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We report a 37 year old multi-parous lady, who in her third trimester of pregnancy, presented to the emergency room with acute diffuse abdominal pain and involuntary guarding. Findings on physical examination were consistent with peritonitis and a decision was made by the admitting team to perform an urgent laparotomy which surprisingly showed a stercoral perforation of the colon.

Abstract Background HBB, IL4, IL12, TNF, LTA, NCR3 and FCGR2A polymorphisms have been associated with malaria resistance in humans, whereas cytophilic immunoglobulin G (IgG) antibodies are thought to play a critical role in immune protection against asexual blood stages of the parasite. Furthermore, HBB, IL4, TNF, and FCGR2A have been associated with both malaria resistance and IgG levels. This suggests that some malaria resistance genes influence the levels of IgG subclass antibodies. Methods In this study, the effect of HBB, IL4, IL12, TNF, LTA, NCR3 and FCGR2A polymorphisms on the levels of IgG responses against Plasmodium falciparum blood-stage extract was investigated in 220 individuals living in Burkina Faso. The Pearson’s correlation coefficient among IgG subclasses was determined. A family-based approach was used to assess the association of polymorphisms with anti-P. falciparum IgG, IgG1, IgG2, IgG3 and IgG4 levels. Results After applying a multiple test correction, several polymorphisms were associated with IgG subclass or IgG levels. There was an association of i) haemoglobin C with IgG levels; ii) the FcγRIIa H/R131 with IgG2 and IgG3 levels; iii) TNF-863 with IgG3 levels; iv) TNF-857 with IgG levels; and, v) TNF1304 with IgG3, IgG4, and IgG levels. Conclusion Taken together, the results support the hypothesis that some polymorphisms affect malaria resistance through their effect on the acquired immune response, and pave the way towards further comprehension of genetic control of an individual’s humoral response against malaria.

Abstract Background There is accumulating evidence that host heparan sulphate proteoglycans play an important role in the life cycle of Plasmodium through their heparan sulphate chains, suggesting that genetic variations in genes involved in heparan sulphate biosynthesis may influence parasitaemia. Interestingly, Hs3st3a1 and Hs3st3b1 encoding enzymes involved in the biosynthesis of heparan sulphate are located within a chromosomal region linked to Plasmodium chabaudi parasitaemia in mice. This suggests that HS3ST3A1 and HS3ST3B1 may influence P. falciparum parasitaemia in humans. Methods Polymorphisms within HS3ST3A1 and HS3ST3B1 were identified in 270 individuals belonging to 44 pedigrees and living in Burkina Faso. Linkage and association between parasitaemia and the polymorphisms were assessed with MERLIN and FBAT. A genetic interaction analysis was also conducted based on the PGMDR approach. Results Linkage between P. falciparum parasitaemia and the chromosomal region containing HS3ST3A1 and HS3ST3B1 was detected on the basis of the 20 SNPs identified. In addition, rs28470223 located within the promoter of HS3ST3A1 was associated with P. falciparum parasitaemia, whereas the PGMDR analysis revealed a genetic interaction between HS3ST3A1 and HS3ST3B1. Seventy-three significant multi-locus models were identified after correcting for multiple tests; 37 significant multi-locus models included rs28470223, whereas 38 multi-locus models contained at least one mis-sense mutation within HS3ST3B1. Conclusion Genetic variants of HS3ST3A1 and HS3ST3B1 are associated with P. falciparum parasitaemia. This suggests that those variants alter both the function of heparan sulphate proteoglycans and P. falciparum parasitaemia.

