Transitions of care for older adults discharged home from the emergency department: an inductive thematic content analysis of patient comments.

OBJECTIVE: Improving care transitions for older adults can reduce emergency department (ED) visits, adverse events, and empower community autonomy. We conducted an inductive qualitative content analysis to identify themes emerging from comments to better understand ED care transitions. METHODS: The LEARNING WISDOM prospective longitudinal observational cohort includes older adults (≥ 65 years) who experienced a care transition after an ED visit from both before and during COVID-19. Their comments on this transition were collected via phone interview and transcribed. We conducted an inductive qualitative content analysis with randomly selected comments until saturation. Themes that arose from comments were coded and organized into frequencies and proportions. We followed the Standards for Reporting Qualitative Research (SRQR). RESULTS: Comments from 690 patients (339 pre-COVID, 351 during COVID) composed of 351 women (50.9%) and 339 men (49.1%) were analyzed. Patients were satisfied with acute emergency care, and the proportion of patients with positive acute care experiences increased with the COVID-19 pandemic. Negative patient comments were most often related to communication between health providers across the care continuum and the professionalism of personnel in the ED. Comments concerning home care became more neutral with the COVID-19 pandemic. CONCLUSION: Patients were satisfied overall with acute care but reported gaps in professionalism and follow-up communication between providers. Comments may have changed in tone from positive to neutral regarding home care over the COVID-19 pandemic due to service slowdowns. Addressing these concerns may improve the quality of care transitions and provide future pandemic mitigation strategies.

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending-Dose Study To Investigate the Safety, Tolerability, and Pharmacokinetics of an Anti-Influenza B Virus Monoclonal Antibody, MHAB5553A, in Healthy Volunteers.

Influenza B can cause significant morbidity and mortality. MHAB5553A, a human monoclonal immunoglobulin G1 (IgG1) antibody that binds to a highly conserved region of the hemagglutinin protein of influenza B virus, is being examined as a novel therapeutic for the treatment of influenza B patients with severe disease. This phase 1, randomized, double-blind, placebo-controlled, single-ascending-dose study was conducted to assess the safety, tolerability, and pharmacokinetics (PK) of MHAB5553A. Twenty-six healthy male and female volunteers of >18 years of age were randomized into five cohorts receiving a single intravenous (i.v.) dose of 120, 1,200, 3,600, 8,400, or 10,800 mg MHAB5553A or placebo (four active:one placebo, except for the 120-mg cohort [4:2]). Subjects were followed for 120 days after dosing. No subject discontinued the study, no dose-limiting adverse events or serious adverse events were reported, and a maximum tolerated dose (MTD) was not defined. The most commonly reported adverse events were cold symptoms and headache; most were mild and occurred at a similar rate across all cohorts. MHAB5553A showed no relevant time- or dose-related changes in laboratory values or vital signs compared to the placebo. The observed serum PK was linear and generally dose proportional, and the observed nasal PK was nonlinear and generally non-dose proportional. MHAB5553A is generally well tolerated in healthy volunteers up to at least a single i.v. dose of 10,800 mg and demonstrated linear serum PK consistent with those of a human IgG1 antibody lacking known endogenous targets in humans. (This study has been registered at ClinicalTrials.gov under registration no. NCT02528903.).

Evolution and Emergence of Enteroviruses through Intra- and Inter-species Recombination: Plasticity and Phenotypic Impact of Modular Genetic Exchanges in the 5' Untranslated Region.

