Disordered sleep and its association with academic performance and functioning.

Sleep disorders are prevalent among college students and are associated with poor academic performance. Few studies have included a clinical interview to comprehensively assess sleep disorder diagnostic criteria or assessed academic functioning (e.g., class attendance). College students (n = 277) were recruited to complete sleep questionnaires, a sleep diary for two weeks and, if indicated, a semi-structured clinical interview. Based on questionnaire data, students were categorized as being at risk versus not at risk for a sleep disorder. Based on the semi-structured clinical interview, students were categorized as meeting versus not meeting diagnostic criteria for a sleep disorder. Academic performance and functioning were assessed in all students to determine the association between the presence of sleep disorders and academic performance and functioning. In models adjusted for age, sex, race, and credit hours completed, students at risk for a sleep disorder (38.6% of the sample) reported missing more classes due to oversleeping (p = 0.001) and illness (p = 0.014), and fell asleep in class more often (p = 0.030) than their peers not at risk. Students with a sleep disorder (24.8% of the sample) reported missing more classes due to illness (p = 0.024) than those without a sleep disorder. There were no differences in grade point average between students at risk versus not at risk or with versus without a sleep disorder. Sleep disorder symptoms and diagnoses were significantly associated with worse academic functioning but not performance. Assessment and treatment of sleep disorders early in college students' career may be important for optimal academic functioning. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-022-00423-3.

Evaluation of intranasal nafamostat or camostat for SARS-CoV-2 chemoprophylaxis in Syrian golden hamsters.

Successful development of a chemoprophylaxis against SARS-CoV-2 could provide a tool for infection prevention implementable alongside vaccination programmes. Camostat and nafamostat are serine protease inhibitors that inhibit SARS-CoV-2 viral entry in vitro but have not been characterised for chemoprophylaxis in animal models. Clinically, nafamostat is limited to intravenous delivery and while camostat is orally available, both drugs have extremely short plasma half-lives. This study sought to determine whether intranasal dosing at 5 mg/kg twice daily was able to prevent airborne transmission of SARS-CoV-2 from infected to uninfected Syrian golden hamsters. SARS-CoV-2 viral RNA was above the limits of quantification in both saline- and camostat-treated hamsters 5 days after cohabitation with a SARS-CoV-2 inoculated hamster. However, intranasal nafamostat-treated hamsters remained RNA negative for the full 7 days of cohabitation. Changes in body weight over the course of the experiment were supportive of a lack of clinical symptomology in nafamostat-treated but not saline- or camostat-treated animals. These data are strongly supportive of the utility of intranasally delivered nafamostat for prevention of SARS-CoV-2 infection and further studies are underway to confirm absence of pulmonary infection and pathological changes.

Feasibility study for the value of pelvic floor distension in predicting mode of birth for women undergoing Vaginal Birth After Caesarean.

INDRODUCTION & HYPOTHESIS: Women having Vaginal Birth (VB) have different soft tissue dynamics to women requiring emergency Lower Section Caesarean Section (LSCS). AIMS: To assess the role of ultrasound in the assessment of LH distensibility in predicting outcomes for women wishing for Vaginal Birth After Caesarean section (VBAC). To inform subsequent trial design including understanding womens attitudes to the use of ultrasound in prediction of vaginal birth. METHODS: Nulliparous, previous VB and previous LSCS underwent a transvaginal ultrasound. This scan looked at the distensibility of the LH and then correlated with mode of birth. Analysis used logistic regression and ROC curves analysis for static measurements and distensibility. A second cohort was also asked about their views as to the usefulness of such a tool to help inform on the utility of such a model. RESULTS: The original hypothesis confirmed maternal BMI, Anterior Posterior (AP) diameter at rest and AP distensibility all being significant predictors of VB in nulliparous women. As expected this relationship was also seen in women who had previously had a vaginal birth. Of the VBAC group, 23 women had LSCS. Five were Robson category, 18 had emergency LSCS in labour. 25 women had VB. Whilst there were trends towards lesser distensibility in VBAC women who delivered vaginally, none of these reached sgnificance. The concept of the use of scanning to inform women as to likelihood of successful vaginal birth was supported by the survey. CONCLUSION: Previously noted characteristics in nulliparous women for pelvic floor distension were confirmed. This relationship was not demonstrated for the VBAC cohort. We were unable to establish criteria for a simple ultrasound model to predict VB in women wishing for VBAC. Overall, women would welcome such model if it were available.

