Impact of Motor Therapy with Dynamic Body-Weight Support on Functional Independence Measures in Traumatic Brain Injury: An Exploratory Study

BACKGROUND: Contemporary goals of rehabilitation after traumatic brain injury (TBI) aim to improve cognitive and motor function by applying concepts of neuroplasticity. This can be challenging to carry out in TBI patients with motor, balance, and cognitive impairments. OBJECTIVE: To determine whether use of dynamic body-weight support (DBWS) would allow safe administration of intensive motor therapy during inpatient rehabilitation and whether its use would yield greater improvement in functional recovery than standard-of-care (SOC) therapy in adults with TBI. METHODS: Data in this retrospective cohort study was collected from patients with TBI who receive inpatient rehabilitation incorporating DBWS (n = 6) and who received inpatient rehabilitation without DBWS (SOC, n = 6). The primary outcome measure was the change in Functional Independence Measures (FIM) scores from admission to discharge. RESULTS: There was significant improvement in total FIM scores at discharge compared to admission for both the DBWS (p = 0.001) and SOC (p = 0.005) groups. Overall, the DBWS group had greater improvement in total FIM score and FIM subscales compared to the SOC group. CONCLUSIONS: Our results suggest DBWS has the potential to allow a greater intensity of therapy during inpatient rehabilitation and yield better outcomes compared to SOC in patients with TBI

Inequitable Housing Practices and Youth Internalizing Symptoms: Mediation Via Perceptions of Neighborhood Cohesion

Disordered urban environments negatively impact mental health symptoms and disorders. While many aspects of the built environment have been studied, one influence may come from inequitable, discriminatory housing practices such as redlining, blockbusting, and gentrification. The patterns of disinvestment and reinvestment that follow may be an underlying mechanism predicting poor mental health. In this study, we examine pathways between such practices and internalizing symptoms (i.e., anxiety and depression) among a sample of African American youth in Baltimore, Maryland, considering moderation and mediation pathways including neighborhood social cohesion and sex. In our direct models, the inequitable housing practices were not significant predictors of social cohesion. In our sex moderation model, however, we find negative influences on social cohesion: for girls from gentrification, and for boys from blockbusting. Our moderated mediation model shows that girls in gentrifying neighborhoods who experience lower social cohesion have higher levels of internalizing symptoms. Likewise for boys, living in a formerly blockbusted neighborhood generates poorer social cohesion, which in turn drives higher rates of internalizing symptoms. A key implication of this work is that, in addition to standard measures of the contemporary built environment, considering other invisible patterns related to discriminatory and inequitable housing practices is important in understanding the types of neighborhoods where anxiety and depression are more prevalent. And while some recent work has discussed the importance of considering phenomena like redlining in considering long‐term trajectories of neighborhoods, other patterns such as blockbusting and gentrification may be equally important

Inequitable Housing Practices and Youth Internalizing Symptoms: Mediation Via Perceptions of Neighborhood Cohesion

Disordered urban environments negatively impact mental health symptoms and disorders. While many aspects of the built environment have been studied, one influence may come from inequitable, discriminatory housing practices such as redlining, blockbusting, and gentrification. The patterns of disinvestment and reinvestment that follow may be an underlying mechanism predicting poor mental health. In this study, we examine pathways between such practices and internalizing symptoms (i.e., anxiety and depression) among a sample of African American youth in Baltimore, Maryland, considering moderation and mediation pathways including neighborhood social cohesion and sex. In our direct models, the inequitable housing practices were not significant predictors of social cohesion. In our sex moderation model, however, we find negative influences on social cohesion: for girls from gentrification, and for boys from blockbusting. Our moderated mediation model shows that girls in gentrifying neighborhoods who experience lower social cohesion have higher levels of internalizing symptoms. Likewise for boys, living in a formerly blockbusted neighborhood generates poorer social cohesion, which in turn drives higher rates of internalizing symptoms. A key implication of this work is that, in addition to standard measures of the contemporary built environment, considering other invisible patterns related to discriminatory and inequitable housing practices is important in understanding the types of neighborhoods where anxiety and depression are more prevalent. And while some recent work has discussed the importance of considering phenomena like redlining in considering long-term trajectories of neighborhoods, other patterns such as blockbusting and gentrification may be equally important

Biogeochemistry and microbial diversity in the marine cavity beneath the McMurdo Ice Shelf, Antarctica:Biogeochemistry under the MCM ice shelf

