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Agudelo et al. discover expanded clones of similar antibodies from the memory B cells of tick-borne encephalitis virus–infected and vaccinated donors; however, the most potent and broadly neutralizing antibodies derive from donors recovering from natural infection., Tick-borne encephalitis virus (TBEV) is an emerging human pathogen that causes potentially fatal disease with no specific treatment. Mouse monoclonal antibodies are protective against TBEV, but little is known about the human antibody response to infection. Here, we report on the human neutralizing antibody response to TBEV in a cohort of infected and vaccinated individuals. Expanded clones of memory B cells expressed closely related anti-envelope domain III (EDIII) antibodies in both groups of volunteers. However, the most potent neutralizing antibodies, with IC50s below 1 ng/ml, were found only in individuals who recovered from natural infection. These antibodies also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses. Structural analysis revealed a conserved epitope near the lateral ridge of EDIII adjoining the EDI–EDIII hinge region. Prophylactic or early therapeutic antibody administration was effective at low doses in mice that were lethally infected with TBEV.

Neutralizing antibodies that target the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein are among the most promising approaches against COVID-191,2. A bispecific IgG1-like molecule (CoV-X2) has been developed on the basis of C121 and C135, two antibodies derived from donors who had recovered from COVID-193. Here we show that CoV-X2 simultaneously binds two independent sites on the RBD and, unlike its parental antibodies, prevents detectable spike binding to the cellular receptor of the virus, angiotensin-converting enzyme 2 (ACE2). Furthermore, CoV-X2 neutralizes wild-type SARS-CoV-2 and its variants of concern, as well as escape mutants generated by the parental monoclonal antibodies. We also found that in a mouse model of SARS-CoV-2 infection with lung inflammation, CoV-X2 protects mice from disease and suppresses viral escape. Thus, the simultaneous targeting of non-overlapping RBD epitopes by IgG-like bispecific antibodies is feasible and effective, and combines the advantages of antibody cocktails with those of single-molecule approaches. The bispecific IgG1-like CoV-X2 prevents SARS-CoV-2 spike binding to ACE2, neutralizes SARS-CoV-2 and its variants of concern, protects against disease in a mouse model, whereas the parental monoclonal antibodies generate viral escape.

During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21-5. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titres: less than 1:50 in 33% and below 1:1,000 in 79%, while only 1% showed titres above 1:5,000. Antibody sequencing revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titres, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50 values) as low as single digit nanograms per millitre. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.

The purpose of this study was to analyze the characteristics of individuals working in the field of neuropsychology in Italy, as part of a larger study examining the practice of neuropsychology across various countries. They were asked about their background, professional training, current work situation, types of assessment, preferred diagnostic procedures, as well as the rehabilitation techniques, their targeted populations, teaching responsibilities, and research activities. A total of 154 professionals completed an online survey from April 28, 2016 through June 30, 2016. The majority of participants were women, with a mean age of 42.6 years. Participants reported working for the National Health System, in private practice, or in private rehabilitation facilities. Overall, they reported being very satisfied with their work. Those who identified themselves as neuropsychologists primarily assessed individuals with dementia, stroke, movement disorders, and traumatic brain injury. While the majority of participants declared no problems with the instruments they used, others reported complaints, including but not limited to the financial cost of current neuropsychological tests and the lack of psychometric support. The main perceived obstacles were the lack of willingness to collaborate among professionals, the scarcity of academic training programs, and the lack of clinical training opportunities.

Background Endogenous ovarian hormones as well as exogenous oestradiol and progesterone play an important role in cognitive processing. Specifically, these hormones play a role in different aspects of memory, both in terms of storage capacity and temporal duration of the mnemonic track. These hormones also have various effects on different types of memory (i.e., verbal, visuo-spatial, prospective). This study investigated the effects of hormones on topographic memory, a type of memory specifically needed to recall a pathway and to acquire spatial information about locations, distances, and directions. Methods We compared 25 naturally cycling women (NCW) in two different cycling phases, the early follicular phase (4th - 5th days) and the mid-luteal phase (20th-21st days), with 26 women taking oral contraceptives (OC) tested in the active pill phase (20th to 21st day of OC cycle) and the inactive pill phase (2nd to 4th day of OC cycle). Both groups performed the Walking Corsi Test to assess topographic memory in their respective cycling phases. Women were instructed to learn an eight-step sequence path and recall the path five minutes later. Results We found that the two groups differed in terms of learning the 8-step sequence path; OC users were always better (4–5 days vs. 20–21 days) than NCW. No differences emerged in the delayed recall of the same path. Conclusions As already observed in other memory domains (i.e., verbal memory, emotional memory), OC users showed an advantage in terms of topographic learning. Our results might be explained by hormonal mechanisms and may suggest the future application of OC in women with topographic disorders or visuo-spatial difficulties.

