Antigenic characterisation of yeast-expressed lyssavirus nucleoproteins

In Europe, three genotypes of the genus Lyssavirus, family Rhabdoviridae, are present, classical rabies virus (RABV, genotype 1), European bat lyssavirus type 1 (EBLV-1, genotype 5) and European bat lyssavirus type 2 (EBLV-2, genotype 6). The entire authentic nucleoprotein (N protein) encoding sequences of RABV (challenge virus standard, CVS, strain), EBLV-1 and EBLV-2 were expressed in yeast Saccharomyces cerevisiae at high level. Purification of recombinant N proteins by caesium chloride gradient centrifugation resulted in yields between 14-17, 25-29 and 18-20 mg/l of induced yeast culture for RABV-CVS, EBLV-1 and EBLV-2, respectively. The purified N proteins were evaluated by negative staining electron microscopy, which revealed the formation of nucleocapsid-like structures. The antigenic conformation of the N proteins was investigated for their reactivity with monoclonal antibodies (mAbs) directed against different lyssaviruses. The reactivity pattern of each mAb was virtually identical between immunofluorescence assay with virus-infected cells, and ELISA and dot blot assay using the corresponding recombinant N proteins. These observations lead us to conclude that yeast-expressed lyssavirus N proteins share antigenic properties with naturally expressed virus protein. These recombinant proteins have the potential for use as components of serological assays for lyssaviruses.     

Effect of Resin-based and Bioceramic Root Canal Sealers on Postoperative Pain: A Split-mouth Randomized Controlled Trial

Introduction

The aim of this study was to compare the effect of resin-based and bioceramic root canal sealers on the occurrence and intensity of postoperative pain in patients with asymptomatic apical periodontitis (AAP).

Emerging drugs for age-related macular degeneration

Age-related macular degeneration (AMD) is a leading cause of blindness that until recently had no recognised drug treatment. In wet AMD, choroidal neovascularisation (CNV) causes a profound loss of central vision. CNV is a complex process in which tissue ischaemia and/or inflammation is thought to trigger production of angiogenic signal molecules. The release of VEGF appears to be particularly important. Verteporfin photodynamic therapy was the first drug therapy to be licensed for the treatment of some types of wet AMD. Other treatments directly targeting VEGF or other aspects of angiogenesis, such as pegaptanib, ranibizumab and anecortave acetate, have either recently been licensed or are in the advanced stages of development. These and other promising treatment options such as combination strategies are reviewed.     

Peripherally mediated antinociception of the mu-opioid receptor agonist 2-[(4,5alpha-epoxy-3-hydroxy-14beta-methoxy-17-methylmorphinan-6beta-yl)amino]acetic acid (HS-731) after subcutaneous and oral administration in rats with carrageenan-induced hindpaw inflammation

Opioids induce analgesia by activating opioid receptors not only within the central nervous system but also on peripheral sensory neurons. This study investigated peripherally mediated antinociception produced by the mu-opioid receptor agonist 2-[(4,5alpha-epoxy-3-hydroxy-14beta-methoxy-17-methylmorphinan-6beta-yl)amino]acetic acid (HS-731) after s.c. and oral administration in rats with carrageenan-induced hindpaw inflammation. Antinociceptive effects after s.c. administration were assessed 3 h after intraplantar carrageenan injection and compared with those of centrally acting mu-opioid agonists 14-methoxymetopon and morphine. Opioid agonists caused dose-dependent increases in inflamed paw withdrawal latencies to mechanical and thermal stimulation. The time course of action was different, in that HS-731 (20 microg/kg s.c.) produced significant long-lasting effects up to 4 h after administration, whereas 14-methoxymetopon (20 microg/kg) and morphine (2 mg/kg) reached their peak of action at 10 to 30 min, and their effect declined rapidly thereafter. Subcutaneous administration of the peripherally selective opioid antagonist naloxone methiodide inhibited antinociception elicited by HS-731 (20 microg/kg s.c.), whereas it was ineffective against 14-methoxymetopon (20 microg/kg s.c.). Moreover, the antinociception produced by 100 microg/kg s.c. HS-731 was dose-dependently reversed by s.c. naloxone methiodide. This indicates that HS-731 preferentially activates peripheral opioid receptors, whereas 14-methoxymetopon mediates analgesia via central mechanisms. Orally administered HS-731 significantly reduced hyperalgesia in the inflamed paw induced by carrageenan, which was reversible by s.c. administered naloxone methiodide. These results show that systemic (s.c. and oral) treatment with the mu-opioid agonist HS-731 produces potent and long-lasting antinociception through peripheral mechanisms in rats with carrageenan-induced hindpaw inflammation.     

