photoelectron spectroscopy, and photon and light-based techniques, such as x-ray fluorescence, multi-beam optical stress sensors, and optical cameras. All of these techniques can be utilized up to mTorr pressures, allowing both in situ and in operando studies to be conducted. Results are presented on lithium wetting experiments of argon-irradiated tungsten-based composites, surface stress measurements of tungsten films during deuterium ion irradiation, and temperature-programmed desorption of deuterium-irradiated graphite to demonstrate the in situ capabilities of this new facility.

sRNA-Effector: A tool to expedite discovery of small RNA regulators.

microRNAs (miRNAs) are small regulatory RNAs that repress target mRNA transcripts through base pairing. Although the mechanisms of miRNA production and function are clearly established, new insights into miRNA regulation or miRNA-mediated gene silencing are still emerging. In order to facilitate the discovery of miRNA regulators or effectors, we have developed sRNA-Effector, a machine learning algorithm trained on enhanced crosslinking and immunoprecipitation sequencing and RNA sequencing data following knockdown of specific genes. sRNA-Effector can accurately identify known miRNA biogenesis and effector proteins and identifies 9 putative regulators of miRNA function, including serine/threonine kinase STK33, splicing factor SFPQ, and proto-oncogene BMI1. We validated the role of STK33, SFPQ, and BMI1 in miRNA regulation, showing that sRNA-Effector is useful for identifying new players in small RNA biology. sRNA-Effector will be a web tool available for all researchers to identify potential miRNA regulators in any cell line of interest.

Exploring Goal-Setting and Achievement Within Reablement: A Comparative Case Study of Three Countries.

Purpose: Over the last two decades, reablement programs have been studied and implemented internationally. Goal-setting and multidisciplinary collaboration are central elements of reablement. Unfortunately, limited intervention descriptions leave questions on how they are applied in practice and how goals set by the user are achieved. As a consequence, healthcare providers and organizations often lack knowledge to implement and align reablement to their national and local context. This study aimed to collect data on goal-setting and achievement, and multidisciplinary collaboration within reablement services to provide insight into how these processes inform reablement practice as well as to explore the experiences of healthcare professionals in Norway, New Zealand, and the Netherlands. Material and Methods: A qualitative exploratory design was used comprising three focus group interviews with 20 healthcare professionals (nursing and allied health) involved in reablement programs from the three countries. Purposive sampling was employed considering a mix of gender, age and educational level. Results: Findings reflected healthcare professionals' experiences and reablement processes in three main themes: (1) Goal-setting processes; clearly demonstrating goal-setting as an essential part of reablement and contributing to better understanding of users' motives; (2) Impact of goal-setting on multidisciplinary collaboration; promoting a sense of community, learning climate, job satisfaction and task-shifting; and (3) Behavior change techniques used to reach users' goals, promoting self-reflection and changing users' perspectives. Conclusion: This study offers valuable insights from three countries. Goal-setting serves a crucial role enabling effective reablement implementation across diverse contexts. More specifically, to facilitate tailoring of reablement programs to the user's needs as well as establish more effective multidisciplinary collaboration by promoting trust, shared vision, and utilizing each other's expertise. However, despite the acknowledgement of the significance of reablement, it was reported by all that a cultural shift is necessary for users, informal caregivers as well as healthcare professionals.

The UK research ethics committee: Making the case for better serving the underserved - can we do better?

Research ethics committees exist internationally to review research proposals to protect the rights and safety of human participants and researchers involved in research. These committees recruit a panel of expert and lay members, mostly on an unpaid voluntary basis, with relevant scientific experience to appraise these studies. Contemporary data in the UK show that women and people over 55 years old are overrepresented in these committee panels in the Health Research Authority, suggesting that there are potential barriers to inclusivity and participation. A variety of global approaches to tackle these barriers include targeting specific populations, such as faith or community leaders, or implementing quotas have been adopted. Further research is needed to understand likely barriers preventing participation in research ethics committees in the UK and how they may be overcome.