Ice shelves surround ~ 75% of Antarctica's coastline and are highly sensitive to climate change; several have recently collapsed and others are predicted to in the near future. Marine waters beneath ice shelves harbor active ecosystems, while adjacent seas can be important areas of bottom water formation. Despite their oceanographic significance, logistical constraints have resulted in few opportunities to directly sample sub-ice shelf cavities. Here, we present the first data on microbial diversity and biogeochemistry beneath the McMurdo Ice Shelf (MIS) near Ross Island, Antarctica. Physicochemical profiles obtained via a 56 m deep borehole through the MIS revealed three vertically layered water masses (Antarctic Surface Water [AASW], Ice Shelf Water [ISW], and modified High Salinity Shelf Water [mHSSW]). Metabolically active, moderately diverse (Shannon diversity from 2.06 to 5.74) microbial communities were detected in the AASW and mHSSW. Heterotrophic bacterial production and dissolved organic matter concentrations were higher (12-37% and 24%, respectively) in mHSSW relative to AASW. Chemoautotrophic production was 5.3 nmol C L-1 d-1 and 6.0 nmol C L-1 d-1 in the AASW and mHSSW, respectively. Phytoplankton cells were more abundant and larger in the mHSSW sample relative to the AASW, which indicates sinking of phytoplankton produced in surface waters and, together with southerly flowing currents (0.09-0.16 m s-1), horizontal advection of phytoplankton from McMurdo Sound. Advected phytoplankton carbon together with in situ chemoautotrophic production provide important sources of organic matter and other reduced compounds to support ecosystem processes in the dark waters in the ice shelf cavity

Interferon-γ signaling in human iPSC-derived neurons recapitulates neurodevelopmental disorder phenotypes.

Maternal immune activation increases the risk of neurodevelopmental disorders. Elevated cytokines, such as interferon-γ (IFN-γ), in offspring's brains play a central role. IFN-γ activates an antiviral cellular state, limiting viral entry and replication. Moreover, IFN-γ is implicated in brain development. We tested the hypothesis that IFN-γ signaling contributes to molecular and cellular phenotypes associated with neurodevelopmental disorders. Transient IFN-γ treatment of neural progenitors derived from human induced pluripotent stem cells increased neurite outgrowth. RNA sequencing analysis revealed that major histocompatibility complex class I (MHCI) genes were persistently up-regulated through neuronal differentiation-an effect that was mediated by IFN-γ-induced promyelocytic leukemia protein (PML) nuclear bodies. Critically, IFN-γ-induced neurite outgrowth required both PML and MHCI. We also found evidence that IFN-γ disproportionately altered the expression of genes associated with schizophrenia and autism, suggesting convergence between genetic and environmental risk factors. Together, these data implicate IFN-γ signaling in neurodevelopmental disorder etiology

Oral steroids for the resolution of otitis media with effusion (OME) in children (OSTRICH): study protocol for a randomised controlled trial

Background Otitis media with effusion (OME) is an accumulation of fluid in the middle ear affecting about 80% of children by the age of 4 years. While OME usually resolves spontaneously, it can affect speech, behaviour and development. Children with persistent hearing loss associated with OME are usually offered hearing aids or insertion of ventilation tubes through the tympanic membrane. Oral steroids may be a safe and effective treatment for OME, which could be delivered in primary care. It has the potential to benefit large numbers of children and reduce the burden of care on them and on health services. However, previous trials have either been too small with too short a follow up period, or of too poor quality to give a definite answer. The aim of the OSTRICH trial is to determine if a short course of oral steroids improves the hearing of children with OME in the short and longer term. Methods/Design 380 participants (children aged 2-8 years) are recruited from Hospital Ear, Nose and Throat departments in Wales and England. A trained clinician seeks informed consent from parents of children with symptoms attributable to OME for at least 3 months and with confirmed bilateral hearing loss at study entry. Participants are randomised to a course of oral steroid or a matched placebo for one week. Outcomes include audiometry, tympanometry and otoscopy assessments, symptoms, adverse effects, functional health status, quality of life, resource use and cost effectiveness. Participants are followed up at 5 weeks, and at 6 and 12 months after the day of randomisation. The primary outcome is audiometry-confirmed satisfactory hearing at 5 weeks. Discussion There is an important evidence gap regarding clinical and cost effectiveness of short courses of oral steroid treatment for OME. Identifying an effective, safe, non-surgical intervention for OME in children for use in primary care would be of great benefit to children, their families and the NHS

Development of the Uncertainty Communication Checklist: A Patient-Centered Approach to Patient Discharge From the Emergency Department

