Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

REVERSAL OF DEPRESSANT EFFECTS OF XYLAZINE-KETAMINE ANESTHESIA IN RABBITS USING EITHER AN ALPHA-2 ANTAGONIST (YOHIMBINE) OR A MIXED ALPHA-1 AND ALPHA-2 ANTAGONIST (TOLAZOLINE)

Program year: 1996/1997Digitized from print original stored in HDRNine rabbits were studied after injection intramuscularly with xylazine¹ (8mg/kg) and ketamine² (50mg/kg). Twenty minutes later, rabbits received intravenous injections of yohimbine³ (0.5mg/kg), tolazoline⁴(6.6mg/kg), or physiological saline (0.5ml). Treatments were randomized according to Latin square design and at least seven days were allowed between treatment in each rabbit. Recordings were taken at ten-minute intervals for 80 minutes. Mean time to sternal recumbency (as measured from time of injection of reversal drugs or saline) was significantly shortened to 91±21 minutes with yohimbine and 83±19 minutes with tolazoline as compared to 117±13 minutes with saline. Though not statistically significant (p≤.05), mean time to standing (128±40 minutes for yohimbine, 114±23 minutes for tolazoline, 134i17 minutes for saline), mean time to walking (128±44 minutes for yohimbine, 111±27 minutes for tolazoline, 142:11 minutes for saline), and mean time to walking with full coordination (150±37 minutes for yohimbine, 142±23 minutes for tolazoline, 187±60 minutes for saline) were shortened with both drugs as compared to saline. Relapses to unconsciousness did not occur. Palpebral and withdrawal- responses returned much more rapidly with yohimbine than with the other two drugs. These responses returned more quickly with tolazoline than with saline. 'Heart rates were highest after yohimbine. In all three groups, heart rates were significantly different from each other. Respiratory rates, though not significant, were higher with yohimbine and tolazoline than with saline. Though both yohimbine and tolazoline were effective for reversing xylazine-ketamine anesthesia in rabbits at the dosages given, tolazoline provided the most desirable recovery. Both antagonists, however, would be useful for enhancing arousal in xylazine-ketamine depressed rabbits

Executive Function and Social Cognition in Children and Adolescents with Borderline Personality Features

Models of Borderline Personality Disorder (BPD) highlight a role of environmental and neurocognitive developmental risk factors, yet empirical research into the developmental trajectory of this disorder is limited. The primary aim of the current thesis was to investigate associations between borderline personality features (BPF) and the neurocognitive domains of executive function and social cognition in late childhood and early adolescence. Previous research has identified high risk of comorbidity between BPD and internalizing and externalizing disorders of childhood. Therefore, a secondary aim of the current study was to examine neurocognitive performance controlling for overlapping symptoms of childhood psychopathology. A mixed clinical and community sample of 81 children and adolescents, aged between 10-14, completed a comprehensive web-based neurocognitive battery that examined the following cognitive domains; executive function, attention, memory and social cognition. Results indicated a non-significant trend of BPF predicting performance on an EF task of cognitive inhibition; however this trend disappeared when internalizing and externalizing symptoms of emotional problems, conduct problems and hyperactivity/inattention were controlled. Furthermore the results of the current study indicated a non-significant trend in delayed memory performance for individuals with BPF and non-significant trends of BPF as a predictor of emotion recognition; where older participants with BPF displayed reduced accuracy in identifying anger but enhanced accuracy for the identification of sadness. In addition, age was found to be related to reduced accuracy in identifying happiness, but only in participants with higher levels of BPF. These deficits were found to be independent of internalizing and externalizing symptoms. The current study provides preliminary evidence of neurocognitive deficits in children and adolescents with sub-threshold symptoms of BPD

Psychogenic non-epileptic seizures in children and adolescents: Part I – Diagnostic formulations

