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The functional neuroanatomy of cerebellar systems has been extensively studied during the past decades by means of experimental animal studies, anatomoclinical studies, as well as structural and functional neuroimaging studies in patients and healthy subjects. Within a system of closed-loop circuits, this wealth of studies identified reciprocal projections between the cerebellar structures and the supratentorial areas subserving sensorimotor, cognitive, and affective function. It has been shown that cerebellar output is mediated by the deep cerebellar nuclei, mainly by the dentate nucleus (DN), which project to the supratentorial cortex via the thalamus (cerebello-thalamo-cortical pathway). In turn, the cortical areas that are the target of cerebellar output project back to the cerebellum via the pons (cortico-ponto-cerebellar pathway). Regions of the cerebellar cortex that receive input from a specific supratentorial area, are the same regions that project back to that supratentorial area, thus forming closed-loop circuits. These projections are largely crossed, connecting the cerebral hemispheres primarily with the contralateral cerebellar hemispheres.

Purpose: As noninvasive biomarkers are an important unmet need for neuroendocrine neoplasms (NEN), biomarker potential of genome-wide molecular profiling of plasma cell-free DNA (cfDNA) was prospectively studied in patients with NEN. Experimental Design: Longitudinal plasma samples were collected from patients with well-differentiated, metastatic gastroenteropancreatic and lung NEN. cfDNA was subjected to shallow whole-genome sequencing to detect genome-wide copy-number alterations (CNA) and estimate circulating tumor DNA (ctDNA) fraction, and correlated to clinicopathologic and survival data. To differentiate pancreatic NENs (PNEN) from pancreatic adenocarcinomas (PAAD) using liquid biopsies, a classification model was trained using tissue-based CNAs and validated in cfDNA. Results: One hundred and ninety-five cfDNA samples from 43 patients with NEN were compared with healthy control cfDNA (N = 100). Plasma samples from patients with PNEN (N = 21) were used for comparison with publicly available PNEN tissue (N = 98), PAAD tissue (N = 109), and PAAD cfDNA (N = 96). Thirty percent of the NEN cfDNA samples contained ctDNA and 44% of the patients had at least one ctDNA-positive (ctDNA+) sample. CNAs detected in cfDNA were highly specific for NENs and the classification model could distinguish PAAD and PNEN cfDNA samples with a sensitivity, specificity, and AUC of 62%, 86%, and 79%, respectively. ctDNA-positivity was associated with higher World Health Organization (WHO) grade, primary tumor location, and higher chromogranin A and neuron-specific enolase values. Overall survival was significantly worse for ctDNA+ patients and increased ctDNA fractions were associated with poorer progression-free survival. Conclusions: Sequential genome-wide profiling of plasma cfDNA is a novel, noninvasive biomarker with high specificity for diagnosis, prognosis, and follow-up in metastatic NENs.

Background Primary health care providers (PHCPs) are assumed to be at high risk of a COVID-19 infection, as they are exposed to patients with usually less personal protective equipment (PPE) than other frontline health care workers (HCWs). Nevertheless, current research efforts focussed on the assessment of COVID-19 seroprevalence rates in the general population or hospital HCWs. Objective We aimed to determine the seroprevalence in PHCPs during the second SARS-CoV-2 wave in Flanders (Belgium) and compared it to the seroprevalence in the general population. We also assessed risk factors, availability of PPE and attitudes towards the government guidelines over time. Methods A prospective cohort of PHCPs (n = 698), mainly general practitioners, was asked to complete a questionnaire and self-sample capillary blood by finger-pricking at five distinct points in time (June–December 2020). We analysed the dried blood spots for IgG antibodies using a Luminex multiplex immunoassay. Results The seroprevalence of PHCPs remained stable between June and September (4.6–5.0%), increased significantly from October to December (8.1–13.4%) and was significantly higher than the seroprevalence of the general population. The majority of PHCPs were concerned about becoming infected, had adequate PPE and showed increasing confidence in government guidelines. Conclusions The marked increase in seroprevalence during the second COVID-19 wave shows that PHCPs were more at risk during the second wave compared to the first wave in Flanders. This increase was only slightly higher in PHCPs than in the general population suggesting that the occupational health measures implemented provided sufficient protection when managing patients.

SARS-CoV-2 human-to-animal transmission can lead to the establishment of novel reservoirs and the evolution of new variants with the potential to start new out- breaks in humans. We tested Norway rats inhabiting the sewer system of Antwerp, Belgium, for the presence of SARS-CoV-2 following a local COVID-19 epidemic peak. In addition, we discuss the use and interpretation of SARS-CoV-2 serological tests on non-human samples. Between November and December 2020, Norway rat oral swabs, faeces and tissues from the sewer system of Antwerp were collected to be tested by RT-qPCR for the presence of SARS-CoV-2. Serum samples were screened for the presence of anti-SARS-CoV-2 IgG antibodies using a Luminex microsphere immunoas- say (MIA). Samples considered positive were then checked for neutralizing antibodies using a conventional viral neutralization test (cVNT). The serum of 35 rats was tested by MIA showing three potentially positive sera that were later negative by cVNT. All tissue samples of 39 rats analysed tested negative for SARS-CoV-2 RNA. This is the first study that evaluates SARS-CoV-2 infection in urban rats. We can conclude that the sample of rats analysed had never been infected with SARS-CoV-2. However, mon- itoring activities should continue due to the emergence of new variants prone to infect Muridae rodents.

Melanomas are malignant tumors arising from melanocytes. A vast majority of melanomas occur on cutaneous surfaces. Rarely, melanomas can also be found in various extracutaneous sites where melanocytes are scarcely present. Here, we present a 58-year-old Caucasian man who was referred to the ENT department of the Antwerp University Hospital with the complaint of a mass in the left oropharynx and a palpable cervical lymph node. Fiberoptic endoscopy showed a black mass arising from the left pharyngeal wall at the superior border of the oropharynx. Fluorodeoxyglucose positron emission tomography computed tomography (FDG-PET-CT) and magnetic resonance imaging (MRI) of the liver revealed liver metastases and lymph node metastases along the coeliac trunk branches and in the left neck. A transoral biopsy confirmed the diagnosis of primary mucosal melanoma, and the tumor was staged as pT4aN2M1. A full-body inspection by the dermatology department did not reveal any suspected skin lesions. Immunotherapy with nivolumab and ipilimumab was started. To conclude, mucosal melanomas are rare, yet very aggressive and have a dismal prognosis. The epidemiologic, genetic, and biologic differences between mucosal and cutaneous melanomas have adverse implications for both treatment and prognosis of mucosal melanoma. Imaging, including PET scan, is of great importance in evaluating the extent of the lesion and distant metastases.

