The SARS-CoV-2 viral load in COVID-19 patients is lower on face mask filters than on nasopharyngeal swabs.

Face masks and personal respirators are used to curb the transmission of SARS-CoV-2 in respiratory droplets; filters embedded in some personal protective equipment could be used as a non-invasive sample source for applications, including at-home testing, but information is needed about whether filters are suited to capture viral particles for SARS-CoV-2 detection. In this study, we generated inactivated virus-laden aerosols of 0.3-2 microns in diameter (0.9 µm mean diameter by mass) and dispersed the aerosolized viral particles onto electrostatic face mask filters. The limit of detection for inactivated coronaviruses SARS-CoV-2 and HCoV-NL63 extracted from filters was between 10 to 100 copies/filter for both viruses. Testing for SARS-CoV-2, using face mask filters and nasopharyngeal swabs collected from hospitalized COVID-19-patients, showed that filter samples offered reduced sensitivity (8.5% compared to nasopharyngeal swabs). The low concordance of SARS-CoV-2 detection between filters and nasopharyngeal swabs indicated that number of viral particles collected on the face mask filter was below the limit of detection for all patients but those with the highest viral loads. This indicated face masks are unsuitable to replace diagnostic nasopharyngeal swabs in COVID-19 diagnosis. The ability to detect nucleic acids on face mask filters may, however, find other uses worth future investigation.

Contactless graphene conductivity mapping on a wide range of substrates with terahertz time-domain reflection spectroscopy.

We demonstrate how terahertz time-domain spectroscopy (THz-TDS) operating in reflection geometry can be used for quantitative conductivity mapping of large area chemical vapour deposited graphene films on sapphire, silicon dioxide/silicon and germanium. We validate the technique against measurements performed with previously established conventional transmission based THz-TDS and are able to resolve conductivity changes in response to induced back-gate voltages. Compared to the transmission geometry, measurement in reflection mode requires careful alignment and complex analysis, but circumvents the need of a terahertz transparent substrate, potentially enabling fast, contactless, in-line characterisation of graphene films on non-insulating substrates such as germanium.

Low-bias terahertz amplitude modulator based on split-ring resonators and graphene.

Split-ring resonators represent the ideal route to achieve optical control of the incident light at THz frequencies. These subwavelength metamaterial elements exhibit broad resonances that can be easily tuned lithographically. We have realized a design based on the interplay between the resonances of metallic split rings and the electronic properties of monolayer graphene integrated in a single device. By varying the major carrier concentration of graphene, an active modulation of the optical intensity was achieved in the frequency range between 2.2 and 3.1 THz, achieving a maximum modulation depth of 18%, with a bias as low as 0.5 V.

Behavioural, neurochemical and neuroendocrine effects of the endogenous ß-carboline harmane in fear-conditioned rats.

The putative endogenous imidazoline binding site ligand harmane enhances neuronal activation in response to psychological stress and alters behaviour in animal models of anxiety and antidepressant efficacy. However, the neurobiological mechanisms underlying harmane's psychotropic effects are poorly understood. We investigated the effects of intraperitoneal injection of harmane (2.5 and 10 mg/kg) on fear-conditioned behaviour, hypothalamo-pituitary-adrenal axis activity, and monoaminergic activity within specific fear-associated areas of the rat brain. Harmane had no significant effect on the duration of contextually induced freezing or 22 kHz ultrasonic vocalisations and did not alter the contextually induced suppression of motor activity, including rearing. Harmane reduced the duration of rearing and tended to increase freezing in non-fear-conditioned controls, suggesting potential sedative effects. Harmane increased plasma ACTH and corticosterone concentrations, and serotonin (in hypothalamus, amygdaloid cortex, prefrontal cortex and hippocampus) and noradrenaline (prefrontal cortex) content, irrespective of fear-conditioning. Furthermore, harmane reduced dopamine and serotonin turnover in the PFC and hypothalamus, and serotonin turnover in the amygdaloid cortex in both fear-conditioned and non-fear-conditioned rats. In contrast, harmane increased dopamine and noradrenaline content and reduced dopamine turnover in the amygdala of fear-conditioned rats only, suggesting differential effects on catecholaminergic transmission in the presence and absence of fear. The precise mechanism(s) mediating these effects of harmane remain to be determined but may involve its inhibitory action on monoamine oxidases. These findings support a role for harmane as a neuromodulator, altering behaviour, brain neurochemistry and neuroendocrine function.

Annexin-A1 protein and its relationship to cortisol in human saliva.