People with epilepsy often report experiencing memory problems though these are not always detectable using standard neuropsychological measures. One form of difficulty that may be relatively prevalent in epilepsy is termed accelerated long-term forgetting (ALF), typically described as relatively greater loss of memory over days or weeks following initial encoding. The current study used remote assessment to examine memory and forgetting over one week in a broad community sample of people with epilepsy and healthy control participants, using two recently developed tests, one verbal (the Crimes test) and one visual (the Four Doors test). These were administered as part of a short battery of cognitive measures, run remotely with participants over Zoom. Across this community-derived sample, people with epilepsy reported more memory complaints and demonstrated significantly faster forgetting on both the verbal and visual tests. This difference was not attributable to level of initial learning performance and was not detectable through delayed recall on a standard existing test. Our results suggests that ALF may be more common than suspected in people with epilepsy, leading to a potentially important source of memory problems that are currently undetected by standard memory tests., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Working memory is an active system responsible for the temporary maintenance and processing of information in the support of cognition and action. In keeping with this, a growing body of research has explored the close links between working memory and attention, and how these might be harnessed to impact performance and possibly improve working memory efficiency. This is theoretically and practically important, given that working memory is a central hub in complex cognition yet is extremely capacity- and resource-limited. We review work carried out over the last 10 years or so looking at how high "value" items in working memory can be strategically prioritised through selective attention, drawing principally from visual working memory paradigms with young adult participants, while also discussing how the core effects extend to different task domains and populations. A consistent set of core findings emerges, with improved memory for items that are allocated higher value but no change in overall task performance, and a recency advantage regardless of point allocation when items are encountered sequentially. Value-directed prioritisation is effortful, under top-down strategic control, and appears to vary with perceptual distraction and executive load. It is driven by processes operating during encoding, maintenance, and retrieval, though the extent to which these are influenced by different features of the task context remains to be mapped out. We discuss implications for working memory, attention, and strategic control, and note some possible future directions of travel for this promising line of research., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Not being in employment, education, or training (NEET) is associated with poor health (physical and mental) and social exclusion. We investigated whether England's statutory school readiness measure conducted at 4-5 years provides a risk signal for NEET in late adolescence., Methods: We identified 8,118 individuals with school readiness measures at 4-5 years and NEET records at 16-17 years using Connected Bradford, a bank of linked routinely collected datasets. Children were categorised as 'school ready' if they reached a 'Good Level of Development' on the Early Years Foundation Stage Profile. We used probit regression and structural equation modelling to investigate the relationship between school readiness and NEET status and whether it primarily relates to academic attainment., Results: School readiness was significantly associated with NEET status. A larger proportion of young people who were not school ready were later NEET (11%) compared to those who were school ready (4%). Most of this effect was attributable to shared relationships with academic attainment, but there was also a direct effect. Measures of deprivation and Special Educational Needs were also strong predictors of NEET status., Conclusions: NEET risk factors occur early in life. School readiness measures could be used as early indicators of risk, with interventions targeted to prevent the long-term physical and mental health problems associated with NEET, especially in disadvantaged areas. Primary schools are therefore well placed to be public health partners in early intervention strategies., (© 2024. The Author(s).)

Research has demonstrated that individuals can direct their attention to valuable information in both working memory and long-term memory tasks with observable effects on performance. However, it is currently unclear whether prioritising an item for a working memory task automatically translates into a boost at long-term memory. This was examined in two experiments using relatively short (250 ms per item; Experiment 1) and longer (500 ms per item; Experiment 2) encoding times. Participants first completed a visual working memory task, in which they were presented with series of photographs of everyday objects. Following a brief delay (1,000 ms), they completed a four-alternative forced-choice test. Prior to encoding, participants were informed of the point values associated with each item. In some trials, the first item in the sequence was worth more points than the rest. In other trials, all items were equally valuable. After a filled delay, participants completed a surprise long-term memory task. At working memory, a value effect was reliably observed on recognition accuracy, along with some evidence of faster response times for high-value items. However, there was little consistent evidence of this effect automatically persisting into long-term memory. Thus, the benefits of attentional prioritization in working memory do not always translate into longer-term performance. More broadly, this provides further evidence that manipulations that enhance working memory performance do not necessarily enhance long-term memory., (© 2024. The Author(s).)

Objective: To investigate at a population level whether England's universal assessment of 'school readiness' is associated with later identification of special educational needs (SEN). Also, whether ethnic differences exist in SEN identification (white British versus ethnic minority) and whether this varies as a function of school readiness., Method: Analysis included 53 229 individuals aged 5-12 years from the Connected Bradford Database (2012/2013-2019/2020). Logistic regression analyses examined: (1) whether reaching a 'good level of development' on England's 'school readiness' assessment was associated with later SEN identification; and (2) whether interactions exist between school readiness and ethnicity., Results: 32 515 of 53 229 children reached a good level of development, of which 3036 (9.3%) were identified as having SEN. In contrast, 10 171 of 20 714 (49.1%) of children who did not reach a good level of development were later identified as having SEN. Children not reaching a good level of development had increased odds of being later identified as having SEN after controlling for covariates (OR: 8.50, 95% CI: 8.10 to 8.91). In children who did not reach a good level of development, white British children had higher odds of being identified as having SEN compared with ethnic minority peers (OR: 1.22, 95% CI: 1.11 to 1.34). No ethnic differences of having SEN were observed in children reaching a good level of development (OR: 1.04, 95% CI: 0.93 to 1.16)., Conclusions: School readiness assessments are associated with later SEN identification. Structural inequalities may exist in SEN identification in children not entering formal education 'school ready'. Such assessments could facilitate earlier identification of SEN and reduce structural inequalities in its identification., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: The Born in Bradford's Better Start (BiBBS) interventional birth cohort study was designed as an innovative cohort platform for efficient evaluation of early life interventions delivered through the Better Start Bradford programme. There are a growing number of interventional cohorts being implemented internationally. This paper provides an interim analysis of BiBBS in order to share learning about the feasibility and value of this method. Methods: Recruitment began in January 2016 and will complete in December 2023 with a target sample of 5,000 pregnancies. An interim analysis was completed for all pregnancies recruited between January 2016 and November 2019 with an expected due date between 1 st April 2016 and 8 th March 2020. Descriptive statistics were completed on the data. Results: Of 4,823 eligible pregnancies, 2,626 (54%) pregnancies were recruited, resulting in 2,392 mothers and 2,501 children. The sample are representative of the pregnant population (61% Pakistani heritage; 12% White British; 8% other South Asian and 6% Central and Eastern European ethnicity). The majority of participants (84%) live in the lowest decile of the Index of Multiple Deprivation, and many live in vulnerable circumstances. A high proportion (85%) of BiBBS families have engaged in one or more of the Better Start Bradford interventions. Levels of participation varied by the characteristics of the interventions, such as the requirement for active participation and the length of commitment to a programme. Conclusions: We have demonstrated the feasibility of recruiting an interventional cohort that includes seldom heard families from ethnic minority and deprived backgrounds. The high level of uptake of interventions is encouraging for the goal of evaluating the process and outcomes of multiple early life interventions using the innovative interventional cohort approach. BiBBS covers a period before, during and after the coronavirus disease 2019 (COVID-19) pandemic which adds scientific value to the cohort., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Dickerson J et al.)

