Glioblastoma multiforme (GBM) is the most prevalent primary brain tumour, with an incidence of 2 per 100,000. The standard clinical treatments do not sufficiently target cell migration and invasion, leading to recurrence after surgical resection and resistance after chemotherapy and radiotherapy. Pre-clinical studies are being conducted to construct artificial substrates that can mimic the tumour microenvironment (TME) to prevent GBM cells from migrating along their primary route through blood vessels and white matter tracts. Alongside, targeted therapies using anti-migratory or ‘migrastatic’ drugs are also being developed. This study aimed to review the therapeutic translational strategies emerging from the study of the GBM microenvironment and anti-migratory drugs.

A systematic literature search was carried out using search key terms and synonyms. Full-paper screening was performed based on specific inclusion and exclusion criteria.

From the systems interrogated, the ‘Nanofibre’ assay is suitable to simulate white matter tracts, while hydrogel-based invasion assays and GBM cerebral organoid (GLICO) mimic the brain extracellular matrix. Inhibitors with anti-migratory activity found in this study are active involving distinct molecular mechanisms and have been tested on cell migration assays.

Overall, we have analysed therapeutic strategies emerging from an artificial GBM TME approach and from the identification of anti-migratory inhibitors. Both carry potential to improve treatment options to prevent tumour dissemination and spread for GBM.

Despite infection control guidance, sporadic nosocomial coronavirus disease 2019 (COVID-19) outbreaks occur. We describe a complex severe acute respiratory coronavirus virus 2 (SARS-CoV-2) cluster with interfacility spread during the SARS-CoV-2 δ (delta) pandemic surge in the Midwest.

This study was conducted in (1) a hematology-oncology ward in a regional academic medical center and (2) a geographically distant acute rehabilitation hospital.

We conducted contact tracing for each COVID-19 case to identify healthcare exposures within 14 days prior to diagnosis. Liberal testing was performed for asymptomatic carriage for patients and staff. Whole-genome sequencing was conducted for all available clinical isolates from patients and healthcare workers (HCWs) to identify transmission clusters.

In the immunosuppressed ward, 19 cases (4 patients, 15 HCWs) shared a genetically related SARS-CoV-2 isolate. Of these 4 patients, 3 died in the hospital or within 1 week of discharge. The suspected index case was a patient with new dyspnea, diagnosed during preprocedure screening. In the rehabilitation hospital, 20 cases (5 patients and 15 HCWs) positive for COVID-19, of whom 2 patients and 3 HCWs had an isolate genetically related to the above cluster. The suspected index case was a patient from the immune suppressed ward whose positive status was not detected at admission to the rehabilitation facility. Our response to this cluster included the following interventions in both settings: restricting visitors, restricting learners, restricting overflow admissions, enforcing strict compliance with escalated PPE, access to on-site free and frequent testing for staff, and testing all patients prior to hospital discharge and transfer to other facilities.

Stringent infection control measures can prevent nosocomial COVID-19 transmission in healthcare facilities with high-risk patients during pandemic surges. These interventions were successful in ending these outbreaks.

PD patients commonly exhibit executive dysfunction early in the disease course which may or may not predict further cognitive decline over time. Early emergence of visuospatial and memory impairments, in contrast, are more consistent predictors of an evolving dementia syndrome. Most prior studies using fMRI have focused on mechanisms of executive dysfunction and have demonstrated that PD patients exhibit hyperactivation that is dependent on the degree of cognitive impairment, suggestive of compensatory strategies. No study has evaluated whether PD patients with normal cognition (PD-NC) and PD patients with Mild Cognitive Impairment (PD-MCI) exhibit compensatory activation patterns during visuospatial task performance.

10 PD-NC, 12 PD-MCI, and 14 age and sex-matched healthy controls (HC) participated in the study. PD participants were diagnosed with MCI based on the Movement Disorders Society Task Force, Level II assessment (comprehensive assessment). Functional magnetic resonance imaging (fMRI) was performed during a motion discrimination task that required participants to identify the direction of horizontal global coherent motion embedded within dynamic visual noise under Low and High coherence conditions. Behavioral accuracy and functional activation were evaluated using 3 * 2 analyses of covariance (ANCOVAs) (group [HC, PD-NC, PD-MCI] * Coherence [High vs. Low]) accounting for age, sex, and education. Analyses were performed in R (v4.1.2(Team, 2013)).