Incontinentia Pigmenti (IP, OMIM#308300) is a rare X-linked genomic disorder (about 1,400 cases) that affects the neuroectodermal tissue and Central Nervous System (CNS). The objective of this study was to describe the cognitive-behavioural profile in children in order to plan a clinical intervention to improve their quality of life. A total of 14 girls (age range: from 1 year and 2 months to 12 years and 10 months) with IP and the IKBKG/NEMO gene deletion were submitted to a cognitive assessment including intelligence scales, language and visuo-spatial competence tests, learning ability tests, and a behavioural assessment. Five girls had severe to mild intellectual deficiencies and the remaining nine had a normal neurodevelopment. Four girls were of school age and two of these showed no intellectual disability, but had specific disabilities in calculation and arithmetic reasoning. This is the first description of the cognitive-behavioural profile in relation to developmental age. We stress the importance of an early assessment of learning abilities in individuals with IP without intellectual deficiencies to prevent the onset of any such deficit.

Objective Several authors have proposed that the cerebellum has an important role in functions of higher order as a general mode of sequence detection, independently from the nature of the information. The aim of this study was to verify whether the cerebellum mediates the processing of navigational sequential information and to determine whether it is influenced by the modality of the stimuli presentation. Method We tested 12 cerebellar patients and 12 healthy age-matched participants in 2 comparable navigational tasks (Walking Corsi Test and the Magic Carpet) requiring to memorizing a sequence of spatial locations. The 2 tasks differ each other for the modality of stimuli presentation: in the Walking Corsi Test the sequence is shown by an examiner that walks on the carpet, whereas in the Magic Carpet it is shown by a computer that lights up the tiles in the sequence. We hypothesize that different mental processes are implicated between the Walking Corsi Test and the Magic Carpet. Indeed, whereas watching the examiner, who performs the sequence on the carpet, allows the patient to simulate the action mentally in the Walking Corsi Test, such simulation cannot be triggered in the Magic Carpet. Results Our results showed that cerebellar patients obtained scores significantly lower than control participants only in the Magic Carpet. Conclusions We interpreted the patients' performance as a specific deficit in detecting and ordering single independent stimuli as a sequence, when the maintenance of stimulus-response associations is more demanding. (PsycINFO Database Record

Developmental topographical disorientation (DTD) causes impaired spatial orientation and navigation from early childhood with no evidence of cerebral damage. Using fMRI and a landmark sequencing task, we investigated the hypothesis that Dr Wai's abnormal cerebral activation pattern was related to his peculiar behavioral profile. Although Dr Wai was able to correctly perform landmark sequencing, he showed a lack of activity in regions activated in all control subjects and activity in areas that were not activated in any control subject. These results are discussed in light of cognitive and functional model of navigation, with relevant implications for DTD physiology.

Cognitive reserve (CR) has been defined as the ability to optimize or maximize performance through differential recruitment of brain networks. In the present study, we aimed at providing evidence for a consistent brain network underpinning CR in healthy and pathological aging. To pursue this aim, we performed a coordinate-based meta-analysis of 17 functional magnetic resonance imaging studies on CR proxies in healthy aging, Alzheimer’s disease (AD), and mild cognitive impairment (MCI). We found that different brain areas were associated with CR proxies in healthy and pathological aging. A wide network of areas, including medial and lateral frontal areas, that is, anterior cingulate cortex and dorsolateral prefrontal cortex, as well as precuneus, was associated with proxies of CR in healthy elderly patients. The CR proxies in patients with AD and amnesic-MCI were associated with activation in the anterior cingulate cortex. These results were discussed hypothesizing the existence of possible compensatory mechanisms in healthy and pathological aging.

Post-traumatic stress disorder (PTSD) is an anxiety condition that can develop after exposure to trauma such as physical or sexual assault, injury, combat-related trauma, natural disaster or death. Although an increasing number of neurobiological studies carried out over the past 20 years have allowed clarifying the neural substrate of PTSD, the neural modifications underpinning PTSD are still unclear. Here we used activation likelihood estimation meta-analysis (ALE) to determine whether PTSD has a consistent neural substrate. We also explored the possibility that different traumatic events produce different alterations in the PTSD neural network. In neuroimaging studies of PTSD, we found evidence of a consistent neural network including the bilateral insula and cingulate cortex as well as the parietal, frontal and limbic areas. We also found that specific networks of brain areas underpin PTSD after different traumatic events and that these networks may be related to specific aspects of the traumatic events. We discuss our results in light of the functional segregation of the brain areas involved in PTSD.

