When do pictures reduce false memory?

© 2019, The Psychonomic Society, Inc. An important discovery in false-memory research is Israel and Schacter’s (Psychonomic Bulletin & Review, 4, 577-581, 1997) finding that presenting pictures at study relative to words alone reduces false memory in the DRM paradigm, a result that has been replicated many times. The standard interpretation is that memory for visual processing of the pictures can be used to reject the critical distractors, which were not explicitly present at study. Beginning from the empirical observation that the pictures used by Israel and Schacter are not consistently labelled with the DRM word they are supposed to represent, we present a series of four studies designed to determine if it is the presentation of pictures or the mismatch between the pictures and the words that reduces false memory. The results across the four experiments demonstrate that picture presentation at study is neither necessary nor sufficient to reduce false memory in the DRM and the categorical associate paradigms. However, we discuss other studies in which picture processing clearly is responsible for reduction of false alarms and note that these studies use study materials and memory tests that are different from the DRM and categorical associate paradigms in that critical lures are externally provided rather than generated. We speculate that the effectiveness of memory for visual processing for reducing false memory may depend on the source of the false memory, but this remains for future research

Three Interventions for Financial Therapy: Fostering an Examination of Financial Behaviors and Beliefs

Three interventions that address the emotional components of handling finances are proposed. Drawn from a stepwise model of financial therapy, the three interventions introduced here have the specific aim of incorporating the emotional attributes of traditional financial behaviors and beliefs. First, the Financial Genogram identifies family of origin issues that may affect financial behaviors; second, the Financial Landscape intervention is used when emotional stress occurs in collecting and examining financial documents; and third, the Financial Mirror broadens clients’ perspectives of their financial behaviors. Issues in future research and implementation of the Five Step model are addressed in treating financially distressed clients

Phage Therapy of Mycobacterium Infections: Compassionate Use of Phages in 20 Patients With Drug-Resistant Mycobacterial Disease

Mycobacteriophage; Nontuberculous mycobacteria; Phage therapyMicobacteriófago; Micobacterias no tuberculosas; Terapia de fagosMicobacteriòfag; Micobacteris no tuberculosos; Teràpia de fagsBackground Nontuberculous Mycobacterium infections, particularly Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification. Methods Mycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid. Results No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favorable clinical or microbiological responses were observed in 11 patients. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in 8 patients, potentially contributing to lack of treatment response in 4 cases, but were not consistently associated with unfavorable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these. Conclusions Phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections

Differential susceptibility to obesity between male, female and ovariectomized female mice

All authors are with the Department of Nutritional Sciences, University of Texas at Austin, Austin, Texas, USABackground: The prevalence of obesity has increased dramatically. A direct comparison in the predisposition to obesity between males, premenopausal females, and postmenopausal females with various caloric intakes has not been made. To determine the effects of sex and ovarian hormones on the susceptibility to obesity, we conducted laboratory studies with mice. To eliminate confounders that can alter body weight gain, such as age and food consumption; we used mice with the same age and controlled the amount of calories they consumed. -- Methods: We determined sex-specific susceptibility to obesity between male, non-ovariectomized female, and ovariectomized female mice. To compare susceptibility to gaining body weight between males and females, animals from each sex were exposed to either a 30% calorie-restricted, low-fat (5% fat), or high-fat (35% fat) diet regimen. To establish the role of ovarian hormones in weight gain, the ovaries were surgically removed from additional female mice, and then were exposed to the diets described above. Percent body fat and percent lean mass in the mice were determined by dual energy x-ray absorptiometry (DEXA). -- Results: In all three diet categories, male mice had a greater propensity of gaining body weight than female mice. However, ovariectomy eliminated the protection of female mice to gaining weight; in fact, ovariectomized female mice mimicked male mice in their susceptibility to weight gain. In summary, results show that male mice are more likely to become obese than female mice and that the protection against obesity in female mice is eliminated by ovariectomy. -- Conclusion: Understanding metabolic differences between males and females may allow the discovery of better preventive and treatment strategies for diseases associated with body weight such as cancer and cardiovascular disease.Nutritional [email protected]

The discovery of potent, selective, and reversible inhibitors of the house dust mite peptidase allergen Der p 1: an innovative approach to the treatment of allergic asthma.

Blocking the bioactivity of allergens is conceptually attractive as a small-molecule therapy for allergic diseases but has not been attempted previously. Group 1 allergens of house dust mites (HDM) are meaningful targets in this quest because they are globally prevalent and clinically important triggers of allergic asthma. Group 1 HDM allergens are cysteine peptidases whose proteolytic activity triggers essential steps in the allergy cascade. Using the HDM allergen Der p 1 as an archetype for structure-based drug discovery, we have identified a series of novel, reversible inhibitors. Potency and selectivity were manipulated by optimizing drug interactions with enzyme binding pockets, while variation of terminal groups conferred the physicochemical and pharmacokinetic attributes required for inhaled delivery. Studies in animals challenged with the gamut of HDM allergens showed an attenuation of allergic responses by targeting just a single component, namely, Der p 1. Our findings suggest that these inhibitors may be used as novel therapies for allergic asthma

The mTOR regulated RNA-binding protein LARP1 requires PABPC1 for guided mRNA interaction.