Genetic recombination shapes the diversity of RNA viruses, including enteroviruses (EVs), which frequently have mosaic genomes. Pathogenic circulating vaccine-derived poliovirus (cVDPV) genomes consist of mutated vaccine poliovirus (PV) sequences encoding capsid proteins, and sequences encoding nonstructural proteins derived from other species' C EVs, including certain coxsackieviruses A (CV-A) in particular. Many cVDPV genomes also have an exogenous 5' untranslated region (5' UTR). This region is involved in virulence and includes the cloverleaf (CL) and the internal ribosomal entry site, which play major roles in replication and the initiation of translation, respectively. We investigated the plasticity of the PV genome in terms of recombination in the 5' UTR, by developing an experimental model involving the rescue of a bipartite PV/CV-A cVDPV genome rendered defective by mutations in the CL, following the co-transfection of cells with 5' UTR RNAs from each of the four human EV species (EV-A to -D). The defective cVDPV was rescued by recombination with 5' UTR sequences from the four EV species. Homologous and nonhomologous recombinants with large deletions or insertions in three hotspots were isolated, revealing a striking plasticity of the 5' UTR. By contrast to the recombination of the cVDPV with the 5' UTR of group II (EV-A and -B), which can decrease viral replication and virulence, recombination with the 5' UTRs of group I (EV-C and -D) appeared to be evolutionarily neutral or associated with a gain in fitness. This study illustrates how the genomes of positive-strand RNA viruses can evolve into mosaic recombinant genomes through intra- or inter-species modular genetic exchanges, favoring the emergence of new recombinant lineages.

Two Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending-Dose Studies To Investigate the Safety, Tolerability, and Pharmacokinetics of an Anti-Influenza A Virus Monoclonal Antibody, MHAA4549A, in Healthy Volunteers.

Hospitalized patients with severe influenza are at significant risk for morbidity and mortality. MHAA4549A is a human monoclonal immunoglobulin (Ig) G1 antibody that binds to a highly conserved stalk region of the influenza A virus hemagglutinin protein and neutralizes all tested seasonal human influenza A virus strains. Two phase 1 trials examined the safety, tolerability, and pharmacokinetics of MHAA4549A in healthy volunteers. Both single ascending-dose trials were randomized, double blinded, and placebo controlled. Trial 1 randomized 21 healthy adults into four cohorts receiving a single intravenous dose of 1.5, 5, 15, or 45 mg/kg MHAA4549A or placebo. Trial 2 randomized 14 healthy adults into two cohorts receiving a single intravenous fixed dose of 8,400 mg or 10,800 mg of MHAA4549A or placebo. Subjects were followed for 120 days after dosing. No subject was discontinued in either trial, and no serious adverse events were reported. The most common adverse event in both studies was mild headache (trial 1, 4/16 subjects receiving MHAA4549A and 1/5 receiving placebo; trial 2, 4/8 subjects receiving MHAA4549A and 2/6 receiving placebo). MHAA4549A produced no relevant time- or dose-related changes in laboratory values or vital signs compared to those with placebo. No subjects developed an antitherapeutic antibody response following MHAA4549A administration. MHAA4549A showed linear serum pharmacokinetics, with a mean half-life of 22.5 to 23.7 days. MHAA4549A is safe and well tolerated in healthy volunteers up to a single intravenous dose of 10,800 mg and demonstrates linear serum pharmacokinetics consistent with those of a human IgG1 antibody lacking known endogenous targets in humans. (These trials have been registered at ClinicalTrials.gov under registration no. NCT01877785 and NCT02284607).

The CREB3-Herp signalling module limits the cytosolic calcium concentration increase and apoptosis induced by poliovirus.

Poliovirus (PV)-induced apoptosis seems to play a major role in central nervous system (CNS) tissue injury, a crucial feature of the pathogenesis of poliomyelitis. We have previously shown that calcium (Ca2+) flux from the endoplasmic reticulum (ER) to the cytosol during PV infection is involved in apoptosis induction in human neuroblastoma cells. We show here that PV infection is associated with a transient upregulation of Herp (homocysteine-induced ER protein), a protein known to promote the degradation of ER-resident Ca2+ channels. Herp gene transcription is controlled by the transcription factor CREB3 (cAMP response element-binding protein 3). We found that the CREB3/Herp pathway limited the increase in cytosolic Ca2+ concentration and apoptosis early in PV infection. This may reduce the extent of PV-induced damage to the CNS during poliomyelitis.

