Miracle-dz/UniFAR-FTUs huggingface dataset:
Underlying mechanisms of pronociceptive consequences of prolonged morphine exposure

The opioid analgesics, commonly exemplified by morphine, represent the best option for the treatment of severe pain and for the management of chronic pain states, of both malignant and nonmalignant origin. It is well recognized that the prolonged use of opioids is associated with a requirement for ever‐increasing doses in order to maintain pain relief at an acceptable and consistent level. This phenomenon is termed analgesic tolerance. While the concept that tolerance can develop as a result of cellular adaptations to the presence of the opioid has been proposed, it is now becoming abundantly clear that tolerance may also be related to a state of hyperalgesia that results from exposure to the opioid itself. Patients who receive long‐term opioid therapy sometimes develop unexpected, abnormal pain. Similar paradoxical opioid‐induced pain has been confirmed in a number of animal studies, even during the period of continuous opioid delivery. A number of recent studies have demonstrated that such pain may be secondary to neuroplastic changes that occur in the brain and spinal cord. One such change may be the activation of descending pain facilitation mechanisms arising from the rostral ventromedial medulla (RVM) elicited in part by increased activity of cholecystokinin (CCK) in the RVM. A cascade of pronociceptive events may follow, such as opioid‐induced upregulation of spinal dynorphin levels that promotes enhanced input from primary afferent nociceptors. This mechanism appears to depend on intact descending pathways from the RVM, since interrupting this pathway abolishes enhanced abnormal pain. Furthermore, extended opioid exposure also can elicit increased calcitonin gene related peptide (CGRP) and substance P expression in the dorsal root ganglia. It is probable that increased pain elicited by opioids is a critical factor in the behavioral manifestation of opioid tolerance because the same manipulations that block abnormal pain also block antinociceptive tolerance. Taken together, such studies show that opioids elicit systems‐level adaptations resulting in pain due to descending facilitation, upregulation of spinal dynorphin, and enhanced, evoked release of excitatory transmitters from primary afferents. These adaptive changes in response to sustained exposure to opioids indicate the need for the evaluation of the clinical consequences of long‐term opioid administration. Additionally, these findings suggest a need for novel chemistry involving design of agents that may counteract opiate‐induced neuroplastic adaptations resulting in pain relief without analgesic tolerance. © 2005 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2005
Interaction of mazindol with alcohol in mice

Combined anorectic‐alcohol misuse is a prevalent problem in Brazil. In order to understand better the interactive effects of ethanol (EtOH) and mazindol (MZ), we examined the effects of EtOH (1.2 g/kg) and MZ (5.0 mg/kg) given alone or in combination, on mouse behaviour. The results indicate that EtOH plus MZ induces a significantly greater increase in locomotor activity of mice than either constituent alone. However, no such interactive effect was detected in the place preference and in the plus‐maze test of anxiety. MZ given alone was found to increase the locomotor activity and to possess rewarding effects as measured in the place preference conditioning. At the dose selected, EtOH alone showed anxiolytic and rewarding effects. These results provide some evidence of increased behavioural effects in mice due to combinations of EtOH and MZ. These findings suggest that a major determinant of combined anorectic‐alcohol misuse may be the increased stimulating effects produced by such combination.
A framework for genetic service provision for haemophilia and other inherited bleeding disorders

Summary. This framework document offers guidance to patients, doctors, nurses, laboratory scientists, funders and hospitals on the provision of clinical and laboratory genetic services for haemophilia. With recent advances in molecular laboratory techniques it is now possible to give the vast majority of individual patients and family members very reliable genetic information. To enable these genetic data to be used for both the optimal treatment of patients with inherited bleeding disorders and for appropriate reproductive decisions in carriers, there needs to be a clear and robust framework for systematically acquiring the necessary clinical, personal, family and laboratory information upon which decisions can be made. This document provides guidance on the range and standards of clinical and laboratory genetic services which should be offered to patients and their families. Included are arrangements for genetic counselling and testing (including consent and confidentially issues), management of early pregnancy, standards for laboratory genetic services, as well as advice on data storage, security and retrieval.
Localization of a cerebellar timing process using PET