Factors Associated With Experiences of Harassment or Abuse Among Lesbian, Gay, Bisexual, Trans, Queer, and Asexual Young People With Disability in Australia.

Lesbian, gay, bisexual, trans, queer, and asexual (LGBTQA+) young people with disability are known to experience higher rates of harassment or abuse than LGBTQA+ young people without disability. This study focused on participants in Australia and identified factors associated with harassment or abuse among LGBTQA+ adolescents and young adults who reported a disability as well as associations with mental health outcomes. Analyses were conducted from a national survey that included 2,500 LGBTQA+ people who reported a disability and were aged 14 to 21 years. Measures included experiences in the past 12 months of verbal and physical harassment or abuse due to one's sexual orientation or gender identity, sexual harassment or abuse, mental health, suicidality, and sociodemographic traits. Overall, 48.4% of participants with disability reported experiencing verbal harassment or abuse, 12.4% physical harassment or abuse, and 29.7% sexual assault or harassment. In multivariable regression analyses, verbal harassment or abuse was significantly more likely among trans men, participants with an intellectual disability, and those who were "out" to most or all of their family. Physical harassment or abuse was significantly more likely among participants with a physical or sensory disability. Sexual harassment or abuse was significantly more likely among trans women and participants with a physical or sensory disability. Participants who experienced harassment or abuse were also significantly more likely to have attempted suicide in the past 12 months. These findings will assist policymakers and practitioners in identifying contexts linked to a heightened risk of abuse among LGBTQA+ young people with disability and further underscore an immediate need to address and prevent harm in this population.

Good Gone Bad: Complications of Chemotherapy, Immunotherapy, and Radiotherapy on the CNS.

With recent advancements in cancer therapy, especially immunotherapy, overall survival of many cancers has increased and patient toxicity has been reduced. However, many complications of traditional cancer therapy are still prevalent and complications of novel therapies are just beginning to appear. The neuroradiologist may be the first to visualize signs of these complications on imaging. This article describes the notable imaging findings of several unique and characteristic complications of CNS cancer therapy, including toxicities of chemotherapies, immunotherapies, and radiotherapy. Complications of chemotherapeutic agents covered include methotrexate-induced and disseminated necrotizing leukoencephalopathy, and chemotherapy-induced myelopathy. Immunotherapy complications included are Tacrolimus-related Optic Neuropathy, Rituximab and Immune reconstitution inflammatory syndrome-associated Progressive Multifocal Leukoencephalopathy, Bevacizumab-associated late radiation-induced neurotoxicity, and Ipilimumab-induced hypophysitis. Lastly, radiation-induced neurotoxicities are covered, including myelopathy, radiation necrosis, cerebral atrophy, leukoencephalopathy, optic neuropathy, mineralizing microangiopathy, stroke-like migraine attacks, osteonecrosis, and vasculopathies. Neuroradiologists will increasingly encounter patients who have undergone treatment with more than 1 therapeutic modality, resulting in overlapping findings as well. Recognition of the common complications of these therapies on imaging is critical to minimizing the effects of these potential short- and long-term complications.

HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing.

Despite remarkable progress, a cure for HIV-1 infection remains elusive. Rebound competent latent and transcriptionally active reservoir cells persevere despite antiretroviral therapy and rekindle infection due to inefficient proviral silencing. We propose a novel "block-lock-stop" approach, entailing long term durable silencing of viral expression towards an irreversible transcriptionally inactive latent provirus to achieve long term antiretroviral free control of the virus. A graded transformation of remnant HIV-1 in PLWH from persistent into silent to permanently defective proviruses is proposed, emulating and accelerating the natural path that human endogenous retroviruses (HERVs) take over millions of years. This hypothesis was based on research into delineating the mechanisms of HIV-1 latency, lessons from latency reversing agents and advances of Tat inhibitors, as well as expertise in the biology of HERVs. Insights from elite controllers and the availability of advanced genome engineering technologies for the direct excision of remnant virus set the stage for a rapid path to an HIV-1 cure.

Exploring older care recipients' sleep status as a predictor for informal carer distress: evidence from New Zealand's interRAI home care assessment data.