Role of galectin-3 in the initial control of Leishmania infection.

Galectin-3 belongs to a family of galectins, evolutionarily conserved glycan binding proteins (lectins) that have recently attracted much attention as modulators in adaptive immune responses. Previously, galectins have been considered lectins that bind only to endogenous "self" glycans. Further, galectins are synthesized and stored in the cytosol, where there are virtually no glycan-containing proteins, raising doubts over the biological significance of their glycan binding capacity. As discussed in this review, with particular emphasis on the role of galectin-3 in the innate immune response against the protozoan parasite Leishmania, several recent studies have suggested that galectin-3 could recognize L. major-specific pathogen-associated molecular pattern and, in parallel, facilitate the infiltration of neutrophils to the infected sites that helps reduce the initial parasite burden once galectin-3 is released as a damage-associated molecular pattern. Thus, while further investigation is necessary, based on the current results, it could be proposed that galectin-3 can hinge two areas of the innate immune recognition system, DAMP and PAMP pathways in the early host responses against various pathogens.

Natural products with protein tyrosine phosphatase inhibitory activity.

Protein tyrosine phosphatases (PTPs) play an essential role in maintaining the proper tyrosine phosphorylation state of proteins. Abnormal tyrosine phosphorylation has been implicated in diseases as diverse as type 2 diabetes, cancer, immune disorders and neurological disorders, and thus inhibitors of PTPs have been investigated as potential treatments of these diseases. Natural products are widely regarded to be privileged structures in drug discovery efforts, and are therefore a good starting point for the development of PTP inhibitors. Here we describe reported natural product PTP inhibitors as well as methods to screen for natural product PTP inhibitors using bioassay-guided fractionation. These methods are illustrated using the example of a family of bromotyrosine-derived PTP inhibitors isolated from two marine sponges. We also identify potential pitfalls and false-positives, in particular compounds that are oxidizing agents that react irreversibly with the PTP.

The Golgi protein ACBD3, an interactor for poliovirus protein 3A, modulates poliovirus replication.

We have shown that the circulating vaccine-derived polioviruses responsible for poliomyelitis outbreaks in Madagascar have recombinant genomes composed of sequences encoding capsid proteins derived from poliovaccine Sabin, mostly type 2 (PVS2), and sequences encoding nonstructural proteins derived from other human enteroviruses. Interestingly, almost all of these recombinant genomes encode a nonstructural 3A protein related to that of field coxsackievirus A17 (CV-A17) strains. Here, we investigated the repercussions of this exchange, by assessing the role of the 3A proteins of PVS2 and CV-A17 and their putative cellular partners in viral replication. We found that the Golgi protein acyl-coenzyme A binding domain-containing 3 (ACBD3), recently identified as an interactor for the 3A proteins of several picornaviruses, interacts with the 3A proteins of PVS2 and CV-A17 at viral RNA replication sites, in human neuroblastoma cells infected with either PVS2 or a PVS2 recombinant encoding a 3A protein from CV-A17 [PVS2-3A(CV-A17)]. The small interfering RNA-mediated downregulation of ACBD3 significantly increased the growth of both viruses, suggesting that ACBD3 slowed viral replication. This was confirmed with replicons. Furthermore, PVS2-3A(CV-A17) was more resistant to the replication-inhibiting effect of ACBD3 than the PVS2 strain, and the amino acid in position 12 of 3A was involved in modulating the sensitivity of viral replication to ACBD3. Overall, our results indicate that exchanges of nonstructural proteins can modify the relationships between enterovirus recombinants and cellular interactors and may thus be one of the factors favoring their emergence.

Recrutement des kinases PI4KIII aux organelles de réplication virale au cours de l'infection par le poliovirus et d'autres virus à ARN de polarité positive.