The mammalian target of rapamycin (mTOR) is a critical regulator of cell growth, integrating multiple signalling cues and pathways. Key among the downstream activities of mTOR is the control of the protein synthesis machinery. This is achieved, in part, via the co-ordinated regulation of mRNAs that contain a terminal oligopyrimidine tract (TOP) at their 5'ends, although the mechanisms by which this occurs downstream of mTOR signalling are still unclear. We used RNA-binding protein (RBP) capture to identify changes in the protein-RNA interaction landscape following mTOR inhibition. Upon mTOR inhibition, the binding of LARP1 to a number of mRNAs, including TOP-containing mRNAs, increased. Importantly, non-TOP-containing mRNAs bound by LARP1 are in a translationally-repressed state, even under control conditions. The mRNA interactome of the LARP1-associated protein PABPC1 was found to have a high degree of overlap with that of LARP1 and our data show that PABPC1 is required for the association of LARP1 with its specific mRNA targets. Finally, we demonstrate that mRNAs, including those encoding proteins critical for cell growth and survival, are translationally repressed when bound by both LARP1 and PABPC1

Spatial Dimensions of Dengue Virus Transmission across Interepidemic and Epidemic Periods in Iquitos, Peru (1999–2003)

To target prevention and control strategies for dengue fever, it is essential to understand how the virus travels through the city. We report spatial analyses of dengue infections from a study monitoring school children and adult family members for dengue infection at six-month intervals from 1999–2003, in the Amazonian city of Iquitos, Peru. At the beginning of the study, only DENV serotypes 1 and 2 were circulating. Clusters of infections of these two viruses were concentrated in the northern region of the city, where mosquito indices and previous DENV infection were both high. In 2002, DENV-3 invaded the city, replacing DENV-1 and -2 as the dominant strain. During the invasion process, the virus spread rapidly across the city, at low levels. After this initial phase, clusters of infection appeared first in the northern region of the city, where clusters of DENV-1 and DENV-2 had occurred in prior years. Most of the clusters we identified had radii >100 meters, indicating that targeted or reactive treatment of these high-risk areas might be an effective proactive intervention strategy. Our results also help explain why vector control within 100 m of a dengue case is often not successful for large-scale disease prevention

Tissue-specific immunopathology in fatal COVID-19

Funding: Inflammation in COVID-19: Exploration of Critical Aspects of Pathogenesis (ICECAP) receives funding and support from the Chief Scientist Office (RapidResearch in COVID-19 programme [RARC-19] funding call, “Inflammation in Covid-19: Exploration of Critical Aspects of Pathogenesis; COV/EDI/20/10” to D.A.D., C.D.L., C.D.R., J.K.B., and D.J.H.), LifeArc (through the University of Edinburgh STOPCOVID funding award to K.D., D.A.D., and C.D.L.), UK Research and Innovation (UKRI) (Coronavirus Disease [COVID-19] Rapid Response Initiative; MR/V028790/1 to C.D.L., D.A.D., and J.A.H.), and Medical Research Scotland (CVG-1722-2020 to D.A.D., C.D.L., C.D.R., J.K.B., and D.J.H.). C.D.L. is funded by a Wellcome Trust Clinical Career Development Fellowship(206566/Z/17/Z). J.K.B. and C.D.R. are supported by the Medical Research Council (grant MC_PC_19059) as part of the International Severe AcuteRespiratory Infection Consortium Coronavirus Clinical Characterisation Consortium (ISARIC-4C). D.J.H., I.H.U., and M.E. are supported by the Industrial Centre for Artificial Intelligence Research in Digital Diagnostics. S.P. is supported by Kidney Research UK, and G.T. is supported by the Melville Trust for the Cure and Care of Cancer. Identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and sequencing work was supported by theU.S. Food and Drug Administration grant HHSF223201510104C (“Ebola Virus Disease: correlates of protection, determinants of outcome and clinicalmanagement”; amended to incorporate urgent COVID-19 studies) and contract 75F40120C00085 (“Characterization of severe coronavirus infection inhumans and model systems for medical countermeasure development and evaluation”; awarded to J.A.H.). J.A.H. is also funded by the Centre of Excellence in Infectious Diseases Research and the Alder Hey Charity. R.P.-R. is directly supported by the Medical Research Council Discovery Medicine North Doctoral Training Partnership. The group of J.A.H. is supported by the National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections at the University of Liverpool in partnership with Public Health England and in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.Rationale: In life-threatening Covid-19, corticosteroids reduce mortality, suggesting that immune responses have a causal role in death. Whether this deleterious inflammation is primarily a direct reaction to the presence of SARS-CoV-2 or an independent immunopathologic process is unknown. Objectives: To determine SARS-CoV-2 organotropism and organ-specific inflammatory responses, and the relationships between viral presence, inflammation, and organ injury. Methods: Tissue was acquired from eleven detailed post-mortem examinations. SARS-CoV-2 organotropism was mapped by multiplex PCR and sequencing, with cellular resolution achieved by in situ viral spike protein detection. Histological evidence of inflammation was quantified from 37 anatomical sites, and the pulmonary immune response characterized by multiplex immunofluorescence. Measurements and main results: Multiple aberrant immune responses in fatal Covid-19 were found, principally involving the lung and reticuloendothelial system, and these were not clearly topologically associated with the virus. Inflammation and organ dysfunction did not map to the tissue and cellular distribution of SARS-CoV-2 RNA and protein, both between and within tissues. An arteritis was identified in the lung, which was further characterised as a monocyte/myeloid-rich vasculitis, and occurred along with an influx of macrophage/monocyte-lineage cells into the pulmonary parenchyma. In addition, stereotyped abnormal reticulo-endothelial responses, including excessive reactive plasmacytosis and iron-laden macrophages, were present and dissociated from viral presence in lymphoid tissues. Conclusions: Tissue-specific immunopathology occurs in Covid-19, implicating a significant component of immune-mediated, virus-independent immunopathology as a primary mechanism in severe disease. Our data highlight novel immunopathological mechanisms, and validate ongoing and future efforts to therapeutically target aberrant macrophage and plasma cell responses as well as promoting pathogen tolerance in Covid-19.Publisher PDFPeer reviewe