Debate continues regarding the possible role of the hippocampus across short-term and working memory tasks. The current study examined the possibility of a hippocampal contribution to precise, high-resolution cognition and conjunctive memory. We administered visual working memory tasks featuring a continuous response component to a well-established developmental amnesic patient with relatively selective bilateral hippocampal damage (Jon) and healthy controls. The patient was able to produce highly accurate response judgments regarding conjunctions of color and orientation or color and location, using simultaneous or sequential presentation of stimuli, with no evidence of any impairment in working memory binding, categorical accuracy, or continuous precision. These findings indicate that hippocampal damage does not necessarily lead to deficits in high-resolution cognitive performance, even when the damage is severe and bilateral., (© 2022 The Authors. Hippocampus published by Wiley Periodicals LLC.)

People are able to prioritize more valuable information in working memory. The current study examined whether this value effect is due to the items of greater value being refreshed more than lower-value items during maintenance. To assess this possibility, we combined a probe value manipulation with a guided-refreshing procedure. Arrays of colored shapes were presented, and after a brief delay, participants reported the color of one randomly probed shape on a continuous color wheel. To manipulate probe value, one item was indicated as more valuable than the rest prior to encoding (i.e., worth more notional points), or all items were indicated as equally valuable. To guide refreshing, in some trials, two arrows were presented during maintenance, each arrow cueing the spatial location of one item. Participants were told to "think of" (i.e., refresh) the cued item. If value boosts are driven by attentional refreshing, cueing an item to be refreshed should enhance performance for items that are of low or equal value, but not items of high value, as these items would be refreshed regardless of the cue. This pattern of outcomes was observed, providing support for the hypothesis that attentional refreshing at least partially accounts for probe value effects in working memory., (© 2022. The Author(s).)

While many memory disorders occur with normal rates of forgetting, an accelerated rate of long-term forgetting (ALF) may occur, sometimes in the absence of a learning deficit. Detecting ALF presents a problem as it is desirable that the learned material is re-tested after each of several delays. This may result in earlier retrievals confounding later tests, with evidence suggesting that both positive and negative interaction can occur between successive tests. An earlier study (Baddeley et al., 2019) tested cued recall of a series of four crimes or four visual scenes by probing a different sample of features from all four crimes/scenes at each delay. Even though no question was asked twice, the interpolated tests markedly reduced the rate of forgetting. We suggest that this decelerated forgetting effect may result from the retrieval of probed features activating other associated features within that episode, hence facilitating their recall on subsequent tests. If so, the effect should be removed when only single and separate episodes, or individual items, are tested at each delay. We test this by probing a separate episode at each delay (Experiment 1), or by replacing integrated episodes with recognition memory for isolated words (Experiments 2 and 3) or visual scenes (Experiments 4 and 5). As predicted, we find no reduction in the rate of forgetting, in contrast to our earlier studies. The theoretical and clinical implications of our results are discussed. We conclude that the previously developed Crimes and Four Doors Tests (Baddeley et al., 2019) and the present single item recognition tests are complementary and are both likely to be necessary to ensure the reliable detection of ALF., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Atypical Teratoid Rhabdoid Tumor (AT/RT) is a rare pediatric central nervous system cancer often characterized by deletion or mutation of SMARCB1, a tumor suppressor gene. In this study, we found that SMARCB1 regulates Human Endogenous Retrovirus K (HERV-K, subtype HML-2) expression. HML-2 is a repetitive element scattered throughout the human genome, encoding several intact viral proteins that have been associated with stem cell maintenance and tumorigenesis. We found HML-2 env expression in both the intracellular and extracellular compartments in all AT/RT cell lines (n = 4) and in 95% of AT/RT patient tissues (n = 37) evaluated. SMARCB1 knock-down in neural stem cells (NSCs) led to an upregulation of HML-2 transcription. We found that SMARCB1 binds adjacent to the HML-2 promoter, repressing its transcription via chromatin immunoprecipitation; restoration of SMARCB1 expression in AT/RT cell lines significantly downregulated HML-2 expression. Further, targeted downregulation of HML-2 transcription via CRISPR-dCas9 coupled with suppressor proteins led to cellular dispersion, decreased proliferation, and cell death in vitro. HML-2 knock-down with shRNA, siRNA, and CRISPR-dCas9 significantly decreased Ras expression as measured by qRT-PCR, suggesting that HML-2 modulates MAPK/ERK signaling in AT/RT cells. Overexpression of NRAS was sufficient to restore cellular proliferation, and MYC, a transcription factor downstream of NRAS, was bound to the HERV-K LTR significantly more in the absence of SMARCB1 expression in AT/RT cells. We show a mechanism by which these undifferentiated tumors remain pluripotent, and we demonstrate that their formation is aided by aberrant HML-2 activation, which is dependent on SMARCB1 and its interaction with MYC.