Psychogenic non-epileptic seizures (PNES) are a nonspecific, umbrella category that is used to collect together a range of atypical neurophysiological responses to emotional distress, physiological stressors and danger. Because PNES mimic epileptic seizures, children and adolescents with PNES usually present to neurologists or to epilepsy monitoring units. After a comprehensive neurological evaluation and a diagnosis of PNES, the patient is referred to mental health services for treatment. This study documents the diagnostic formulations – the clinical formulations about the probable neurophysiological mechanisms – that were constructed for 60 consecutive children and adolescents with PNES who were referred to our Mind-Body Rehabilitation Programme for treatment. As a heuristic framework, we used a contemporary reworking of Janet’s dissociation model: PNES occur in the context of a destabilized neural system and reflect a release of prewired motor programmes following a functional failure in cognitive-emotional executive control circuitry. Using this framework, we clustered the 60 patients into six different subgroups: (1) dissociative PNES (23/60; 38%), (2) dissociative PNES triggered by hyperventilation (32/60; 53%), (3) innate defence responses presenting as PNES (6/60; 10%), (4) PNES triggered by vocal cord adduction (1/60; 2%), (5) PNES triggered by activation of the valsalva manoeuvre (1/60; 1.5%) and (6) PNES triggered by reflex activation of the vagus (2/60; 3%). As described in the companion article, these diagnostic formulations were used, in turn, both to inform the explanations of PNES that we gave to families and to design clinical interventions for helping the children and adolescents gain control of their PNES

Psychogenic non-epileptic seizures in children and adolescents: Part II – explanations to families, treatment, and group outcomes

Psychogenic non-epileptic seizures (PNES) – time-limited disturbances of consciousness and motor-sensory control, not accompanied by ictal activity on electroencephalogram (EEG) – are best conceptualized as atypical neurophysiological responses to emotional distress, physiological stressors and danger. Patients and families find the diagnosis of PNES difficult to understand; the transition from neurology (where the diagnosis is made) to mental health services (to which patients are referred for treatment) can be a bumpy one. This study reports how diagnostic formulations constructed for 60 consecutive children and adolescents with PNES were used to inform both the explanations about PNES that were given to them and their families and the clinical interventions that were used to help patients gain control over PNES. Families were able to accept the diagnosis of PNES and engage in treatment when it was explained how emotional distress, illness and states of high arousal could activate atypical defence responses in the body and brain – with PNES being an unwanted by-product of this process. Patients and their families made good use of therapeutic interventions. A total of 75% of children/adolescents (45/60) regained normal function and attained full-time return to school. Global Assessment of Functioning scores increased from 41 to 67 (t(54) = 10.09; p < .001). Outcomes were less favourable in children/adolescents who presented with chronic PNES and in those with a chronic, comorbid mental health disorder that failed to resolve with treatment. The study highlights that prompt diagnosis, followed by prompt multidisciplinary assessment, engagement, and treatment, achieves improved outcomes in children/adolescents with PNES

Minimal Effect of CD103 Expression on the Control of a Chronic Antiviral Immune Response

Impaired antiviral CD8 and CD4 T-cell responses are often associated with chronic viral infections. Cell-intrinsic as well as cell-extrinsic mechanisms are thought to dampen such responses, for example programmed death 1 receptor (PD-1) expression on T cells, and interleukin (IL)-10 production primarily by dendritic cells (DCs), have been shown to support viral persistence by suppressing immune responses. Here we demonstrate that CD103, an alpha E integrin necessary for T-cell homing and retention in the gut and other epithelia expressed by the majority of naïve CD8+, and CD4+CD25+ T cells and some DC subsets, is unnecessary for controlling T-cell responses during chronic lymphocytic choriomeningitis virus clone 13 (LCMV cl13) infection. T-cell analysis following viral infection showed that the primary as well as the memory CD8+ and CD4+ T-cell responses among CD103-sufficient and CD103-deficient mice were identical. In addition, no rescue of cytokine production by virus-specific T cells or alterations in viral titers in the absence of intrinsic CD103 expression was observed. Interestingly, CD103 levels on the effector CD8+ T cells became reduced soon after virus infection, with a small proportion of cells co-expressing PD-1 and CD103. In contrast, although no substantial differences in the frequency and number of the CD4+CD25+ cell population were seen, CD103 expression increased significantly over time in this population, correlating with viral persistence. Thus, a lack of CD103 expression does not affect functional impairment of effector T-cell responses during chronic viral infection