PD-MCI (0.702± 0.269) patients exhibited significantly lower accuracy on the motion discrimination task than HC (0.853 ± 0.241; p = 0.033) and PD-NC (0.880 ± 0.208; p =0.039). A Group * Coherence interaction was identified in which several regions, including orbitofrontal, posterior parietal and occipital cortex, showed increased activation during High relative to Low coherence trials in the PD patient groups but not in the HC group. HC showed default mode deactivation and frontal-parietal activation during Low relative to High coherence trials that was not evident in the patient groups.

PD-MCI patients exhibited worse visuospatial performance on a motion discrimination task than PD-NC and HC participants and exhibited hyperactivation of the posterior parietal and occipital regions during motion discrimination, suggesting possible compensatory activation.

Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.

To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au.

This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5–0.9 mg/kg or midazolam 0.025–0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4.

The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1–69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2–8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h.

Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.

919,000 Rohingya refugees live in overcrowded camps in Cox’s Bazar, Bangladesh after fleeing violence in Myanmar. The Médecins Sans Frontières (MSF) Goyalmara Hospital offers the highest level of pediatric and neonatal care serving the Rohingya refugees and palliative care is gradually being integrated due to high mortality and medical complexity of patients. The purpose of this study was to understand the moral experiences of staff involved in providing palliative care to inform program implementation at Goyalmara Hospital and in other humanitarian contexts.

This focused ethnography was conducted between March-August 2021 at Goyalmara Hospital. Data collection involved participant-observation, individual interviews (22), focus group discussions (5), and analysis of protocols and other documents. Interviews and focus groups were audio-recorded, translated, and transcribed. A coding scheme was developed, and data coded using NVivo 11.

A key finding of this study was the important yet contested role of clinical guidelines and policies in palliative care related decision-making which was shaped by the authority and impermanent presence of international staff in the project. Staff saw clinical guidelines as a valuable resource that supported a consistent approach to care over time, and some locally hired staff used clinical guidelines as a tool to support their point of view during care planning discussions with international staff. Others felt that palliative care guidelines and other policies were inappropriately or rigidly applied, particularly surrounding decisions to refer (or not refer) patients to a higher level of care, or to discontinue certain medical treatments at end of life.

MSF staff experienced tension between the need for clarity and consistency, and the need to tailor guidelines to the context, patient, and family. Open discussion of staff concerns may alleviate moral distress and alert teams to areas where advocacy, staff psycho-social support, training, or clinical mentoring are needed.

Our purpose-built dementia unit investigates temperature and Behavioural and Psychological Symptoms of Dementia (BPSD). We sought to control for diurnality. Sundown Syndrome (SS) is emergence or worsening of BPSD in the late afternoon or early evening. The literature affords debate. Our methods of controlling for time as a confounder for temperature generated contributions which we offer here.

Data were collected from two Older People's Organic wards within the Cumbria, Northumberland Tyne and Wear NHS Foundation Trust. Collection used the Trust's “Talk First” data system. That is an established, verified record, including “aggression” (non-contact) or “violence” (contact). Data from 16 months, September 2019 to January 2021 were analysed.

Patients had moderate or severe dementia. Wards care for a maximum of 14 patients and serve either men or women. Data for the communal corridor and day room of each ward were analysed. This gave four site

We used two methods. The first was basic, the overall histogram of incidents through the day.

The second analysis counts “incident signals” from each time or temperature. Each actual occurring combination of temperature and time is assigned a “cell”. The background rate of all incidents per all cells is known. Any incident in any rare cell has low binomial probability. Low probabilities mean high “signal”. The square of sums of signals across each hour provides each hour's “incident signal”.

Median ages were 79 (women) and 82 (men). There were 99 incidents.

The histogram has two peaks, around lunchtime and evening. Late afternoon is relatively safe. Thermal incident signals are summarised as moderately coherent. Diurnal incident signals controlling for temperature did not show any coherent trend.

We proffer approaches for controlling for temperature and time of day. The project has limits. We have a small sample. We have not compared sunset times; but that is not relevant to the mid-day peak. We present secondary data from an evaluation aimed at temperature. More favourably this is an a priori sample, shows the same thing is two ways, and adds to debate on an important and critiqued construct. Though SS uses “sun” as a shorthand, any effect will be mediated bio-psychosocially via light, social interaction, heat, circadian rhythms, etc. Our data support social interaction more than time of day. This may add to or challenge SS as a construct.