SELF-SCORED IMPAIRMENTS IN FUNCTIONING AND DISABILITY IN POST-COVID SYNDROME FOLLOWING MILD COVID-19 INFECTION

ObjectivesTo investigate functioning, activity and disability in people with post-COVID syndrome.DesignCross-sectional.Subjects/patientsParticipants were recruited online via Facebook and a stakeholders’ organization for post-COVID syndrome in Sweden.MethodsSociodemographic data and International Classification of Functioning, Disability and Health (ICF)-based questionnaire were collected via an online platform and analysed.ResultsA total of 100 participants were included (mean age 44.5 years, 82% women, 61% with higher education, and 56% working full- or part-time). For the ICF component Body Functions, the most impaired functions were: fatigability and energy drive (98–99%); higher cognitive functions (74–94%); sleep functions (98%); muscle functions (93%); respiratory functions (92%); heart functions (82%); emotional functions (80%); sexual functions (77%); pain problems (56–90%); and thermoregulatory functions (68%). For the component Activity, the most frequent limitations were: handling stressful situations (98%); remunerative employment (95%); recreation and leisure (94%); climbing the stairs (94%); doing housework (84%); and informal socializing (64%). The most frequent degrees of impairment/limitations were light and moderate, except for severe-complete for fatigue, higher cognitive functions, multitasking, handling stressful situations; and recreation and leisure activities.ConclusionPost-COVID syndrome following a mild COVID-19 infection can result in impaired body functions and activities. These results support the importance of a multidisciplinary rehabilitation approach for these patients.LAY ABSTRACTThe SARS-CoV-2 (COVID-19) pandemic has infected several hundred million people worldwide to date. A proportion of people with COVID-19 who develop a mild initial illness, mainly staying at home or requesting few days of hospitalization, do not subsequently recover fully. Some of them develop new persistent symptoms and an increased level of disability, affecting their functioning. This study describes functioning and disability in people with post-COVID syndrome after a mild initial infection, using a self-scored questionnaire based on the International Classification of Functioning and Disability. A total of 100 participants were included in the study. Participants were relatively young and healthy prior to the infection. The majority were female, with a high level of education, and mostly working full- or part-time. Many disabling symptoms were found to persist, indicating the need for further research into post-COVID syndrome, and supporting the use of a multidisciplinary rehabilitation approach for these patients.Key words: post-COVID syndrome, International Classification of Functioning, Disability and Health, fatigue, functioning, activity, quality of life