The non-invasive prenatal test (NIPT) is a highly sensitive blood analysis tool that allows for the early detection of multiple chromosomal abnormalities, including Down syndrome. Prenatal testing in general and a positive test outcome in particular leave pregnant parents facing difficult ethical decisions and life-changing dilemmas. The language used by medical practitioners in this context has the potential to exert a strong influence on parents in their decision-making process. During counseling, health care professionals (HCPs) are expected to encourage parents to make an informed yet autonomous decision, which hinges on maximally unbiased, clear and consistent communication from the HCP. It is still unclear whether medical students are aware of this importance of unbiased communication, how they perceive the role of HCPs in the prenatal counseling process, and what perspectives they have regarding the disabilities screened for. Our research project aims to address this gap, presenting the results of a transdisciplinary survey completed by 245 medical students at KU Leuven. In particular, the survey investigates: (1) the students' view on the ideal prenatal counseling process; (2) their knowledge of NIPT and Down syndrome (the most prevalent disability NIPT screens for); and (3) their general attitudes towards disabilities. Results reveal that more than 50% of medical students do not feel prepared for genetic counseling. The survey further shows a lack of knowledge and some clearly negative attitudes towards life with disability; 20% of medical students agree that a life with Down syndrome should be avoided. Overall, results indicate fairly heterogeneous distribution of knowledge and fairly diverse attitudes of the students, suggesting revisions in the current curriculum might be needed to increase the homogeneity towards counseling and disabilities in the medical student population.

Background It is currently unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection will remain a rare event, only occurring in individuals who fail to mount an effective immune response, or whether it will occur more frequently when humoral immunity wanes following primary infection. Methods A case of reinfection was observed in a Belgian nosocomial outbreak involving 3 patients and 2 healthcare workers. To distinguish reinfection from persistent infection and detect potential transmission clusters, whole genome sequencing was performed on nasopharyngeal swabs of all individuals including the reinfection case’s first episode. Immunoglobulin A, immunoglobulin M, and immunoglobulin G (IgG) and neutralizing antibody responses were quantified in serum of all individuals, and viral infectiousness was measured in the swabs of the reinfection case. Results Reinfection was confirmed in a young, immunocompetent healthcare worker as viral genomes derived from the first and second episode belonged to different SARS-CoV-2 clades. The symptomatic reinfection occurred after an interval of 185 days, despite the development of an effective humoral immune response following symptomatic primary infection. The second episode, however, was milder and characterized by a fast rise in serum IgG and neutralizing antibodies. Although contact tracing and viral culture remained inconclusive, the healthcare worker formed a transmission cluster with 3 patients and showed evidence of virus replication but not of neutralizing antibodies in her nasopharyngeal swabs. Conclusions If this case is representative of most patients with coronavirus disease 2019, long-lived protective immunity against SARS-CoV-2 after primary infection might not be likely.

We report on sample IS/17575 since it generated highly divergent results in the Belgian SARS-CoV-2 serology external quality assessment scheme. Sample IS/17575 was serum originating from a 30 years old male patient. 124 diagnostic laboratories analysed this sample. A total of 168 results was returned (including 5 doubles). Overall, 38 were positive. All tests against S1 were positive except the Euroimmun IgG ELISA and the Ortho clinical Diagnostics VITROS IgG CLIA. All tests against S1/S2 (Liaison, Diasorin) resulted in a signal above cutoff. Assays against RBD, mostly generate a negative result. An exception are the Wantai SARS-CoV2 ELISA's. All tests targeting N protein were negative. The survey shows, when >6 months post-infection, assays targeting at least S1, and preferably S1 combined with S2, are the most sensitive. This finding accentuates the necessity of external quality assessment schedules and importance of antigenic composition of serologic SARS-CoV-2 assays.

Cerebellar mutism can be considered the hallmark feature of the cerebellar mutism syndrome (CMS), previously also frequently termed the posterior fossa syndrome (PFS). The syndrome consists of specific linguistic, cognitive, behavioral, and affective symptoms following acute posterior fossa damage in children and adults. Although the symptoms have been exceptionally associated with non-tumoral etiologies, CMS usually develops after a brief period of relatively normal functioning in the immediate postoperative phase following posterior fossa tumor surgery. The incidence of CMS in the pediatric population is estimated to range between 7% and 50%. Although similar symptoms have been occasionally reported in adults, CMS is typically viewed as a clinical condition affecting children. An international consensus as to the definition of CMS was recently reached. However, this accepted definition specifically addresses the pediatric variant of the syndrome associated with posterior fossa surgery (postoperative pediatric CMS, POPCMS). In this chapter, the more general term CMS (instead of POPCMS) will be used to denote similar symptoms also occurring in adults, and with non-tumoral etiologies. Although the semiology of CMS has extensively been described, the underlying pathophysiological mechanisms still remain largely unclear. This chapter presents a brief overview of the intriguing semiological combination of transient cerebellar mutism and cognitive, behavioral, and affective alterations following acute posterior fossa lesions. Furthermore, the most important pathophysiological hypotheses and the proposed therapeutic interventions will be briefly discussed.

Aedes aegypti and Aedes albopictus are arbovirus vectors of public health concern. Although the Democratic Republic of the Congo (DRC) faces a long-standing risk of Aedes-borne viruses, data on insecticide resistance of Aedes populations are absent. To address this gap, we investigated insecticide susceptibility of Ae. aegypti and Ae. albopictus in areas with a high risk of arbovirus transmission. We also investigated the frequency of knock-down resistance (kdr) mutations in Ae. aegypti. Immature stages of Ae. aegypti and Ae. albopictus were collected from two sites in Kinshasa (Lingwala and Cité Verte) between April and July 2017 and reared to the adult stage. Wild-caught adult Ae. aegypti were collected in 2016 in another site (Ngaliema). Female Ae. aegypti (from Lingwala) and Ae. albopictus (from Cité Verte) were used in WHO tube insecticide susceptibility tests. The F1534C, V1016I and V410L kdr mutations were genotyped in Ae. aegypti from Lingwala and Ngaliema. We observed Ae. aegypti to be susceptible to bendiocarb, propoxur and malathion, suspected resistant to permethrin, and resistant to deltamethrin and DDT. Aedes albopictus was susceptible to bendiocarb, propoxur, malathion and permethrin, suspected resistant to deltamethrin and resistant to DDT. While F1534C and V1016I were not detected, a few Ae. aegypti from Lingwala were heterozygous for the mutation V410L. This study reports for the first time the insecticide resistance status of Aedes spp. and the detection of the kdr mutation V410L in Ae. aegypti in DRC. Given the resistance profile, carbamates and potentially malathion are recommended insecticide options against Ae. aegypti in Kinshasa. It will be important to develop Aedes control strategies based on the resistance patterns of Aedes in Kinshasa.