One characteristic of infections with RNA viruses of positive polarity is the generation of new specialized membrane structures acting as platforms accommodating the complexes involved in replication of the viral genome. The functionality of these "replication organelles" is dependent on interactions between viral nonstructural proteins, recruited host factors and viral RNAs. Poliovirus, the causal agent of paralytic poliomyelitis, is the model most frequently used for identification of the viral and cellular components involved in this process. Several recent studies have suggested that the efficiency of genome replication for poliovirus and other members of the Picornaviridæ family results from the recruitment of a phosphatidylinositol (PI) kinase, PI4KIIIß (phosphatidylinositol-4-kinase IIIß), which generates a lipid membrane microenvironment rich in PI4P (phosphatidylinositol-4-phosphate) at sites of replication. The nonstructural protein 3A of these viruses has been shown to play a role in the enrichment of replication organelle membranes in PI4KIIIß, but the mechanisms of kinase recruitment seem to differ between members of this family of viruses. Hepatitis C, from the Flaviviridæ family, recruits another PI4KIII kinase, PI4KIIIα, to sites of replication, through another nonstructural protein, NS5A. In this review, we will describe the various recently proposed models and the potential role of PI4P lipids. Finally, we will show that PI4KIII kinases are potential targets for the development of antiviral drugs targeting many positive-polarity RNA viruses.

Enhanced gene silencing in cells cured of persistent virus infection by RNA interference.

We compared HEp-2-derived cells cured of persistent poliovirus infection by RNA interference (RNAi) with parental cells, to investigate possible changes in the efficiency of RNAi. Lower levels of poliovirus replication were observed in cured cells, possibly facilitating virus silencing by antiviral small interfering RNAs (siRNAs). However, green fluorescent protein (GFP) produced from a measles virus vector and also GFP and luciferase produced from plasmids that do not replicate in human cells were more effectively silenced by specific siRNAs in cured than in control cells. Thus, cells displaying enhanced silencing were selected during curing by RNAi. Our results strongly suggest that the RNAi machinery of cured cells is more efficient than that of parental cells.

Calcium flux between the endoplasmic reticulum and mitochondrion contributes to poliovirus-induced apoptosis.

We show that poliovirus (PV) infection induces an increase in cytosolic calcium (Ca(2+)) concentration in neuroblastoma IMR5 cells, at least partly through Ca(2+) release from the endoplasmic reticulum lumen via the inositol 1,4,5-triphosphate receptor (IP(3)R) and ryanodine receptor (RyR) channels. This leads to Ca(2+) accumulation in mitochondria through the mitochondrial Ca(2+) uniporter and the voltage-dependent anion channel (VDAC). This increase in mitochondrial Ca(2+) concentration in PV-infected cells leads to mitochondrial dysfunction and apoptosis.

Recombination between polioviruses and co-circulating Coxsackie A viruses: role in the emergence of pathogenic vaccine-derived polioviruses.

Ten outbreaks of poliomyelitis caused by pathogenic circulating vaccine-derived polioviruses (cVDPVs) have recently been reported in different regions of the world. Two of these outbreaks occurred in Madagascar. Most cVDPVs were recombinants of mutated poliovaccine strains and other unidentified enteroviruses of species C. We previously reported that a type 2 cVDPV isolated during an outbreak in Madagascar was co-circulating with coxsackieviruses A17 (CA17) and that sequences in the 3' half of the cVDPV and CA17 genomes were related. The goal of this study was to investigate whether these CA17 isolates can act as recombination partners of poliovirus and subsequently to evaluate the major effects of recombination events on the phenotype of the recombinants. We first cloned the infectious cDNA of a Madagascar CA17 isolate. We then generated recombinant constructs combining the genetic material of this CA17 isolate with that of the type 2 vaccine strain and that of the type 2 cVDPV. Our results showed that poliovirus/CA17 recombinants are viable. The recombinant in which the 3' half of the vaccine strain genome had been replaced by that of the CA17 genome yielded larger plaques and was less temperature sensitive than its parental strains. The virus in which the 3' portion of the cVDPV genome was replaced by the 3' half of the CA17 genome was almost as neurovirulent as the cVDPV in transgenic mice expressing the poliovirus cellular receptor gene. The co-circulation in children and genetic recombination of viruses, differing in their pathogenicity for humans and in certain other biological properties such as receptor usage, can lead to the generation of pathogenic recombinants, thus constituting an interesting model of viral evolution and emergence.