Minds and Brains, Sleep and Psychiatry.

OBJECTIVE: This article offers a philosophical thesis for psychiatric disorders that rests upon some simple truths about the mind and brain. Specifically, it asks whether the dual aspect monism-that emerges from sleep research and theoretical neurobiology-can be applied to pathophysiology and psychopathology in psychiatry. METHODS: Our starting point is that the mind and brain are emergent aspects of the same (neuronal) dynamics; namely, the brain-mind. Our endpoint is that synaptic dysconnection syndromes inherit the same dual aspect; namely, aberrant inference or belief updating on the one hand, and a failure of neuromodulatory synaptic gain control on the other. We start with some basic considerations from sleep research that integrate the phenomenology of dreaming with the neurophysiology of sleep. RESULTS: We then leverage this treatment by treating the brain as an organ of inference. Our particular focus is on the role of precision (i.e., the representation of uncertainty) in belief updating and the accompanying synaptic mechanisms. CONCLUSIONS: Finally, we suggest a dual aspect approach-based upon belief updating (i.e., mind processes) and its neurophysiological implementation (i.e., brain processes)-has a wide explanatory compass for psychiatry and various movement disorders. This approach identifies the kind of pathophysiology that underwrites psychopathology-and points to certain psychotherapeutic and psychopharmacological targets, which may stand in mechanistic relation to each other.

Sentience and the Origins of Consciousness: From Cartesian Duality to Markovian Monism.

This essay addresses Cartesian duality and how its implicit dialectic might be repaired using physics and information theory. Our agenda is to describe a key distinction in the physical sciences that may provide a foundation for the distinction between mind and matter, and between sentient and intentional systems. From this perspective, it becomes tenable to talk about the physics of sentience and 'forces' that underwrite our beliefs (in the sense of probability distributions represented by our internal states), which may ground our mental states and consciousness. We will refer to this view as Markovian monism, which entails two claims: (1) fundamentally, there is only one type of thing and only one type of irreducible property (hence monism). (2) All systems possessing a Markov blanket have properties that are relevant for understanding the mind and consciousness: if such systems have mental properties, then they have them partly by virtue of possessing a Markov blanket (hence Markovian). Markovian monism rests upon the information geometry of random dynamic systems. In brief, the information geometry induced in any system-whose internal states can be distinguished from external states-must acquire a dual aspect. This dual aspect concerns the (intrinsic) information geometry of the probabilistic evolution of internal states and a separate (extrinsic) information geometry of probabilistic beliefs about external states that are parameterised by internal states. We call these intrinsic (i.e., mechanical, or state-based) and extrinsic (i.e., Markovian, or belief-based) information geometries, respectively. Although these mathematical notions may sound complicated, they are fairly straightforward to handle, and may offer a means through which to frame the origins of consciousness.

Management of tracheostomy-related tracheomegaly in a patient with COVID-19 pneumonitis.

Acquired tracheomegaly is a rare condition associated with pulmonary fibrosis, connective tissue disease and the use of cuffed tracheal tubes. We describe the urgent tracheal re-intubation and subsequent tracheal repair of a previously well 58-year-old man who developed tracheostomy-related tracheomegaly during prolonged mechanical ventilation for coronavirus disease 2019 pneumonitis. Urgent tracheal re-intubation was required due to a persistent cuff leak, pneumomediastinum and malposition of the tracheostomy tube. We describe the additional challenges and risks associated with airway management in patients with tracheomegaly, and discuss how even in urgent cases these can be mitigated through planning and teamwork. We present a stepwise approach to tracheal re-intubation past a large tracheal dilatation, including the use of an Aintree catheter inserted via the existing tracheal stoma for oxygenation or tracheal re-intubation if required. Computed tomography imaging was valuable in characterising the defect and developing a safe airway management strategy before starting the procedure. This report emphasises the role of planning, teamwork and the development of an appropriate airway strategy in the safe management of complex cases.