OBJECTIVE To quantify the degree of dural compression and assess the association between site and direction of compression and articular process (AP) size and degree of dural compression with CT myelography. ANIMALS 26 client-oriented horses with ataxia. PROCEDURES Spinal cord-to-dura and AP-to-cross-sectional area of the C6 body ratios (APBRs) were calculated for each noncompressive site and site that had > 50% compression of the subarachnoid space. Site of maximum compression had the largest spinal cord-to-dura ratio. Fisher exact test and linear regression analyses were used to assess the association between site and direction of compression and mean or maximum APBR and spinal cord-todura ratio, respectively. RESULTS Mean ± SD spinal cord-to-dura ratio was 0.31 ± 0.044 (range, 0.20 to 0.41) for noncompressive sites and 0.44 ± 0.078 (0.29 to 0.60) for sites of maximum compression. Sites of maximum compression were intervertebral and extra-dural, most frequently at C6 through 7 (n = 10), followed by C3 through 4 (6). Thirteen horses had dorsolateral and lateral compression at the AP joints, secondary to AP (n = 7) or soft tissue proliferation (6). Site significantly affected direction of compression, and directions of compression from occiput through C4 were primarily ventral and lateral, whereas from C6 through T1 were primarily dorsal and dorsolateral. No linear relationship was identified between mean or maximum APBR and spinal cord-to-dura ratio. CONCLUSIONS AND CLINICAL RELEVANCE CT myelography may be useful for examination of horses with suspected cervical compressive myelopathy. Degree of compression can be assessed quantitatively, and site of compression significantly affected direction of compression.

In this study of the humoral immune response after the SARS-CoV-2 mRNA vaccination, low seroconversion rates were noted in both kidney transplant recipients and dialysis patients after first dose administration. While in DP the seroconversion rate levelled up to 92.8% after a second dose of SARS-CoV-2 mRNA vaccination, KTR stayed behind with a seroconversion rate of 62.4%. Futhermore, vaccination with the mRNA-1273 vaccine (Moderna) resulted in both higher seroconversion rates and mean log-transformed antibody titer concentrations compared to BNT162b2 (Pfizer).

The vast majority of studies investigating immune checkpoint inhibition (ICI) in patients with breast cancer have focused on triple-negative breast cancer (TNBC). In this study, we compared the tumor immune microenvironment (TIME) between TNBC and hormone receptor-negative HER2-positive breast cancer based on a selection of immune markers at the protein level in an institutional retrospective series. Additionally, we performed a similar comparison using publicly available transcriptomics data. Altogether, the results show a comparable TIME in both groups, with possible implications for the use of ICI in patients with hormone receptor-negative HER2-positive breast tumors. ispartof: NPJ BREAST CANCER vol:7 issue:1 ispartof: location:United States status: published

A six-year-old warmblood horse was presented with a longstanding frontlimb lameness with mild digital flexor tenosynovitis and swelling of the distomedial pastern. Ultrasonography and magnetic resonance revealed a dense mass lesion in the distal aspect of the digital flexor tendon sheath, with a partial lamellar architecture, absence of internal vascularization and adjacent smooth pressure osteolysis of the middle phalanx. After surgical excision, histopathology confirmed an epithelial inclusion cyst. Epithelial inclusion cysts, also known as keratinizing or follicular cysts, are expansile benign mass-like lesions of aberrant epidermal tissue. In the horse, they are known to occur in cutaneous and several non-cutaneous tissues. In the digital flexor tendon sheath, they have rarely been described. Given their often chronic presentation in this location, they may appear as an atypical dense mass on imaging, uncommon for cystic lesions. Complete tenoscopic removal, even for larger masses, is achievable and considered curative with good prognosis for return.

Semantic processing is a fundamental aspect in human communication. The cortical organization of semantic processing has been exhaustively described, in contrast to inconsistent results on the function of subcortical grey matter structures. Hence, this manuscript reports a systematic review and meta-analysis on the subcortical involvement in verbal semantic comprehension in healthy individuals. The 50 included studies indicate specific contributions by the cerebellum, thalamus and caudate nucleus respectively. In particular, the right posterior cerebellum is proposed to be involved in a semantic executive system and in adequate decision-making. The left thalamus, regulated by the caudate nucleus, might function as a subcortical hub, controlling the access and integration of cortically organized semantic features. Furthermore, a contribution of the cerebellum, thalamus and caudate nucleus in semantic prediction generation and evaluation at sentence level is preliminarily suggested. More research is required to gain insights into the role of the putamen, globus pallidus and subthalamic nucleus.

Male accessory-gland proteins are known to affect female physiology in multiple ways, maximizing a male's reproductive success-often at a cost to the female. Due to this inherent sexual conflict, accessory gland proteins (ACPs) are generally studied in separate-sex organisms. While ACPs have also been identified in simultaneous hermaphrodites as an important part of post-copulatory sexual selection processes, their study has lagged behind that of ACPs in organisms with separate sexes. In the great pond snail, Lymnaea stagnalis, an ACP affecting egg laying, ovipostatin, is produced in the prostate gland. Based on the published partial Ovipostatin gene sequence, we now provide the complete mRNA and gene sequences, and confirm that gene expression is prostate gland-specific. More importantly we observed a significant increase in Ovipostatin expression in sperm donors after ejaculation. Ovipostatin gene expression did not differ between donors giving their ejaculate first (primary donors) and those donating an ejaculate after having been inseminated (secondary donors). These observations support a role for ovipostatin in reproduction and highlight the importance of standardizing the time point when measuring expression levels of ACPs.

Recent research has revealed that the cerebellum plays a critical role in social reasoning and in particular in understanding false beliefs and making trait attributions. One hypothesis is that the cerebellum is responsible for the understanding of sequences of motions and actions, which may be a prerequisite for social understanding. To investigate the role of action sequencing in mentalizing, we tested patients with generalized cerebellar degenerative lesions on tests of social understanding and compared their performance with matched healthy volunteers. The tests involved understanding violations of social norms making trait and causal attributions on the basis of short behavioral sentences and generating the correct chronological order of social actions depicted in cartoons (picture sequencing task). Cerebellar patients showed clear deficits only on the picture sequencing task when generating the correct order of cartoons depicting false belief stories and showed at or close to normal performance for mechanical stories and overlearned social scripts. In addition, they performed marginally worse on trait attributions inferred from verbal behavioral descriptions. We conclude that inferring the mental state of others through understanding the correct sequences of their actions requires the support of the cerebellum., SCOPUS: ar.j, info:eu-repo/semantics/published

