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Functional-anatomic study of episodic retrieval using fMRI. I. Retrieval effort versus retrieval success.

A number of recent functional imaging studies have identified brain areas activated during tasks involving episodic memory retrieval. The identification of such areas provides a foundation for targeted hypotheses regarding the more specific contributions that these areas make to episodic retrieval. As a beginning effort toward such an endeavor, whole-brain functional magnetic resonance imaging (fMRI) was used to examine 14 subjects during episodic word recognition in a block-designed fMRI experiment. Study conditions were manipulated by presenting either shallow or deep encoding tasks. This manipulation yielded two recognition conditions that differed with regard to retrieval effort and retrieval success: shallow encoding yielded low levels of recognition success with high levels of retrieval effort, and deep encoding yielded high levels of recognition success with low levels of effort. Many brain areas were activated in common by these two recognition conditions compared to a low-level fixation condition, including left and right prefrontal regions often detected during PET episodic retrieval paradigms (e.g., R. L. Buckner et al., 1996, J. Neurosci. 16, 6219-6235) thereby generalizing these findings to fMRI. Characterization of the activated regions in relation to the separate recognition conditions showed (1) bilateral anterior insular regions and a left dorsal prefrontal region were more active after shallow encoding, when retrieval demanded greatest effort, and (2) right anterior prefrontal cortex, which has been implicated in episodic retrieval, was most active during successful retrieval after deep encoding. We discuss these findings in relation to component processes involved in episodic retrieval and in the context of a companion study using event-related fMRI.

Adolescent↗

Clinical and cognitive factors associated with verbal memory task performance in patients with schizophrenia.

OBJECTIVE: The authors have previously shown the role of depression, slowing of processing speed, and selective attention deficit in verbal memory task performance in schizophrenia. They wished to determine the specific contribution of each of these factors to various types of memory impairment. METHOD: The negative symptom score from the Positive and Negative Syndrome Scale, the Hamilton Depression Rating Scale score, a measure of processing speed, and a measure of selective attention were entered as predictors in regression analyses. Furthermore, analyses of covariance were conducted on the memory measures to test the significance of the differences between schizophrenic patients and healthy comparison subjects after control for processing speed and selective attention. RESULTS: Depression was associated only with deep encoding reflected by semantic clustering. Selective attention was associated only with superficial encoding reflected by serial recall. Slowing of processing speed was associated with both deep and superficial encoding. Negative symptoms were not associated with memory impairment except for the avolition item from the Scale for the Assessment of Negative Symptoms. Processing speed accounted for all the group differences on the memory measures that reflected superficial encoding. In addition, a subgroup of patients with no or minor depression was not significantly impaired on deep encoding relative to the healthy comparison group. CONCLUSIONS: The authors suggest that verbal memory impairment in schizophrenia is a consequence of depression and slowness, rather than a primary feature of the disease.

Adult↗

Ultrasound screening for deep venous thrombosis after total knee arthroplasty. 2-year reassessment.

The efficacy of ultrasound compared with ascending venography for the detection of deep venous thrombosis immediately after total knee arthroplasty was assessed after a 2-year interval. One hundred thirty-seven patients were eligible for the study; however, 31 patients received only one of the screening methods and a color Doppler examination was inconclusive in six patients. Therefore, 100 patients had a Doppler examination and a venogram. Overall, the sensitivity of ultrasound was 85%, the specificity 97%, the positive predictive value 85%, the negative predictive value 97%, and the accuracy 95%. The sensitivity in the calf was 83%, in the popliteal vein 86%, and in the femoral vein 100%. Two years ago, the initial assessment of ultrasound for the detection of deep venous thrombosis after surgery in patients who had total joint arthroplasty revealed a 75% sensitivity, 99% specificity, 91% positive predictive value, 97% negative predictive value, and 97% accuracy. The sensitivity in the calf was 83%; the sensitivity in the popliteal vein was 40%; and the sensitivity in the femoral vein was 50%. After 2 years of using this screening test with one technician and one radiologist, an improvement with this noninvasive technique was shown. However, it was found that Doppler imaging is not as sensitive as venography for detecting calf thrombi. Any imaging technique should be validated by each institution to determine the validity of the instrument and the learning curve of the technician administering the examination.