Clear communication with patients upon emergency department (ED) discharge is important for patient safety during the transition to outpatient care. Over one-third of patients are discharged from the ED with diagnostic uncertainty, yet there is no established approach for effective discharge communication in this scenario. From 2017 to 2019, the authors developed the Uncertainty Communication Checklist for use in simulation-based training and assessment of emergency physician communication skills when discharging patients with diagnostic uncertainty. This development process followed the established 12-step Checklist Development Checklist framework and integrated patient feedback into 6 of the 12 steps. Patient input was included as it has potential to improve patient-centeredness of checklists related to assessment of clinical performance. Focus group patient participants from 2 clinical sites were included: Thomas Jefferson University Hospital, Philadelphia, PA, and Northwestern University Hospital, Chicago, Illinois. The authors developed a preliminary instrument based on existing checklists, clinical experience, literature review, and input from an expert panel comprising health care professionals and patient advocates. They then refined the instrument based on feedback from 2 waves of patient focus groups, resulting in a final 21-item checklist. The checklist items assess if uncertainty was addressed in each step of the discharge communication, including the following major categories: introduction, test results/ED summary, no/uncertain diagnosis, next steps/follow-up, home care, reasons to return, and general communication skills. Patient input influenced both what items were included and the wording of items in the final checklist. This patient-centered, systematic approach to checklist development is built upon the rigor of the Checklist Development Checklist and provides an illustration of how to integrate patient feedback into the design of assessment tools when appropriate

RAD51 foci as a biomarker predictive of platinum chemotherapy response in ovarian cancer

PURPOSE: To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples. EXPERIMENTAL DESIGN: RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (n = 5), organoids (n = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery n = 31, validation n = 148). Samples were defined as RAD51-High if \u3e10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated. RESULTS: RAD51 scores correlated with in vitro response to platinum chemotherapy in established and primary ovarian cancer cell lines (Pearson r = 0.96, P = 0.01). Organoids from platinum-nonresponsive tumors had significantly higher RAD51 scores than those from platinum-responsive tumors (P \u3c 0.001). In a discovery cohort, RAD51-Low tumors were more likely to have a pathologic complete response (RR, 5.28; P \u3c 0.001) and to be platinum-sensitive (RR, ∞; P = 0.05). The RAD51 score was predictive of chemotherapy response score [AUC, 0.90; 95% confidence interval (CI), 0.78-1.0; P \u3c 0.001). A novel automatic quantification system accurately reflected the manual assay (92%). In a validation cohort, RAD51-Low tumors were more likely to be platinum-sensitive (RR, ∞; P \u3c 0.001) than RAD51-High tumors. Moreover, RAD51-Low status predicted platinum sensitivity with 100% positive predictive value and was associated with better progression-free (HR, 0.53; 95% CI, 0.33-0.85; P \u3c 0.001) and overall survival (HR, 0.43; 95% CI, 0.25-0.75; P = 0.003) than RAD51-High status. CONCLUSIONS: RAD51 foci are a robust marker of platinum chemotherapy response and survival in ovarian cancer. The utility of RAD51 foci as a predictive biomarker for HGSOC should be tested in clinical trials

Simulation-based mastery learning compared to standard education for discussing diagnostic uncertainty with patients in the emergency department: a randomized controlled trial.

BACKGROUND: Diagnostic uncertainty occurs frequently in emergency medical care, with more than one-third of patients leaving the emergency department (ED) without a clear diagnosis. Despite this frequency, ED providers are not adequately trained on how to discuss diagnostic uncertainty with these patients, who often leave the ED confused and concerned. To address this training need, we developed the Uncertainty Communication Education Module (UCEM) to teach physicians how to discuss diagnostic uncertainty. The purpose of the study is to evaluate the effectiveness of the UCEM in improving physician communications. METHODS: The trial is a multicenter, two-arm randomized controlled trial designed to teach communication skills using simulation-based mastery learning (SBML). Resident emergency physicians from two training programs will be randomly assigned to immediate or delayed receipt of the two-part UCEM intervention after completing a baseline standardized patient encounter. The two UCEM components are: 1) a web-based interactive module, and 2) a smart-phone-based game. Both formats teach and reinforce communication skills for patient cases involving diagnostic uncertainty. Following baseline testing, participants in the immediate intervention arm will complete a remote deliberate practice session via a video platform and subsequently return for a second study visit to assess if they have achieved mastery. Participants in the delayed intervention arm will receive access to UCEM and remote deliberate practice after the second study visit. The primary outcome of interest is the proportion of residents in the immediate intervention arm who achieve mastery at the second study visit. DISCUSSION: Patients\u27 understanding of the care they received has implications for care quality, safety, and patient satisfaction, especially when they are discharged without a definitive diagnosis. Developing a patient-centered diagnostic uncertainty communication strategy will improve safety of acute care discharges. Although use of SBML is a resource intensive educational approach, this trial has been deliberately designed to have a low-resource, scalable intervention that would allow for widespread dissemination and uptake. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (NCT04021771). Registration date: July 16, 2019