Learning Integrated Health System to Mobilize Context-Adapted Knowledge With a Wiki Platform to Improve the Transitions of Frail Seniors From Hospitals and Emergency Departments to the Community (LEARNING WISDOM): Protocol for a Mixed-Methods Implementation Study.

BACKGROUND: Elderly patients discharged from hospital experience fragmented care, repeated and lengthy emergency department (ED) visits, relapse into their earlier condition, and rapid cognitive and functional decline. The Acute Care for Elders (ACE) program at Mount Sinai Hospital in Toronto, Canada uses innovative strategies, such as transition coaches, to improve the care transition experiences of frail elderly patients. The ACE program reduced the lengths of hospital stay and readmission for elderly patients, increased patient satisfaction, and saved the health care system over Can $4.2 million (US $2.6 million) in 2014. In 2016, a context-adapted ACE program was implemented at one hospital in the Centre intégré de santé et de services sociaux de Chaudière-Appalaches (CISSS-CA) with a focus on improving transitions between hospitals and the community. The quality improvement project used an intervention strategy based on iterative user-centered design prototyping and a "Wiki-suite" (free web-based database containing evidence-based knowledge tools) to engage multiple stakeholders. OBJECTIVE: The objectives of this study are to (1) implement a context-adapted CISSS-CA ACE program in four hospitals in the CISSS-CA and measure its impact on patient-, caregiver-, clinical-, and hospital-level outcomes; (2) identify underlying mechanisms by which our context-adapted CISSS-CA ACE program improves care transitions for the elderly; and (3) identify underlying mechanisms by which the Wiki-suite contributes to context-adaptation and local uptake of knowledge tools. METHODS: Objective 1 will involve staggered implementation of the context-adapted CISSS-CA ACE program across the four CISSS-CA sites and interrupted time series to measure the impact on hospital-, patient-, and caregiver-level outcomes. Objectives 2 and 3 will involve a parallel mixed-methods process evaluation study to understand the mechanisms by which our context-adapted CISSS-CA ACE program improves care transitions for the elderly and by which our Wiki-suite contributes to adaptation, implementation, and scaling up of geriatric knowledge tools. RESULTS: Data collection started in January 2019. As of January 2020, we enrolled 1635 patients and 529 caregivers from the four participating hospitals. Data collection is projected to be completed in January 2022. Data analysis has not yet begun. Results are expected to be published in 2022. Expected results will be presented to different key internal stakeholders to better support the effort and resources deployed in the transition of seniors. Through key interventions focused on seniors, we are expecting to increase patient satisfaction and quality of care and reduce readmission and ED revisit. CONCLUSIONS: This study will provide evidence on effective knowledge translation strategies to adapt best practices to the local context in the transition of care for elderly people. The knowledge generated through this project will support future scale-up of the ACE program and our wiki methodology in other settings in Canada. TRIAL REGISTRATION: ClinicalTrials.gov NCT04093245; https://clinicaltrials.gov/ct2/show/NCT04093245. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17363.

Induction of galectin-1 expression by HTLV-I Tax and its impact on HTLV-I infectivity.