Though there is substantial evidence that individuals can prioritize more valuable information in visual working memory (WM), little research has examined this in the verbal domain. Four experiments were conducted to investigate this and the conditions under which effects emerge. In each experiment, participants listened to digit sequences and then attempted to recall them in the correct order. At the start of each block, participants were either told that all items were of equal value, or that an item at a particular serial position was worth more points. Recall was enhanced for these higher value items (Experiment 1a), a finding that was replicated while rejecting an alternative account based on distinctiveness (Experiment 1b). Thus, valuable information can be prioritized in verbal WM. Two further experiments investigated whether these boosts remained when participants completed a simple concurrent task disrupting verbal rehearsal (Experiment 2), or a complex concurrent task disrupting verbal rehearsal and executive resources (Experiment 3). Under simple concurrent task conditions, prioritization boosts were observed, but with increased costs to the less valuable items. Prioritization effects were also observed under complex concurrent task conditions, although this was accompanied by chance-level performance at most of the less valuable positions. A substantial recency advantage was also observed for the final item in each sequence, across all conditions. Taken together, this indicates that individuals can prioritize valuable information in verbal WM even when rehearsal and executive resources are disrupted, though they do so by neglecting or abandoning other items in the sequence. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Objectives: In young adults, the ability to verbally recall instructions in working memory is enhanced if the sequences are physically enacted by the participant (self-enactment) or the experimenter (demonstration) during encoding. Here we examine the effects of self-enactment and demonstration at encoding on working memory performance in older and younger adults., Method: Fifty young (18-23 years) and 40 older (60-89 years) adults listened to sequences of novel action-object pairs before verbally recalling them in the correct order. There were three different encoding conditions: spoken only, spoken + demonstration, and spoken + self-enactment. We included two different levels of difficulty to investigate whether task complexity moderated the effect of encoding condition and whether this differed between age groups., Results: Relative to the spoken only condition, demonstration significantly improved young and older adults' serial recall performance, but self-enactment only enhanced performance in the young adults, and this boost was smaller than the one gained through demonstration., Discussion: Our findings suggest that additional spatial-motoric information is beneficial for older adults when the actions are demonstrated to them, but not when the individual must enact the instructions themselves., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Visual working memory for features and bindings is susceptible to age-related decline. Two experiments were used to examine whether older adults are able to strategically prioritise more valuable information in working memory and whether this could reduce age-related impairments. Younger (18-33 years) and older (60-90 years) adults were presented with coloured shapes and, following a brief delay, asked to recall the feature that had accompanied the probe item. In Experiment 1, participants were either asked to prioritise a more valuable object in the array (serial position 1, 2, or 3) or to treat them all equally. Older adults exhibited worse overall memory performance but were as able as younger adults to prioritise objects. In both groups, this ability was particularly apparent at the middle serial position. Experiment 2 then explored whether younger and older adults' prioritisation is affected by presentation time. Replicating Experiment 1, older adults were able to prioritise the more valuable object in working memory, showing equivalent benefits and costs as younger adults. However, processing speed, as indexed by presentation time, was shown not to limit strategic prioritisation in either age group. Taken together, these findings demonstrate that, although older adults have poorer visual working memory overall, the ability to strategically direct attention to more valuable items in working memory is preserved across ageing.