Degenerative joint disease is one of the main causes of equine early retirement from pleasure riding or a performance career. The disease is initially triggered by an abnormal loading of normal cartilage or a normal loading of abnormal cartilage. This primary insult is accompanied with joint inflammation, which leads to further progressive degeneration of the articular cartilage and changes in the surrounding tissues. Therefore, in search for an effective treatment, 75 adult horses with early signs of degenerative fetlock joint disease were enrolled in a randomized, multicenter, double-blinded, and placebo-controlled study. Fifty animals were injected intra-articularly with the investigational veterinary product (IVP) consisting of allogeneic chondrogenic induced mesenchymal stem cells (ciMSCs) with equine allogeneic plasma, and 25 horses were injected with 0.9% NaCl (saline) control product. From week 3 to 18 after treatment, lameness scores (P

The aging central nervous system (CNS) of mammals displays progressive limited regenerative abilities. Recovery after loss of neurons is extremely restricted in the aged brain. Many research models fall short in recapitulating mammalian aging hallmarks or have an impractically long lifespan. We established a traumatic brain injury model in the African turquoise killifish (Nothobranchius furzeri), a regeneration‐competent vertebrate that evolved to naturally age extremely fast. Stab‐wound injury of the aged killifish dorsal telencephalon unveils an impaired and incomplete regeneration response when compared to young individuals. In the young adult killifish, brain regeneration is mainly supported by atypical non‐glial progenitors, yet their proliferation capacity clearly declines with age. We identified a high inflammatory response and glial scarring to also underlie the hampered generation of new neurons in aged fish. These primary results will pave the way to unravel the factor age in relation to neurorepair, and to improve therapeutic strategies to restore the injured and/or diseased aged mammalian CNS., Neuroregeneration after stab‐wound injury is incomplete in aged killifish, caused by reduced proliferation of specialized non‐glial progenitors (NGPs) and mammalian‐like glial scarring. It seems that aged killifish deploy the restricted regenerative program, typically associated with mammals, instead of successful neurorepair as shown here for young adult killifish.

In May-June 2021, we detected Aedes albopictus adults near the central hospital in Boende, the capital city of the Tshuapa province of the Democratic Republic of the Congo (DRC). We identified the mosquitoes using morphological and molecular techniques (COI barcoding). This is the first report of this species in the DRC outside of Kinshasa and Kongo Central. Given the central location of Boende in the Congo Basin, our finding suggests that the vector might also have spread to other cities which are located upstream of the Congo River and its major tributaries. Because Aedes albopictus is an important vector for human arbovirus transmission, we highlight the need to investigate its distribution range and to update disease risk maps in Central Africa.

SummaryThe African turquoise killifish combines a short lifespan with spontaneous age-dependent loss of neuroregenerative capacity. The stem cell niches driving neuroregeneration and their molecular signatures remain elusive. To investigate this, we performed scRNA-seq of the adult telencephalon, combined with full-length transcriptomics using ISO-seq. Our results unveil about 25 cell types including neurons and progenitors of glial-and non-glial nature. Subclustering of progenitors identifies four radial glia (RG), and two non-glial progenitor (NGP) cell states. Combining the molecular profiles with spatial mapping of the RG clusters, reveals two spatially divergent astroglia, one ependymal, and one neuroepithelial-like subtype. We propose neuroepithelial-like RG and NGPs to be the start and intercessor populations of both neuro- and gliogenic lineages. Neuronal classification reveals distinct subtypes and lineages corresponding to excitatory and inhibitory neurons. This catalogue of telencephalon cell types is an extensive resource to understand the molecular basis of intrinsic plasticity shaping adult neuro- and gliogenesis.HighlightsScRNA-seq and ISO-seq identified a complete cell catalogue of the adult killifish telencephalonProgenitor diversity revealed the presence of spatially-defined (astro)glial subtypesA neuroepithelial radial glia population marks the start point of neurogenesis, accompanied by proliferative non-glial progenitorsImmature neurons form transcriptional subgroups that correspond to excitatory and inhibitory mature neuronal cell typesThis cellular atlas is a basis for studying neurogenesis and neuro-regeneration upon injury, disease and aging

We determined near complete and complete monkeypox virus genomes in a shrew (Crocidura littoralis), two squirrels (Funisciurus anerythrus, Funisciurus bayonii), and produced shorter sequences from two rats (Stochomys longicaudatus, Cricetomys sp. 2) originating from the Democratic Republic of the Congo. This suggests that a number of rodents besides squirrels (families Muridae and Nesomyidae) and shrews (order Eulipotyphla) are potential monkeypox virus reservoirs.

Primary health care providers (PHCPs), especially general practitioners (GPs) are essential to organise health care efficiently. During the COVID-19 pandemic, they also keep the pressure off hospitals. PHCPs are assumed to be at high risk of a COVID-19 infection, as they are exposed to a large portion of the population (usually with less personal protective equipment than other frontline health care workers(HCWs)). Nevertheless, previous seroprevalence studies focussed on the general population or HCWs in hospital settings, rather than PHCPs. The aim of this study was to determine the seroprevalence of PHCPs after the first and during the second SARS-CoV-2 wave in Flanders (Belgium) and compare it to the seroprevalence in the general population (blood donors). A prospective cohort of PHCPs, mainly GPs (n=698) was screened for IgG antibodies against SARS-CoV-2 at five different time-points (June-December 2020). The dried blood spots they produced were analysed using a Luminex multiplex immunoassay. The seroprevalence of PHCPs remained stable between June and September 2020 (4.6-5.0%), but increased significantly from October to December (8.1-13.4%) 2020. The seroprevalence of PHCPs was not significantly higher than the seroprevalence of the blood donors at the end of December 2020. In conclusion, the sharp increase in seroprevalence during the second COVID-19 wave in Flanders shows that PHCPs were more at risk during the second wave compared to the first one. However, the increase was in line with the general population suggesting that PHCPs mainly got infected in their private settings.

BackgroundSARS-CoV-2 human-to-animal transmission can lead to the establishment of novel reservoirs and the evolution of new variants with the potential to start new outbreaks in humans.AimWe tested Norway rats inhabiting the sewer system of Antwerp, Belgium, for the presence of SARS-CoV-2 following a local COVID-19 epidemic peak. In addition, we discuss the use and interpretation of SARS-CoV-2 serological tests on non-human samples.MethodsBetween November and December 2020, Norway rat oral swabs, feces and tissues from the sewer system of Antwerp were collected to be tested by RT-qPCR for the presence of SARS-CoV-2. Serum samples were screened for the presence of anti-SARS-CoV-2 IgG antibodies using a Luminex microsphere immunoassay (MIA). Samples considered positive were then checked for neutralizing antibodies using a conventional viral neutralization test (cVNT).ResultsThe serum of 35 rats was tested by MIA showing 3 potentially positive sera that were later shown to be negative by cVNT. All tissue samples of 39 rats analyzed tested negative for SARS-CoV-2 RNA.ConclusionThis is the first study that evaluates SARS-CoV-2 infection in urban rats. We can conclude that the sample of 39 rats had never been infected with SARS-CoV-2. We show that diagnostic serology tests can give misleading results when applied on non-human samples. SARS-CoV-2 monitoring activities should continue due to the emergence of new variants prone to infect Muridae rodents.