BACKGROUND: Cell-free Human T-cell Leukemia Virus type I (HTLV-I) virions are poorly infectious and cell-to-cell contact is often required to achieve infection. Other factors might thus importantly contribute in increasing infection by HTLV-I. Galectin-1 is a galactoside-binding lectin which is secreted by activated T lymphocytes. Several functions have been attributed to this protein including its capacity to increase cell-to-cell adhesion. Based on previous studies, we postulated that this protein could also accentuate HTLV-I infection. RESULTS: Herein, we demonstrate that galectin-1 expression and release are higher in HTLV-I-infected T cells in comparison to uninfected T cells. Furthermore, galectin-1 expression was activated in various cell lines expressing the wild type viral Tax protein while this induction was minimal upon expression of NF-kappaB activation-defective TaxM22. Cotransfection of these Tax expression vectors with galectin-1 promoter-driven luciferase constructs confirmed that Tax upregulated galectin-1 promoter activity. However, a NF-kappaB-independent mechanism was strongly favoured in this induction of galectin-1 expression as no activation of the promoter was apparent in Jurkat cells treated with known NF-kappaB activators. Using HTLV-I envelope pseudotyped HIV-1 virions, galectin-1 was shown to increase infectivity. In addition, a co-culture assay with HTLV-I-infected cells also indicated an increase in cell fusion upon addition of galectin-1. This effect was not mediated by factors present in the supernatant of the HTLV-I-infected cells. CONCLUSION: These data suggest that HTLV-I Tax increases galectin-1 expression and that this modulation could play an important role in HTLV-I infection by stabilizing both cell-to-cell and virus-cell interactions.

Performance of the French version of the 4AT for screening the elderly for delirium in the emergency department.

OBJECTIVES: Delirium is very frequent in older patients presenting to the emergency department (ED), but is often undetected. The purpose of this study was to evaluate the performance of the French version of the 4 A's Test (4AT-F) for the detection of delirium and cognitive impairment in older patients. METHODS: The study was conducted in four Canadian ED. Participants (n= 320) were independent or semi-independent patients (able to perform ≥5 activities of daily living) aged 65 and older and had an 8-hour exposure to the ED environment. The Telephone Interview for Cognitive Status (TICS-m), the Confusion Assessment Method (CAM) as well as the 4AT-F were administered to patients at the initial interview. The CAM and 4AT-F were then administered twice a day during the patients' ED or hospital stay. The 4AT-F's sensitivity and specificity were compared to those of the CAM (for delirium), and to that of the TICS (for cognitive impairment). RESULTS: Our results suggest that the 4AT-F has a sensitivity of 84% (95% CI: [76, 93]) and a specificity of 74% (95% CI: [70, 78]) for delirium, as well as a sensitivity of 49% (95% CI: [34, 64]) and a specificity of 87% (95% CI: [82, 92]) for cognitive impairment. CONCLUSION: The 4AT-F is a fast and reliable screening tool for delirium and cognitive impairment in ED. Due to its quick administration time, it allows a systematic screening of patients at risk of delirium, without significantly increasing the workload of the ED staff.

Prevention and treatment of enteric viral infections: possible benefits of probiotic bacteria.

The structure and function of the intestinal epithelium is briefly described, with the principal mechanisms involved in diarrhea. Human enteric viruses and probiotics are presented. We then review how probiotic bacteria could interfere with virus-induced pathology, we present our own view and describe specific interactions that would be valuable targets for future studies.

Risk factors of pancreatic fistula and delayed gastric emptying after pancreaticoduodenectomy with pancreaticogastrostomy.

BACKGROUND: Pancreatic fistula (PF) and delayed gastric emptying (DGE) are, respectively, the most frightening and most frequent complications after pancreaticoduodenectomy (PD). This study was undertaken to determine which independent factors influence the development of PF and DGE after PD. STUDY DESIGN: Between January 1996 and December 2005, 131 consecutive patients underwent a PD with pancreaticogastrostomy. A total of 22 items, entered prospectively, were examined with univariate and multivariate analysis. PF was defined as amylase-rich fluid collected by needle aspiration from an intraabdominal collection or from the drainage placed intraoperatively from day 3. DGE was defined as the need for nasogastric decompression beyond the 10(th) postoperative day. RESULTS: PF occurred in 14 patients (10.7%), with a mean length of hospital stay of 40.1+/-16.6 days. DGE occurred in 41 patients (31.3%), with a mean length of hospital stay of 35.5+/-13.6 days. PF and DGE increased postoperative length of stay. Multivariate analysis identified two independent factors for PF: heart disease as a risk factor and arterial hypertension as a protective factor. According to these two predictive factors, the observed rates of PF ranged from 4.1% to 66.6%. Age and early enteral feeding with nasojejunal tube were independent risk factors for DGE. DGE was statistically more frequent when surgical complications occurred or when an intraabdominal collection was present. CONCLUSIONS: Heart disease was a risk factor and arterial hypertension was a protective factor of PF. Age and early enteral feeding were independent risk factors for DGE. DGE is linked to the occurrence of other postoperative intraabdominal complications.