Adult↗

'Deep-sea spiders' that walk through the water

Deep-sea isopods of the family Munnopsidae exhibit four modes of swimming: forward striding, slow backward pedalling, fast backward pedalling and escape, the first two of which use asymmetric phases of leg movement. Instead of moving the left and right limbs (pereopods, P2­P7) of a segment in-phase (e.g. RP2LP2, RP3LP3, RP4LP4), as do most aquatic insects, leg movement is more like that of fast-walking insects, where closest synchrony occurs between diagonal limbs (e.g. RP2LP3, RP3LP4, RP4LP2). This is similar to the alternating tripod gait used by many animals on land to prevent them from toppling over. It therefore seems likely that this group of isopods learned to walk before they could swim.

Journal Article↗

Mapping cerebral blood flow changes during auditory-cued conditioned fear in the nontethered, nonrestrained rat.

Conditioned fear (CF) is one of the most frequently used behavioral paradigms; however, little work has mapped changes in cerebral perfusion during CF in the rat-the species which has dominated CF research. Adult rats carrying an implanted minipump were exposed to a tone (controls, n = 8) or a tone conditioned in association with footshocks (CS group, n = 9). During reexposure to the tone 24 h later, animals were injected intravenously by remote activation with [14C]-iodoantipyrine using the pump. Significant group differences in regional CBF-related tissue radioactivity (CBF-TR) were determined by region-of-interest analysis of brain autoradiographs, as well as in the reconstructed, three-dimensional brain by statistical parametric mapping (SPM). CS animals demonstrated significantly greater, fear-enhanced increases in CBF-TR in auditory cortex than controls. The lateral amygdala was activated, whereas the basolateral/basomedial and central amygdala were deactivated. In the hippocampus and medial prefrontal cortex, CBF-TR increased significantly ventrally but not dorsally. Significant activations were noted in medial striatum and the thalamic midline and intralaminar nuclei. However, the ventrolateral/dorsolateral striatum and its afferents from motor and somatosensory cortex were deactivated, consistent with the behavioral immobility seen during CF. Significant activations were also noted in the lateral septum, periaqueductal gray, and deep mesencephalic nucleus/tegmental tract. Our results show that auditory stimuli endowed with aversive properties through conditioning result in significant redistribution of cerebral perfusion. SPM is a useful tool in the brain mapping of complex rodent behaviors, in particular the changes in activation patterns in limbic, thalamic, motor, and cortical circuits during CF.

Animals↗

Mechanisms underlying disease-causing variants in promoters and enhancers.

The study of human monogenic disorders has been a powerful tool for generating a deep understanding of protein function/dysfunction and for uncovering underlying biological mechanisms. Here we explore the insights that an expanding catalog of noncoding monogenic disease variants can provide into the functions of the noncoding genome. We focus on small genetic alterations (one to a few tens of base pairs) in cis-regulatory elements-promoters, enhancers and silencers-and their potential mechanisms of action, such as loss or gain of function. We discuss the challenges in determining pathogenicity for variants in the noncoding genome, discuss why there might be so few concrete examples and highlight the opportunities for advancing this area of human genetics by using experimental and machine-learning tools.

Journal Article↗

Geographic information systems and the spiritual dimension of health: a short position paper.