Insight and Dissociation in Lucid Dreaming and Psychosis.

Dreams and psychosis share several important features regarding symptoms and underlying neurobiology, which is helpful in constructing a testable model of, for example, schizophrenia and delirium. The purpose of the present communication is to discuss two major concepts in dreaming and psychosis that have received much attention in the recent literature: insight and dissociation. Both phenomena are considered functions of higher order consciousness because they involve metacognition in the form of reflective thought and attempted control of negative emotional impact. Insight in dreams is a core criterion for lucid dreams. Lucid dreams are usually accompanied by attempts to control the dream plot and dissociative elements akin to depersonalization and derealization. These concepts are also relevant in psychotic illness. Whereas insightfulness can be considered innocuous in lucid dreaming and even advantageous in psychosis, the concept of dissociation is still unresolved. The present review compares correlates and functions of insight and dissociation in lucid dreaming and psychosis. This is helpful in understanding the two concepts with regard to psychological function as well as neurophysiology.

Microbiology and antimicrobial susceptibility of otitis externa: a changing pattern of antimicrobial resistance.

OBJECTIVE: Otitis externa is a common presentation to secondary care otolaryngology clinics. Despite this, few studies have investigated the microbiology and antimicrobial resistance of otitis externa. This study aimed to examine these issues. METHODS: Analysis identified 302 swabs taken from 217 patients (100 male, 117 female), between 1 January 2015 and 30 March 2016, at our rapid access otolaryngology clinic. RESULTS: In total, 315 organisms were isolated; the most frequent was Pseudomonas aeruginosa (31.1 per cent), followed by candida species (22.9 per cent) and Staphylococcus aureus (11.7 per cent). P aeruginosa was sensitive to ciprofloxacin in 97.7 per cent of cases and to gentamicin in 78.4 per cent. CONCLUSION: Compared with studies worldwide, the relative proportions of different organisms causing otitis externa and the patterns of antimicrobial resistance differ. Increasing resistance of P aeruginosa to aminoglycosides demonstrates a changing pattern of antimicrobial resistance that has not been previously reported. Reassuringly, quinolone antibiotics remain highly effective when treating P aeruginosa.

Active Inference, Curiosity and Insight.

This article offers a formal account of curiosity and insight in terms of active (Bayesian) inference. It deals with the dual problem of inferring states of the world and learning its statistical structure. In contrast to current trends in machine learning (e.g., deep learning), we focus on how people attain insight and understanding using just a handful of observations, which are solicited through curious behavior. We use simulations of abstract rule learning and approximate Bayesian inference to show that minimizing (expected) variational free energy leads to active sampling of novel contingencies. This epistemic behavior closes explanatory gaps in generative models of the world, thereby reducing uncertainty and satisfying curiosity. We then move from epistemic learning to model selection or structure learning to show how abductive processes emerge when agents test plausible hypotheses about symmetries (i.e., invariances or rules) in their generative models. The ensuing Bayesian model reduction evinces mechanisms associated with sleep and has all the hallmarks of "aha" moments. This formulation moves toward a computational account of consciousness in the pre-Cartesian sense of sharable knowledge (i.e., con: "together"; scire: "to know").

Towards a Functional Understanding of PGO Waves.