OBJECTIVES: Understanding factors affecting informal carers' well-being is important to support healthy ageing at home. Sleep disturbances of care recipients are increasingly recognised as affecting the well-being of both parties. This research assesses the relationship between indicators of care recipients' sleep status and carer distress, as well as carer distress with subsequent admission to residential aged care, using prospectively collected Home Care International Residential Assessment Instrument (interRAI-HC) assessment data. PARTICIPANTS: Data were sourced from 127 832 assessments conducted between 2012 and 2019 for people aged 55 years or older who had support from at least one informal carer. The majority (59.4%) of care recipients were female and 59.1% were defined as having cognitive impairment or dementia (CIoD). SETTING: New Zealand. DESIGN: Logistic regression modelling was used to assess the independent relationships between indicators of care recipients' sleep status (difficulty sleeping and fatigue) and primary caregivers' distress (feeling overwhelmed or distressed). Kaplan meier curves illustrated the subsequent relationship between caregiver distress and care recipients' transitions to aged residential care. RESULTS: Care recipients' sleeping difficulty (32.4%) and moderate-severe fatigue (46.6%) were independently associated with caregiver distress after controlling for key demographic and health factors included in the assessment. Distress was reported by 39.9% of informal caregivers and was three times more likely among those supporting someone with a CIoD. Caregiver distress was significantly associated with care recipients' earlier admission into aged residential care. CONCLUSIONS: Indicators of sleep disturbance among care recipients are associated with increased likelihood of carer distress. This has implications for managing the overall home-care situation and long-term care needs, as well as the well-being of both parties. Findings will inform research and development of measures, services and interventions to improve the sleep and waking health of older people, including those with CIoD and family caregivers.

Impact of sleep deprivation on neurocognition and inflammation in rhesus macaques.

Sleep deprivation in humans is associated with both cognitive impairment and immune dysregulation. An animal model of neuropathogenesis may provide insight to understand the effects of sleep deprivation on the brain. Human neurocognition is more closely mirrored by nonhuman primates (NHP) than other animals. As such, we developed an NHP model to assess the impact of sleep deprivation on neurocognition and markers of systemic immune activation. Six male rhesus macaques underwent three rounds of sleep deprivation (48 h without sleep) at days 0, 14, and 28. We performed domain specific cognitive assessments using the Cambridge Neuropsychological Test Automated Battery (CANTAB) via a touch screen before and after 24 and 48 h of sleep deprivation. Immune activation markers were measured in the blood by multiplex assay and flow cytometry. Although we observed variability in cognitive performance between the three rounds of sleep deprivation, cognitive impairments were identified in all six animals. We noted more cognitive impairments after 48 h than after 24 h of sleep deprivation. Following 48 h of sleep deprivation, elevations in markers of immune activation in the blood were observed in most animals. The observed impairments largely normalized after sleep. The co-occurrence of systemic immune alterations and cognitive impairment establishes this model as useful for studying the impact of sleep deprivation on neurobehavior and immune perturbations in rhesus macaques.

Prostaglandin E2 activates melanin-concentrating hormone neurons to drive diet-induced obesity.

Hypothalamic inflammation reduces appetite and body weight during inflammatory diseases, while promoting weight gain when induced by high-fat diet (HFD). How hypothalamic inflammation can induce opposite energy balance outcomes remains unclear. We found that prostaglandin E2 (PGE2), a key hypothalamic inflammatory mediator of sickness, also mediates diet-induced obesity (DIO) by activating appetite-promoting melanin-concentrating hormone (MCH) neurons in the hypothalamus in rats and mice. The effect of PGE2 on MCH neurons is excitatory at low concentrations while inhibitory at high concentrations, indicating that these neurons can bidirectionally respond to varying levels of inflammation. During prolonged HFD, endogenous PGE2 depolarizes MCH neurons through an EP2 receptor-mediated inhibition of the electrogenic Na+/K+-ATPase. Disrupting this mechanism by genetic deletion of EP2 receptors on MCH neurons is protective against DIO and liver steatosis in male and female mice. Thus, an inflammatory mediator can directly stimulate appetite-promoting neurons to exacerbate DIO and fatty liver.