It is increasingly recognized that gut microbiota have a major effect on the physiology, biology, ecology and evolution of their animal hosts. Because in social insects, the gut microbiota is acquired through the diet and by contact with nest provisions, it can be hypothesized that regular supplementation of microorganisms to the diet will have an impact on the fitness of the consumer and on the development of the whole colony. To test this hypothesis, we investigated how supplementation of bacteria, yeasts, and combinations of the two to either pollen or nectar affected colony development in the social bumblebee Bombus terrestris. Three yeasts and three bacterial species that live at the flower-insect interface were used in the experiments and the development of bumblebee colonies was monitored over a period of 10 weeks. The results showed that administration of microbes via pollen had a stronger positive impact on colony development than when provided via sugar water. Supplementation of bacteria led, in general, to a faster egg laying, higher brood size and increased production of workers during the first weeks, whereas yeasts or a combination of yeasts and bacteria had less impact on colony development. However, the results differed between microbial species, with Wickerhamiella bombiphila and Rosenbergiella nectarea showing the strongest increase in colony development. Torulaspora delbrueckii induced early male production, which is likely a fitness cost. We conclude that the tested bacteria-yeast consortia did not result in better colony development than the interacting species alone. ispartof: OECOLOGIA vol:195 issue:3 pages:689-703 ispartof: location:Germany status: published

High-throughput serological tests that can detect neutralizing antibodies against SARS-CoV-2 are desirable for serosurveillance and vaccine efficacy evaluation. Although the conventional neutralization test (cVNT) remains the gold standard to confirm the presence of neutralizing antibodies in sera, the test is too labour-intensive for massive screening programs and less reproducible as live virus and cell culture is involved. Here, we performed an independent evaluation of a commercially available surrogate virus neutralization test (sVNT, GenScript cPass™) that can be done without biosafety level 3 containment in less than 2 hours. When using the cVNT and a Luminex multiplex immunoassay (MIA) as reference, the sVNT obtained a sensitivity of 94% (CI 90-96%) on a panel of 317 immune sera that were obtained from hospitalized and mild COVID-19 cases from Belgium and a sensitivity of 89% (CI 81-93%) on a panel of 184 healthcare workers from the Democratic Republic of Congo. We also found strong antibody titer correlations (rs>0.8) among the different techniques used. In conclusion, our evaluation suggests that the sVNT could be a powerful tool to monitor/detect neutralising antibodies in cohort and population studies. The technique could be especially useful for vaccine evaluation studies in sub-Saharan Africa where the basic infrastructure to perform cVNTs is lacking.

Early March 2019, health authorities of Matadi in the Democratic Republic of the Congo alerted a sudden increase in acute fever/arthralgia cases, prompting an outbreak investigation. We collected surveillance data, clinical data, and laboratory specimens from clinical suspects (for CHIKV-PCR/ELISA, malaria RDT), semi-structured interviews with patients/caregivers about perceptions and health seeking behavior, and mosquito sampling (adult/larvae) for CHIKV-PCR and estimation of infestation levels. The investigations confirmed a large CHIKV outbreak that lasted February–June 2019. The total caseload remained unknown due to a lack of systematic surveillance, but one of the two health zones of Matadi notified 2686 suspects. Of the clinical suspects we investigated (n = 220), 83.2% were CHIKV-PCR or IgM positive (acute infection). One patient had an isolated IgG-positive result (while PCR/IgM negative), suggestive of past infection. In total, 15% had acute CHIKV and malaria. Most adult mosquitoes and larvae (>95%) were Aedes albopictus. High infestation levels were noted. CHIKV was detected in 6/11 adult mosquito pools, and in 2/15 of the larvae pools. This latter and the fact that 2/6 of the CHIKV-positive adult pools contained only males suggests transovarial transmission. Interviews revealed that healthcare seeking shifted quickly toward the informal sector and self-medication. Caregivers reported difficulties to differentiate CHIKV, malaria, and other infectious diseases resulting in polypharmacy and high out-of-pocket expenditure. We confirmed a first major CHIKV outbreak in Matadi, with main vector Aedes albopictus. The health sector was ill-prepared for the information, surveillance, and treatment needs for such an explosive outbreak in a CHIKV-naïve population. Better surveillance systems (national level/sentinel sites) and point-of-care diagnostics for arboviruses are needed.

Background and objectives: We provide a case analysis for a 28-year-old, native Dutch-speaking lady who developed Foreign Accent Syndrome (FAS), a few weeks after falling down the staircase. In addition to FAS, which gave the impression she spoke with a German accent, German(-like) words and structures occurred. Speech symptoms were aggravated by increased stress, fatigue or emotional pressure, and this triggered jargon speech. It was hypothesized her FAS and jargon developed on a functional basis.Methods: In-depth analyses of the patient's medical background, neuropsychological and neurolinguistic tests and psychodiagnostic exams were done. The patient participated in an fMRI experiment. In a syllable repetition paradigm, motor speech activations were compared to those of healthy individuals, to see whether they were altered, which would be expected in case of a neurological etiology.Results: Medical history disclosed prior traumatic experiences for which she sought help, but no neurological incidents. Repeated neuropsychological and neurolinguistic tests showed deficits in recent memory and executive functioning. The patient demonstrated great difficulties with picture naming. Clinically, language switching and mixing as well as recurring jargon speech was found. Formal psychodiagnostic tests did not identify a clear disorder, but psychodiagnostic interviews were consistent with a DSM-5 conversion disorder. The fMRI study demonstrated that speech network activations corresponded to those found in healthy participants.Conclusion: The clinical neurolinguistic characteristics, outcome of the fMRI experiment, together with the clinical psychodiagnostic findings were strongly indicative for an underlying functional etiology for the FAS and jargon speech, presenting as symptoms of conversion disorder. (C) 2020 Asociacion Universitaria de Zaragoza para el Progreso de la Psiquiatria y la Salud Mental. Published by Elsevier Espana, S.L.U. All rights reserved.

A diagnosis of COVID-19 is based on a positive PCR test for SARS-CoV-2. Over the past year, PCR testing capacity has varied globally due to the availability of tests, and testing strategies have targeted mainly symptomatic individuals. Therefore, the spread of the virus is probably wider than the numbers reported by official surveillance systems that are based on PCR results. Serology tests detect antibodies against SARS-CoV-2, which start being measurable around 1–2 weeks after infection. They are used in seroprevalence studies to estimate the proportion of people in a population that has been infected, including asymptomatic infection. These studies are of particular importance in African countries, where reported testing and incidence are among the lowest in the world.