In the fifty years since the discovery of JC polyomavirus (JCPyV), the body of research representing our collective knowledge on this virus has grown substantially. As the causative agent of progressive multifocal leukoencephalopathy (PML), an often fatal central nervous system disease, JCPyV remains enigmatic in its ability to live a dual lifestyle. In most individuals, JCPyV reproduces benignly in renal tissues, but in a subset of immunocompromised individuals, JCPyV undergoes rearrangement and begins lytic infection of the central nervous system, subsequently becoming highly debilitating-and in many cases, deadly. Understanding the mechanisms allowing this process to occur is vital to the development of new and more effective diagnosis and treatment options for those at risk of developing PML. Here, we discuss the current state of affairs with regards to JCPyV and PML; first summarizing the history of PML as a disease and then discussing current treatment options and the viral biology of JCPyV as we understand it. We highlight the foundational research published in recent years on PML and JCPyV and attempt to outline which next steps are most necessary to reduce the disease burden of PML in populations at risk.

Angiostrongylus cantonensis is a pathogenic nematode and the cause of neuroangiostrongyliasis, an eosinophilic meningitis more commonly known as rat lungworm disease. Transmission is thought to be primarily due to ingestion of infective third stage larvae (L3) in gastropods, on produce, or in contaminated water. The gold standard to determine the effects of physical and chemical treatments on the infectivity of A. cantonensis L3 larvae is to infect rodents with treated L3 larvae and monitor for infection, but animal studies are laborious and expensive and also raise ethical concerns. This study demonstrates propidium iodide (PI) to be a reliable marker of parasite death and loss of infective potential without adversely affecting the development and future reproduction of live A. cantonensis larvae. PI staining allows evaluation of the efficacy of test substances in vitro, an improvement upon the use of lack of motility as an indicator of death. Some potential applications of this assay include determining the effectiveness of various anthelmintics, vegetable washes, electromagnetic radiation and other treatments intended to kill larvae in the prevention and treatment of neuroangiostrongyliasis.

The trigeminal nucleus caudalis (TNc) receives extensive afferent innervation from peripheral sensory neurons of the trigeminal ganglion (TG), and is the first central relay in the circuitry underpinning orofacial pain. Despite the initial characterization of the neurons in the superficial laminae, many questions remain. Here we report on electrophysiological properties of 535 superficial lamina I/II TNc neurons. Based on their firing pattern, we assigned these cells to five main groups, including (1) tonic, (2) phasic, (3) delayed, (4) H-current, and (5) tonic-phasic neurons, groups that exhibit distinct intrinsic properties and share some similarity with groups identified in the spinal dorsal horn. Driving predominantly nociceptive TG primary afferents using optogenetic stimulation in TRPV1/ChR2 animals, we found that tonic and H-current cells are most likely to receive pure monosynaptic input, whereas delayed neurons are more likely to exhibit inputs that appear polysynaptic. Finally, for the first time in TNc neurons, we used unsupervised clustering analysis methods and found that the kinetics of the action potentials and other intrinsic properties of these groups differ significantly from one another. Unsupervised spectral clustering based solely on a single voltage response to rheobase current was sufficient to group cells with shared properties independent of action potential discharge pattern, indicating that this approach can be effectively applied to identify functional neuronal subclasses. Together, our data illustrate that cells in the TNc with distinct patterns of TRPV1/ChR2 afferent innervation are physiologically diverse, but can be understood as a few major groups of cells having shared functional properties., (© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