Since the start of the COVID-19 pandemic in December 2019, several hundred million people have been infected, resulting in several million deaths worldwide and overloaded healthcare systems in many countries. The SARS-CoV-2 virus is known to affect the host in different ways: from asymptomatic infection to lethal course, probably depending on the host’s immune response (1). A neurological impact of the SARS-CoV-2 virus has been speculated, both in the pathways of respiratory failure (2) and in other neurological symptoms (3). The acute symptomatology of COVID-19 is now well-characterized, as acute respiratory failure, thrombosis, kidney failure, etc. (4, 5), and long-term symptoms are now affecting patients during the subacute (3–6 months after infection) and chronic periods (longer than 6 months after infection). Long-COVID or post-COVID syndrome appears in both hospitalized (6) and un-hospitalized patients (7). Follow-up of patients hospitalized during the acute period has identified ongoing symptoms, such as fatigue, breathing difficulties, cognitive symptoms, persistent musculoskeletal pain, sleeping difficulties, etc. (8, 9). Regardless of the severity of the initial infection, persistent fatigue appears to be the most bothersome symptom in patients with post-COVID syndrome (10). The World Health Organization (WHO) appealed to healthcare providers regarding post-COVID syndrome and estimates that approximately 10% of all infected people may develop post-COVID syndrome (11). However, knowledge about post-COVID syndrome is scare, and future levels of healthcare needs for these patients might be extremely high. There is an urgent need for scientific data about post-COVID syndrome, and the role of rehabilitation interventions to prevent disability in these patients.Although the clinical picture of post-COVID syndrome is broad, one way to analyse it is to assess functioning, activity and disability according to the International Classification of Functioning, Disability and Health (ICF). The ICF is a classification of health and health-related domains describing functioning, activity and disability, which was officially endorsed by all 191 WHO Member States in the Fifty-fourth World Health Assembly on 22 May 2001 (resolution WHA 54.21) (12). ICF is the WHO’s framework in categorizing health and disability at both individual and population levels and is recommended for use in clinical and research practise. The ICF Core Sets were developed for several (chronic) health conditions (13–18), but, until now, not for post-COVID syndrome.The aim of the current study was therefore to assess functioning, activity, and disability, using an adapted list of ICF categories for patients with post-COVID syndrome.     

Effects of the Inerventions method on gross motor function in children with spastic cerebral palsy

Aim of the study

To investigate the effect of the Inerventions method on gross motor function in children with spastic cerebral palsy (CP).

Differences in mnemonic processing by neurons in the human hippocampus and parahippocampal regions

Different structures within the medial-temporal lobe likely make distinct contributions to declarative memory. In particular, several current psychological and computational models of memory predict that the hippocampus and parahippocampal regions play different roles in the formation and retrieval of declarative memories [e.g., Norman, K. A., & O'Reilly, R. C. Modeling hippocampal and neocortical contributions to recognition memory: A complementary-learning systems approach. Psychological Review, 110, 611-646, 2003]. Here, we examined the neuronal firing patterns in these two regions during recognition memory. Recording directly from neurons in humans, we find that cells in both regions respond to novel stimuli with an increase in firing (excitation). However, already on the second presentation of a stimulus, neurons in these regions show very different firing patterns. In the parahippocampal region there is dramatic decrease in the number of cells responding to the stimuli, whereas in the hippocampus there is recruitment of a large subset of neurons showing inhibitory (decrease from baseline firing) responses. These results suggest that inhibition is a mechanism used by cells in the human hippocampus to support sparse coding in mnemonic processing. The findings also provide further evidence for the division of labor in the medial-temporal lobe with respect to declarative memory processes.     

Are frontotemporal lobar degeneration, progressive supranuclear palsy and corticobasal degeneration distinct diseases?

New findings relating to the clinical, genetic and molecular bases of neurodegenerative disorders have led to a shift away from traditional nomenclatures of clinical syndromes. Historically, frontotemporal lobar degeneration (FTLD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) were classified on the basis of distinct clinical and pathological features. In recent years, however, advances in molecular and genetic research have led clinicians to suggest that the similar etiologies of the three disorders warrant their amalgamation into a single disorder with three subtypes. In this Review, we consider the utility and validity of combining FTLD, CBD and PSP. The earliest reports of these disorders demonstrate their distinctiveness, whereas recent findings challenge traditional nomenclatures by showing etiological overlap. For example, tau inclusions have been confirmed in patients with CBD and those with PSP, and in some patients with FTLD, implying that all three disorders are 'tauopathies'. Furthermore, most patients with progressive nonfluent aphasia, a subtype of FTLD, show PSP or CBD post-mortem. Even tau-related cases of FTLD, CBD and PSP are distinguishable on the basis of other criteria, however, and many FTLD cases do not show tau pathology. We argue, therefore, that FTLD, CBD and PSP should be considered as pathologically similar but distinct syndromes. New research criteria for CBD and PSP should note that progressive nonfluent aphasia is often a precursor of these conditions.