Discomfort and agitation in older adults with dementia.

BACKGROUND: A majority of patients with dementia present behavioral and psychological symptoms, such as agitation, which may increase their suffering, be difficult to manage by caregivers, and precipitate institutionalization. Although internal factors, such as discomfort, may be associated with agitation in patients with dementia, little research has examined this question. The goal of this study is to document the relationship between discomfort and agitation (including agitation subtypes) in older adults suffering from dementia. METHODS: This correlational study used a cross-sectional design. Registered nurses (RNs) provided data on forty-nine residents from three long-term facilities. Discomfort, agitation, level of disability in performing activities of daily living (ADL), and severity of dementia were measured by RNs who were well acquainted with the residents, using the Discomfort Scale for patients with Dementia of the Alzheimer Type, the Cohen-Mansfield Agitation Inventory, the ADL subscale of the Functional Autonomy Measurement System, and the Functional Assessment Staging, respectively. RNs were given two weeks to complete and return all scales (i.e., the Cohen-Mansfield Agitation Inventory was completed at the end of the two weeks and all other scales were answered during this period). Other descriptive variables were obtained from the residents' medical file or care plan. RESULTS: Hierarchical multiple regression analyses controlling for residents' characteristics (sex, severity of dementia, and disability) show that discomfort explains a significant share of the variance in overall agitation (28%, p < 0.001), non aggressive physical behavior (18%, p < 0.01) and verbally agitated behavior (30%, p < 0.001). No significant relationship is observed between discomfort and aggressive behavior but the power to detect this specific relationship was low. CONCLUSION: Our findings provide further evidence of the association between discomfort and agitation in persons with dementia and reveal that this association is particularly strong for verbally agitated behavior and non aggressive physical behavior.

Non-invasive alternatives to the Wada test in the presurgical evaluation of language and memory functions in epilepsy patients.

The cognitive outcome of the surgical removal of an epileptic focus depends on the assessment of the localisation and functional capacity of language and memory areas which need to be spared by the neurosurgeon. Traditionally, presurgical evaluation of epileptic patients has been achieved by means of the intracarotid amobarbital test assisted by neuropsychological measures. However, the advent of neuroimaging techniques has provided new ways of assessing these functions by means of non-invasive or minimally invasive methods, such as anatomical and functional magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, transcranial magnetic stimulation, functional transcranial Doppler monitoring, magnetoencephalography and near infrared spectroscopy. This paper aims at comparing and evaluating the traditional and recent preoperative approaches from a neuropsychological perspective.

A Rapid Method for Engineering Recombinant Polioviruses or Other Enteroviruses.

The cloning of large enterovirus RNA sequences is labor-intensive because of the frequent instability in bacteria of plasmidic vectors containing the corresponding cDNAs. In order to circumvent this issue we have developed a PCR-based method that allows the generation of highly modified or chimeric full-length enterovirus genomes. This method relies on fusion PCR which enables the concatenation of several overlapping cDNA amplicons produced separately. A T7 promoter sequence added upstream the fusion PCR products allows its transcription into infectious genomic RNAs directly in transfected cells constitutively expressing the phage T7 RNA polymerase. This method permits the rapid recovery of modified viruses that can be subsequently amplified on adequate cell-lines.