Ponto-Geniculo-Occipital (PGO) waves are biphasic field potentials identified in a range of mammalian species that are ubiquitous with sleep, but can also be identified in waking perception and eye movement. Their role in REM sleep and visual perception more broadly may constitute a promising avenue for further research, however what was once an active field of study has recently fallen into stasis. With the reality that invasive recordings performed on animals cannot be replicated in humans; while animals themselves cannot convey experience to the extent required to elucidate how PGO waves factor into awareness and behavior, innovative solutions are required if significant research outcomes are to ever be realized. Advances in non-invasive imaging technologies and sophistication in imaging methods now offer substantial scope to renew the study of the electrophysiological substrates of waking and dreaming perception. Among these, Magnetoencephalogram (MEG) stands out through its capacity to measure deep brain activations with high temporal resolution. With the current trend in sleep and dream research to produce translational findings of psychopathological and medical significance, in addition to the clear links that PGO wave generation sites share, pharmacologically, with receptors involved in expression of mental illness; there is a strong case to support scientific research into PGO waves and develop a functional understanding of their broader role in human perception.

Patient and physician views of accompanied consultations in occupational health.

BACKGROUND: Accompanied (triadic) consultations, or consultations where a third person is present, are poorly researched and little research has been carried out in an occupational health (OH) setting. AIMS: To elicit the views of patients and OH physicians about accompanied consultations. METHODS: OH receptionists gave a self-administered questionnaire to patients after they attended OH consultations with a companion. We interviewed participating OH physicians to ascertain their views on accompanied consultations. RESULTS: Twenty-six patient questionnaires were completed (response rate 52%). Seventy-three per cent (19) of responders were accompanied by a spouse and 12% (3) by non-family members. Patients reported their companion was helpful with recall of information (100%), supportive (100%), provided extra information to the physician (81%) and enabled them to discuss the outcome afterwards (92%). In two consultations, the companion attended to provide support on procedural matters. Patients were not concerned that the consultation might involve sensitive discussion or physical examination. OH physicians reported concerns that the companion would make the consultation more difficult or influence its outcome. They felt that written information, guidelines and training in how to manage accompanied consultations would be useful. CONCLUSIONS: Patients who attended OH consultations with a companion felt the companion was beneficial to the consultation and did not have concerns about personal issues. OH physicians felt that further guidance and training on accompanied consultations would be useful. Written information could usefully be provided to patients attending an OH consultation with a companion.

Screening of Blood Donations for Zika Virus Infection - Puerto Rico, April 3-June 11, 2016.

Transfusion-transmitted infections have been documented for several arboviruses, including West Nile and dengue viruses (1). Zika virus, a flavivirus transmitted primarily by Aedes aegypti mosquitoes that has been identified as a cause of congenital microcephaly and other serious brain defects (2), became recognized as a potential threat to blood safety after reports from a 2013-2014 outbreak in French Polynesia. Blood safety concerns were based on very high infection incidence in the population at large during epidemics, the high percentage of persons with asymptomatic infection, the high proportion of blood donations with evidence of Zika virus nucleic acid upon retrospective testing, and an estimated 7-10-day period of viremia (3). At least one instance of transfusion transmission of Zika virus has been documented in Brazil after the virus emerged there, likely in 2014 (4). Rapid epidemic spread has followed to other areas of the Americas, including Puerto Rico.

Standardized methods to generate mock (spiked) clinical specimens by spiking blood or plasma with cultured pathogens.

AIMS: To demonstrate standardized methods for spiking pathogens into human matrices for evaluation and comparison among diagnostic platforms. METHODS AND RESULTS: This study presents detailed methods for spiking bacteria or protozoan parasites into whole blood and virus into plasma. Proper methods must start with a documented, reproducible pathogen source followed by steps that include standardized culture, preparation of cryopreserved aliquots, quantification of the aliquots by molecular methods, production of sufficient numbers of individual specimens and testing of the platform with multiple mock specimens. Results are presented following the described procedures that showed acceptable reproducibility comparing in-house real-time PCR assays to a commercially available multiplex molecular assay. CONCLUSIONS: A step by step procedure has been described that can be followed by assay developers who are targeting low prevalence pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: The development of diagnostic platforms for detection of low prevalence pathogens such as biothreat or emerging agents is challenged by the lack of clinical specimens for performance evaluation. This deficit can be overcome using mock clinical specimens made by spiking cultured pathogens into human matrices. To facilitate evaluation and comparison among platforms, standardized methods must be followed in the preparation and application of spiked specimens.