Salivary cortisol is commonly used as a clinical biomarker of endocrine status and also as a marker of psychosocial stress. Annexin-A1 (AnxA1) is an anti-inflammatory protein whose expression is modulated by glucocorticoids. Our principal objectives were to (i) detect the presence of and (ii) measure AnxA1 protein in whole human saliva and to (iii) investigate whether salivary cortisol and AnxA1 are correlated in healthy humans. A total of 37 healthy participants (male and female) were used in the study. Saliva was collected using salivette tubes. Salivary cortisol and AnxA1 protein were sampled at between 3 and 6 time points over 24h and measured for cortisol and AnxA1 protein using specific ELISA's. The presence of salivary AnxA1 protein was confirmed by Western blotting. AnxA1 protein is detectable in whole human saliva, as detected by Western blot analysis and ELISA. A diurnal rhythm was evident in both salivary cortisol (P<0.01) and AnxA1 (P<0.01) and was defined as a significant difference in time 0 (waking) samples compared to 'bed' (2300 h) samples. AnxA1 protein did not exhibit an awakening response (P>0.05), whereas salivary cortisol was significantly elevated between time 0 and 30 min post waking (P<0.001). AnxA1 protein correlates positively with salivary cortisol, indicating that cortisol is most likely a regulator of AnxA1 in human saliva.

Hypothalamic-pituitary-adrenal axis activity and upper respiratory tract infection in young children transitioning to primary school.

RATIONALE: We have previously reported an increase in salivary cortisol in a cohort of 4-year-old children transitioning to primary school. We hypothesised that increased cortisol in response to this acute naturalistic stress in early development may be immunostimulatory and associated with positive health outcomes. OBJECTIVES: We tested this hypothesis by measuring upper respiratory tract infection (URI) across the first 6 months of school, in relation to salivary cortisol at the end of the second week following school transition METHODS: Seventy children supplied morning and evening saliva samples for cortisol assay. Children were psychologically assessed for temperament and behavioural adaptation. Symptoms of URI were recorded in diary form, and variables relating to URI occurrence, duration and severity were assessed. RESULTS: Children with higher evening cortisol at school transition experienced significantly fewer episodes of URI over the following 6 months. Diurnal cortisol change was negatively correlated with number of illnesses across the 6 months, indicating an association between a greater decline in cortisol across the day and a greater number of colds. URI severity was associated with the greatest resistance to URI infection in children who were less socially isolated and who had a smaller diurnal change in cortisol across the day. CONCLUSIONS: Our results showing that higher cortisol is associated with lower URI may be explained by proposing that increased cortisol in response to the naturalistic stress of school transition may prime the immune system to develop resistance to URI at this critical stage of a child's development.

Sex differences in hypothalamic-pituitary-adrenal axis function in patients with chronic pain syndrome.

Chronic pain is often equated with chronic stress yet the relationship between chronic pain and hypothalamic-pituitary-adrenal (HPA) axis activity is poorly understood. The objective of this study was to examine diurnal functioning of the HPA axis in patients with clinically defined non-inflammatory chronic pain syndrome (CPS) compared to controls. The sample consisted of 37 adults with CPS and 47 healthy controls. All participants provided saliva samples at awakening, 12:00, 18:00 and 21:00 h on two consecutive days, as well as completing self-report questionnaires relating to anxiety and depression. The CPS group had a significantly lower overall mean diurnal salivary cortisol concentration compared to the control group (p < 0.01) but no significant differences were found between the two groups for repeated cortisol sampling across the day. However, a three-way interaction of time of day by patient status by sex was found (p < 0.032), with lower cortisol concentration in male patients compared to female patients in the afternoon period. No significant group effect was found for the rate of decline in the circadian rise in cortisol concentration. These data demonstrate that CPS is associated with a degree of hypocortisolemia, particularly in male patients. The altered dynamics of cortisol secretion in CPS in relation to the onset and duration of pain in patients remains to be determined.

Diurnal cortisol and coping responses in close relatives of persons with acquired brain injury: a longitudinal mixed methods study.

OBJECTIVE: To examine the impact of having a close relative experience a severe brain injury. DESIGN: Six-month longitudinal mixed methods concurrent embedded study. Quantitative data provided the primary database and qualitative data provided the secondary source. METHODS: Assessment included psychosocial factors of perceived stress, traumatic stress symptoms, coping and social support in addition to salivary cortisol as a biological marker of stress. Written accounts of the experience were provided in response to an open-ended question. Participants composed 15 close relatives of adults with severe brain injury admitted to a specialist rehabilitation facility (mean age 49.4 years; SD 11.79). Assessments were conducted on admission, at 6 weeks, 3 months and 6 months post-admission. RESULTS: Quantitative data revealed high traumatic stress at admission, with a non-significant decline at follow-up. Diurnal cortisol output declined significantly from baseline to all follow-up assessments. Coping sub-scales of acceptance and religion were repeated associated with cortisol indices at baseline, 6 weeks, 3 months and 6 months follow-up. Qualitative data revealed two themes; 'relational impact' and 'passage of time'. CONCLUSIONS: Findings offer the potential for effective and timely intervention in family members of persons with severe brain injury.