JC polyomavirus (JCPyV) is a ubiquitous human pathogen that causes progressive multifocal leukoencephalopathy (PML). The entry receptors for JCPyV belong to the 5-hydroxytryptamine 2 receptor (5-HT 2 R) family, but how individual members of the family function to facilitate infection is not known. We used proximity ligation assay (PLA) to determine that JCPyV interacts with each of the 5-HT 2 receptors (5-HT 2 Rs) in a narrow window of time during entry. We used CRISPR-Cas9 to randomly introduce stop codons in the gene for each receptor and discovered that the second intracellular loop of each was necessary for infection. This loop contains a motif possibly involved in receptor internalization by β-arrestin. Mutation of this motif and small interfering RNA (siRNA) knockdown of β-arrestin recapitulated the results of our CRISPR-Cas9 screen, showing that this motif is critical. Our results have implications for the role these receptors play in virus infection and for their normal functioning as receptors for serotonin., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Recent research found no evidence that children aged 7-10 years are able to direct their attention to more valuable information in working memory. The current experiments examined whether children demonstrate this ability when the reward system used to motivate participants is engaging and age-appropriate. This was explored across different memory loads (3- vs. 4-item arrays) and modes of presentation (sequential vs. simultaneous). Younger (7-8 years) and older children (9-10 years) were shown 3 or 4 colored shapes and asked to recall the color of one probed item following a brief delay. Items were either presented sequentially (Experiment 1) or simultaneously (Experiment 2). Children completed a differential probe value condition, in which the first shape (Experiment 1) or the top-left shape (Experiment 2) was worth more points than the other items, and an equal probe value condition, in which all shapes were equally valuable. Children were told they could use the points collected to play a specially designed game at the end of the session, and that they would be given a prize if they collected enough points. When items were presented sequentially, significant probe value effects emerged, with children showing higher accuracy for the first item when this serial position was more valuable. This effect was consistent across age group and memory load. When items were encountered simultaneously, both groups showed probe value effects in the higher (4-item) memory load condition. This indicates that children can prioritize more valuable information in working memory when sufficiently motivated to do so. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The endemic human JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy in immune-suppressed patients. The mechanisms of virus infection in vivo are not understood because the major target cells for virus in the brain do not express virus receptors and do not bind virus. We found that JCPyV associates with extracellular vesicles (EVs) and can infect target cells independently of virus receptors. Virus particles were found packaged inside extracellular vesicles and attached to the outer side of vesicles. Anti-JCPyV antisera reduced infection by purified virus but had no effect on infection by EV-associated virus. Treatment of cells with the receptor-destroying enzyme neuraminidase inhibited infection with purified virus but did not inhibit infection by EV-associated virus. Mutant pseudoviruses defective in sialic acid receptor binding could not transduce cells as purified pseudovirions but could do so when associated with EVs. This alternative mechanism of infection likely plays a critical role in the dissemination and spread of JCPyV both to and within the central nervous system. IMPORTANCE JC polyomavirus (JCPyV) is a ubiquitous human pathogen that causes progressive multifocal leukoencephalopathy (PML), a severe and often fatal neurodegenerative disease in immunocompromised or immunomodulated patients. The mechanisms responsible for initiating infection in susceptible cells are not completely known. The major attachment receptor for the virus, lactoseries tetrasaccharide c (LSTc), is paradoxically not expressed on oligodendrocytes or astrocytes in human brain, and virus does not bind to these cells. Because these are the major cell types targeted by the virus in the brain, we hypothesized that alternative mechanisms of infection must be responsible. Here we provide evidence that JCPyV is packaged in extracellular vesicles from infected cells. Infection of target cells by vesicle-associated virus is not dependent on LSTc and is not neutralized by antisera directed against the virus. This is the first demonstration of a polyomavirus using extracellular vesicles as a means of transmission., (Copyright © 2019 Morris-Love et al.)

Recent research has indicated that visual working memory capacity for unidimensional items might be boosted by focusing on all presented items, as opposed to a subset of them. However, it is not clear whether the same outcomes would be observed if more complex items were used which require feature binding, a potentially more demanding task. The current experiments, therefore, examined the effects of encoding strategy using multidimensional items in tasks that required feature binding. Effects were explored across a range of different age groups (Experiment 1) and task conditions (Experiment 2). In both experiments, participants performed significantly better when focusing on a subset of items, regardless of age or methodological variations, suggesting this is the optimal strategy to use when several multidimensional items are presented and binding is required. Implications for task interpretation and visual working memory function are discussed.

In visual working memory tasks, memory for an item is enhanced if participants are told that the item is relatively more valuable than others presented within the same trial. Experiment 1 explored whether these probe value boosts (termed prioritization effects in previous literature) are affected by probe frequency (i.e., how often the more valuable item is tested). Participants were presented with four colored shapes sequentially and asked to recall the color of one probed item following a delay. They were informed that the first item was more valuable (differential probe value) or as valuable as the other items (equal probe value), and that this item would be tested more frequently (differential probe frequency) or as frequently (equal probe frequency) as the other items. Probe value and probe frequency boosts were observed at the first position, though both were accompanied by costs to other items. Probe value and probe frequency boosts were additive, suggesting the manipulations yield independent effects. Further supporting this, experiment 2 revealed that probe frequency boosts are not reliant on executive resources, directly contrasting with previous findings regarding probe value. Taken together, these outcomes suggest there may be several ways in which attention can be directed in working memory., (© 2018 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.)

The ability to encode, retain, and implement instructions within working memory is central to many behaviours, including classroom activities which underpin learning. The three experiments presented here explored how action-planned, enacted, and observed-impacted 6- to 10-year-old's ability to follow instructions. Experiment 1 (N = 81) found enacted recall was superior to verbal recall, but self-enactment at encoding had a negative effect on enacted recall and verbal recall. In contrast, observation of other-enactment (demonstration) at encoding facilitated both types of recall (Experiment 2a: N = 81). Further, reducing task demands through a reduced set of possible actions (Experiment 2b; N = 64) led to a positive effect of self-enactment at encoding for later recall (both verbal and enacted). Expecting to enact at recall may lead to the creation of an imaginal spatial-motoric plan at encoding that boosts later recall. However, children's ability to use the additional spatial-motoric codes generated via self-enactment at encoding depends on the demands the task places on central executive resources. Demonstration at encoding appears to reduce executive demands and enable use of these additional forms of coding.