The WHO's well known definition of health stressed the indivisibility of human well-being, physical and otherwise, by stating that health is "not merely the absence of disease or infirmity". The spiritual dimension of health is well covered in the medical literature. Different locations on Earth are associated with different interrelated profiles: physical, biological, environmental, socio-economic, cultural, and also spiritual profiles, that do affect and are affected by health (including its spiritual dimension), disease, healthcare, and pastoral care. A number of reviews have been recently published covering the use of Geographic Information Systems (GIS) in understanding and harnessing the importance of location in the health sector. However, no publication so far has discussed the role of GIS in relation to the spiritual dimension of health. This position paper is an attempt to fill in this gap without going into deep details. GIS role in pastoral care ranges from assisting in pattern and trend detection, and in informed decision-making and resource management, to providing routing and educational functions, and even assessing the impact of missionary radio broadcasts. A review of some of the software tools that are currently available in this field is also provided. GIS are ideal tools for improving and coordinating the integration of the health (physical), social, and spiritual/ pastoral dimensions of individual and community care. However to achieve the full potential of GIS in these areas, we still need to combat many cultural and organisational barriers, while making the tools cheaper and much easier to learn and use.

Journal Article↗

Multi-Omics and Integrative Analytics in Natural Products Discovery.

Natural products (NPs) have long been an essential source of new bioactive compounds for drug discovery; however, traditional methods for screening and isolating these compounds can be slow and often yield diminishing returns. Fortunately, advanced multi-omics and computational approaches present powerful solutions to these challenges. This review highlights innovative methodologies that integrate metabolomics, genomics, transcriptomics, and proteomics with bioinformatics and analytical chemistry to accelerate NP discovery. For instance, untargeted metabolomics platforms like high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) and Global Natural Products Social (GNPS) molecular networking allow for comprehensive profiling of new compounds, while targeted isotope-labeling strategies enhance this process. Additionally, genome and metagenome mining tools such as antibiotics and secondary metabolite analysis shell (antiSMASH), Deep Biosynthetic Gene Cluster (DeepBGC), and Pipeline for Reconstructing Integrated Syntheses of Metabolites (PRISM) quickly identify biosynthetic gene clusters (BGCs) in both cultured and uncultured organisms, often using heterologous expression to validate products. Transcriptomic analyses, including RNA sequencing (RNA-seq), co-expression networks, and fluxomics, help clarify how pathways are regulated, while quantitative proteomics techniques like tandem mass tags/isobaric tags for relative and absolute quantitation (TMT/iTRAQ) and label-free methods, along with chemoproteomics approaches such as cellular thermal shift assay and thermal proteome profiling (TPP), uncover molecular targets and their mechanisms of action. This review also places significant emphasis on the role of artificial intelligence (AI) and machine learning (ML) in integrating multi-omics data, spanning activities from constructing gene-metabolite correlation networks to leveraging knowledge graphs and graph neural networks for data fusion and functional prediction. Finally, this review concludes by discussing the synergistic benefits of multi-omics for natural-product discovery, addressing current technical challenges, and exploring future directions toward high-throughput, intelligent data integration for next-generation NP research.

Biological Products↗

Of bedpans and ivory towers? Nurse academics' identities and the sacred and profane: a Bernsteinian analysis and discussion paper.

AIM: In light of debates arising from recent developments in Irish nursing education, this paper analyses tensions in the positioning of nursing in academia in terms of notions of the sacred and profane, and the symbolic boundaries between them, and discusses the implications of this analysis for nurse academics' identities. BACKGROUND: The entry of nursing education to the higher education sector has occurred against a discursive backcloth of opposition which constructs nursing work as either sacred, and under threat from the academy, or profane, and unworthy of a place in it. METHOD: Conceptual resources derived from the work of Basil Bernstein are deployed to analyse the forces driving the loom weaving this discursive backcloth. These forces are conceptualised as deriving from deep-seated fears and anxieties sparked by changes in the strength of symbolically important boundaries between constructions of the sacred and profane in the fields of nursing and higher education. These constructions are explicated. FINDINGS: Bernstein regards secure academic identities as inhering in strong boundaries between disciplines and between the fields of education and work. The transfer of nursing education from health to the higher education sector and nurse academics' attempts to articulate a nursing-discipline specific knowledge base can be understood in these terms. This analysis challenges nurse academics who promote disciplinary eclecticism and those who legitimate academic nursing principally in terms of the acquisition of generic and transferable lifelong learning skills. CONCLUSIONS: To counter a discourse that constructs them as a profane presence in higher education, some nurse academics have articulated a discourse of legitimation that constructs (academic) nursing as a sacred endeavour. Whether this can provide the grounds of their legitimacy and the basis of their careers as distinctively nursing academics is unclear at this stage of nursing's development as an academic discipline.