Acute assessment services for patient flow assistance in hospital emergency departments.

BACKGROUND: Emergency departments (EDs) are facing serious and significant issues in the delivery of effective and efficient care to patients. Acute assessment services have been implemented at many hospitals internationally to assist in maintaining patient flow for identified groups of patients attending the ED. Identifying the risks and benefits, and optimal configurations of these services may be beneficial to those wishing to utilise an acute assessment service to improve patient flow. OBJECTIVES: To assess the effects of acute assessment services on patient flow following attendance at a hospital ED. SEARCH METHODS: We searched MEDLINE, CENTRAL, Embase and two trials registers on 24 September 2022 to identify studies. No restrictions were imposed on publication year, publication type, or publication language. SELECTION CRITERIA: Studies eligible for inclusion were randomised trials and cluster-randomised trials with at least two intervention and two control sites. Participants were adults (as defined by study authors) receiving care either in the ED or the acute assessment service, where both were based in the hospital setting. The comparison was hospital-based acute assessment services with usual, ED-only care. The outcomes of this review were mortality at time point closest to 30 days, length of stay in the service (in minutes), and waiting time to see a doctor (in minutes). DATA COLLECTION AND ANALYSIS: We followed the standard procedures of Cochrane Effective Practice and Organisation of Care for this review (https://epoc.cochrane.org/resources). MAIN RESULTS: We identified a total of 5754 records in the search. Following assessment of 3609 de-duplicated records, none were found to be eligible for inclusion in this review. AUTHORS' CONCLUSIONS: At present there are no randomised controlled trials exploring the effects of acute assessment services on patient flow in hospital-based emergency departments compared to usual, ED-only care.

Increasing Clinical Trial Participation of Black Women Diagnosed with Breast Cancer.

Despite racial disparities in breast cancer mortality, Black women remain underrepresented in clinical trials. In this mixed methods research, 48 Black women were engaged via focus group discussions and in-depth interviews to better understand the lived experience of women with breast cancer. The results of this qualitative study informed the development of a subsequent online survey to identify barriers, motivators, and other factors that influence decision-making by Black women diagnosed with breast cancer when considering clinical trial participation. Among the 257 Black survey participants, most (95%) were aware of clinical trials; of those, most viewed them as lifesaving (81%) and/or benefiting others (90%). Negative perceptions such as serious side effects (58%), not receiving real treatment (52%), or risk of potential harm (62%) were indicated. Barriers included financial expenses (49%), concerns that their condition could be made worse (29%), that they would receive a placebo (28%), or that treatment was unapproved (28%). Participants were more likely than their health care providers (HCPs) to initiate discussions of clinical trials (53% versus 33%), and 29% of participants indicated a need for more information about risks and benefits, even after having those conversations. The most trustworthy sources of information on clinical trials were HCPs (66%) and breast cancer support groups (64%). These results suggest that trusted communities are key for providing education on clinical trials. However, there is also a need for HCPs to proactively discuss clinical trials with patients to ensure that they are adequately informed about all aspects of participation.

ACR Appropriateness Criteria® Management of Vertebral Compression Fractures: 2022 Update.

Vertebral compression fractures (VCFs) can have a variety of etiologies, including trauma, osteoporosis, or neoplastic infiltration. Osteoporosis related fractures are the most common cause of VCFs and have a high prevalence among all postmenopausal women with increasing incidence in similarly aged men. Trauma is the most common etiology in those >50 years of age. However, many cancers, such as breast, prostate, thyroid, and lung, have a propensity to metastasize to bone, which can lead to malignant VCFs. Indeed, the spine is third most common site of metastases after lung and liver. In addition, primary tumors of bone and lymphoproliferative diseases such as lymphoma and multiple myeloma can be the cause of malignant VCFs. Although patient clinical history could help raising suspicion for a particular disorder, the characterization of VCFs is usually referred to diagnostic imaging. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

HRCT-MRI fusion: A novel imaging protocol surpasses current modalities in localizing spontaneous cerebrospinal fluid leaks.