Objective: Placental abruption is a clinical term used when premature separation of the placenta from the uterine wall occurs prior to delivery of the fetus. Hypertension, substance abuse, smoking, intrauterine infection and recent trauma are risk factors for placental abruption. In this study, we sought for clinical factors that increase the risk for perinatal mortality in patients admitted to the hospital with the clinical diagnosis of placental abruption., Materials and Methods: We identified all placental abruption cases managed over the past 6 years at our Center. Those with singleton pregnancies and a diagnosis of abruption based on strict clinical criteria were selected. Eleven clinical variables that had potential for increasing the risk for perinatal mortality were selected, logistic regression analysis was used to identify variables associated with perinatal death., Results: Sixty-one patients were included in the study with 16 ending in perinatal death (26.2%). Ethnicity, maternal age, gravidity, parity, use of tobacco, use of cocaine, hypertension, asthma, diabetes, hepatitis C, sickle cell disease and abnormalities of amniotic fluid volume were not the main factors for perinatal mortality. Gestational age at delivery, birthweight and history of recent trauma were significantly associated with perinatal mortality. The perinatal mortality rate was 42% in patients who delivered prior to 30 weeks of gestation compared to 15% in patients who delivered after 30 weeks of gestation (p < 0.05). A three-fold increase in severe trauma was reported in the group of patients with perinatal mortality than in the group with perinatal survivors (25% versus 7%, respectively, p < 0.05)., Conclusions: In patients admitted to hospital for placental abruption delivery prior to 30 weeks of gestation and a history of abdominal trauma are independent risk factors for perinatal death.

The Kleihauer-Betke (KB) test evaluates fetal blood in the maternal circulation, and is often used when placental abruption is suspected. At our centre, it is the protocol to perform a KB test in all suspected cases of abruption. We carried out a retrospective study of all cases of abruption that occurred at our centre over 6 years. Of the 68 confirmed cases of placental abruption, only three had positive KB tests, giving a sensitivity of only 4.4%. Thus, in the overwhelming majority of cases of confirmed abruption, the KB test was negative. Our findings indicate that the KB test has poor sensitivity for placental abruption and should not be used in the detection of abruption.

Today, the intrauterine device (IUD) is by far the most popular form of long term reversible contraception in the world. Side effects from the IUD are minimal and complications are rare. Uterine perforation and migration of the IUD outside the uterine cavity are the most serious complications. Physician visualization and/or the patient feeling retrieval threads at the cervical os are confirmation that the IUD has not been expelled or migrated. We present a case of a perforated, intraperitoneal IUD with threads noted at the cervical os. Office removal was not possible using gentle traction on the threads. Multiple imaging and endoscopic modalities were used to try and locate the IUD including pelvic ultrasound, diagnostic hysteroscopy, cystoscopy, and pelvic magnetic resonance imaging (MRI). The studies gave conflicting results on location of the IUD. Ultimately, the missing IUD was removed via laparoscopy.

Since Buschke and Löwenstein first described the giant condyloma in 1925 (which subsequently was named Buschke-Löwenstein tumor), there have been scattered reports over the past 90 years describing presentation and different avenues of treatment for patients with this condition. It is well known that immunocompromised individuals are at an increased risk of anogenital disease caused by human papillomavirus (HPV). In this report, we present the management of two HIV positive patients with giant condylomas. Both patients presented with urinary outflow obstruction and sepsis. Though giant condylomas are a rare phenomenon, these two cases underscore the importance of early treatment intervention, especially in the immunocompromised patient.

Background: The purpose of this study is to compare mode of delivery for both nulliparous and multiparous women at term that underwent elective induction of labor to those who arrived in spontaneous labor., Methods: Medical records of 807 deliveries were reviewed. There were 566 labor patients and 241 elective induction patients., Results: Women who underwent elective induction of labor were more likely to undergo cesarean delivery compared to those women who arrived in spontaneous labor (41.1% versus 9.9%, P = 0.001). This was true for both nulliparous women (49% versus 31%, P < 0.0001), and multiparous women (22.7% versus 1.6%, P < 0.0001). The rate of operative vaginal delivery was also increased in the elective induction of labor group (8.4% versus 3.6%, P < 0.0001). Operative vaginal delivery was statistically significant in multiparous women (21% versus 4.1%, P < 0.0001), but not in nulliparous women (10.1% versus 9.8%, P = NS)., Conclusion: Elective induction of labor at term is associated with an increased risk of cesarean section in both nulliparous and multiparous women. There is also an increased risk of an operative vaginal delivery in multiparous women who underwent elective induction of labor.

Completion of uterine curettage may be challenging following uterine perforation even under sonographic and laparoscopic monitoring. This report illustrates the use of a flexible intubating stylet as a guide to place the suction curette into the uterine cavity when sonography and laparoscopy alone are not successful. Use of a malleable instrument such as an intubating stylet as a guide should be considered an option when insertion of the suction curette into the uterine cavity is complicated by anatomic variation and uterine perforation.