Endomorphins in rheumatoid arthritis, osteoarthritis, and experimental arthritis.

The opioid tetrapeptides endomorphins (EM)-1 and EM-2 are widely expressed in central nervous system and immune tissues of rats and humans. Their analgesic properties are well characterized but they also have anti-inflammatory properties. EM-1 significantly attenuated the onset of hindpaw inflammation in adjuvant-induced arthritis in rats. Immunohistochemical staining demonstrated the presence of EMs in T cells, macrophages, and fibroblasts in synovial tissues from patients with osteo- or rheumatoid arthritis (RA). In an ex vivo superfusion system, EM-1 potently inhibited the release of proinflammatory cytokines interleukin (IL)-6 and IL-8 from synovial tissues from patients with osteo- or RA. These results demonstrate that EMs are endogenously synthesized within human immune cells and have the potential to act as potent therapeutic agents in the treatment of chronic inflammatory disease. We discuss the clinical potential for EM analogues chemically modified to resist proteolytic degradation and identify modified protease-resistant analogues with enhanced bioactivity.

Effect of novel therapeutic glucocorticoids on circadian rhythms of hormones and cytokines in rheumatoid arthritis.

The morning stiffness and pain of rheumatoid arthritis (RA) is accompanied by a rise in serum interleukin-6 (IL-6) from 2 am to 7 am. Using a formulation that releases prednisone at 2 am (after ingestion at 10 pm), we studied the circadian dynamics of serum IL-6, other cytokines, and cortisol in 9 patients before and after 2 weeks, therapy. Significant improvements occurred in morning stiffness, pain, disease activity, and the acute-phase response. Only IL-6 showed measurable cytokine circadian variation, its high pretreatment peak was abolished, and changes in IL-6 correlated with the changes in morning stiffness. Following treatment, afternoon and evening serum cortisol was reduced, but in the early morning cortisol peak concentration increased. Thus the severity of morning symptoms is related to nocturnal serum IL-6 concentration. The specific timing of the medication, linked to the interaction between IL-6 and the hypothalamic-pituitary-adrenal (HPA) axis, may correct a postulated deficiency in HPA control in RA.

New insights into cytokine gene expression in the rat hypothalamus following endotoxin challenge.

Peripheral injection of the endotoxin LPS in rats 3 weeks prior to a second injection of LPS derived from another bacterial strain results in elevated corticosterone and decreased pro-inflammatory cytokines in the blood. We further investigated this model by measuring cytokine expression in the hypothalamus and spleen. In LPS-pretreated rats, hypothalamic expression of a range of cytokines was attenuated in response to the second injection of LPS while splenic expression was elevated. This is the first demonstration that prior exposure to an endotoxin can differentially affect cytokine expression in the brain and peripheral tissues when a host is confronted with a second, acute, pro-inflammatory stimulus. Changes in hypothalamic cytokine expression in endotoxin pretreated rats may provide new evidence for the involvement of central cytokine pathways in modulating peripheral inflammation and mediating psychopathological alterations associated with inflammatory diseases.

Use of the dexamethasone-corticotrophin releasing hormone test to assess hypothalamic-pituitary-adrenal axis function in rheumatoid arthritis.

Objectives. Hypothalamic-Pituitary-Adrenal axis function may be abnormal in rheumatoid arthritis (RA). A pilot study in 7 patients suggested impaired glucocorticoid feedback in some patients after the dexamethasone-corticotrophin releasing hormone (CRH) test. This study aimed to investigate the dexamethasone-corticotrophin releasing factor test in a larger group of patients and relate the results to characteristics of the disease. Methods. Outpatients with active RA (>/=3 swollen and tender joints and C-reactive protein > 10 mg/L) took dexamethasone (1.5 mg) at 23:00 hour in the evening. Next day, baseline saliva and plasma samples were collected, CRH was infused at 11:00 hour, and 4 serial blood and saliva samples were collected. Plasma samples were stored at -80 degrees C and a radioimmunoassay performed for saliva and plasma cortisol. Results. All 20 participants showed normal dexamethasone suppression and mounted no response to the CRH challenge. In samples with measurable cortisol, there was a strong correlation between saliva and plasma values (r = 0.876, n = 26, P < .01). Conclusion. No abnormalities were found in the Dexamethasone-CRH test in RA patients in contrast to a previous pilot study. Salivary cortisol measurement may offer an alternative noninvasive technique to plasma cortisol in RA patients in future studies.

Re-exposure to endotoxin induces differential cytokine gene expression in the rat hypothalamus and spleen.