We used positron emission tomography (PET) to localize a cerebellar timing function.Six healthy volunteers estimated time differences by comparing a test interval (defined by two tones) with a standard interval. In the timing condition, subjects lifted their right index finger if the test interval was shorter and their right middle finger if it was longer than the standard interval. In the control condition, the two intervals were identical and subjects had to alternate between lifting their index and middle fingers. We examined regional cerebral blood flow (rCBF) using the standard C15 O2 inhalation technique. Comparison of control and rest conditions revealed significant increases of rCBF during the control condition in the inferior parts of the ipsilateral cerebellar hemisphere, reflecting finger movements. Comparison of timing and control conditions showed additional activations of the cerebellar vermis and hemispheres bilaterally during the timing condition, reflecting the cerebellar timing process. We conclude that the cerebellum is involved in time-critical perception (``timing''). This nonmotor task can be separated from a motor task (finger movement). NEUROLOGY 1995;45: 1540-1545
19F NMR magnetization transfer between 5‐FBAPTA and its complexes. An alternative means for measuring free Ca2+ concentration, and detection of complexes with protein in erythrocytes

The 19F NMR Ca2+‐indicator molecule 5,5'‐difluoro‐1,2‐bis(o‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid (5‐FBAPTA) was used in a procedure that enhances its range of applications to measuring free Ca2+ concentrations in buffer solutions and human erythrocytes. Even if the signal from the Ca‐5‐FBAPTA complex was not visible, the concentration of the complex could be calculated from saturation transfer spectra. This was demonstrated with well characterized buffer solutions in vitro and shown to also apply to concentrated haemolysates. The analysis required a precise estimate of the dissociation rate constant of the complex; this was found to be 295/s at 37°C and the corresponding association rate constant was 4.1×108 L/mol/s. These values differ from those obtained previously in different buffer conditions and by two different NMR methods. A series of spectra were acquired from haemolysates containing 5‐FBAPTA, in which saturating irradiation was applied at a frequency that was progressively off‐set from the carrier frequency. Saturation transfer to the free 5‐FBAPTA was seen from irradiation at frequencies different from that of Ca‐5‐FBAPTA, thus suggesting the presence of complexes with proteins.
It’s the Motive That Counts: Perceived Sacrifice Motives and Gratitude in Romantic Relationships

Gratitude is robustly linked to many positive outcomes for individuals and relationships (e.g., greater life and relationship satisfaction). However, little is known about how romantic partners come to feel grateful for each other’s pro-relational acts, such as when a partner makes a sacrifice. The present research examines how perceptions of partner sacrifice motives evoke gratitude. We distinguish between partner, relationship, and self-focused motives, and how they are guided by approach or avoidance orientations. We expected that perceiving a partner to sacrifice for partner-focused approach motives (i.e., to promote the partner’s well-being) should evoke gratitude, as this type of motive may signal a genuine departure from self-interest. Moreover, we expected these motives to provoke greater perceptions of partner responsiveness, which should partially explain why they elicit gratitude. In contrast, perceiving a partner to sacrifice for relationship-focused motives (e.g., to promote the well-being of the relationship), or self-focused motives (e.g., to feel good about oneself), should not evoke gratitude—irrespective of an approach or avoidance orientation—as these motives may, to some extent, be perceived as tainted by self-interest. Two studies of romantic couples (N = 413), using diary methods (Studies 1 and 2) and having couples converse about a major sacrifice in the laboratory (Study 2), consistently showed that perceived partner-focused approach motives promote gratitude and that this association is partly mediated by perceived partner responsiveness. In contrast, relationship and self-focused motives (approach and avoidance oriented) were not associated with gratitude. Implications regarding perceiving and displaying sacrifice motives are discussed.
Prevalence and factors associated with thriving in older adulthood: a 10-year population-based study.