Accompanied consultations in occupational health.

BACKGROUND: Accompanied consultations are often reported as difficult by occupational physicians but have not been studied in the occupational health setting. AIMS: To collect information about accompanied consultations and the impact of the companion on the consultation. METHODS: We collected data on all accompanied consultations by two occupational physicians working in a private sector occupational health service over the course of 16 months. Accompanied consultations were matched to non-accompanied consultations for comparison. RESULTS: We collected data on 108 accompanied consultations. Accompanied consultations were more likely to be connected with ill health retirement (P < 0.01), have a neurological diagnosis or multiple diagnoses (P < 0.01), be rated as complex (P < 0.01) and take longer than 30 minutes (P < 0.01) than non-accompanied consultations. Over half of the companions (54%) were a spouse or partner. An impact by the companion was recorded in 81% of consultations but this was most frequently that they had provided information (56%) and in over a quarter the impact was recorded as helpful. Interruptions were recorded in 28% of accompanied consultations but only 6% of consultations had free text suggesting that the consultation or companion was difficult. CONCLUSIONS: Accompanied consultations are likely to be more challenging in terms of the reason for referral, the presenting medical problems, the complexity of the case and the duration of the consultation. However, the companion is more likely to be of benefit than cause difficulty. Occupational health practitioners may benefit from better understanding of accompanied consultations and guidance on their management.

Demonstration of the Pre-Emergency Use Authorization Path Using 3 Minor Groove Binder-Hydrolysis Probe Assays to Detect Escherichia coli O104:H4.

BACKGROUND: The Department of Defense (DoD) and the Food and Drug Administration (FDA) have collaboratively worked on a pre-Emergency Use Authorization (pre-EUA) process for in vitro diagnostic (IVD) devices, using FDA's regulatory flexibilities under the EUA authorities. The pre-EUA process enables FDA review of data in anticipation of a request for an EUA, advancing US government public health emergency preparedness efforts. METHODS: The IVD device developed to detect Escherichia coli O104:H4, for which an EUA has not been issued, serves as an example to illustrate that process. Specifically, DoD designed real-time PCR assays to target the virulent E. coli strain O104:H4 (etiological agent of the 2011 German outbreak) including: fliC (flagellin), Agg3C (AAF), and rfb (wbwC) on the basis of the published sequences. RESULTS: After development and optimization of these 3 specific assays, a defined protocol was followed to determine and document the sensitivity and specificity of each assay analytically. CONCLUSIONS: FDA reviewed these data and returned commentary on additional required experiments to complete the pre-EUA process and expedite the use of the device should there be an emergency need for an IVD device to detect this virulent E. coli strain before such a test is cleared by FDA.

Not only but also: REM sleep creates and NREM Stage 2 instantiates landmark junctions in cortical memory networks.

This article argues both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep contribute to overnight episodic memory processes but their roles differ. Episodic memory may have evolved from memory for spatial navigation in animals and humans. Equally, mnemonic navigation in world and mental space may rely on fundamentally equivalent processes. Consequently, the basic spatial network characteristics of pathways which meet at omnidirectional nodes or junctions may be conserved in episodic brain networks. A pathway is formally identified with the unidirectional, sequential phases of an episodic memory. In contrast, the function of omnidirectional junctions is not well understood. In evolutionary terms, both animals and early humans undertook tours to a series of landmark junctions, to take advantage of resources (food, water and shelter), whilst trying to avoid predators. Such tours required memory for emotionally significant landmark resource-place-danger associations and the spatial relationships amongst these landmarks. In consequence, these tours may have driven the evolution of both spatial and episodic memory. The environment is dynamic. Resource-place associations are liable to shift and new resource-rich landmarks may be discovered, these changes may require re-wiring in neural networks. To realise these changes, REM may perform an associative, emotional encoding function between memory networks, engendering an omnidirectional landmark junction which is instantiated in the cortex during NREM Stage 2. In sum, REM may preplay associated elements of past episodes (rather than replay individual episodes), to engender an unconscious representation which can be used by the animal on approach to a landmark junction in wake.