We describe a patient who, after right hemisphere damage, showed severe, persistent, pure representational neglect but no evidence of perceptual neglect and no deficits in spatial working memory when evaluated with a traditional clinical test (Corsi Block Tapping test). This finding provides evidence against a full explanation of representational neglect within the context of visuo-spatial working memory. Indeed, this patient showed a peculiar deficit in navigational tasks requiring re-orientation in a novel environment by means of his mental representation of the environment. Since no representational neglect was observed in tests requiring mental representation of single or multiple objects (i.e., o'clock test) we suggest that in our patient representational neglect is caused by damage to the cognitive system involved in coding and storing environmental information to be used during navigation.

We tested navigational abilities of brain-damaged patients suffering from representational or perceptual neglect asking them to retrieve a location according to salient spatial cues included in a rectangular empty room. Both groups of patients showed difficulties in learning the spatial definition of the target location in relation to two landmarks. However in a delayed attempt performed after several trials the group of patients with perceptual neglect proved able to easily retrieve the target location. In this condition they performed as controls showing a spared ability to navigate according to a stable representation of the room in long-term memory. In contrast the difficulty of patients with representational neglect remained unchanged across experimental conditions. At variance with clinical assessment, in which patients show asymmetrical performances in describing a well-known environment from memory, this latter result depicts a behavioural counterpart of the disorder, namely the inability to orient in a new environment according to an inner representation. Data are further discussed in order to provide a description of the cognitive mechanisms required for space representation for navigation.

Introduction The coding of space as near and far is not only determined by arm-reaching distance, but is also dependent on how the brain represents the extension of the body space. Recent reports suggest that the dissociation between reaching and navigational space is not limited to perception and action but also involves memory systems. It has been reported that gender differences emerged only in adverse learning conditions that required strong spatial ability. Methods In this study we investigated navigational versus reaching memory in air force pilots and a control group without flight experience. We took into account temporal duration (working memory and long-term memory) and focused on working memory, which is considered critical in the gender differences literature. Results We found no gender effects or flight hour effects in pilots but observed gender effects in working memory (but not in learning and delayed recall) in the nonpilot population (Women's mean = 5.33; SD= 0.90; Men's mean = 5.54; SD= 0.90). We also observed a difference between pilots and nonpilots in the maintenance of on-line reaching information: pilots (mean = 5.85; SD=0.76) were more efficient than nonpilots (mean = 5.21; SD=0.83) and managed this type of information similarly to that concerning navigational space. In the navigational learning phase they also showed better navigational memory (mean = 137.83; SD=5.81) than nonpilots (mean = 126.96; SD=15.81) and were significantly more proficient than the latter group. Discussion There is no gender difference in a population of pilots in terms of navigational abilities, while it emerges in a control group without flight experience. We found also that pilots performed better than nonpilots. This study suggests that once selected, male and female pilots do not differ from each other in visuo-spatial abilities and spatial navigation.

The aim of this study was to determine whether an egocentric topographical working memory (WM) deficit is present in the early stages of Alzheimer's disease (AD) with respect to other forms of visuospatial WM. Further, we would investigate whether this deficit could be present in patients having AD without topographical disorientation (TD) signs in everyday life assessed through an informal interview to caregivers. Seven patients with AD and 20 healthy participants performed the Walking Corsi Test and the Corsi Block-Tapping Test. The former test requires memorizing a sequence of places by following a path and the latter is a well-known visuospatial memory task. Patients with AD also performed a verbal WM test to exclude the presence of general WM impairments. Preliminary results suggest that egocentric topographical WM is selectively impaired, with respect to visuospatial and verbal WM, even without TD suggesting an important role of this memory in the early stages of AD.