BACKGROUND Interest in the determinants of "successful aging" is growing. Nonetheless, successful aging remains ill defined, and its appropriate measurement is hotly contested. Most studies have focused on the absence of disability or deficits in physical performance as outcomes. The present study extends this research by using the Health Utilities Index Mark 3 (HUI3), a multidimensional measure of health status, to examine the maintenance of exceptionally good health among older participants in the Canadian National Population Health Survey (1994--2004). METHODS The maintenance of exceptionally good health in old age was examined prospectively among 2432 individuals (65-85 years old at baseline) who met the inclusion criteria. The participants were classified into one of four health trajectories: thrivers (who maintained exceptional health with no or only mild disability), nonthrivers (who experienced a moderate or severe disability), the deceased, and the institutionalized. RESULTS In 10 years of follow-up, 190 (8%) were thrivers (HUI3 score > or = 0.89 at all interviews), 1076 (47%) were nonthrivers, 893 (36%) died, and 273 (9%) were institutionalized. The maintenance of exceptionally good health among the elderly participants was related to younger age at baseline, socioeconomic status (higher income), psychosocial factors (including lower psychological distress), and behavioral factors (never smoked and moderate alcohol use). CONCLUSIONS The maintenance of exceptionally good health in old age is related, at least in part, to modifiable lifestyle factors. However, elevated socioeconomic status also distinguishes those who are able to maintain exceptionally good health.
Meeting the unique challenges of assessing internet gaming disorder.

appears to impact youth and young adults to a large extent [6,7], while the vast majority of individuals who seek treatment for gambling are middle-aged or older [3,4]. King & Delfabbro [1] note that a potential differentiation between gambling and gaming relates to skill. Although we agree that one’s success in the outcomes of video games is usually more skill-dependent than in many forms of gambling, the nature of a disorder, and consideration regarding its treatment, generally does not depend upon one’s skills, be they perceived or real. Will focusing upon skill be useful in treating gaming? We are not sure. However, we completely agree that a cognitive intervention adapted from gambling treatment that addresses erroneous beliefs related to randomness, chance and probabilities will not be a primary therapeutic approach for reducing gaming. Just as preoccupation is only one potential aspect of internet gaming disorder, it is only one aspect of other addictions, and psychiatric disorders more generally. Overall functioning is considered in diagnoses, and although irrational beliefs can exist in the context of disordered gambling, these beliefs are not a criterion for that disorder. Diagnostic criteria do not need to cover all mechanisms of a disorder, nor all relevant elements of treatment; instead, their intent is to distinguish reliably and validly between individuals with and without a disorder. Expressions of psychiatric disorders, and their specific symptoms, also vary across cultures and individuals. The goal of psychiatric diagnosis is to transcend some of the inherent individual differences, while classifying clinically problematic expressions. As the field of addictions moves forward, it will be imperative to evaluate empirically similarities and differences across these conditions and their treatment.
Molecular mechanisms in the initiation phase of Wallerian degeneration

Axonal degeneration is an early hallmark of nerve injury and many neurodegenerative diseases. The discovery of the Wallerian degeneration slow mutant mouse, in which axonal degeneration is delayed, revealed that Wallerian degeneration is an active progress and thereby illuminated the mechanisms underlying axonal degeneration. Nicotinamide mononucleotide adenylyltransferase 2 and sterile alpha and armadillo motif‐containing protein 1 play essential roles in the maintenance of axon integrity by regulating the level of nicotinamide adenine dinucleotide, which seems to be the key molecule involved in the maintenance of axonal health. However, the function of nicotinamide mononucleotide remains debatable, and we discuss two apparently conflicting roles of nicotinamide mononucleotide in Wallerian degeneration. In this article, we focus on the roles of these molecules in the initiation phase of Wallerian degeneration to improve our understanding of the mechanisms underpinning this phenomenon.
Effectiveness of Application of PLISSIT Counseling Model on Sexuality for Breast Cancer's Women Undergoing Treatment