This study was designed to investigate whether the pattern of hypothalamic and splenic cytokine expression induced by peripheral administration of a bacterial lipopolysaccharide (LPS) is affected by prior exposure to LPS derived from another bacterial strain. Injection of LPS from Salmonella enteritidis (LPS(2)) alone resulted in increased hypothalamic gene expression of IL-1beta, IL-6, TNFalpha, IL-1ra and IL-10. However, pre-exposure to LPS derived from Escherichia coli (LPS(1)) 3 weeks before, significantly attenuated hypothalamic IL-1ra, IL-6 and IL-10 expression. IL-1beta expression also tended to be lower. This pattern contrasted with the robust cytokine expression in the spleen of LPS(2)-treated rats previously exposed to LPS(1), since pre-treatment with endotoxin resulted in a significantly greater response of IL-1beta and IL-1ra to LPS(2). Expression of TNFalpha and IL-10 also tended to be higher. Pre-treatment with LPS(1) did not significantly affect the marked increase in corticosterone and adrenaline blood levels induced by LPS(2). Thus, while endotoxin pre-exposure seemed not to induce a "tolerant" state in the periphery as judged by the immune and endocrine parameters evaluated upon re-stimulation, expression of four of the six cytokines measured was decreased in the hypothalamus. This is the first demonstration that endotoxin priming can differentially affect cytokine expression in the central nervous system and peripheral tissues when a host is confronted with a second, acute, pro-inflammatory stimulus. These results may provide new evidence for the involvement of cytokine pathways in the central nervous system in modulating peripheral inflammation and mediating cognitive and behavioural alterations during inflammatory diseases.

The effects of synthetic and endogenous imidazoline binding site ligands on neuronal activity in discrete brain regions of naive and restraint-stressed rats.

We have mapped Fos expression to investigate brain regions activated by synthetic selective I(2) (BU224) and endogenous (harmane) imidazoline binding site ligands in naive and restraint-stressed rats. Systemic administration of BU224 or harmane to naive rats increased Fos-like immunoreactivity (FLI) in the hypothalamic paraventricular nucleus (PVN), hippocampal dentate gyrus (DG), central and medial nuclei of the amygdala (CeA, MeA) and the locus coeruleus (LC). FLI in restraint-stressed rats was increased in all 5 regions by harmane, and in the CeA, MeA and LC by BU224. Dual-labelling of FLI cells in the PVN of naive rats showed an increase in the number of corticotrophin-releasing-factor-containing cells (CRF) activated by BU224 and harmane. Several CRF-containing neurons in the PVN expressed alpha(1)-adrenoceptors and were densely surrounded by catecholaminergic axons and terminals. Our results provide a functional neuroanatomical framework which may explain the stimulatory effects of imidazoline ligands on basal and stress-induced neuronal and neuroendocrine activity.

Modulation of stress by imidazoline binding sites: implications for psychiatric disorders.

In this review, we present evidence for the involvement of imidazoline binding sites (IBS) in modulating responses to stress, through central control of monoaminergic and hypothalamo-pituitary-adrenal (HPA) axis activity. Pharmacological and physiological evidence is presented for differential effects of different IBS subtypes on serotoninergic and catecholaminergic pathways involved in control of basal and stress-stimulated HPA axis activity. IBS ligands can modulate behavioural and neuroendocrine responses in animal models of stress, depression and anxiety, and a body of evidence exists for alterations in central IBS expression in psychiatric patients, which can be normalised partially or fully by treatment with antidepressants. Dysfunction in monoaminergic systems and the HPA axis under basal and stress-induced activation has been extensively reported in psychiatric illnesses. On the basis of the literature, we suggest a potential therapeutic role for selective IBS ligands in the treatment of depression and anxiety disorders.

A prospective study of diurnal cortisol responses to the social experience of school transition in four-year-old children: anticipation, exposure, and adaptation.

This study examined psychosocial influences on hypothalamic-pituitary-adrenal axis activity in 105 4-year-old children transitioning to primary school. Measuring before, during, and after school transition over a period of up to 12 months, salivary cortisol was assessed on awakening and early evening. Parents reported child temperament and teachers recorded adaptive behavior. Whilst cortisol at awakening and early evening increased from baseline to school transition, effects were not significant. A significant decrease occurred between transition and follow-up and from baseline to follow-up for both awakening and evening cortisol. Poorer effortful control was associated with high morning and steeper diurnal slope of cortisol at transition whilst surgency/extroversion was associated individually with greater morning and evening cortisol at transition and adaptation. Greater increase in internalizing social isolation during the first 6 months of school in more surgent/extrovert children predicted higher morning and evening cortisol at follow-up. This study is the first to explore these adaptive relationships over a 12-month period and supports social isolation over time as a key element in developmental endocrine activation.