Studies suggest that genetic factors are associated with the etiology of learning disabilities. Incontinentia Pigmenti (IP, OMIM#308300), which is caused by mutations of the IKBKG/NEMO gene, is a rare X-linked genomic disorder (1:10000/20:000) that affects the neuroectodermal tissues. It always affects the skin and sometimes the hair, teeth, nails, eyes and central nervous system (CNS). Data from IP patients demonstrate the heterogeneity of the clinical phenotype; about 30% have CNS manifestations. This extreme variability suggests that IP patients might also have learning disabilities. However, no studies in the literature have evaluated the cognitive profile of IP patients. In fact, the learning disability may go unnoticed in general neurological analyses, which focus on major disabling manifestations of the CNS. Here, we investigated the neuropsychological outcomes of a selected group of IP-patients by focusing on learning disabilities. We enrolled 10 women with IP (7 without mental retardation and 3 with mild to severe mental retardation) whose clinical diagnosis had been confirmed by the presence of a recurrent deletion in the IKBKG/NEMO gene. The participants were recruited from the Italian patients' association (I.P.A.SS.I. Onlus). They were submitted to a cognitive assessment that included the Wechsler Adult Intelligence scale and a battery of tests examining reading, arithmetic and writing skills. We found that 7 patients had deficits in calculation/arithmetic reasoning and reading but not writing skills; the remaining 3 had severe to mild intellectual disabilities. Results of this comprehensive evaluation of the molecular and psychoneurological aspects of IP make it possible to place "learning disabilities'' among the CNS manifestations of the disease and suggest that the IKBKG/NEMO gene is a genetic determinant of this CNS defect. Our findings indicate the importance of an appropriate psychoneurological evaluation of IP patients, which includes early assessment of learning abilities, to prevent the onset of this deficit.

Selective visuo-spatial memory deficits can seriously affect many aspects of daily life; for example, an individual may not remember where he put an object or which path he took to reach his destination. In general, visuo-spatial memory is assessed through pen-and-paper tests that mainly assess memory components in peripersonal space. Recent studies (Piccardi et al. in Exp Brain Res 206:171-177, 2010; Piccardi et al. in Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 18:362-384, 2011) have shown that brain-damaged patients selectively fail on navigation memory tasks but not on other tests of visuo-spatial memory ability. These findings underline the need for a standardized test that measures memory in navigation separately from other types of visuo-spatial memory. Here, we report the validation of the Walking Corsi Test (WalCT: Piccardi et al. in Neurosci Lett 432:127-131, 2008) on 289 individuals aged 15-86 years. The WalCT is a new instrument that assesses topographical memory in real environments and reproduces on a large-scale version the Corsi Block-Tapping Test (CBT: Corsi in Unpublished doctoral dissertation, McGill University, Montreal, 1972). The WalCT has been used in clinical practice and has proven sensitive in detecting navigational memory deficits even in individuals who have no other memory impairments (Piccardi et al. in Exp Brain Res 206:171-177, 2010; Piccardi et al. in Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 18:362-384, 2011; Bianchini et al. in Neuropsychologia 48:1563-1573, 2010 ).

The long-term effects of cannabis on human cognition are still unclear, but, considering that cannabis is a widely used substance and, overall, its potential use in therapeutic interventions, it is important to evaluate them. We hypothesize that the discrepancies among studies could be attributed to the specific cognitive function investigated and that skills subserved by the hippocampus, such as the spatial orientation abilities and, specifically, the ability to form and use cognitive maps, should be more compromised than others. Indeed it has been showed that cannabis users have a reduced hippocampus and that the hippocampus is the brain region in which cannabis has the greatest effect since it contains the highest concentration of cannabinoid receptors. To test this hypothesis we asked 15 heavy cannabis users and 19 nonusers to perform a virtual navigational test, the CMT, that assesses the ability to form and use cognitive maps. We found that using cannabis has no effect on these hippocampus-dependent orientation skills. We discuss the implications of our findings and how they relate to evidence reported in the literature that the intervention of functional reorganization mechanisms in cannabis user allows them to cope with the cognitive demands of navigational tasks.

Background: It is well known that cognitive and emotional changes occur during pregnancy, but little is known about their magnitude or their time of occurrence and recovery. During pregnancy memory is one of the most impaired cognitive functions. Although long-term aspects of memory have been investigated, other aspects of memory have not yet been explored (i.e., navigational memory and reaching memory). Case presentation: Here we describe the changes in reaching and walking memory that occurred during pregnancy and one year after delivery in an Italian female military pilot (Case 1) with high spatial ability. In memory tests she showed a classical dissociation between performance in reaching and walking distance, which indicated a failure of working memory, learning, and storage in reaching space. This suggests that her expertise served as a protective factor mitigating her low walking memory performance, and saving the topographical component. We compared her performance with that of two non-pregnant control groups (i.e., women pilots and non-pilots) and found that Case 1’s reaching memory performance was significantly worse than that of the control groups. Even one year postpartum, Case 1’s performance was not yet the same as that of the other pilots. Conclusions: These findings contribute to our knowledge of the specific, as yet unexplored, aspects of memory deficits in women pilots during pregnancy and postpartum and suggest the need for better neuropsychological assessment before these women return to work in operational environments.