Background: A breast cancer's diagnosis and treatment can bring changes related to women’s body image and sexuality, which can have a devastating impact on intimate relationships and sexuality. The study aim to examine the effectiveness of PLISSIT Counseling Model on female sexuality, body image and couple satisfaction for breast cancer women undergoing treatment. Subjects &methods a quasi-experimental design was used. The study was conducted at Out-patient Oncology Institute, Menoufia University-Egypt. A purposive sample of 66 women with breast cancer was included. Four tools were used to collect data. , a structured interviewing questionnaire, body image scale, female sexual function index (FSDI), the revised dyadic adjustment scale. Results. A significant relationship was found between treatment side effects pre and post intervention regarding nausea & vomiting, diarrhea and pain. The mean score of body image, couple satisfaction and sexual dysfunction were improved after application of PLISST counseling model. Conclusion: application of PLISSIT model was effective in enhancing sexual functioning, body image and couple satisfaction for breast cancer women under treatment regimen. Recommendation: Adopting PLISSIT sexual counseling model in addressing sexual dysfunction in a cancer treatment institutions. Applying the evidence –based nursing interventions to address and manage the effects of breast cancer on sexuality.
The EMIP-FR Study: the evolution of scientific background as a non-controlled parameter.

We have read with interest the editorial comment on the final report of the study EMIP-FR. We completely agree with Dr Tognoni on the importance of publishing the results of negative clinical studies. We also agree on the need to be extremely cautious in deriving wishful conclusions on the potential positive effects based on ‘a posteriori’ subset analysis, although we think that the possibility of performing such new studies cannot be rejected ‘a priori’. If additional investigations provide a sound mechanistic explanation for the selective beneficial effect of trimetazidine in patients with acute myocardial infarction not receiving thrombolytic therapy the feasibility and potential benefits of new clinical studies to test this hypothesis should be considered and weighed against the risk and costs. However, we disagree with Tognoni’s extrapolations and statements regarding the clinical relevance of reperfusion injury. While the clinical importance of reperfusion injury may be debatable, it is simply a matter of logic that the negative results of a particular intervention against a particular hypothetical mechanism of reperfusion injury do not exclude the existence of the phenomenon, its clinical relevance, or the possibility of its prevention by other therapeutic interventions. This is more so because ischaemia–reperfusion leads to extremely complex and imperfectly understood biochemical derangements that can eventually lead to cell death by necrosis or apoptosis. Among them oxygen free radicals, the mechanism hypothetically targeted by trimetazidine in the EMIP Project, could be of lesser importance. The evidence that antiradical treatments may limit necrosis after transient coronary occlusion is weak and highly controversial. On the contrary, there is increasingly solid evidence that interventions set up to interfere with other pathomechanisms of cell death, like alterations of cellular cation homeosthasis leading to excessive contractile activation and hypercontracture, can effectively limit myocardial cell death when applied at the time of reperfusion. The main contribution of the EMIP Project to the issue of the clinical relevance of reperfusion injury could remind us that the era during which reperfusion injury was synonymous with oxygen free radical injury is well over.
Regulation of naphthalene catabolic genes of plasmid NAH7

Tn5 insertion mutations defining a regulatory gene, nahR, of the naphthalene catabolic pathway encoded by the NAH7 plasmid were mapped within a small NAH7 region only a few hundred bases upstream of the nahG gene, the most promoter-proximal gene of the nahGHIJK operon. The nahR mutations blocked the induction of both the nahABCDEF and nahGHIJK operons, and the defect was completely corrected in the presence of the wild-type allele in a trans position. The pleiotropic, recessive, and negative nature of these mutations indicates that the nahR gene specifies a regulatory element which is required to activate both nah operons.
Analysis of user need in image archives