Attitude↗

Ethics in technological culture: a programmatic proposal for a pragmatist approach.

Neither traditional philosophy nor current applied ethics seem able to cope adequately with the highly dynamic character of our modern technological culture. This is because they have insufficient insight into the moral significance of technological artifacts and systems. Here, much can be learned from recent science and technology studies (STS). They have opened up the black box of technological developments and have revealed the intimate intertwinement of technology and society in minute detail. However, while applied ethics is characterized by a certain "technology blindness," the most influential approaches within STS show a "normative deficit" and display on agnostic or even antagonistic attitude toward ethics. To repair the blind spots of both applied ethics and STS, the authors sketch the contours of a pragmatist approach. They will explore the tasks and tools of a pragmatist ethics and pay special attention to the exploration of future worlds disclosed and shaped by technology and the management of deep value conflicts inherent in a pluralistic society.

Bioethical Issues↗

Two-component arterial blood pressure conditional response in rat.

The objective of these experiments was to quantify the pattern of change in arterial blood pressure (BP) during a discriminative aversive classical conditioning paradigm in rat using a new "high resolution" computer analysis. Sprague-Dawley rats (n = 5) were restrained in a soft, conical cloth pouch and conditioned using a 6 sec. pulsed tone (CS+) followed by a 0.5 sec. tail shock; a steady tone, never followed by shock, served as a CS-. BP peaked at 16.4 +/- 6.5 mm Hg (mean +/- SD) above control at 1.5 +/- 0.1 sec. after onset of CS+. This "first component" ("C1") also occurred during CS- (12.1 +/- 3.8 mm Hg), although the magnitudes of the two were significantly (p < 0.05) different. Another group of rats (n = 8) was treated identically except the tones were 15 seconds long. The conditional BP response consisted of two components. C1 was reminiscent of that seen using the short tone: for CS+ a peak of 13.6 +/- 5.6 mm Hg at 1.5 sec. or, for CS-, of 10.0 +/- 4.3 at 1.3 sec. (p < 0.05). In CS+ trials BP peaked again ("C2," 7.4 +/- 2.5 mm Hg) at 8.3 +/- 1.2 sec. There was no statistically significant C2 for CS- trials, clearly demonstrating discrimination between tones. The unconditional BP response in both groups consisted of two large, closely spaced peaks in BP. Respiration was recorded in 3 additional rats. After shock delivery these subjects often showed a sudden shift between (1) a regular respiratory pattern with moderate chest excursion and (2) apneic episodes interspersed with single, deep breaths. This latter pattern was associated with large, low frequency fluctuations in BP. Continued development of the rat conditioning paradigm is especially warranted because of the ability to record sympathetic nerve activity in intact, awake subjects and the large number of readily available genetic strains, which model human pathological states.

Animals↗

Deep processing activates the medial temporal lobe in young but not in old adults.