A 24-year-old morbidly obese African American gravida 1, with a history of severe asthma complicated by multiple inpatient admissions, presents at 30 weeks gestation with a foreign body in her left main stem bronchus. After a failed bronchoscopy postpartum, the patient slipped into respiratory failure and was subsequently intubated, spending two weeks in the intensive care unit. After two more attempts of trying to retrieve the foreign object from her lung via bronchoscopy, she eventually contracted a postobstructive pneumonia and underwent a left lower lung lobectomy for curative treatment.

This Account provides an overview of the methods that are currently being used to study the electromagnetics of silver and gold nanoparticles, with an emphasis on the determination of extinction and surface-enhanced Raman scattering (SERS) spectra. These methods have proven to be immensely useful in recent years for interpreting a wide range of nanoscience experiments and providing the capability to describe optical properties of particles up to several hundred nanometers in dimension, including arbitrary particle structures and complex dielectric environments (adsorbed layers of molecules, nearby metal films, and other particles). While some of the methods date back to Mie's celebrated work a century ago, others are still at the forefront of algorithm development in computational electromagnetics. This Account gives a qualitative description of the physical and mathematical basis behind the most commonly used methods, including both analytical and numerical methods, as well as representative results of applications that are relevant to current experiments. The analytical methods that we discuss are either derived from Mie theory for spheres or from the quasistatic (Gans) model as applied to spheres and spheroids. In this discussion, we describe the use of Mie theory to determine electromagnetic contributions to SERS enhancements that include for retarded dipole emission effects, and the use of the quasistatic approximation for spheroidal particles interacting with dye adsorbate layers. The numerical methods include the discrete dipole approximation (DDA), the finite difference time domain (FDTD) method, and the finite element method (FEM) based on Whitney forms. We discuss applications such as using DDA to describe the interaction of two gold disks to define electromagnetic hot spots, FDTD for light interacting with metal wires that go from particle-like plasmonic response to the film-like transmission as wire dimension is varied, and FEM studies of electromagnetic fields near cubic particles.

Single-use conductivity and microbial sensors were used to investigate the effect of both species (chloride, nitrate, and sulphate) and concentration/osmolarity of anions on the metabolic activity of Escherichia coli. A new disposable, single-use conductivity sensor is described which is compatible with the CellSense mediated amperometric biosensor system. The effect of changing salinity and nitrate concentration on the response of E. coli to 3,5-dichlorophenol and mercuric chloride was determined. The implications for toxicity assessment of a hybrid sensing system, allowing the simultaneous monitoring of physico-chemical and biological data, are discussed.

We constructed maps for eight chromosomes (1, 6, 9, 10, 13, 20, X and (previously) 22), representing one-third of the genome, by building landmark maps, isolating bacterial clones and assembling contigs. By this approach, we could establish the long-range organization of the maps early in the project, and all contig extension, gap closure and problem-solving was simplified by containment within local regions. The maps currently represent more than 94% of the euchromatic (gene-containing) regions of these chromosomes in 176 contigs, and contain 96% of the chromosome-specific markers in the human gene map. By measuring the remaining gaps, we can assess chromosome length and coverage in sequenced clones.

Arachidonic acid, cellulase, CuSO4, a sonicate of Phytophthora infestans mycelium and a spore suspension of Penicillium chrysogenum all elicited the formation of the sesquiterpenoid phytoalexins lubimin, 3-hydroxylubimin and rishitin in fruit cavities of Datura stramonium. 3-Hydroxylubimin was the predominant phytoalexin formed after treatment of the fruits with arachidonic acid, cellulase and the P. infestans preparation. Copper sulphate was a potent elicitor of lubimin but not 3-hydroxylubimin. The fungus P. chrysogenum metabolized lubimin and 3-hydroxylubimin to 15-dihydrolubimin and 3-hydroxy-15-dihydrolubimin respectively, both in fruit cavities inoculated with spores of this fungus and in pure culture. The 15-dihydrolubimin formed in the fruits by the fungus was further metabolized (by the fruits) to both isolubimin and 3-hydroxy-15-dihydrolubimin. The precursor-product relationships between all of the subject compounds was investigated by feeding experiments with (3)H-labelled compounds. 2-Dehydro-[15-(3)H1]lubimin was rapidly and efficiently incorporated into lubimin and may be the direct precursor of lubimin in planta. 3-Hydroxy[2-(3)H1]lubimin was incorporated into the nor-eudesmane rishitin but 10-epi-3-hydroxy[2-(3)H1]lubimin was not. An updated scheme for the biosynthesis and metabolism of lubimin and related compounds in infected tissues of solanaceous plants is presented.