Neural correlates of insight in dreaming and psychosis.

The idea that dreaming can serve as a model for psychosis has a long and honourable tradition, however it is notoriously speculative. Here we demonstrate that recent research on the phenomenon of lucid dreaming sheds new light on the debate. Lucid dreaming is a rare state of sleep in which the dreamer gains insight into his state of mind during dreaming. Recent electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) data for the first time allow very specific hypotheses about the dream-psychosis relationship: if dreaming is a reasonable model for psychosis, then insight into the dreaming state and insight into the psychotic state should share similar neural correlates. This indeed seems to be the case: cortical areas activated during lucid dreaming show striking overlap with brain regions that are impaired in psychotic patients who lack insight into their pathological state. This parallel allows for new therapeutic approaches and ways to test antipsychotic medication.

Virtual reality and consciousness inference in dreaming.

This article explores the notion that the brain is genetically endowed with an innate virtual reality generator that - through experience-dependent plasticity - becomes a generative or predictive model of the world. This model, which is most clearly revealed in rapid eye movement (REM) sleep dreaming, may provide the theater for conscious experience. Functional neuroimaging evidence for brain activations that are time-locked to rapid eye movements (REMs) endorses the view that waking consciousness emerges from REM sleep - and dreaming lays the foundations for waking perception. In this view, the brain is equipped with a virtual model of the world that generates predictions of its sensations. This model is continually updated and entrained by sensory prediction errors in wakefulness to ensure veridical perception, but not in dreaming. In contrast, dreaming plays an essential role in maintaining and enhancing the capacity to model the world by minimizing model complexity and thereby maximizing both statistical and thermodynamic efficiency. This perspective suggests that consciousness corresponds to the embodied process of inference, realized through the generation of virtual realities (in both sleep and wakefulness). In short, our premise or hypothesis is that the waking brain engages with the world to predict the causes of sensations, while in sleep the brain's generative model is actively refined so that it generates more efficient predictions during waking. We review the evidence in support of this hypothesis - evidence that grounds consciousness in biophysical computations whose neuronal and neurochemical infrastructure has been disclosed by sleep research.

Flaxseed lignan complex administration in older human type 2 diabetics manages central obesity and prothrombosis-an invitation to further investigation into polypharmacy reduction.

Aim. Animal and human study evidence supports the hypothesis that flaxseed lignan complex (FLC) at a dose of 600 mg secoisolariciresinol diglucoside (SDG)/day for three months would combat hyperglycaemia, dyslipidemia, blood pressure, central obesity, prothrombotic state, inflammation, and low density lipoprotein (LDL) oxidation. Methods. Sixteen type 2 diabetic patients completed this double-blind, randomised crossover placebo-controlled study. A univariate repeated measures analysis of covariance (significance P < 0.05) was followed by a mixed linear model effects analysis corrected for multiple comparisons (MCC). Results. Prior to MCC, FLC caused decreased fasting plasma glucose, A1c, inflammation (c-reactive protein (CRP) and interleukin-6 (IL-6)), and increased bleeding time. After correction for multiple comparisons, FLC induced a statistically significant increase in bleeding time and smaller waist circumference gain. No treatment effect occurred in the other variables before or after adjustment. Conclusions. It is concluded that FLC significantly increased bleeding time thus reducing the prothrombotic state, reduced central obesity gain as measured by waist circumference, and did not affect significantly the other dependent variables measured after adjustment for multiple comparisons. These findings, not yet published in human type 2 diabetes, suggest that this FLC dose over at least three months, may, subject to further investigation, reduce polypharmacy.