BackgroundIt is currently unclear whether SARS-CoV-2 re-infection will remain a rare event, only occurring in individuals who fail to mount an effective immune response, or whether it will occur more frequently when humoral immunity wanes following primary infection.MethodsA case of re-infection was observed in a Belgian nosocomial outbreak involving 3 patients and 2 health care workers. To distinguish re-infection from persistent infection and detect potential transmission clusters, whole genome sequencing was performed on nasopharyngeal swabs of all individuals including the re-infection case’s first episode. IgA, IgM, and IgG and neutralizing antibody responses were quantified in serum of all individuals, and viral infectiousness was measured in the swabs of the reinfection case.ResultsRe-infection was confirmed in a young, immunocompetent health care worker as viral genomes derived from the first and second episode belonged to different SARS-CoV-2 clades. The symptomatic re-infection occurred after an interval of 185 days, despite the development of an effective humoral immune response following symptomatic primary infection. The second episode, however, was milder and characterized by a fast rise in serum IgG and neutralizing antibodies. Although contact tracing and virus culture remained inconclusive, the health care worker formed a transmission cluster with 3 patients and showed evidence of virus replication but not of neutralizing antibodies in her nasopharyngeal swabs.ConclusionIf this case is representative of most Covid-19 patients, long-lived protective immunity against SARS-CoV-2 might not be likely.

Tauopathies, such as Alzheimer's disease (AD), are neurodegenerative disorders characterized by the deposition of hyperphosphorylated tau aggregates. Proteopathic tau seeds spread through the brain in a temporospatial pattern, indicative of transsynaptic propagation. It is hypothesized that reducing the uptake of tau seeds and subsequent induction of tau aggregation could be a potential approach for abrogating disease progression in AD. Here, we studied to what extent different endosomal routes play a role in the neuronal uptake of preformed tau seeds. Using pharmacological and genetic tools, we identified dynamin-1, actin, and Rac1 as key players. Furthermore, inhibition of PIKfyve, a protein downstream of Rac1, reduced both the trafficking of tau seeds into lysosomes and the induction of tau aggregation. Our work shows that tau aggregates are internalized by a specific endocytic mechanism and that their fate once internalized can be pharmacologically modulated to reduce tau seeding in neurons.

Large-scale serosurveillance of severe acute respiratory syndrome coronavirus type 2 (SARS- CoV-2) will only be possible if serological tests are sufficiently reliable, rapid and inexpensive. Current assays are either labour-intensive and require specialised facilities (e.g. virus neutralization assays), or expensive with suboptimal specificity (e.g. commercial ELISAs). Bead-based assays offer a cost-effective alternative and allow for multiplexing to test for antibodies of other pathogens. Here, we compare the performance of four antigens for the detection of SARS-CoV-2 specific IgG antibodies in a panel of sera that includes both severe (n=40) and mild (n=52) cases, using a neutralization and a Luminex bead-based assay. While we show that neutralising antibody levels are significantly lower in mild than in severe cases, we demonstrate that a combination of recombinant nucleocapsid protein (NP), receptor- binding domain (RBD) and the whole spike protein (S1S2) results in a highly sensitive (96%) and specific (99%) bead-based assay that can detect IgG antibodies in both groups. Although S1-specific IgG levels correlate most strongly with neutralizing antibody levels, they fall below the detection threshold in 10% of the cases in our Luminex assay. In conclusion, our data supports the use of RBD, NP and S1S2 for the development of SARS-CoV-2 serological bead- based assays. Finally, we argue that low antibody levels in mild/asymptomatic cases might complicate the epidemiological assessment of large-scale surveillance studies.

In Alzheimer’s disease, the density and spread of aggregated tau protein track well with neurodegeneration and cognitive decline, making the imaging of aggregated tau a compelling biomarker. A structure–activity relationship exploration around an isoquinoline hit, followed by an exploration of tolerated fluorination positions, allowed us to identify 9 (JNJ-64326067), a potent and selective binder to aggregated tau with a favorable pharmacokinetic profile and no apparent off-target binding. This was confirmed in rat and monkey positron emission tomography studies using [18F]9.

The Natal multimammate mouse (Mastomys natalensis) is the reservoir host of Lassa virus (LASV), an arenavirus that causes Lassa haemorrhagic fever in humans in West Africa. While previous studies suggest that spillover risk is focal within rural villages due to the spatial behaviour of the rodents, the level of clustering was never specifically assessed. Nevertheless, detailed information on the spatial distribution of infected rodents would be highly valuable to optimize LASV-control campaigns, which are limited to rodent control or interrupting human–rodent contact considering that a human vaccine is not available. Here, we analysed data from a four-year field experiment to investigate whether LASV-infected rodents cluster in households in six rural villages in Guinea. Our analyses were based on the infection status (antibody or PCR) and geolocation of rodents (n = 864), and complemented with a phylogenetic analysis of LASV sequences (n = 119). We observed that the majority of infected rodents were trapped in a few houses (20%) and most houses were rodent-free at a specific point in time (60%). We also found that LASV strains circulating in a specific village were polyphyletic with respect to neighbouring villages, although most strains grouped together at the sub-village level and persisted over time. In conclusion, our results suggest that: (i) LASV spillover risk is heterogeneously distributed within villages in Guinea; (ii) viral elimination in one particular village is unlikely if rodents are not controlled in neighbouring villages. Such spatial information should be incorporated into eco-epidemiological models that assess the cost-efficiency of LASV control strategies.

Magnetoencephalographic imaging (MEGI) offers a non-invasive alternative for defining preoperative language lateralization in neurosurgery patients. MEGI indeed can be used for accurate estimation of language lateralization with a complex language task - auditory verb generation. However, since language function may vary considerably in patients with focal lesions, it is important to optimize MEGI for estimation of language function with other simpler language tasks. The goal of this study was to optimize MEGI laterality analyses for two such simpler language tasks that can have compliance from those with impaired language function: a non-word repetition (NWR) task and a picture naming (PN) task. Language lateralization results for these two tasks were compared to the verb-generation (VG) task. MEGI reconstruction parameters (regions and time windows) for NWR and PN were first defined in a presurgical training cohort by benchmarking these against laterality indices for VG. Optimized time windows and regions of interest (ROIs) for NWR and PN were determined by examining oscillations in the beta band (12-30 Hz) a marker of neural activity known to be concordant with the VG laterality index (LI). For NWR, additional ROIs include areas MTG/ITG and for both NWR and PN, the postcentral gyrus was included in analyses. Optimal time windows for NWR were defined as 650-850 ms (stimulus-locked) and -350 to -150 ms (response-locked) and for PN -450 to -250 ms (response-locked). To verify the optimal parameters defined in our training cohort for NWR and PN, we examined an independent validation cohort (n = 30 for NWR, n = 28 for PN) and found high concordance between VG laterality and PN laterality (82%) and between VG laterality and NWR laterality (87%). Finally, in a test cohort (n = 8) that underwent both the intracarotid amobarbital procedure (IAP) test and MEG for VG, NWR, and PN, we identified excellent concordance (100%) with IAP for VG + NWR + PN composite LI, high concordance for PN alone (87.5%), and moderate concordance for NWR alone (66.7%). These findings provide task options for non-invasive language mapping with MEGI that can be calibrated for language abilities of individual patients. Results also demonstrate that more accurate estimates can be obtained by combining laterality estimates obtained from multiple tasks. MEGI.