KEY POINTS: HRCT-MRI fusion is a new imaging modality that can be used to diagnose spontaneous CSF leaks. HRCT-MRI fusion has better accuracy in localizing CSF leaks compared to MRI and HRCT alone.

Secondary malignancies in non-Hodgkin lymphoma survivors: 40 years of follow-up assessed by treatment modality.

BACKGROUND: Survivors of non-Hodgkin lymphoma (NHL) have increased secondary malignancy (SM) risk. We quantified this risk by patient and treatment factors. METHODS: Standardized incidence ratios (SIR, observed-to-expected [O/E] ratio) were assessed in 142,637 NHL patients diagnosed from 1975 to 2016 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Comparisons were made between subgroups in terms of their SIRs relative to respective endemic populations. RESULTS: In total, 15,979 patients developed SM, more than the endemic rate (O/E 1.29; p < 0.05). Compared with white patients, relative to respective endemic populations, ethnic minorities had a higher risk of SM (white O/E 1.27, 95% CI 1.25-1.29; black O/E 1.40, 95% CI 1.31-1.48; other O/E 1.59, 95% CI 1.49-1.70). Relative to respective endemic populations, patients who received radiotherapy had similar SM rates to those who did not (O/E 1.29 each), but irradiated patients had increased breast cancer (p < 0.05). Patients who received chemotherapy had higher SM rates than those who did not (O/E 1.33 vs. 1.24, p < 0.05) including more leukemia, Kaposi sarcoma, kidney, pancreas, rectal, head and neck, and colon cancers (p < 0.05). CONCLUSIONS: This is the largest study to examine SM risk in NHL patients with the longest follow-up. Treatment with radiotherapy did not increase overall SM risk, while chemotherapy was associated with a higher overall risk. However, certain subsites were associated with a higher risk of SM, and they varied by treatment, age group, race and time since treatment. These findings are helpful for informing screening and long-term follow-up in NHL survivors.

Head and Neck Sarcoma Tumor Board Survival Guide for Neuroradiologists: Imaging Findings, History, and Pathology.

Sarcomas of the head and neck carry a poor prognosis as diagnosis is often delayed until a late stage of the disease. Accordingly, it is essential to be familiar with the clinical and imaging features of sarcomas to suggest an appropriate differential diagnosis for collaborating surgeons and pathologists. However, as there are only 1000-1500 cases in the United States annually, many radiologists lack experience with pertinent imaging findings of sarcoma and lack knowledge of both treatment and necessary follow-up. In this review, a brief discussion of WHO definitions and histopathology is included to decode information provided by pathologists. Finally, staging and treatments are illuminated to aid the radiologist with initial imaging staging and follow-up care. This review aims to increase the comprehensive knowledge of a neuroradiologist and further their value to the multidisciplinary tumor board.

Asymmetric dysregulation of glutamate dynamics across the synaptic cleft in a mouse model of Alzheimer's disease.

Most research on glutamate spillover focuses on the deleterious consequences of postsynaptic glutamate receptor overactivation. However, two decades ago, it was noted that the glial coverage of hippocampal synapses is asymmetric: astrocytic coverage of postsynaptic sites exceeds coverage of presynaptic sites by a factor of four. The fundamental relevance of this glial asymmetry remains poorly understood. Here, we used the glutamate biosensor iGluSnFR, and restricted its expression to either CA3 or CA1 neurons to visualize glutamate dynamics at pre- and postsynaptic microenvironments, respectively. We demonstrate that inhibition of the primarily astrocytic glutamate transporter-1 (GLT-1) slows glutamate clearance to a greater extent at presynaptic compared to postsynaptic membranes. GLT-1 expression was reduced early in a mouse model of AD, resulting in slower glutamate clearance rates at presynaptic but not postsynaptic membranes that opposed presynaptic short-term plasticity. Overall, our data demonstrate that the presynapse is particularly vulnerable to GLT-1 dysfunction and may have implications for presynaptic impairments in a variety of brain diseases.