This paper describes a project in which an analysis was undertaken of user queries addressed to seven libraries which manage archives of widely varying still and moving image material. The sampling procedure is described, in which queries obtained from each library were broadly categorised by image content, identification and accessibility. Attention is focused on the image content requests, for which a categorisation based on facet analysis is developed. The analytical tool which is used for this purpose is based on a schema already well established for the analysis of levels of meaning in images. The project demonstrates the possibility of formulating a general categorisation of requests which seek widely different still and moving image material. The paper concludes with observations on the potential value of embedding such a schema within the user interface of unmediated-query visual information retrieval systems.
Severe Hypotension Associated With the Prone Position in a Child With Scoliosis and Pectus Excavatum Undergoing Posterior Spinal Fusion

Study Design Case report. Objective We report a case of severe hypotension associated with prone positioning in a child with scoliosis and pectus excavatum. Summary of Background Data Pectus excavatum is commonly associated with scoliosis and can impact cardiac function. Methods Retrospective case analysis. Results After a modified Ravitch procedure to repair the pectus excavatum, the patient was able to undergo posterior spinal fusion. Conclusions Pediatric deformity surgery requires a multidisciplinary approach.
Lysosomes as key organelles in the pathogenesis of prion encephalopathies

The causation, structural origin, and mechanism of formation of spongiform lesions in transmissible encephalopathies are unknown. We have used immunogold electron microscopy to locate ubiquitin conjugates, hsp 70, and β‐glucuronidase (markers of the lysosomal compartment) and prion protein(PrP) in both control and scrapie‐infected mouse brain.
Temperature and pressure denaturation of chignolin: Folding and unfolding simulation by multibaric‐multithermal molecular dynamics method

A multibaric‐multithermal molecular dynamics (MD) simulation of a 10‐residue protein, chignolin, was performed. All‐atom model with the Amber parm99SB force field was used for the protein and the TIP3P model was used for the explicit water molecules. This MD simulation covered wide ranges of temperature between 260 and 560 K and pressure between 0.1 and 600 MPa and sampled many conformations without getting trapped in local‐minimum free‐energy states. Folding events to the native β‐hairpin structure occurred five times and unfolding events were observed four times. As the temperature and/or pressure increases, fraction of folded chignolin decreases. The partial molar enthalpy change ΔH and partial molar volume change ΔV of unfolding were calculated as ΔH = 24.1 ± 4.9 kJ/mol and ΔV = −5.6 ± 1.5 cm3/mol, respectively. These values agree well with recent experimental results. Illustrating typical local‐minimum free‐energy conformations, folding and unfolding pathways were revealed. When chignolin unfolds from the β‐hairpin structure, only the C terminus or both C and N termini open first. It may undergo an α‐helix or 310‐helix structure and finally unfolds to the extended structure. Difference of the mechanism between temperature denaturation and pressure denaturation is also discussed. Temperature denaturation is caused by making the protein transferred to a higher entropy state and making it move around more with larger space. The reason for pressure denaturation is that water molecules approach the hydrophobic residues, which are not well hydrated at the folded state, and some hydrophobic contacts are broken. Proteins 2012;. © 2012 Wiley Periodicals, Inc.
The addition of opioids to local anaesthetics in brachial plexus block: the comparative effects of morphine, buprenorphine and sufentanil

We compared the duration of analgesia produced by a mixture of lignocaine and bupivacaine, either alone or combined with morphine (75 μgkg−1), buprenorphine (3 μgkg−1) or sufentanil (0.2 μgkg−1) in 80 patients after brachial plexus block for orthopaedic surgery of the upper limb. The characteristics of analgesia were evaluated hourly using a visual analogue scale. The analgesia was considered satisfactory for scores of 30 or less. The median duration (range) of satisfactory analgesia was: 11.5 (8–15) h without an opioid, 21 (9–27) h with morphine, 20 (14–34) h with buprenorphine and 24.5 (11–38) h with sufentanil. We conclude that the addition of an opioid to a local anaesthetic mixture lengthens the duration of analgesia.