The Natal multimammate mouse (Mastomys natalensis) is the reservoir host of Lassa virus, an arenavirus that causes Lassa haemorrhagic fever in humans in West Africa. Because no vaccine exists and therapeutic options are limited, preventing infection through rodent control and human behavioural measures is currently considered to be the only option. In order to assess the efficacy of rodent control, we performed a 4-year field experiment in rural Upper Guinea and developed a mathematical model to simulate different control strategies (annual density control, continuous density control, and rodent vaccination). For the field study, rodenticide baits were placed each year in three rural villages, while three other villages were used as controls. Rodents were trapped before and after every treatment and their antibody status and age were determined. Data from the field study were used to parameterize the mathematical model. In the field study, we found a significant negative effect of rodent control on seroprevalence, but this effect was small especially given the effort. Furthermore, the rodent populations recovered rapidly after rodenticide application, leading us to conclude that an annual control strategy is unlikely to significantly reduce Lassa virus spillover to humans. In agreement with this finding, the mathematical model suggests that the use of continuous control or rodent vaccination is the only strategy that could lead to Lassa virus elimination. These field and model results can serve as a guide for determining how long and frequent rodent control should be done in order to eliminate Lassa virus in rural villages. The research was funded by the German Research Foundation (DFG FI 1781/1&2-1, LE SPP 1596, GU 883/3-1 and GU 883/3-2) and by the University of Antwerp and the Antwerp study centre for disease (ASCID) Grant Number GOA BOF FFB3567. Joachim Marien is a research fellow of the Flemish Interuniversity Council (VLIR-UOS). Benny Borremans is supported by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 707840.

Background Dysphagia is a common and serious complication after (chemo)radiotherapy (CRT) for head-and-neck cancer (HNC) patients. Prophylactic swallowing exercises (PSE) can have a significantly positive effect on post-treatment swallowing function. However, low adherence rates are a key issue in undermining this positive effect. This current randomized trial will investigate the effect of adherence-improving measures on patients’ swallowing function, adherence and quality of life (QOL). Methods This ongoing trial will explore the difference in adherence and swallowing-related outcome variables during and after PSE in HNC patients performing the same therapy schedule, receiving different delivery methods. One hundred and fifty patients treated in various hospitals will be divided into three groups. Group 1 performs PSE at home, group 2 practices at home with continuous counseling through an app and group 3 receives face-to-face therapy by a speech and language pathologist. The exercises consist of tongue-strengthening exercises and chin-tuck against resistance with effortful swallow. The Iowa Oral Performance Instrument and the Swallowing Exercise Aid are used for practicing. Patients are evaluated before, during and after treatment by means of strength measurements, swallowing and QOL questionnaires. Discussion Since low adherence rates undermine the positive impact of PSE on post-treatment swallowing function, there is need to develop an efficient PSE protocol maximizing adherence rates. Trial registration ISRCTN, ID: ISRCTN98243550. Registered retrospectively on 21 December 2018.

Thin-film composite (TFC) membranes with a polyamide top layer are a widespread membrane type in reverse osmosis and nanofiltration applications. Despite their good initial performance, they often suffer from a high fouling tendency. A new form of interfacial polymerization, in which ionic liquids (ILs) are introduced as the non-aqueous reaction phase, was developed in our previous work. This resulted in a more sustainable TFC membrane preparation and an enhanced performance. In this work, the improved fouling resistance of these membranes was proven. Moreover, different steps in the synthesis were analyzed to further enhance time and cost efficiency, as well as environmental impact of the preparation process. Time efficiency was improved by shortening the interfacial polymerization time to 10 s, while waste generation was drastically lowered by recycling the IL for consecutive interfacial polymerization cycles. Moreover, residual trimesoyl chloride (TMC) in the IL could also be recycled, since the IL protected the TMC from being hydrolyzed, even at very high water contents in the IL (> 1000 ppm). Successful introduction of the recycling step, together with the possibility to dry the formed membrane sheets without loss of performance by conditioning with glycerol, clearly demonstrated the upscaling potential of the new preparation method.

Population growth, urbanization, environmental conditions and rapid development have caused particulate matter (PM) levels to rise above all national and international health standards during the last two decades in many South-East Asian countries. These PM levels needs to be reduced urgently as they increase the risk of cardiovascular and respiratory health problems for millions of people. Plants have shown to efficiently reduce PM in the air by accumulation on their leaves. In order to investigate which plant species accumulate most PM, we screened 49 common plant species for their PM accumulation capacity in one of the tropical cities with the highest PM concentrations of the world, Hanoi (Vietnam). Using this subset of plants, we tested if certain leaf characteristics (leaf hydrophilicity, stomatal densities and the specific leaf area) can predict the PM accumulation efficiency of plant species. Our results show that the PM accumulation capacity varies substantially among species and that Muntingia calabura accumulated most PM in our subset of plants. We observed that plants with hydrophilic leaves, a low specific leaf area and a high abaxial stomatal density accumulated significantly more PM. Plants with these characteristics should be preferred by urban architects to reduce PM levels in tropical environments.

Objectives: To understand the subjective pain experience of patients, healthcare providers rely heavily on self-reporting. However, to quantify this unique pain experience, objective parameters are not yet available in daily clinical practice. With regard to patients with failed back surgery syndrome (FBSS) treated with spinal cord stimulation (SCS), pain therapists may recover the individual functional information about the patient's posture from the implantable pulse generator (IPG) of the stimulator. The aim of this study is to investigate whether subjective self-reporting is in correlation with the functional capacities of a patient. Materials and Methods: Thirty-nine patients with FBSS, treated with SCS were included. The accelerometer in the IPG detects positional changes and provides an objective output of seven functional positions (lying back, lying prone, lying left, lying right, transition, upright, and upright + mobile). The Oswestry Disability Index (ODI), VAS-diary, and the Pittsburgh Sleep Quality Index (PSQI) were assessed to evaluate physical functioning, pain intensities, and subjective sleep quality. Additionally, 21 patients wore a wearable actigraph device to objectify sleep quality. The agreement and Spearman correlations between objective and subjective parameters were assessed. Results: Spearman rank correlations revealed no significant correlations between the ODI (subscales walking, sitting, standing, and sleeping) and the output of the IPG (percentage upright + mobile, transition, upright, and lying, respectively). Sleep parameters measured with the Actiwatch and the PSQI were not in agreement. Conclusions: This study demonstrated that self-reporting questionnaires do not correlate with the findings of objective measurements. Therefore, we recommend using both subjective and objective parameters when determining treatment options for FBSS patients.