Age-related impairments in episodic memory have been related to a deficiency in semantic processing, based on the finding that elderly adults typically benefit less than young adults from deep, semantic as opposed to shallow, nonsemantic processing of study items. In the present study, we tested the hypothesis that elderly adults are not able to perform certain cognitive operations under deep processing conditions. We further hypothesised that this inability does not involve regions commonly associated with lexical/semantic retrieval processes, but rather involves a dysfunction of the medial temporal lobe (MTL) memory system. To this end, we used functional MRI on rather extensive groups of young and elderly adults to compare brain activity patterns obtained during a deep (living/nonliving) and a shallow (uppercase/lowercase) classification task. Common activity in relation to semantic classification was observed in regions that have been previously related to semantic retrieval, including mainly left-lateralised activity in the inferior prefrontal, middle temporal, and middle frontal/anterior cingulate gyrus. Although the young adults showed more activity in some of these areas, the finding of mainly overlapping activation patterns during semantic classification supports the idea that lexical/semantic retrieval processes are still intact in elderly adults. This received further support by the finding that both groups showed similar behavioural performances as well on the deep and shallow classification tasks. Importantly, though, the young revealed significantly more activity than the elderly adults in the left anterior hippocampus during deep relative to shallow classification. This finding is in line with the idea that age-related impairments in episodic encoding are, at least partly, due to an under-recruitment of the medial temporal lobe memory system.

Adult↗

The role of involuntary aware memory in the implicit stem and fragment completion tasks: a selective review.

In this article I argue that an awareness of the study episode that arises involuntarily during an implicit stem/fragment completion test can under some conditions lead to enhanced repetition priming effects, even though subjects are not engaged in intentional retrieval. I review findings that are consistent with this possibility, which include the effects of depth of processing, and of typography match and new association priming following deep encoding. A theoretical account of involuntary aware memory couched within Moscovitch's (1995b) memory systems framework which suggests that the medial-temporal lobe/hippocampal (MTL/H) complex functions as a memory module is outlined. A putative mechanism is proposed in which involuntary aware memory of a studied item enhances the size of repetition priming effects by guiding its selection in preference to the competitors.

Attention↗

[The value of evoked potentials in the neurosurgical intensive care unit].

In the neurosurgical intensive care unit 135 patients were studied by means of multi-modality evoked potentials. The majority part of them had low scores on the Glasgow Coma Scale and a higher lever of coma according to WFNS. This fact explains the high mortality (52 per cent). These patient data were compared with the changes of evoked responses (ER) in order to learn something about the value of ER in localisation of lesions, staging, and predicting the outcome of the patients. A classification of EP alterations is introduced. There was no correlation between alteration of evoked potentials and coma stage. The analysis of latencies and inter-peak latencies revealed no correlation between comatous and alert patients. Cerebral conduction time (CCT) did not give further information. In cases of brainstem lesions the alteration of evoked responses were more marked than in the other patients. Most of the patients died who had initially marked changes in ER. The sensitivity of BAER was greater than of SSEP. A loss of response was more frequent in BAER. In deep coma stages the motor evoked responses disappeared. This fact induces problems in diagnosing brain death. Evoked potentials yield further information in patients with coma and drug therapy. They are useful in follow-ups, esp. in predicting the outcome. Evoked responses complete clinical and findings obtained via the diagnostic equipment.

Brain Damage, Chronic↗

In search of a deep psychobiology of hypnosis: visionary hypotheses for a new millennium.

This search for the deep psychobiological foundations of hypnosis begins with a review of some of the paradoxes of historical hypnosis and the impasse of current theory. It is proposed that further progress requires a deeper investigation of how psychosocial cues can modulate the mechanisms of healing at the CNS, autonomic, neuroendocrine and cellular-genetic levels. The dynamics of hypnotic communication and healing from the cognitive-behavior level to the cellular-genetic are outlined in four stages: (1) Information transduction between the experiences of consciousness and the limbic-hypothalamic-pituitary system; (2) The psychosomatic network of messenger molecules and their receptors; (3) The immediate early gene protein cascade; and (4) State dependent memory, learning and behavior. Neuroscience research is outlined for its contributions to a mathematical model of how a psychobiological approach to the therapeutic applications of hypnosis and the placebo response could facilitate neurogenesis in the human hippocampus and healing at the cellular-genetic-protein level throughout the body. A series of ten hypotheses is proposed as a guide for theory and research in therapeutic hypnosis utilizing DNA chip technology in the new millennium.

Forecasting↗

Developing skills in leg ulcer nursing: the lessons learned.

The high treatment costs of inappropriate leg ulcer management are well referenced. Wide variations in practice have also been reported. A training programme for community nurses has been in place in Leicestershire and Rutland NHS Trust for five years. Its objective is to promote evidence-based leg ulcer management. The aim of this prospective audit was to assess and compare the effectiveness of the compression bandage systems used in the trust: the original Charing Cross system (August 1996 to September 1997) and Robinson's Ultra Four kit (October 1997 to December 1998). All patients with leg ulceration were assessed using the Leicestershire leg ulcer assessment form. This was submitted along with an audit tool to the tissue viability service in exchange for a 12-week supply of compression bandages. The audit form was resubmitted after each subsequent 12-week period until the patient either had healed or was withdrawn from the audit. Differences between the two groups in mobility, previous deep vein thrombosis, fixed ankle deformity, the male to female ratio, duration of ulcer and ulcer surface area were noted. Patients using the Ultra Four kit had faster healing times than those given the Charing Cross system, but this was not statistically significant. Cost comparisons between the previous dressing regimen and compression bandaging showed a significance difference (p < 0.001). There was also a significant reduction in nurse time (p < 0.001). The audit results showed that compression bandaging therapy was an effective method of achieving healing in patients with venous leg ulcers and that significant cost savings were made in terms of dressing cost and nurse time. Furthermore, there were potential benefits in continuing compression therapy for the group of non-healers.

Adult↗

Memory and schizophrenia: differential link of processing speed and selective attention with two levels of encoding.

The purpose of this study was to investigate how underlying cognitive deficits such as a defect in processing speed or in selective attention contributed to different types of memory impairment observed in schizophrenia (superficial vs deep encoding). 49 schizophrenic patients and 40 normal controls were administered a verbal memory task. Superficial encoding was assessed by the ability to recall items in their serial order. Deep encoding was assessed by the ability to organise words into semantic categories. Two measures of processing speed (Digit Symbol Substitution Test and Stroop colour time) and one measure of selective attention (Stroop test) were used. Regression analyses were carried out. In the patient group, processing speed contributed to both superficial and deep encoding, and to a global verbal memory score. Selective attention only contributed to the superficial encoding processes. Thus, slowing of processing speed in schizophrenia seems to be more crucial for memory performance, since it affects memory in a pervasive way.

Adult↗

From blue states to up states: a regional view of NMDA-ethanol interactions.

This article summarizes the proceedings of a symposium at the 2005 Research Society on Alcoholism Meeting in Santa Barbara, California, organized and cochaired by John J. Woodward and Dorit Ron. The purpose of the symposium was to discuss recent findings that extend our understanding of the importance of the N-methyl-D-aspartate (NMDA) receptor as a target for ethanol action in the brain. These receptors are ligand-gated ion channels that are activated by the neurotransmitter glutamate and are critically involved in many forms of synaptic plasticity including those associated with learning and memory. In the first presentation, Dorit Ron presented data showing how activation of Fyn or Src tyrosine kinases differentially regulated the cell surface expression and activity of NR2A and NR2B containing NMDA receptors. Danny Winder discussed the effects of ethanol on NMDA receptor-dependent long-term potentiation in the bed nucleus of the stria terminalis (BNST), a brain region associated with the interaction between stress and drug/alcohol use. In the third presentation, Marisa Roberto described adaptations in the expression and function of NMDA receptors in the central nucleus of the amygdala following chronic exposure to ethanol. Finally, John Woodward described the effects of ethanol on the activity of neurons in deep layers of the prefrontal cortex using a novel slice coculture preparation.

Alcoholism↗