TGF-β1, β2 and β3 bind a common receptor to exert vastly diverse effects in cancer, supporting either tumor progression by favoring metastases and inhibiting anti-tumor immunity, or tumor suppression by inhibiting malignant cell proliferation. Global TGF-β inhibition thus bears the risk of undesired tumor-promoting effects. We show that selective blockade of TGF-β1 production by Tregs with antibodies against GARP:TGF-β1 complexes induces regressions of mouse tumors otherwise resistant to anti-PD-1 immunotherapy. Effects of combined GARP:TGF-β1/PD-1 blockade are immune-mediated, do not require FcγR-dependent functions and increase effector functions of anti-tumor CD8+ T cells without augmenting immune cell infiltration or depleting Tregs within tumors. We find GARP-expressing Tregs and evidence that they produce TGF-β1 in one third of human melanoma metastases. Our results suggest that anti-GARP:TGF-β1 mAbs, by selectively blocking a single TGF-β isoform emanating from a restricted cellular source exerting tumor-promoting activity, may overcome resistance to PD-1/PD-L1 blockade in patients with cancer., Inhibiting TGF-β1 to increase immune responses against tumors bears the risk of tumor-promoting toxicity. Here the authors show that selectively blocking TGF-β1 produced by immunosuppressive cells is feasible with anti-GARP:TGF-β1 antibodies and improves the efficacy of PD-1 blockade immunotherapy.

The primary aim was to review the guidelines published by Otolaryngology Societies for performing tracheostomies in the COVID-19 pandemic. A secondary aim was to briefly review the literature for the effectiveness of surgical masks, N-95 and FFP-3 respirators, and power air purifying respirators (PAPRs) in reducing transmission of respiratory viral infections to health care workers while performing tracheostomy. Recommendations are mainly derived from clinical case series/retrospective observational studies from the SARS 2003/2004 outbreaks or experimental evidence for effectiveness for N-95/FFP-3 respirators and PAPRs. Differences do occur due to lack of evidence for COVID-19 as to whether N-95 and FFP-3 respirators are sufficient, or PAPRs should be recommended for tracheostomy. We would recommend adopting a conservative (protective) approach for HCWs teams performing tracheostomies, by routinely utilizing additional PPE such as PAPRs. Recommendations for the timing of tracheostomy also varied, however, almost all recommend a period of delay. The optimum duration of which is still unclear.

Structural changes in the brain take place throughout one's life. Changes related to cognitive decline may delay the stages of the speech production process in the aging brain. For example, semantic memory decline and poor inhibition may delay the retrieval of a concept from the mental lexicon. Electroencephalography (EEG) is a valuable method for identifying the timing of speech production stages. So far, studies using EEG mainly focused on a particular speech production stage in a particular group of subjects. Differences between subject groups and between methodologies have complicated identifying time windows of the speech production stages. For the current study, the speech production stages lemma retrieval, lexeme retrieval, phonological encoding, and phonetic encoding were tracked using a 64-channel EEG in 20 younger adults and 20 older adults. Picture-naming tasks were used to identify lemma retrieval, using semantic interference through previously named pictures from the same semantic category, and lexeme retrieval, using words with varying age of acquisition. Non-word reading was used to target phonological encoding (using non-words with a variable number of phonemes) and phonetic encoding (using non-words that differed in spoken syllable frequency). Stimulus-locked and response-locked cluster-based permutation analyses were used to identify the timing of these stages in the full time course of speech production from stimulus presentation until 100 ms before response onset in both subject groups. It was found that the timing of each speech production stage could be identified. Even though older adults showed longer response times for every task, only the timing of the lexeme retrieval stage was later for the older adults compared to the younger adults, while no such delay was found for the timing of the other stages. The results of a second cluster-based permutation analysis indicated that clusters that were observed in the timing of the stages for one group were absent in the other subject group, which was mainly the case in stimulus-locked time windows. A z-score mapping analysis was used to compare the scalp distributions related to the stages between the older and younger adults. No differences between both groups were observed with respect to scalp distributions, suggesting that the same groups of neurons are involved in the four stages, regardless of the adults' age, even though the timing of the individual stages is different in both groups.

When we feel sad or depressed, our face invariably “drops”. Conversely, when we try to cheer someone up, we might tell them “keep your smile up”, so presupposing that modifying the configuration of their facial muscles will enhance their mood. A crucial assumption that underpins this hypothesis is that mental states are shaped by information originating from the peripheral neuromotor system — a view operationalised as the Facial Feedback Hypothesis. We used botulinum toxin (BoNT-A) injected over the frown area to temporarily paralyse muscles necessary to express anger. Using a pre-post treatment design, we presented participants with gradually changing videos of a face morphing from neutral to full-blown expressions of either anger or happiness and asked them to press a button as soon as they had detected any change in the display. Results indicate that while all participants (control and BoNT-A) improved their reaction times from pre-test to post-test, the BoNT-A group did not when detecting anger in the post-test. We surmise that frown paralysis disadvantaged participants in their ability to improve the detection of anger. Our finding suggests that facial feedback causally affects perceptual awareness of changes in emotion, as well as people’s ability to use perceptual information to learn.

1.A key aim in wildlife disease ecology is to understand how host and parasite characteristics influence parasite transmission and persistence. Variation in host population density can have strong impacts on transmission and outbreaks, and theory predicts particular transmission‐density patterns depending on how parasites are transmitted between individuals. Here, we present the results of a study on the dynamics of Morogoro arenavirus in a population of multimammate mice (Mastomys natalensis). This widespread African rodent, which is also the reservoir host of Lassa arenavirus in West Africa, is known for its strong seasonal density fluctuations driven by food availability. 2.We investigated to what degree virus transmission changes with host population density and how the virus might be able to persist during periods of low host density. 3.A seven‐year capture‐mark‐recapture study was conducted in Tanzania where rodents were trapped monthly and screened for the presence of antibodies against Morogoro virus. Observed seasonal seroprevalence patterns were compared with those generated by mathematical transmission models to test different hypotheses regarding the degree of density‐dependence and the role of chronically infected individuals. 4.We observed that Morogoro virus seroprevalence correlates positively with host density with a lag of one to four months. Model results suggest that the observed seasonal seroprevalence dynamics can be best explained by a combination of vertical and horizontal transmission, and that a small number of animals needs to be infected chronically to ensure viral persistence. 5.Transmission dynamics and viral persistence were best explained by the existence of both acutely and chronically infected individuals, and by seasonally changing transmission rates. Due to the presence of chronically infected rodents, rodent control is unlikely to be a feasible approach for eliminating arenaviruses such as Lassa virus from Mastomys populations.